Eldorado Community: Mitglied der Wissenschaftsgemeinschaft Gottfried Wilhelm LeibnizMitglied der Wissenschaftsgemeinschaft Gottfried Wilhelm Leibnizhttp://hdl.handle.net/2003/243752024-03-28T09:05:19Z2024-03-28T09:05:19ZExamination of predictable factors of perioperative respiratory complications by preoperative forced oscillation technique parametersIgarashi, AkiraInoue, SumitoShibata, YokoNunomiya, KeikoOta, TakahitoIshibashi, YuMurano, HiroakiFuruyama, KodaiYang, SujeongMachida, HiroyoshiNakano, HiroshiSato, KentoSato, MasamichiNemoto, TakakoNishiwaki, MichikoYamauchi, KeikoSuzuki, JunSadahiro, MitsuakiWatanabe, Masafumihttp://hdl.handle.net/2003/401992021-05-26T22:25:00Z2020-12-21T00:00:00ZTitle: Examination of predictable factors of perioperative respiratory complications by preoperative forced oscillation technique parameters
Authors: Igarashi, Akira; Inoue, Sumito; Shibata, Yoko; Nunomiya, Keiko; Ota, Takahito; Ishibashi, Yu; Murano, Hiroaki; Furuyama, Kodai; Yang, Sujeong; Machida, Hiroyoshi; Nakano, Hiroshi; Sato, Kento; Sato, Masamichi; Nemoto, Takako; Nishiwaki, Michiko; Yamauchi, Keiko; Suzuki, Jun; Sadahiro, Mitsuaki; Watanabe, Masafumi
Abstract: In this study, we investigated whether pulmonary function tests such as forced oscillation
technique parameters could predict perioperative respiratory complications. In the results of our
study, perioperative respiratory complications cannot be predicted using the results of preoperative pulmonary function tests and forced oscillation technique parameters. Patients who are
judged by comprehensive preoperative judgment to be suitable for general anesthesia may not
need to consider the risk of perioperative complications using pulmonary function test.2020-12-21T00:00:00ZEditor’s choice 2019Ghallab, Ahmedhttp://hdl.handle.net/2003/401982021-05-26T22:24:56Z2020-12-15T00:00:00ZTitle: Editor’s choice 2019
Authors: Ghallab, Ahmed2020-12-15T00:00:00ZEditor’s choice 2018Ghallab, Ahmedhttp://hdl.handle.net/2003/401972021-05-26T22:24:55Z2020-12-22T00:00:00ZTitle: Editor’s choice 2018
Authors: Ghallab, Ahmed2020-12-22T00:00:00ZLong time blood-transfusion trend in a European general hospitalEnko, DietmarHerrmann, MarkusBaranyi, AndreasSchnedl, Wolfgang J.Halwachs-Baumann, Gabrielehttp://hdl.handle.net/2003/399632020-12-19T02:40:55Z2020-06-19T00:00:00ZTitle: Long time blood-transfusion trend in a European general hospital
Authors: Enko, Dietmar; Herrmann, Markus; Baranyi, Andreas; Schnedl, Wolfgang J.; Halwachs-Baumann, Gabriele
Abstract: Reports about long-time transfusion trends in Austrian hospitals are rare. In our hospital, we implemented an algorithm of preoperative anemia management as part of a patient blood management (PBM) program in October 2011. Anemic individuals with elective surgery underwent an adequate preoperative anemia classification and treatment with erythropoietin and intravenous iron. The aim of this study was to assess red blood cell (RBC), platelet and plasma transfusions before and after implementation of an anemia management program in a general hospital in Austria. This retrospective study evaluated a 12-year trend (2006 – 2017) of RBC, platelet and plasma transfusions in an Austrian general hospital comprising a 6-year period before (2006 – 2011) and a 6-year period after (2012 – 2017) the implementation of an algorithm-guided anemia management. From overall 49,142 transfused RBC units between 2006 - 2017, 22,745 units were transfused in the post-implementation period compared to 26,397 units before PBM initiation (-13.8 %). The plasma unit use decreased also distinctly (787 vs. 1065 units, - 26.1 %) in the period after PBM implementation, whereas a slight decrease of platelet concentration use (807 vs. 843 units, - 4.3 %) was observed, only. This study demonstrates a 12-year pattern of blood use in an Austrian hospital with a distinct decreasing trend of transfused RBC and plasma units during this period. The implementation of PBM activities decreased the need of blood utilization at our institution. Further initiatives are needed to continue this trend in the next years.2020-06-19T00:00:00ZThe multifactorial resistance of Pseudomonas aeruginosaMeliani, Aminahttp://hdl.handle.net/2003/399622020-12-19T02:40:55Z2020-06-17T00:00:00ZTitle: The multifactorial resistance of Pseudomonas aeruginosa
Authors: Meliani, Amina2020-06-17T00:00:00ZCan post-splenectomy thrombocytosis mask essential thrombocythaemia?Langabeer, Stephen E.http://hdl.handle.net/2003/399612020-12-19T02:40:52Z2020-06-08T00:00:00ZTitle: Can post-splenectomy thrombocytosis mask essential thrombocythaemia?
Authors: Langabeer, Stephen E.2020-06-08T00:00:00ZNut consumption and risk of diabetes mellitus in overweight/obese individualsEslami, OmidShidfar, Farzadhttp://hdl.handle.net/2003/399602020-12-19T02:40:55Z2020-05-29T00:00:00ZTitle: Nut consumption and risk of diabetes mellitus in overweight/obese individuals
Authors: Eslami, Omid; Shidfar, Farzad2020-05-29T00:00:00ZGenotoxicity effect of methyl-tertiary butyl ether on rat lymphocytes using comet assayAlishahi, ShimaZendeh-Boodi, ZahraSaadat, Mostafahttp://hdl.handle.net/2003/399592020-12-19T02:40:55Z2020-05-25T00:00:00ZTitle: Genotoxicity effect of methyl-tertiary butyl ether on rat lymphocytes using comet assay
Authors: Alishahi, Shima; Zendeh-Boodi, Zahra; Saadat, Mostafa2020-05-25T00:00:00ZCOVID-19Atolani, OlubunmiBaker, Mariam TemitopeAdeyemi, Oluyomi StephenOlanrewaju, Ismaeel RidwanHamid, Abdulmumeen A.Ameen, Oluduowo M.Oguntoye, Stephen O.Usman, Lamidi A.http://hdl.handle.net/2003/399582020-12-19T02:40:55Z2020-06-15T00:00:00ZTitle: COVID-19
Authors: Atolani, Olubunmi; Baker, Mariam Temitope; Adeyemi, Oluyomi Stephen; Olanrewaju, Ismaeel Ridwan; Hamid, Abdulmumeen A.; Ameen, Oluduowo M.; Oguntoye, Stephen O.; Usman, Lamidi A.
Abstract: The anxiety and trauma associated with the tragic coronavirus disease pandemic coded, COVID-19 led many to indulge in various unorthodox preventive measures such as the extensive indiscriminate use of alcohol-based hand sanitizers (ABHS), abuse, misuse, overdose of prescription drugs like chloroquine, hydroxychloroquine and chloroquine phosphate globally. While some preventive measures are recommended and adopted, such as national lockdown, self-isolation, quarantine, stay-at-home model, avoidance of large gathering, social distancing, wearing of face-masks and hand gloves, periodic hand washing particularly with liquid soaps/detergents under running tap water, avoidance of touching the face among others, the use of ABHS has been more prominent. ABHS contains on average 60-70 % by weight of one or more alcohols. During the 2019/2020 COVID-19 pandemic, the use of ABHS was more renowned to the extent that some individuals recommended the application on the hands every 30 minutes for a period of at least 20 seconds while outside the home. Though, the periodic application of the hand sanitizers seems like an effective on-the-go solution to preventing the spread of the virus, many other associated hazards call for caution. Besides transdermal absorption leading to mortality and morbidity of varying degree; alcohol-alcohol adulteration, deliberate and unintentional ingestion of ABHS may result in respiratory depression, irreversible blindness, intoxication, cirrhosis, acidosis, headache, central nervous system depression, seizure, hypoglycemia, coma, or even death in some cases. The non-ABHS are equally not absolutely safe as many of them contain active agents that are allegedly carcinogenic, toxic, inducing microbial resistance and endocrine disruption. Considered together, this implies that while some may not die from contracting the disease, the preventive measures taken could lead to death or other forms of morbidity thereby revealing that there is indeed, death in preventive measures when done without cautionary measures. This study seeks to highlight some associated risks in the use of ABHS and non-ABHS, whilst advocating the use of safer or ‘greener’ alternative procedure for use as preventive measures particularly during the COVID-19 pandemic.2020-06-15T00:00:00ZCurrent biological and pharmacological updates on wogoninRawat, SaritaGupta, GauravPathak, SachchidanandSingh, Santosh KumarSingh, HimmatMishra, AnuragGilhotra, RituAljabali, Alaa A. A.Dureja, HarishTambuwala, Murtaza M.Chellappan, Dinesh K.Dua, Kamalhttp://hdl.handle.net/2003/399572020-12-19T02:40:54Z2020-05-13T00:00:00ZTitle: Current biological and pharmacological updates on wogonin
Authors: Rawat, Sarita; Gupta, Gaurav; Pathak, Sachchidanand; Singh, Santosh Kumar; Singh, Himmat; Mishra, Anurag; Gilhotra, Ritu; Aljabali, Alaa A. A.; Dureja, Harish; Tambuwala, Murtaza M.; Chellappan, Dinesh K.; Dua, Kamal
Abstract: Wogonin (5, 7-Dihydroxy-8-methoxyflavone) is a traditional naturally occurring flavonoid derived from the root extract of Chinese medicine, named Scutellaria baicalensis Georgi. Wogonin contains various biological properties which include allergic diseases, anti-cancertherapy and anti-inflammatory activities. Wogonin also shows the effects of removing toxins and cleansing heat. Wogonin glycosides are known as wogonosides. Oroxindin, a wogonin glucuronide isolated from Oroxylum indicum, is one of the example of wogonoside. It is also used in Japanese herbal supplement named Sho-Saiko-To, as an important active ingredient. One of the major active constituents of wogonin, Scutellaria baicalensis, shows potent anticancer activities both in vivo and in vitro studies. The anticancer therapeutic activity of wogonin has been shown by regulation of different cell signaling pathways , which includes protein kinase B pathway (serine-threonine kinase) and AMP-activated protein kinase pathways. Wogonin also shows positive therapeutic anticancer effects in breast cancer by inhibiting the 5‑LO/BLT2/ERK/IL‑8/MMP‑9 signaling cascade and established a major pharmacological anticancer activity.2020-05-13T00:00:00ZRecent insights into the biological functions of apigeninKim, Jae KwangPark, Sang Unhttp://hdl.handle.net/2003/399562020-12-19T02:40:54Z2020-07-06T00:00:00ZTitle: Recent insights into the biological functions of apigenin
Authors: Kim, Jae Kwang; Park, Sang Un
Abstract: Apigenin (4′,5,7-trihydroxyflavone) belongs to the group of flavonoids positioned on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) and is most extensively allocated in herbs, vegetables, and fruits. Biosynthetically, apigenin is obtained from the phenylpropanoid pathway and also from the flavone synthesis pathway. The pathway of phenylpropanoid begins from the aromatic amino acids L-phenylalanine or L-tyrosine, both products of the shikimate pathway. In several recent studies, it has been shown that apigenin has a number of valuable bioactive functions, including antibacterial, antiviral, antiproliferative, anti-inflammatory, antioxidant, antiangiogenic, and anticancer activities. From the results of several in vivo and in vitro studies and clinical trials, apigenin has been shown to be an effective curative treatment for rheumatoid arthritis, autoimmune disorders, Parkinson’s disease, Alzheimer’s disease, and several types of cancers. Here, we summarize the key findings of the biological and pharmacological actions of apigenin.2020-07-06T00:00:00ZHepatotoxicity of anesthetic gasesAlbrecht, Wiebkehttp://hdl.handle.net/2003/399552020-12-19T02:40:53Z2020-07-27T00:00:00ZTitle: Hepatotoxicity of anesthetic gases
Authors: Albrecht, Wiebke2020-07-27T00:00:00ZThe link between long-term nut consumption and health outcomesEslami, OmidShidfar, Farzadhttp://hdl.handle.net/2003/399542020-12-19T02:40:56Z2020-08-03T00:00:00ZTitle: The link between long-term nut consumption and health outcomes
Authors: Eslami, Omid; Shidfar, Farzad2020-08-03T00:00:00ZRecent pharmacological advances on genistein in clinical trialsMathew, ShimyVazhappilly, Cijo Georgehttp://hdl.handle.net/2003/399532020-12-19T02:40:54Z2020-08-05T00:00:00ZTitle: Recent pharmacological advances on genistein in clinical trials
Authors: Mathew, Shimy; Vazhappilly, Cijo George2020-08-05T00:00:00ZAnticancer activity of luteolin glycosidesGhallab, Ahmedhttp://hdl.handle.net/2003/399522020-12-19T02:40:54Z2020-08-14T00:00:00ZTitle: Anticancer activity of luteolin glycosides
Authors: Ghallab, Ahmed2020-08-14T00:00:00ZKupffer cells in hepatotoxicityHassan, Rehamhttp://hdl.handle.net/2003/399512020-12-19T02:40:54Z2020-08-14T00:00:00ZTitle: Kupffer cells in hepatotoxicity
Authors: Hassan, Reham2020-08-14T00:00:00ZDo artificial sweeteners increase the risk of non-alcoholic fatty liver disease (NAFLD)?Abbas, TahanyMurad, Walaahttp://hdl.handle.net/2003/399502020-12-19T02:40:56Z2020-08-14T00:00:00ZTitle: Do artificial sweeteners increase the risk of non-alcoholic fatty liver disease (NAFLD)?
Authors: Abbas, Tahany; Murad, Walaa2020-08-14T00:00:00ZVitamin D supplementation in COVID-19Mansour, AsiehMohajeri-Tehrani, Mohammad RezaSajjadi-Jazi, Sayed Mahmoudhttp://hdl.handle.net/2003/399492020-12-19T02:40:56Z2020-08-17T00:00:00ZTitle: Vitamin D supplementation in COVID-19
Authors: Mansour, Asieh; Mohajeri-Tehrani, Mohammad Reza; Sajjadi-Jazi, Sayed Mahmoud2020-08-17T00:00:00ZRethinking “Exercise is Medicine”Li, ShunchangLaher, Ismailhttp://hdl.handle.net/2003/399482020-12-19T02:40:56Z2020-08-18T00:00:00ZTitle: Rethinking “Exercise is Medicine”
Authors: Li, Shunchang; Laher, Ismail2020-08-18T00:00:00ZWhich concentrations are optimal for in vitro testing?Albrecht, Wiebkehttp://hdl.handle.net/2003/399472020-12-19T02:40:57Z2020-08-18T00:00:00ZTitle: Which concentrations are optimal for in vitro testing?
Authors: Albrecht, Wiebke2020-08-18T00:00:00ZReproductive toxicity of boronSeidel, Florianhttp://hdl.handle.net/2003/399462020-12-19T02:40:57Z2020-08-19T00:00:00ZTitle: Reproductive toxicity of boron
Authors: Seidel, Florian2020-08-19T00:00:00ZMitigation of metabolic dyshomeostasis by glucocorticoid-receptor antagonismMadhavan, AishwariyaMurali, KusumaRaghavendra, VaishnaviJoshi, Apurva Kumar Rameshhttp://hdl.handle.net/2003/399452020-12-19T02:40:58Z2020-09-09T00:00:00ZTitle: Mitigation of metabolic dyshomeostasis by glucocorticoid-receptor antagonism
Authors: Madhavan, Aishwariya; Murali, Kusuma; Raghavendra, Vaishnavi; Joshi, Apurva Kumar Ramesh2020-09-09T00:00:00ZImmune responses during neoadjuvant chemotherapy in triple negative breast cancerGhallab, Ahmedhttp://hdl.handle.net/2003/399442020-12-19T02:40:58Z2020-09-11T00:00:00ZTitle: Immune responses during neoadjuvant chemotherapy in triple negative breast cancer
Authors: Ghallab, Ahmed2020-09-11T00:00:00ZTea, coffee and risk of gliomaKawada, Tomoyukihttp://hdl.handle.net/2003/399432020-12-19T02:40:56Z2020-09-14T00:00:00ZTitle: Tea, coffee and risk of glioma
Authors: Kawada, Tomoyuki2020-09-14T00:00:00ZBrazil’s research budgetQuintans-Júnior, Lucindo JoséAlbuquerque, George RegoOliveira, Sérgio CampelloSilva, Robério Rodrigueshttp://hdl.handle.net/2003/399422020-12-19T02:40:56Z2020-09-21T00:00:00ZTitle: Brazil’s research budget
Authors: Quintans-Júnior, Lucindo José; Albuquerque, George Rego; Oliveira, Sérgio Campello; Silva, Robério Rodrigues2020-09-21T00:00:00ZTea and coffee consumption, cognitive impairment and prognosis in older inhabitantsKawada, Tomoyukihttp://hdl.handle.net/2003/399412020-12-19T02:40:57Z2020-10-02T00:00:00ZTitle: Tea and coffee consumption, cognitive impairment and prognosis in older inhabitants
Authors: Kawada, Tomoyuki2020-10-02T00:00:00ZCALR mutations in myeloproliferative neoplasmsLangabeer, Stephen E.http://hdl.handle.net/2003/399402020-12-19T02:40:57Z2020-10-26T00:00:00ZTitle: CALR mutations in myeloproliferative neoplasms
Authors: Langabeer, Stephen E.2020-10-26T00:00:00ZInterferon therapy for preventing COPD exacerbationsMehta, MeenuPaudel, Keshav R.Shukla, Shakti D.Shastri, MadhurSingh, Sachin K.Gulati, MonicaDureja, HarishGupta, GauravSatija, SaurabhHansbro, Philip M.Chellappan, Dinesh K.Dua, Kamalhttp://hdl.handle.net/2003/399392020-12-19T02:40:57Z2020-11-04T00:00:00ZTitle: Interferon therapy for preventing COPD exacerbations
Authors: Mehta, Meenu; Paudel, Keshav R.; Shukla, Shakti D.; Shastri, Madhur; Singh, Sachin K.; Gulati, Monica; Dureja, Harish; Gupta, Gaurav; Satija, Saurabh; Hansbro, Philip M.; Chellappan, Dinesh K.; Dua, Kamal2020-11-04T00:00:00ZEmerging prospects of vitamin D3 in metabolic syndromeSingh, YogendraGupta, GauravGilhotra, Ritu M.Singh, Sachin KumarPrasher, ParteekKrishnan, AnandDua, KamalChellappan, Dinesh Kumarhttp://hdl.handle.net/2003/399382020-12-19T02:40:54Z2020-11-09T00:00:00ZTitle: Emerging prospects of vitamin D3 in metabolic syndrome
Authors: Singh, Yogendra; Gupta, Gaurav; Gilhotra, Ritu M.; Singh, Sachin Kumar; Prasher, Parteek; Krishnan, Anand; Dua, Kamal; Chellappan, Dinesh Kumar2020-11-09T00:00:00ZIvermectinHeimfarth, LuanaSantos, Victor SantanaAraújo, Adriano Antunes de SouzaQuintans-Júnior, Lucindo JoséMartins-Filho, Paulo Ricardohttp://hdl.handle.net/2003/399372020-12-19T02:40:53Z2020-11-09T00:00:00ZTitle: Ivermectin
Authors: Heimfarth, Luana; Santos, Victor Santana; Araújo, Adriano Antunes de Souza; Quintans-Júnior, Lucindo José; Martins-Filho, Paulo Ricardo2020-11-09T00:00:00ZWhat about incorporating selenium in the therapeutic regimen of SARS-CoV-2?Benarba, BachirPandiella, Atanasiohttp://hdl.handle.net/2003/399362020-12-19T02:40:53Z2020-12-07T00:00:00ZTitle: What about incorporating selenium in the therapeutic regimen of SARS-CoV-2?
Authors: Benarba, Bachir; Pandiella, Atanasio2020-12-07T00:00:00ZEfficacy of tranexamic acid in patients with traumatic brain injuryKawada, Tomoyukihttp://hdl.handle.net/2003/399352020-12-19T02:40:52Z2020-12-08T00:00:00ZTitle: Efficacy of tranexamic acid in patients with traumatic brain injury
Authors: Kawada, Tomoyuki2020-12-08T00:00:00ZMicrobial determinants of arthritisShukla, Shakti D.Shastri, Madhur D.Jha, Niraj KumarDua, Kamalhttp://hdl.handle.net/2003/399342020-12-19T02:40:53Z2020-12-09T00:00:00ZTitle: Microbial determinants of arthritis
Authors: Shukla, Shakti D.; Shastri, Madhur D.; Jha, Niraj Kumar; Dua, Kamal2020-12-09T00:00:00ZHighlight report: New insights in liver physiologyEzzat Ahmed, Ahmedhttp://hdl.handle.net/2003/399322020-12-18T02:40:59Z2020-08-31T00:00:00ZTitle: Highlight report: New insights in liver physiology
Authors: Ezzat Ahmed, Ahmed
Abstract: One of the central functions of the liver is excretion of bile into the intestine. Currently, bile excretion is explained by the osmotic model, according to which bile acids are excreted by hepatocytes into the bile canaliculi and since bile acids are osmotically active they draw water into the canalicular lumen. Bile canaliculi are closed at the central side. Therefore, bile was postulated to flow to the open side into the ducts. However, bile flow in canaliculi has never been measured because of the small canalicular diameter which does not allow analysis of flux by conventional methods. Recently, methods have been developed that allow flow analysis in bile canaliculi and ducts. Interestingly, no measurable directed flow was observed in the canaliculi. Instead, small molecules in bile canaliculi reached the larger bile ducts by diffusion. Only there measurable flow sets in. The pathophysiological implications of this novel observation are discussed.2020-08-31T00:00:00ZThe effects of spaced transcranial Direct Current Stimulation combined with conventional dysphagia therapy in Parkinson’s diseaseDashtelei, Ali AkbarNitsche, Michael A.Bakhtiyari, JalalHabibi, Seyed AmirhassanSepandi, MojtabaKhatoonabadi, Ahmad Rezahttp://hdl.handle.net/2003/399312020-12-18T02:40:58Z2020-06-04T00:00:00ZTitle: The effects of spaced transcranial Direct Current Stimulation combined with conventional dysphagia therapy in Parkinson’s disease
Authors: Dashtelei, Ali Akbar; Nitsche, Michael A.; Bakhtiyari, Jalal; Habibi, Seyed Amirhassan; Sepandi, Mojtaba; Khatoonabadi, Ahmad Reza
Abstract: Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system that is characterized by a set of motor and non-motor symptoms. Impaired swallowing or dysphagia is one relatively common motor symptom in patients with PD. We investigated whether neuroplasticity induction by spaced transcranial Direct Current Stimulation (tDCS) combined with conventional swallowing therapy leads to long-lasting effects on swallowing ability in patients with PD. We present a case of a 61-year-old male PD patient with dysphagia. Conventional Swallowing Therapy (CDT) combined with tDCS (bilateral anodal, 1 mA, 20 min, 10 online sessions, twice daily with a 20 min interval in between for five days over two weeks) was applied over the pharyngeal motor cortex. Our findings suggest that anodal tDCS combined with CDT is feasible, safe, and well-tolerated, and leads to a clinically relevant improvement of swallowing functions.2020-06-04T00:00:00ZUndifferentiated pleomorphic sarcoma in the anterior mediastinum with a rapidly progressive courseSato, MasamichiInoue, SumitoArao, TsuyoshiIgarashi, AkiraYamauchi, KeikoSato, KentoNakano, HiroshiWatanabe, Masafumihttp://hdl.handle.net/2003/399302020-12-18T02:40:59Z2020-08-17T00:00:00ZTitle: Undifferentiated pleomorphic sarcoma in the anterior mediastinum with a rapidly progressive course
Authors: Sato, Masamichi; Inoue, Sumito; Arao, Tsuyoshi; Igarashi, Akira; Yamauchi, Keiko; Sato, Kento; Nakano, Hiroshi; Watanabe, Masafumi
Abstract: A 77-year-old woman with heart failure was admitted to our hospital. Computed tomography (CT) of the chest revealed an anterior mediastinal tumor. CT-guided biopsy revealed a malignant nonepithelial tumor of unknown origin. She was not treated with chemotherapy or radiotherapy because of her poor clinical condition. She died 33 days after admission. Following autopsy, we confirmed that the mediastinal tumor had infiltrated the large blood vessels. After final histological examination, undifferentiated pleomorphic sarcoma was diagnosed. Primary mediastinal sarcomas are very rare; clinicians should be aware of their possibility because some cases may progress rapidly as evidenced in this case.2020-08-17T00:00:00ZRecent studies on kaempferol and its biological and pharmacological activitiesKim, Jae KwangPark, Sang Unhttp://hdl.handle.net/2003/399292020-12-18T02:40:57Z2020-05-13T00:00:00ZTitle: Recent studies on kaempferol and its biological and pharmacological activities
Authors: Kim, Jae Kwang; Park, Sang Un2020-05-13T00:00:00ZsiRNA could be a potential therapy for COVID-19Ghosh, SanhitaFirdous, Sayeed MohammadNath, Anirbanhttp://hdl.handle.net/2003/399282020-12-18T02:40:59Z2020-04-22T00:00:00ZTitle: siRNA could be a potential therapy for COVID-19
Authors: Ghosh, Sanhita; Firdous, Sayeed Mohammad; Nath, Anirban2020-04-22T00:00:00ZSevere rhabdomyolysis in homozygote carnitine palmitoyltransferase II deficiencySchnedl, Wolfgang J.Schenk, MichaelEnko, DietmarMangge, Haraldhttp://hdl.handle.net/2003/399272020-12-18T02:40:59Z2020-09-11T00:00:00ZTitle: Severe rhabdomyolysis in homozygote carnitine palmitoyltransferase II deficiency
Authors: Schnedl, Wolfgang J.; Schenk, Michael; Enko, Dietmar; Mangge, Harald
Abstract: Carnitine palmitoyltransferase II (CPT II) deficiency represents an inherited defect in mitochondrial long-chain fatty acid oxidation. Rhabdomyolysis with necrosis of muscle is caused by the destruction of skeletal muscle and leads to systemic, multiorgan complications due to the release of intracellular muscle components. Severe rhabdomyolysis may be triggered by combination of a genetic predisposition, including CPT II deficiency, with additionally acting causes. Generally, patients with CPT II deficiency are rarely clinical recognized and reported. We describe a patient presenting severe rhabdomyolysis due to urosepsis, who, in genetic testing, demonstrated the homozygous CPT II deficiency (c.338C>T, p.Ser113Leu) mutation. The diagnosis of CPT II deficiency helped this patient to put the symptoms into context, and this reduced myopathy and the risk of recurring rhabdomyolysis. We report on this patient to increase awareness of diagnostic and medical management in CPT II deficiency.2020-09-11T00:00:00ZActivation of the ATX-LPA axis by carcinogenic chemicalsHögberg, Johanhttp://hdl.handle.net/2003/399262020-12-18T02:40:54Z2020-04-09T00:00:00ZTitle: Activation of the ATX-LPA axis by carcinogenic chemicals
Authors: Högberg, Johan2020-04-09T00:00:00ZLinac-based radiotherapy for epicondylitis humeriNavaser, MahmoudGhaffari, HamedMashoufi, MehrnazRefahi, Soheilahttp://hdl.handle.net/2003/399252020-12-18T02:40:55Z2020-03-04T00:00:00ZTitle: Linac-based radiotherapy for epicondylitis humeri
Authors: Navaser, Mahmoud; Ghaffari, Hamed; Mashoufi, Mehrnaz; Refahi, Soheila2020-03-04T00:00:00ZClinical characteristics and outcomes of diabetics hospitalized for COVID-19 infectionMansour, AsiehSajjadi-Jazi, Sayed MahmoudKasaeian, AmirKhosravi, BardiaSorouri, MajidAzizi, FatemehRajabi, ZeinabMotamedi, FatemehSirusbakht, AzinEslahi, MasoudMojtabbavi, HeilaAli Reza Sima, Ali RezaRadmard, Amir RezaMohajeri-Tehrani, Mohhamad RezaAbdollahi, Mohammadhttp://hdl.handle.net/2003/399242020-12-18T02:40:59Z2020-11-16T00:00:00ZTitle: Clinical characteristics and outcomes of diabetics hospitalized for COVID-19 infection
Authors: Mansour, Asieh; Sajjadi-Jazi, Sayed Mahmoud; Kasaeian, Amir; Khosravi, Bardia; Sorouri, Majid; Azizi, Fatemeh; Rajabi, Zeinab; Motamedi, Fatemeh; Sirusbakht, Azin; Eslahi, Masoud; Mojtabbavi, Heila; Ali Reza Sima, Ali Reza; Radmard, Amir Reza; Mohajeri-Tehrani, Mohhamad Reza; Abdollahi, Mohammad
Abstract: Some debates exist regarding the association of diabetes mellitus (DM) with COVID-19 infection severity and mortality. In this study, we aimed to describe and compare the clinical characteristics and outcomes of hospitalized COVID-19 patients with and without DM. In this single-centered, retrospective, observational study, we enrolled adult patients with COVID-19 who were admitted to the Shariati hospital, Tehran, Iran, from February 25, 2020, to April 21, 2020. The clinical and paraclinical information as well as the clinical outcomes of patients were collected from inpatient medical records. A total of 353 cases were included (mean age, 61.67 years; 57.51 % male), of whom 111 patients were diabetics (mean age, 63.66 years; 55.86 % male). In comparison to those without DM, diabetic patients with COVID-19 were more likely to have other comorbidities, elevated systolic blood pressure (SBP), elevated blood sugar (BS), lower estimated glomerular filtration rate (eGFR) and elevated blood urea nitrogen (BUN). The association of DM with severe outcomes of COVID-19 infection (i.e. mechanical ventilation, median length of hospital stay and mortality) remained non-significant before and after adjustments for several factors including age, sex, body mass index (BMI), smoking status, and comorbidities. Based on our results DM has not been associated with worse outcomes in hospitalized patients for COVID-19 infection.2020-11-16T00:00:00ZCirc_0010729 knockdown protects cardiomyocytes against hypoxic dysfunction via miR-370-3p/TRAF6 axisZhang, JingjingGao, ChuanyuZhang, JingYe, Faminhttp://hdl.handle.net/2003/399232020-12-18T02:40:57Z2020-11-11T00:00:00ZTitle: Circ_0010729 knockdown protects cardiomyocytes against hypoxic dysfunction via miR-370-3p/TRAF6 axis
Authors: Zhang, Jingjing; Gao, Chuanyu; Zhang, Jing; Ye, Famin
Abstract: Few studies have addressed the mechanism by which circ_0010729 regulates hypoxia-induced cell injury in cardiovascular diseases. However, its role and its regulatory mechanism in myocardial infarction remain to be explored. Cell viability, cycle, apoptosis, and migration were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity assay kit and transwell assay, respectively. Tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were examined by enzyme-linked immunosorbent assay. Glucose metabolism was calculated by detecting ATP production, glucose uptake and lactate production. Levels of circ_0010729, miR-370-3p and TNF Receptor Associated Factor 6 (TRAF6) were detected using quantitative real-time polymerase chain reaction or western blot. The direct interaction between circ_0010729 and TRAF6 or miR-370-3p was verified using dual-luciferase reporter assay and RNA immunoprecipitation assay. Under hypoxia condition, cardiomyocytes suffered from cell viability suppression, cell cycle arrest, cell apoptosis promotion, migration reduction, increase of inflammatory factor IL-6 and TNF-α, as well as glycolysis inhibition. Circ_0010729 expression was up-regulated in the cardiomyocytes at different hypoxia-exposed time points. Circ_0010729 knockdown protected cardiomyocytes against hypoxic dysfunction, while circ_0010729 overexpression showed inverse effects. MiR-370-3p was confirmed to directly bind to circ_0010729 or TRAF6. MiR-370-3p inhibition attenuated the protective effects of circ_0010729 knockdown on hypoxia-modulated cardiomyocyte dysfunction. MiR-370-3p restoration protected cardiomyocytes against hypoxic injury via targeting TRAF6. Besides, circ_0010729 indirectly regulated TRAF6 expression via miR-370-3p. This study demonstrated that circ_0010729 knockdown attenuated hypoxia-induced cardiomyocyte dysfunction via miR-370-3p/TRAF6 axis, indicating a potential therapeutic target for myocardial infarction.2020-11-11T00:00:00ZPotential role of exosome in post-stroke reorganization and/or neurodegenerationAzizi, FatemeAskari, SaharJavadpour, PegahHadjighassem, MahmoudrezaGhasemi, Rasoulhttp://hdl.handle.net/2003/399222020-12-18T02:40:58Z2020-12-11T00:00:00ZTitle: Potential role of exosome in post-stroke reorganization and/or neurodegeneration
Authors: Azizi, Fateme; Askari, Sahar; Javadpour, Pegah; Hadjighassem, Mahmoudreza; Ghasemi, Rasoul
Abstract: Currently, stroke is a common and devastating condition, which is sometimes associated with permanent cerebral damages. Although in early time after stroke, the related treatments are mainly focused on the restoration of cerebral blood flow (CBF), at the same time, some changes are commencing that continue for a long time and need to be specially noticed. Previous studies have proposed several molecular mechanisms in these post-stroke events. Exosomes are a type of vesicle, which are formed and secreted by most cells as a mean to transfer cellular constituents such as proteins, DNA and/or RNA to distant cells. Therefore, they are considered as a novel mechanism of cellular communication. Herein, we reviewed the current knowledge on cascades, which are activated after stroke and consequently lead to the reorganization and/or continuance of tissue damage and development of other disorders such as Neurodegenerative diseases (ND). Thereafter, we summarized the latest proofs about the possible participation of exosomes in transferring some components such as proteins and micro-RNAs (miRs), from the affected areas to other parts of the brain and eventually cause the above-mentioned post-stroke events.2020-12-11T00:00:00ZImmunology of IL-12Ullrich, Karen Anne-MarieSchulze, Lisa LouPaap, Eva-MariaMüller, Tanja MartinaNeurath, Markus F.Zundler, Sebastianhttp://hdl.handle.net/2003/399212020-12-18T02:40:58Z2020-12-11T00:00:00ZTitle: Immunology of IL-12
Authors: Ullrich, Karen Anne-Marie; Schulze, Lisa Lou; Paap, Eva-Maria; Müller, Tanja Martina; Neurath, Markus F.; Zundler, Sebastian
Abstract: As its first identified member, Interleukin-12 (IL-12) named a whole family of cytokines. In response to pathogens, the heterodimeric protein, consisting of the two subunits p35 and p40, is secreted by phagocytic cells. Binding of IL-12 to the IL-12 receptor (IL-12R) on T and natural killer (NK) cells leads to signaling via signal transducer and activator of transcription 4 (STAT4) and subsequent interferon gamma (IFN-γ) production and secretion. Signaling downstream of IFN-γ includes activation of T-box transcription factor TBX21 (Tbet) and induces pro-inflammatory functions of T helper 1 (TH1) cells, thereby linking innate and adaptive immune responses. Initial views on the role of IL-12 and clinical efforts to translate them into therapeutic approaches had to be re-interpreted following the discovery of other members of the IL-12 family, such as IL-23, sharing a subunit with IL-12. However, the importance of IL-12 with regard to immune processes in the context of infection and (auto-) inflammation is still beyond doubt. In this review, we will provide an update on functional activities of IL-12 and their implications for disease. We will begin with a summary on structure and function of the cytokine itself as well as its receptor and outline the signal transduction and the transcriptional regulation of IL-12 secretion. In the second part of the review, we will depict the involvement of IL-12 in immune-mediated diseases and relevant experimental disease models, while also providing an outlook on potential translational approaches.2020-12-11T00:00:00ZArtificial Intelligence and its future potential in lung cancer screeningJoy Mathew, ChristopherDavid, Ashwini MariaJoy Mathew, Chris Mariyahttp://hdl.handle.net/2003/399202020-12-18T02:40:55Z2020-12-11T00:00:00ZTitle: Artificial Intelligence and its future potential in lung cancer screening
Authors: Joy Mathew, Christopher; David, Ashwini Maria; Joy Mathew, Chris Mariya
Abstract: Artificial intelligence (AI) simulates intelligent behavior as well as critical thinking comparable to a human being and can be used to analyze and interpret complex medical data. The application of AI in imaging diagnostics reduces the burden of radiologists and increases the sensitivity of lung cancer screening so that the morbidity and mortality associated with lung cancer can be decreased. In this article, we have tried to evaluate the role of artificial intelligence in lung cancer screening, as well as the future potential and efficiency of AI in the classification of nodules. The relevant studies between 2010-2020 were selected from the PubMed database after excluding animal studies and were analyzed for the contribution of AI. Techniques such as deep learning and machine learning allow automatic characterization and classification of nodules with high precision and promise an advanced lung cancer screening method in the future. Even though several combination models with high performance have been proposed, an effectively validated model for routine use still needs to be improvised. Combining the performance of artificial intelligence with a radiologist’s expertise offers a successful outcome with higher accuracy. Thus, we can conclude that higher sensitivity, specificity, and accuracy of lung cancer screening and classification of nodules is possible through the integration of artificial intelligence and radiology. The validation of models and further research is to be carried out to determine the feasibility of this integration.2020-12-11T00:00:00ZWhy we do what we doGalmarini, Carlos Mariahttp://hdl.handle.net/2003/399192020-12-18T02:40:55Z2020-10-28T00:00:00ZTitle: Why we do what we do
Authors: Galmarini, Carlos Maria
Abstract: The goal of all medical activity is to preserve health in fit people, and to restore the sick into a state of complete physical, mental and social wellbeing. In an effort to determine whether we are achieving this last goal in oncology, herein we review the biological and clinical framework that has led to the foundations of the current anticancer treatment paradigm. Currently, cancer therapy is still based on the ancient axiom that states that the complete eradication of the tumor burden is the only way to achieve a cure. This strategy has led to a substantial improvement in survival rates as cancer mortality rates have dropped in an unprecedented way. Despite this progress, more than 9 million people still die from cancer every year, indicating that the current treatment strategy is not leading to a cancer cure, but to a cancer remission, that is “the temporary absence of manifestations of a particular disease”; after months or years of remission, in most patients, cancer will inevitably recur. Our critical analysis indicates that it is time to discuss about the new key challenges and future directions in clinical oncology. We need to generate novel treatment strategies more suited to the current clinical reality.2020-10-28T00:00:00ZInterplay between reactive oxygen species and autophagy in the course of age-related macular degenerationNita, MałgorzataGrzybowski, Andrzejhttp://hdl.handle.net/2003/399182020-12-18T02:40:55Z2020-09-25T00:00:00ZTitle: Interplay between reactive oxygen species and autophagy in the course of age-related macular degeneration
Authors: Nita, Małgorzata; Grzybowski, Andrzej
Abstract: Pathological biomolecules such as lipofuscin, methylglyoxal-modified proteins (the major precursors of advanced glycationend products), misfolding protein deposits and dysfunctional mitochondria are source of oxidative stress and act as strong autophagic stimulators in age-related macular degeneration. Disturbed autophagy accelerates progression of the disease, since it leads to retinal cells’ death and activates inflammation by the interplay with the NLRP3 inflammasome complex. Vascular dysfunction and hypoxia, as well as circulating autoantibodies against autophagy regulators (anti-S100A9, anti-ANXA5, and anti-HSPA8, A9 and B4) compromise an autophagy-mediated mechanism as well. Metformin, the autophagic stimulator, may act as a senostatic drug to inhibit the senescent phenotype in the age-related macular degeneration. PGC-1α , Sirt1 and AMPK represent new therapeutic targets for interventions in this disease.2020-09-25T00:00:00ZA review on biogenic synthesis, applications and toxicity aspects of zinc oxide nanoparticlesSharma, RajatGarg, RajniKumari, Avneshhttp://hdl.handle.net/2003/399172020-12-18T02:40:56Z2020-09-22T00:00:00ZTitle: A review on biogenic synthesis, applications and toxicity aspects of zinc oxide nanoparticles
Authors: Sharma, Rajat; Garg, Rajni; Kumari, Avnesh
Abstract: Nanoparticles (NPs) have become an important field of research over the past several decades with applications in various sectors, such as biomedical, cosmetic, food and many others, because of their unique characteristics. The green synthesis of nanoparticles has been preferred because of the naturally occurring reductants present in biological systems that decreases exposure to toxic chemicals compared with physico-chemical methods and is eco-friendly. Zinc oxide (ZnO) NPs exhibit broad and potential applications in different fields with their specific characteristics such as surface area, size, shape, low toxicity, optical properties, high binding energy and large band gap. This paper focuses on the bio-synthesis of ZnO NPs by utilizing extracts of different plant parts (stem, flower, fruit, peel, and leaves) through efficient, economical, simple, pure, and eco-friendly green routes. In this process, zinc salts have been used as precursor and phytochemicals in the plant extract reduce the metal salt to lower oxidation state as well as stabilize the ZnO NPs. The morphological and physico-chemical properties of obtained NPs analyzed by various characterization techniques have been discoursed. Further, antimicrobial activity and potential photocatalytic application in terms of the degradation of dyes have also been reviewed in addition to the toxicity aspects of these NPs on human beings and animals.2020-09-22T00:00:00ZInsulin secretionGheibi, SevdaGhasemi, Asgharhttp://hdl.handle.net/2003/399162020-12-18T02:40:56Z2020-09-08T00:00:00ZTitle: Insulin secretion
Authors: Gheibi, Sevda; Ghasemi, Asghar
Abstract: Nitric oxide (NO) is a gas that serves as a ubiquitous signaling molecule participating in physiological activities of various organ systems. Nitric oxide is produced in the endocrine pancreas and contributes to synthesis and secretion of insulin. The potential role of NO in insulin secretion is disputable – both stimulatory and inhibitory effects have been reported. Available data indicate that effects of NO critically depend on its concentration. Different isoforms of NO synthase (NOS) control this and have the potential to decrease or increase insulin secretion. In this review, the role of NO in insulin secretion as well as the possible reasons for discrepant findings are discussed. A better understanding of the role of NO system in the regulation of insulin secretion may facilitate the development of new therapeutic strategies in the management of diabetes.2020-09-08T00:00:00ZBiomaterials based on noncovalent interactions of small moleculesGuo, JiaqiTian, ChanghaoXu, Binghttp://hdl.handle.net/2003/399152020-12-18T02:40:56Z2020-08-05T00:00:00ZTitle: Biomaterials based on noncovalent interactions of small molecules
Authors: Guo, Jiaqi; Tian, Changhao; Xu, Bing
Abstract: Unlike conventional materials that covalent bonds connecting atoms as the major force to hold the materials together, supramolecular biomaterials rely on noncovalent intermolecular interactions to assemble. The reversibility and biocompatibility of supramolecular biomaterials render them with diverse range of functions and lead to rapid development in the past two decades. This review focuses on the noncovalent and enzymatic control of supramolecular biomaterials, with the introduction to various triggering mechanism to initiate self-assembly. Representative applications of supramolecular biomaterials are highlighted in four categories: tissue engineering, cancer therapy, drug delivery, and molecular imaging. By introducing various applications, we intend to show enzymatic control and noncovalent interactions as a powerful tool for achieving spatiotemporal control of biomaterials both in vitro and in vivo for biomedicine.2020-08-05T00:00:00ZState-dependent memory and its modulation by different brain areas and neurotransmittersZarrindast, Mohammad-RezaKhakpai, Fatemehhttp://hdl.handle.net/2003/399132020-12-18T02:40:57Z2020-08-03T00:00:00ZTitle: State-dependent memory and its modulation by different brain areas and neurotransmitters
Authors: Zarrindast, Mohammad-Reza; Khakpai, Fatemeh
Abstract: The state-dependent memory defines as a state that the retrieval of recently obtained information may be potential if the subject exists in a similar physiological situation as for the period of the encoding stage. Studies revealed that exogenous and endogenous compounds could induce state-dependent memory. The state-dependent memory made it probable to differentiate the effects of drugs per se on learning from the effects due to alterations in drug state during the task. Studies proposed the role of regions beyond the limbic formation and illustrated that state-dependent memory produced by various neurotransmitter systems and pharmacological compounds. Our review of the literature revealed that: (a) re-administration of drugs on the same state induce state-dependent memory; (b) many neurotransmitters induce endogenous state-dependent memory; (c) there are cross state-dependent learning and memory between some drugs; (d) some sites of the brain including the CA1 areas of the hippocampus, central nucleus of the amygdala (CeA), septum, ventral tegmental area (VTA), and nucleus accumbens (NAC) are involved in state-dependent memory.2020-08-03T00:00:00ZOsteoporosisFöger-Samwald, UrsulaDovjak, PeterAzizi-Semrad, UrsulaKerschan-Schindl, KatharinaPietschmann, Peterhttp://hdl.handle.net/2003/399112020-12-17T02:40:52Z2020-07-20T00:00:00ZTitle: Osteoporosis
Authors: Föger-Samwald, Ursula; Dovjak, Peter; Azizi-Semrad, Ursula; Kerschan-Schindl, Katharina; Pietschmann, Peter
Abstract: Osteoporosis is a metabolic bone disease that, on a cellular level, results from osteoclastic bone resorption not compensated by osteoblastic bone formation. This causes bones to become weak and fragile, thus increasing the risk of fractures. Traditional pathophysiological concepts of osteoporosis focused on endocrine mechanisms such as estrogen or vitamin D deficiency as well as secondary hyperparathyroidism. However, research over the last decades provided exiting new insights into mechanisms contributing to the onset of osteoporosis, which go far beyond this. Selected mechanisms such as interactions between bone and the immune system, the gut microbiome, and cellular senescence are reviewed in this article. Furthermore, an overview on currently available osteoporosis medications including antiresorptive and bone forming drugs is provided and an outlook on potential future treatment options is given.2020-07-20T00:00:00ZCurrent coronavirus (SARS-CoV-2) epidemiological, diagnostic and therapeutic approachesNabil, AhmedUto, KoichiroElshemy, Mohamed M.Soliman, RehamHassan, Ayman A.Ebara, MitsuhiroShiha, Gamalhttp://hdl.handle.net/2003/399102020-12-17T02:40:53Z2020-07-20T00:00:00ZTitle: Current coronavirus (SARS-CoV-2) epidemiological, diagnostic and therapeutic approaches
Authors: Nabil, Ahmed; Uto, Koichiro; Elshemy, Mohamed M.; Soliman, Reham; Hassan, Ayman A.; Ebara, Mitsuhiro; Shiha, Gamal
Abstract: Coronaviruses are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes. In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Wuhan City, China. The World Health Organization (WHO) declared the coronavirus outbreak as a global pandemic in March 2020. Fever, dry cough and fatigue are found in the vast majority of all COVID-19 cases. Early diagnosis, treatment and future prevention are keys to COVID-19 management. Currently, the unmet need to develop cost-effective point-of-contact test kits and efficient laboratory techniques for confirmation of COVID-19 infection has powered a new frontier of diagnostic innovation. No proven effective therapies or vaccines for SARS-CoV-2 currently exist. The rapidly increasing research regarding COVID-19 virology provides a significant number of potential drug targets. Remdesivir may be the most promising therapy up till now. On May 1, 2020, Gilead Sciences, announced that the U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for the investigational Remdesivir as a potential antiviral for COVID-19 treatment. On May 7, 2020, Gilead Sciences, announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval of Veklury® (Remdesivir) as a treatment for SARS-CoV-2 infection, the virus that causes COVID-19 acute respiratory syndrome, under an exceptional approval pathway. Also, Corticosteroids are recommended for severe cases only to suppress the immune response and reduce symptoms, but not for mild and moderate patients where they are associated with a high-risk side effect. Based on the currently published evidence, we tried to highlight different diagnostic approaches, side effects and therapeutic agents that could help physicians in the frontlines.2020-07-20T00:00:00ZInorganic nitrate, a natural anti-obesity agentBahadoran, ZahraJeddi, SajadGheibi, SevdaMirmiran, ParvinKashfi, KhosrowGhasemi, Asgharhttp://hdl.handle.net/2003/399092020-12-17T02:40:54Z2020-07-06T00:00:00ZTitle: Inorganic nitrate, a natural anti-obesity agent
Authors: Bahadoran, Zahra; Jeddi, Sajad; Gheibi, Sevda; Mirmiran, Parvin; Kashfi, Khosrow; Ghasemi, Asghar
Abstract: Evidence for potential effects of inorganic nitrate (NO3) on body weight is limited to inconsistent findings of animal experiments. In this systematic review and meta-analysis, we aimed to quantify the overall effect of inorganic NO3, administered via drinking water, on body weight gain in rats. We searched PubMed, Scopus, and Embase databases, and the reference lists of published papers. Experiments on male rats, reported data on body weight in NO3-treated animals and controls, were included for quality assessment, meta-analyses, subgroup analyses, and meta-regressions. Of 173 initially obtained studies, 11 were eligible to be included in the analyses, which covered the years 2004 to 2019 and included a total of 43 intervention (n=395) and 43 control (n=395) arms. Overall, the final body weights were significantly lower in the NO3-supplemented groups compared to controls (WMD= –16.8 g, 95 % CI= –27.38, –6.24; P=0.002). Doses of NO3 higher than the median (> 72.94 mg L-1 d-1) and longer NO3 exposure (> 8 weeks) resulted in greater mean differences (WMD= –31.92 g, 95 % CI= –52.90, –10.94 and WMD= –23.16 g, 95 % CI= –35.64, –10.68 g). After exclusion of experiments using high doses of NO3 (> 400 mg L-1 d-1), the overall mean differences in body weights between the groups decreased by approximately 37 % but remained statistically significant (WMD= –10.11 g, 95 % CI= –19.04, –1.19, P=0.026). Mean changes in body weight were affected by age, baseline values in body weight, and the duration of the studies. These preliminary experimental findings strongly support the hypothesis that NO3 can be considered as a natural anti-obesity agent.2020-07-06T00:00:00ZSulforaphane treatment for autism spectrum disorderMcGuinness, GreerKim, Yeonsoohttp://hdl.handle.net/2003/399082021-01-07T11:59:01Z2020-06-26T00:00:00ZTitle: Sulforaphane treatment for autism spectrum disorder
Authors: McGuinness, Greer; Kim, Yeonsoo
Abstract: Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental condition characterized by social communication impairment, delayed development, social function deficit, and repetitive behaviors. The Center for Disease Control reports an increase in ASD diagnosis rates every year. This systematic review evaluated the use of sulforaphane (SFN) therapy as a potential treatment option for individuals with ASD. PubMed.gov, PubMed Central, Natural Medicines, BoardVitals, Google Scholar and Medline were searched for studies measuring the effects of SFN on behavior and cognitive function. All five clinical trials included in this systematic review showed a significant positive correlation between SFN use and ASD behavior and cognitive function. The current evidence shows with minimal side effects observed, SFN appears to be a safe and effective treatment option for treating ASD.2020-06-26T00:00:00ZPathophysiology and therapy of systemic vasculitidesRalli, MassimoCampo, FlaminiaAngeletti, DilettaMinni, AntonioArtico, MarcoGreco, AntonioPolimeni, Antonellade Vincentiis, Marcohttp://hdl.handle.net/2003/399072020-12-17T02:40:55Z2020-06-18T00:00:00ZTitle: Pathophysiology and therapy of systemic vasculitides
Authors: Ralli, Massimo; Campo, Flaminia; Angeletti, Diletta; Minni, Antonio; Artico, Marco; Greco, Antonio; Polimeni, Antonella; de Vincentiis, Marco
Abstract: Systemic vasculitides represent uncommon conditions characterized by the inflammation of blood vessels that can lead to different complex disorders limited to one organ or potentially involving multiple organs and systems. Systemic vasculitides are classified according to the diameter of the vessel that they mainly affect (small, medium, large, or variable). The pathogenetic mechanisms of systemic vasculitides are still partly unknown, as well as their genetic basis. For most of the primary systemic vasculitides, a single gold standard test is not available, and diagnosis is often made after having ruled out other mimicking conditions. Current research has focused on new management protocol and therapeutic strategies aimed at improving long-term patient outcomes and avoiding progression to multiorgan failure with irreversible damage. In this narrative review, authors describe different forms of systemic vasculitides through a review of the literature, with the aim of highlighting the current knowledge and recent findings on etiopathogenesis, diagnosis and therapy.2020-06-18T00:00:00ZAnaplastic thyroid cancerAmaral, MarianaAfonso, Ricardo A.Gaspar, Maria ManuelaReis, Catarina Pintohttp://hdl.handle.net/2003/399062020-12-17T02:40:53Z2020-06-15T00:00:00ZTitle: Anaplastic thyroid cancer
Authors: Amaral, Mariana; Afonso, Ricardo A.; Gaspar, Maria Manuela; Reis, Catarina Pinto
Abstract: Globally, thyroid cancer accounts for 2 % of all cancer diagnoses, and can be classified as well-differentiated or undifferentiated. Currently, differentiated thyroid carcinomas have good prognoses, and can be treated with a combination of therapies, including surgical thyroidectomy, radioactive iodine therapy and hormone-based therapy. On the other hand, anaplastic thyroid carcinoma, a subtype of undifferentiated thyroid carcinoma characterized by the loss of thyroid-like phenotype and function, does not respond to either radioactive iodine or hormone therapies. In most cases, anaplastic thyroid carcinomas are diagnosed in later stages of the disease, deeming them inoperable, and showing poor response rates to systemic chemotherapy. Recently, treatment courses using multiple-target agents are being explored and clinical trials have shown very promising results, such as overall survival rates, progression-free survival and tumor shrinkage. This review is focused on thyroid carcinomas, with particular focus on anaplastic thyroid carcinoma, exploring its undifferentiated nature. Special interest will be given to the treatment approaches currently available and respective obstacles or drawbacks. Our purpose is to contribute to understand why this malignancy presents low responsiveness to current treatments, while overviewing novel therapies and clinical trials.2020-06-15T00:00:00Z3Rs toxicity testing and disease modeling projects in the European Horizon 2020 research and innovation programVinken, Mathieuhttp://hdl.handle.net/2003/399052020-12-17T02:40:53Z2020-06-09T00:00:00ZTitle: 3Rs toxicity testing and disease modeling projects in the European Horizon 2020 research and innovation program
Authors: Vinken, Mathieu
Abstract: The 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, is receiving increasing attention around the world, and has found its way to legislation, in particular in the European Union. This is aligned by growing efforts of the European Commission to support development and implementation of 3Rs methods. The present paper gives an overview of European 3Rs initiatives as part of the different pillars of the Horizon 2020 framework program for research and innovation. Focus is hereby put on projects that address the 3Rs concept in the context of toxicity testing, chemical risk assessment and disease modeling.2020-06-09T00:00:00ZPrognostic role of immune cells in hepatocellular carcinomaSachdeva, MeenakshiArora, Sunil K.http://hdl.handle.net/2003/399042020-12-17T02:40:54Z2020-06-03T00:00:00ZTitle: Prognostic role of immune cells in hepatocellular carcinoma
Authors: Sachdeva, Meenakshi; Arora, Sunil K.
Abstract: Hepatocellular carcinoma (HCC), with rising incidence rates, is the most commonly occurring malignancy of the liver that exerts a heavy disease burden particularly in developing countries. A dynamic cross-talk between immune cells and malignant cells in tumor microenvironment governs the hepatocarcinogenesis. Monitoring immune contexture as prognostic markers is quite relevant and essential to evaluate clinical outcomes and to envisage response to therapy. In this review, we present an overview of the prognostic value of various tumor infiltrating immune cells and the continually evolving immune checkpoints as novel biomarkers during HCC. Tumor infiltration by immune cells such as T cells, NK cells and dendritic cells is linked with improved prognosis and favorable outcome, while the intra-tumoral presence of regulatory T cells (Tregs) or myeloid derived suppressor cells (MDSCs) on the other hand is associated with poor clinical outcome. In addition to these, the overexpression of negative regulatory molecules on tumor cells also provides inhibitory signals to T cells and is associated with poor prognosis. The limitation of a single marker can be overcome by advanced prognostication models and algorithms that evaluate multiple prognostic factors and ultimately aid the clinician in improving the disease free and overall survival of HCC patients.2020-06-03T00:00:00ZArtificial sweeteners are related to non-alcoholic fatty liver diseaseEmamat, HadiGhalandari, HamidTangestani, HadithAbdollahi, AfsounHekmatdoost, Azitahttp://hdl.handle.net/2003/399032020-12-17T02:40:54Z2020-05-12T00:00:00ZTitle: Artificial sweeteners are related to non-alcoholic fatty liver disease
Authors: Emamat, Hadi; Ghalandari, Hamid; Tangestani, Hadith; Abdollahi, Afsoun; Hekmatdoost, Azita
Abstract: Non-alcoholic fatty liver disease (NAFLD) is a systemic and wide-spread disease characterized by accumulation of excess fat in the liver of people who drink little or no alcohol. Artificial sweeteners (ASs) or sugar substitutes are food additives that provide a sweet taste, and are also known as low-calorie or non-calorie sweeteners. Recently people consume increasingly more ASs to reduce their calorie intake. Gut microbiome is a complex ecosystem where 1014 microorganisms play several roles in host nutrition, bone mineralization, immune system regulation, xenobiotics metabolism, proliferation of intestinal cells, and protection against pathogens. A disruption in composition of the normal microbiota is known as ‘gut dysbiosis’ which may adversely affect body metabolism. It has recently been suggested that dysbiosis may contribute to the occurrence of NAFLD. The aim of the present study was to investigate the effects of ASs on the risk of NAFLD. The focus of this review is on microbiota changes and dysbiosis. Increasing evidence shows that ASs have a potential role in microbiota alteration and dysbiosis. We speculate that increased consumption of ASs can further raise the prevalence of NAFLD. However, further human studies are needed to determine this relationship definitively.2020-05-12T00:00:00ZSerotonergic system modulation holds promise for L‐DOPA‐induced dyskinesias in hemiparkinsonian ratsFarajdokht, FereshtehSadigh-Eteghad, SaeedMajdi, AlirezaPashazadeh, FaribaVatandoust, Seyyed MehdiZiaee, MojtabaSafari, FatemehKarimi, PouranMahmoudi, Javadhttp://hdl.handle.net/2003/399022020-12-17T02:40:51Z2020-03-02T00:00:00ZTitle: Serotonergic system modulation holds promise for L‐DOPA‐induced dyskinesias in hemiparkinsonian rats
Authors: Farajdokht, Fereshteh; Sadigh-Eteghad, Saeed; Majdi, Alireza; Pashazadeh, Fariba; Vatandoust, Seyyed Mehdi; Ziaee, Mojtaba; Safari, Fatemeh; Karimi, Pouran; Mahmoudi, Javad
Abstract: The alleged effects of serotonergic agents in alleviating levodopa-induced dyskinesias (LIDs) in parkinsonian patients are debatable. To this end, we systematically reviewed the serotonergic agents used for the treatment of LIDs in a 6-hydroxydopamine model of Parkinson’s disease in rats. We searched MEDLINE via PubMed, Embase, Google Scholar, and Proquest for entries no later than March 2018, and restricted the search to publications on serotonergic agents used for the treatment of LIDs in hemiparkinsonian rats. The initial search yielded 447 citations, of which 49 articles and one conference paper met our inclusion criteria. The results revealed ten different categories of serotonergic agents, including but not limited to 5-HT1A/BR agonists, 5-HT2AR antagonists, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), and tricyclic antidepressants (TCAs), all of which improved LIDs without imposing considerable adverse effects. Although there is promising evidence regarding the role of these agents in relieving LIDs in hemiparkinsonian rats, further studies are needed for the enlightenment of hidden aspect of these molecules in terms of mechanisms and outcomes. Given this, improving the quality of the pre-clinical studies and designing appropriate clinical trials will help fill the bench-to-bedside gap.2020-03-02T00:00:00ZRevealing the astragalin mode of anticandidal actionIvanov, MarijaKannan, AbhilashStojkovic, DejanGlamočlija, JasminaGolič Grdadolnik, SimonaSanglard, DominiqueSoković, Marinahttp://hdl.handle.net/2003/399012020-12-16T02:40:52Z2020-10-29T00:00:00ZTitle: Revealing the astragalin mode of anticandidal action
Authors: Ivanov, Marija; Kannan, Abhilash; Stojkovic, Dejan; Glamočlija, Jasmina; Golič Grdadolnik, Simona; Sanglard, Dominique; Soković, Marina
Abstract: Due to limited arsenal of systemically available antifungal agents, infections caused by Candida albicans are difficult to treat and the emergence of drug-resistant strains present a major challenge to the clinicians worldwide. Hence further exploration of potential novel and effective antifungal drugs is required. In this study we have explored the potential of a flavonoid, astragalin, in controlling the growth of C. albicans, in both planktonic and biofilm forms by microdilution method; and in regulating the morphological switch between yeast and hyphal growth. Astragalin ability to interfere with membrane integrity, ergosterol synthesis and its role in the regulation of genes encoding for efflux pumps has been addressed. In our study, astragalin treatment produced good antimicrobial and significant antibiofilm activity. Anticandidal activity of astragalin was not related to ERG11 downregulation, neither to direct binding to CYP51 enzyme nor was linked to membrane ergosterol assembly. Instead, astragalin treatment resulted in reduced expression of CDR1 and also affected cell membrane integrity without causing cytotoxic effect on human gingival fibroblast cells. Considering that astragalin-mediated decreased expression of efflux pumps increases the concentration of antifungal drug inside the fungal cells, a combinatorial treatment with this agent could be explored as a novel therapeutic option for candidiasis.2020-10-29T00:00:00ZOverexpression and translocation of dynamin 2 promotes tumor aggressiveness in breast carcinomasSajed, RoyaSaeednejad Zanjani, LeiliRahimi, MandanaMansoori, MaryamZarnani, Amir-HassanMadjd, ZahraGhods, Royahttp://hdl.handle.net/2003/399002020-12-16T02:40:52Z2020-10-29T00:00:00ZTitle: Overexpression and translocation of dynamin 2 promotes tumor aggressiveness in breast carcinomas
Authors: Sajed, Roya; Saeednejad Zanjani, Leili; Rahimi, Mandana; Mansoori, Maryam; Zarnani, Amir-Hassan; Madjd, Zahra; Ghods, Roya
Abstract: Dynamin 2 is a GTPase protein that has been implicated in cancer progression through its various roles such as endocytosis, morphogenesis, epithelial-mesenchymal transition (EMT), cellular contractions, and focal adhesion maturation. The increased expression levels of this molecule have been demonstrated with the development of several cancers such as prostate, pancreas, and bladder. However, its clinical significance in breast cancer is unclear yet. In the present study, the membranous, cytoplasmic, and nuclear expression levels of dynamin 2 molecule were evaluated for the first time, using immunohistochemistry (IHC) on tissue microarray (TMA) slides in 113 invasive breast cancer tissues. Moreover, afterward, the association between the dynamin 2 expression and clinicopathological features was determined. Our finding showed that, a higher nuclear expression of dynamin 2 is significantly associated with an increase in tumor stage (P = 0.05), histological grade (P = 0.001), and age of the patients (P = 0.03). In addition, analysis of the cytoplasmic expression levels of this molecule revealed that, there was a statistically significant difference between the expression levels of dynamin 2 among the different breast cancer subtypes (P = 0.003). Moreover, a significant association was found between the increased expression of dynamin 2 membranous and vascular invasion (VI) (P = 0.02). We showed that dynamin 2 protein expression has an association with more aggressive tumor behavior and more advanced disease in the patients with breast cancer; therefore, dynamin 2 molecule could be considered as an indicator of disease progression and aggressiveness.2020-10-29T00:00:00ZInterleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorptionEnko, DietmarZelzer, SieglindeWenninger, JulianHolasek, SandraSchnedl, Wolfgang J.Baranyi, AndreasHerrmann, MarkusMeinitzer, Andreashttp://hdl.handle.net/2003/398992020-12-16T02:40:52Z2020-10-28T00:00:00ZTitle: Interleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption
Authors: Enko, Dietmar; Zelzer, Sieglinde; Wenninger, Julian; Holasek, Sandra; Schnedl, Wolfgang J.; Baranyi, Andreas; Herrmann, Markus; Meinitzer, Andreas
Abstract: The aim of the present study was to investigate possible associations between interleukin-6 (IL-6), interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), lactoferrin and lipopolysaccharide binding protein (LBP) with TRP metabolism and signs of depression in a large cohort of outpatients referred for carbohydrate malabsorption testing. Serum concentrations of IL-6, INF-γ, TNF-α, lactoferrin, LBP, tryptophan (TRP), kynurenine (KYN) and kynuric acid were determined in 250 adults referred for lactose and fructose malabsorption testing. All participants filled out the Beck Depression Inventory (BDI). Serum IL-6 levels were positively correlated with the BDI score (p = 0.001, ρ = 0.205) and indicators of TRP metabolism (KYN/TRP ratio, KYN) (P-values < 0.05, ρ = 0.176 and 0.136). Ninety-five individuals with a BDI score > 13 showed significantly higher IL-6 serum levels (1.7 [1.0 – 2.8] vs. 1.1 [0.8 – 1.7] pg/mL, p < 0.001) compared to 115 individuals with a BDI score ≤ 13. LBP showed a positive correlation with the KYN/TRP ratio (p = 0.005, ρ = 0.177). IL-6 and LBP were associated with indicators of TRP metabolism. IL-6 was found to be linked to signs of depression. Individuals with the presence of depressive symptoms showed higher serum IL-6 levels compared to individuals without depressive symptoms.2020-10-28T00:00:00ZDownregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery diseaseKhanahmadi, MahdiehManafi, BabakTayebinia, HeidarKarimi, JamshidKhodadadi, Irajhttp://hdl.handle.net/2003/398982020-12-16T02:40:51Z2020-10-02T00:00:00ZTitle: Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease
Authors: Khanahmadi, Mahdieh; Manafi, Babak; Tayebinia, Heidar; Karimi, Jamshid; Khodadadi, Iraj
Abstract: The higher expression level of p53 in epithelial adipose tissue (EAT) has previously been reported in atherosclerosis. Since we hypothesized that the expression of p53 is modulated by Sirt1, the aim of this study was to determine the expression levels of Sirt1 and p53 and to investigate their correlation to apoptosis in EAT of patients with coronary artery disease (CAD). Thirty-five patients with more than 50 % stenosis in at least one of the main coronary arteries were considered as CAD group while 29 patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as control group. EAT biopsy samples were collected from all participants during surgery. Sirt1, p53, Bax, and Bcl‑2 gene expression levels were determined in EAT by qRT-PCR and Western blotting was carried out to assess Sirt1 and p53 protein levels. Hematoxylin and eosin staining was used for histopathological analysis. mRNA and protein levels of Sirt1 in EAT were significantly lower in patients with CAD compared with control group, whereas CAD patients showed greater p53 gene and protein expressions. In addition, inverse correlations were observed between Sirt1 and p53 at both mRNA and protein levels. The Bax and ratio of Bax/Bcl-2 gene expressions were higher in CAD group, but no difference was observed in Bcl-2 expression. Histopathological analysis showed apoptotic bodies and infiltrated immune cells in EAT of CAD group. Our results suggest that the Sirt1-p53 axis may involve in atherosclerosis by promotion of apoptosis.2020-10-02T00:00:00ZDifferential engulfment of Staphylococcus aureus and Pseudomonas aeruginosa by monocyte-derived macrophages is associated with altered phagocyte biochemistry and morphologyEl Mohtadi, MohamedPilkington, LisaLiauw, Christopher M.Ashworth, Jason J.Dempsey-Hibbert, NinaBelboul, AminaWhitehead, Kathryn A.http://hdl.handle.net/2003/398972020-12-16T02:40:51Z2020-09-30T00:00:00ZTitle: Differential engulfment of Staphylococcus aureus and Pseudomonas aeruginosa by monocyte-derived macrophages is associated with altered phagocyte biochemistry and morphology
Authors: El Mohtadi, Mohamed; Pilkington, Lisa; Liauw, Christopher M.; Ashworth, Jason J.; Dempsey-Hibbert, Nina; Belboul, Amina; Whitehead, Kathryn A.
Abstract: Knowledge of changes in macrophages following bacterial engulfment is limited. U937-derived macrophages were incubated with Staphylococcus aureus or Pseudomonas aeruginosa. Morphological and biochemical changes in macrophages following host-pathogen interactions were visualized using Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR) respectively. Principal Component Analysis (PCA) was used to assess the variability in the FTIR spectra. Following host-pathogen interactions, survival of S. aureus was significantly lower than P. aeruginosa (P<0.05) and cellular morphology of macrophages was different after incubation with S. aureus compared to P. aeruginosa. Following incubation with S. aureus macrophages were more globular and amorphous in shape whereas long linear pseudopodia were observed following incubation with P. aeruginosa. Distinct FTIR spectra were identified in macrophages post interaction with the different bacteria and PCA analysis demonstrated distinct biochemical differences in the phagocytes following engulfment of the bacteria, with > 99 % of variability in the FTIR spectra explained by the first two principal components. These findings demonstrated that there were clear morphological and biochemical changes in macrophages following engulfment of two different bacterial types suggesting that the biochemical components of the bacterial cell wall influenced the biochemical characteristics and hence the morphology of macrophages in distinct ways.2020-09-30T00:00:00ZIn vitro anticancer activity of Scrophularia amplexicaulis extracts on MCF-7 and WEHI-164 cell lineValiyari, SamiraBeiranvand, ElhamSamimi, AzinYaripour, SaeidBaradaran, BehzadDelazar, AbbasForouzesh, Mehdihttp://hdl.handle.net/2003/398952020-12-15T02:40:57Z2020-09-22T00:00:00ZTitle: In vitro anticancer activity of Scrophularia amplexicaulis extracts on MCF-7 and WEHI-164 cell line
Authors: Valiyari, Samira; Beiranvand, Elham; Samimi, Azin; Yaripour, Saeid; Baradaran, Behzad; Delazar, Abbas; Forouzesh, Mehdi
Abstract: Scrophularia amplexicaulis is an Iranian endemic plant belonging to the Scrophulariaceae family, which is used in traditional medicine to treat many diseases. The aim of this study was to evaluate the in vitro anticancer activity of S. amplexicaulis extracts against human breast carcinoma (MCF-7) and mouse fibrosarcoma (WEHI-164) cell lines. The ground aerial parts of S. amplexicaulis were soxhlet-extracted with n-hexane, dichloromethane and methanol. MTT assay exhibited that dichloromethane and methanol extracts remarkably inhibited the growth of MCF-7 and WEHI-164 cancer cells in a dose-and time-dependent manner with little cytotoxicity on normal cell line HUVEC. Cell death ELISA, TUNEL assay, and the cleavage of poly ADP-ribose polymerase (PARP) uncovered that the cytotoxic effects of dichloromethane and methanol extracts were attributed to apoptosis in cancerous cells. Furthermore, quantitative real-time PCR revealed significant increases in the mRNA expression levels of p-53, caspase-3, caspase-9, Bax, and also a decrease in Bcl-2 expression. These results suggested that the extracts mainly induced apoptosis via a mitochondria-mediated intrinsic pathway. Notably, dichloromethane extract had higher cytotoxic and apoptotic activities than that of methanol extract, against both cancer cell lines, particularly MCF-7 cells. Our results indicate that S. amplexicaulis may serve as a promising source of potent agents for the treatment of human cancers.2020-09-22T00:00:00ZThe association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancerRahmani, FarzadAvan, AmirAmerizadeh, ForouzanFerns, Gordon A.Talebian, SaharShahidsales, Soodabehhttp://hdl.handle.net/2003/398942020-12-15T02:40:55Z2020-09-14T00:00:00ZTitle: The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer
Authors: Rahmani, Farzad; Avan, Amir; Amerizadeh, Forouzan; Ferns, Gordon A.; Talebian, Sahar; Shahidsales, Soodabeh
Abstract: Colorectal cancer is among the most aggressive tumors, and its development involves an interplay between various genetic and environmental familial risk factors. Several genetic polymorphisms have been reported to be associated with colorectal cancer in recent studies. In this current study, we aimed to evaluate the possible relationship between a CDKN2A/B, single nucleotide polymorphisms (SNP) (rs10811661), with the risk of colorectal cancer. A total of 541 individuals with, or without cancer were recruited. DNA was extracted, and genotyped using a Taq-Man based real‐time PCR method. The rs10811661 SNP was associated with an increased risk of colorectal cancer (additive model: OR=3.46, CI= 1.79-6.69, p<0.0001 and recessive model: 5.72, CI= 3.12-10.49, p<0.0001). The distribution of minor alleles in the total population for homozygote allele was 9.2 %, while this was 20.1 % for heterozygotes. In summary, our findings indicate that the rs10811661 polymorphism of the CDKN2A/B gene was strongly related to the occurrence of colorectal cancer suggesting its potential role as a prognostic biomarker for the management of colorectal cancer.2020-09-14T00:00:00ZNegative impact of COVID-19 pandemic on sleep quantitative parameters, quality, and circadian alignmentSalehinejad, Mohammad AliMajidinezhad, MaryamGhanavati, ElhamKouestanian, SaharVicario, Carmelo M.Nitsche, Michael A.Nejati, Vahidhttp://hdl.handle.net/2003/398932020-12-15T02:40:55Z2020-09-11T00:00:00ZTitle: Negative impact of COVID-19 pandemic on sleep quantitative parameters, quality, and circadian alignment
Authors: Salehinejad, Mohammad Ali; Majidinezhad, Maryam; Ghanavati, Elham; Kouestanian, Sahar; Vicario, Carmelo M.; Nitsche, Michael A.; Nejati, Vahid
Abstract: The COVID-19 pandemic has spread worldwide, affecting millions of people and exposing them to home quarantine, isolation, and social distancing. While recent reports showed increased distress and depressive/anxiety state related to COVID-19 crisis, we investigated how home quarantine affected sleep parameters in healthy individuals. 160 healthy individuals who were in home quarantine in April 2020 for at least one month participated in this study. Participants rated and compared their quantitative sleep parameters (time to go to bed, sleep duration, getting-up time) and sleep quality factors, pre-and during home quarantine due to the COVID-19 pandemic. Furthermore, participants’ chronotype was determined to see if sleep parameters are differentially affected in different chronotypes. Time to fall asleep and get-up in the morning were significantly delayed in all participants, indicating a significant circadian misalignment. Sleep quality was reported to be significantly poorer in all participants and chronotypes. Poor sleep quality included more daily disturbances (more sleep disturbances, higher daily dysfunctions due to low quality of sleep) and less perceived sleep quality (lower subjective sleep quality, longer time taken to fall asleep at night, more use of sleep medication for improving sleep quality) during home quarantine. Home quarantine due to COVID-19 pandemic has a detrimental impact on sleep quality. Online interventions including self-help sleep programs, stress management, relaxation practices, stimulus control, sleep hygiene, and mindfulness training are available interventions in the current situation.2020-09-11T00:00:00ZProsopis juliflora leave extracts induce cell death of MCF-7, HepG2, and LS-174T cancer cell linesElbehairi, Serag Eldin I.Ezzat Ahmed, AhmedAlshati, Ali A.Al-Kahtani, Mohammed A.Alfaifi, Mohammad Y.Alsyaad, Khalid M.Alalmie, Ali Yahya A.Elimam Ahamed, Mohammed M.Moustafa, Mahmoud F.Alhag, Sadeq K.Al-Abd, Ahmed M.Abbas, Ahmed M.http://hdl.handle.net/2003/398922020-12-15T02:40:56Z2020-09-09T00:00:00ZTitle: Prosopis juliflora leave extracts induce cell death of MCF-7, HepG2, and LS-174T cancer cell lines
Authors: Elbehairi, Serag Eldin I.; Ezzat Ahmed, Ahmed; Alshati, Ali A.; Al-Kahtani, Mohammed A.; Alfaifi, Mohammad Y.; Alsyaad, Khalid M.; Alalmie, Ali Yahya A.; Elimam Ahamed, Mohammed M.; Moustafa, Mahmoud F.; Alhag, Sadeq K.; Al-Abd, Ahmed M.; Abbas, Ahmed M.
Abstract: Prosopis juliflora (P. juliflora) is a widespread phreatophytic tree, which belongs to the Fabaceae family. The goal of the present study is to investigate the potential anti-cancer effect of P. juliflora leave extracts and to identify its chemical composition. For this purpose, MCF-7 (breast), HepG2 (liver), and LS-174T (colorectal) cancer cell lines were cultivated and incubated with various concentrations of P. juliflora leave extracts, and its impact on cell viability, proliferation, and cell cycle stages was investigated. P. juliflora leave extracts induced concentration-dependent cytotoxicity against all tested cancer cell lines. The calculated IC50 was 18.17, 33.1 and 41.9 μg/ml for MCF-7, HePG2 and LS-174T, respectively. Detailed analysis revealed that the cytotoxic action of P. juliflora extracts was mainly via necrosis but not apoptosis. Moreover, DNA content flow cytometry analysis showed cell-specific anti-proliferative action and cell cycle stages arrest. In order to identify the anti-cancer constituents of P. juliflora, the ethyl extracts were analyzed by liquid chromatography-mass spectrometry. The major constituents identified in the ethyl extracts of P. juliflora leaves were hydroxymethyl-pyridine, nicotinamide, adenine, and poly-(methyl methacrylate) (PMMA). In conclusion, P. juliflora ethyl acetate extracts have a potential anti-cancer effect against breast adenocarcinoma, hepatocellular carcinoma, and colorectal adenocarcinoma, and is enriched with anti-cancer constituents.2020-09-09T00:00:00ZAssessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrierEnko, DietmarZelzer, SieglindNiedrist, TobiasHolasek, SandraBaranyi, AndreasSchnedl, Wolfgang J.Herrmann, MarkusMeinitzer, Andreashttp://hdl.handle.net/2003/398912020-12-15T02:40:56Z2020-09-09T00:00:00ZTitle: Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier
Authors: Enko, Dietmar; Zelzer, Sieglind; Niedrist, Tobias; Holasek, Sandra; Baranyi, Andreas; Schnedl, Wolfgang J.; Herrmann, Markus; Meinitzer, Andreas
Abstract: Recently, the microbiome-derived trimethylamine-N-oxide (TMAO) was shown to be present in human cerebrospinal fluid (CSF). However, data on the potential of TMAO crossing the blood-CSF barrier are still lacking. This retrospective study aimed at investigating possible associations between the CSF/serum albumin (QALB) and TMAO (QTMAO) quotient and evaluating QTMAO values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with QALB and QTMAO determination, were evaluated. Serum and CSF TMAO measurements were performed on a tandem mass spectrometry SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA) coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies Santa Clara, CA, USA). Serum and CSF albumin were measured on the Atellica® NEPH 630 system (Siemens Healthineers, Erlangen, Germany). CSF TMAO levels were positively correlated with serum TMAO levels (ρ = 0.709, p < 0.001). The QALB was significantly associated with the QTMAO (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 – Q3) QTMAO values (4.7 (2.8 – 7.5) vs. 3.8 (2.5 – 5.7) x 10-1, p = 0.002) compared to 173 individuals with normal blood-CSF barrier function. CSF and serum TMAO concentrations were significantly associated in 290 CSF/serum pairs from lumbar punctures of clinical routine. QALB showed a relevant influence on QTMAO. Present results indicate that TMAO may cross the blood-CSF barrier.2020-09-09T00:00:00ZPolygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathwaysAbd Rashid, NorhashimaHussan, FaridaHamid, AsmahAdib Ridzuan, Nurul RaudzahHalim, Syarifah Aisyah Syed AbdulAbdul Jalil, Nahdia AfiifahNajib, Nor Haliza MohamadTeoh, Seong LinBudin, Siti Balkishttp://hdl.handle.net/2003/398902020-12-15T02:40:52Z2020-09-09T00:00:00ZTitle: Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways
Authors: Abd Rashid, Norhashima; Hussan, Farida; Hamid, Asmah; Adib Ridzuan, Nurul Raudzah; Halim, Syarifah Aisyah Syed Abdul; Abdul Jalil, Nahdia Afiifah; Najib, Nor Haliza Mohamad; Teoh, Seong Lin; Budin, Siti Balkis
Abstract: Oxidative stress, inflammation and apoptosis are thought as primary mediators of cisplatin-induced hepatotoxicity. The objective of this study was to determine the protective effect of Polygonum minus essential oil in cisplatin-induced hepatotoxicity. A total of forty-two male rats were randomly divided into seven groups: control, cisplatin, β-caryophyllene 150 mg/kg (BCP), PmEO 100 mg/kg + cisplatin (PmEO100CP), PmEO 200 mg/kg + cisplatin (PmEO200CP), PmEO 400 mg/kg + cisplatin (PmEO400CP) and PmEO 400 mg/kg (PmEO400). Rats in the BCP, PmEO100CP, PmEO200CP, PmEO400CP and PmEO400 group received respective treatment orally for 14 consecutive days prior to cisplatin injection. All animals except for those in the control group and PmEO400 were administered with a single dose of cisplatin (10 mg/kg) intraperitoneally on day 15 and all animals were sacrificed on day 18. PmEO100CP pretreatment protected against cisplatin-induced hepatotoxicity by decreasing CYP2E1 and indicators of oxidative stress including malondialdehyde, 8-OHdG and protein carbonyl which was accompanied by increased antioxidant status (glutathione, glutathione peroxidase, superoxide dismutase and catalase) as compared to cisplatin group. PmEO100CP pretreatment also modulated changes in liver inflammatory markers (TNF-α, IL-1α, IL-1β, IL-6 and IL-10). PmEO100CP administration also notably reduced cisplatin-induced apoptosis significantly as compared to cisplatin group. In conclusion, our results suggested that P. minus essential oil at a dose of 100 mg/kg may protect against cisplatin-induced hepatotoxicity possibly via inhibition of oxidative stress, inflammation and apoptosis.2020-09-09T00:00:00ZKnockdown of CSNK2β suppresses MDA-MB231 cell growth, induces apoptosis, inhibits migration and invasionKarna, Shibendra Kumar LalLone, Bilal AhmadAhmad, FaizShahi, NerinaPokharel, Yuba Rajhttp://hdl.handle.net/2003/398892020-12-15T02:40:54Z2020-09-07T00:00:00ZTitle: Knockdown of CSNK2β suppresses MDA-MB231 cell growth, induces apoptosis, inhibits migration and invasion
Authors: Karna, Shibendra Kumar Lal; Lone, Bilal Ahmad; Ahmad, Faiz; Shahi, Nerina; Pokharel, Yuba Raj
Abstract: Breast cancer is the most common cancer among women worldwide. Among different types of breast cancer known, treatment of triple-negative breast cancer is a major challenge because of its aggressiveness and poor prognosis; thus, identification of specific drivers is required for targeted therapies of breast cancer malignancy. Protein Casein Kinase (CSNK) is a serine/threonine kinase that exists as a tetrameric complex consisting of two catalytic (α and /or α') and two regulatory β subunits. CSNK2β can also function independently without catalytic subunits and exist as a distinct population in cells. This study aims to elucidate the role of Casein Kinase 2β (CSNK2β) gene in cell proliferation, cell cycle, migration and apoptosis of triple-negative breast cancer MDA-MB-231 cells. The silencing of CSNK2β in MDA-MB-231 cells resulted in decreased cell viability and colony formation. Cell cycle analysis showed a significant arrest of cells in G2M phase. Hoechst and CM-H2DCFDA staining showed nuclear condensation and augmented intracellular reactive oxygen species (ROS) production. Furthermore, silencing of CSNK2β in MDA-MB-231 cells modulated the apoptotic machinery- BAX, Bcl-xL, and caspase 3; autophagy machinery-Beclin-1 and LC3-1; and inhibited the vital markers (p-ERK, c-Myc, NF-κB, E2F1, PCNA, p38-α) associated with cell proliferation and DNA replication pathways. In addition, knockdown of CSNK2β also affected the migration potential of MDA-MB-231, as observed in the wound healing and transwell migration assays. Altogether, the study suggests that CSNK2β silencing may offer future therapeutic target in triple-negative breast cancer.2020-09-07T00:00:00ZCurcumin as an indirect methylation inhibitor modulates the effects of Toxoplasma gondii on genes involved in male fertilitySaki, JasemSabaghan, MohamadArjmand, RezaTeimoori, AliRashno, MohammadSaki, GhasemShojaee, Saeedehhttp://hdl.handle.net/2003/398882020-12-15T02:40:54Z2020-08-24T00:00:00ZTitle: Curcumin as an indirect methylation inhibitor modulates the effects of Toxoplasma gondii on genes involved in male fertility
Authors: Saki, Jasem; Sabaghan, Mohamad; Arjmand, Reza; Teimoori, Ali; Rashno, Mohammad; Saki, Ghasem; Shojaee, Saeedeh
Abstract: Toxoplasma gondii is a common protozoan parasite, which infects warm-blooded mammals, including mice and humans, throughout the world. The negative effects of T. gondii infection on the human reproductive system have been documented, especially in females. However, only few studies have examined the effects of T. gondii infection on the male reproductive system. Previous research shows that T. gondii can induce DNA methylation in some gene promoters, which are key regulators of spermatogenesis. Therefore, this study aimed to evaluate the effects of curcumin on the activity of DNA methyltransferases (DNMTs), as well as selected genes, involved in spermatogenesis in spermatogenic cells. In the spermatogenic cells exposed to T. gondii, there was a significant increase in DNMT1 and DNMT3A gene expression and a significant reduction in HSPA1A, MTHR, and DAZL gene expression, compared to the controls. The present results showed that curcumin could regulate changes in T. gondii-mediated gene expression. The effect of T. gondii on DNMT activity was also investigated in this study. A 40 % increase in DNMT activity was observed due to T. gondii infection. However, DNMT activity was restored by treatment with 20 μM curcumin for eight hours. The results revealed that T. gondii increases the NF-κB activity, compared to the control group. The increase in NF-κB activity, induced by T. gondii, was inhibited by curcumin. In conclusion, T. gondii, by increasing DNMT expression and activity, leads to an increase in NF-κB activity in cells. On the other hand, curcumin reduced DNA methylation, induced by T. gondii, owing to its NF-κB-inhibiting properties. Therefore, curcumin, as a hypomethylating agent, can be potentially used to alleviate the negative effects of T. gondii on the male reproductive system.2020-08-24T00:00:00ZPlasma vascular endothelial growth factor B is elevated in non-alcoholic fatty liver disease patients and associated with blood pressure and renal dysfunctionYe, XiaofengKong, WenZafar, Mohammad IshraqZeng, JunchaoYang, RuiChen, Lu-Luhttp://hdl.handle.net/2003/398862021-01-07T11:58:21Z2020-08-20T00:00:00ZTitle: Plasma vascular endothelial growth factor B is elevated in non-alcoholic fatty liver disease patients and associated with blood pressure and renal dysfunction
Authors: Ye, Xiaofeng; Kong, Wen; Zafar, Mohammad Ishraq; Zeng, Junchao; Yang, Rui; Chen, Lu-Lu
Abstract: Vascular endothelial growth factor B (VEGF-B) is a critical metabolic regulator in insulin resistance, and lipid distribution. We intended to ascertain the relationship between circulating VEGF-B and non-alcoholic fatty liver disease (NAFLD) in the general public. We recruited a total of 194 general participants for a routine physical health examination; of these, 84 participants were identified with NAFLD and 110 without NAFLD based on ultrasonographic findings. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), HbA1c, liver function, kidney function, plasma VEGF-B levels and indexes of metabolic syndrome (blood pressure, fasting plasma glucose, fasting lipids) were evaluated. Plasma VEGF-B values were significantly higher in individuals with NAFLD compared to those without NAFLD (P = 0.022), and analysis of covariance confirmed this result. VEGF-B showed a positive correlation with γ-glutamyl transpeptidase (γ-GT) and HOMA-IR in univariate analysis (q = 0.242; P = 0.001; q =0.174; P = 0.019, respectively). Multiple linear regression analysis showed that γ-GT and ALT were independently correlated with VEGF-B even after adjusted for gender and age (q = 0.286; P = 0.01; q =0.237; P = 0.033, respectively). Moreover, plasma VEGF-B showed a powerful correlation with blood pressure and renal dysfunction. Plasma VEGF-B might be a new clinical variable related to NAFLD and could be a proper biomarker for the early detection of hypertension and renal dysfunction. However, further studies with large cohorts’ size are warranted to validate our findings.2020-08-20T00:00:00ZAssociation between resilience and a functional polymorphism in the serotonin transporter (SLC6A4) geneGonzález-Giraldo, YeimyForero, Diego A.http://hdl.handle.net/2003/398852020-12-15T02:40:56Z2020-08-19T00:00:00ZTitle: Association between resilience and a functional polymorphism in the serotonin transporter (SLC6A4) gene
Authors: González-Giraldo, Yeimy; Forero, Diego A.
Abstract: Resilience is a mechanism used by humans to adapt to adverse situations. It is a protective factor against mental health problems. This process can be influenced by environmental and genetic factors. Several genes have been associated with interindividual differences in resilience levels, but the results are inconclusive. Therefore, the aim of this meta-analysis was to evaluate the effect of a functional polymorphism (5-HTTLPR) in the SLC6A4 gene on resilience levels. A search in PubMed, HugeNavigator and Google Scholar databases was carried out and 16 studies about the association of 5-HTTLPR polymorphism and resilience in humans were identified. The OpenMeta[Analyst] program was employed to perform statistical analysis using a random-effects model. The final analysis included 9 studies, for a total of 4,080 subjects. Significant results were found when the standardized mean differences (SMD) of LL and SL carriers were compared, (SMD: -0.087 (confidence interval: -0.166 to -0.008; I2: 0 %); P value: 0.031). A significant result was also found in an analysis comparing SS/SL versus LL genotypes (SMD: -0.231; confidence interval: -0.400 to -0.061, P value: 0.008; I2: 0 %). This is the first meta-analysis performed to identify the pooled association of a functional polymorphism in the serotonin transporter gene and resilience. The current results suggest that the L/L genotype is associated with resilience. Further studies are necessary to elucidate the role of genetics on the resilience mechanisms.2020-08-19T00:00:00ZLncRNA HOTAIR promotes MPP+-induced neuronal injury in Parkinson’s disease by regulating the miR-874-5p/ATG10 axisZhao, JingyaLi, HongliChang, Nahttp://hdl.handle.net/2003/398842020-12-15T02:40:57Z2020-08-05T00:00:00ZTitle: LncRNA HOTAIR promotes MPP+-induced neuronal injury in Parkinson’s disease by regulating the miR-874-5p/ATG10 axis
Authors: Zhao, Jingya; Li, Hongli; Chang, Na
Abstract: Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Long non-coding RNAs (lncRNAs) play an important role in many neurological diseases, including PD. This study aimed to investigate the role of lncRNA HOX transcript antisense RNA (HOTAIR) in PD pathogenesis and its potential mechanism. SK-N-SH cells were exposed to 1-methyl-4-phenylpyridinium (MPP+) to mimic PD model in vitro. The levels of HOTAIR, miR-874-5p and autophagy-related 10 (ATG10) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The expression of apoptosis-related proteins was measured by western blot. The levels of neuroinflammation-related factors were detected by enzyme-linked immunosorbent assay (ELISA). Commercial kits was used to monitor lactate dehydrogenase (LDH) activity, reactive oxygen (ROS) generation and superoxide dismutase (SOD) activity. The interaction among HOTAIR, miR-874-5p and ATG10 were verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. HOTAIR and ATG10 were up-regulated, and miR-874-5p was down-regulated in dose- and time-dependent manners in MPP+-treated SK-N-SH cells. HOTAIR knockdown reduced MPP+-induced neuronal damage. HOTAIR aggrandized MPP+-triggered neuronal injury by sponging miR-874-5p. Also, miR-874-5p attenuated MPP+-triggered neuronal damage by targeting ATG10. Moreover, HOTAIR regulated ATG10 expression via sponging miR-874-5p. HOTAIR promoted MPP+-induced neuronal injury via modulating the miR-874-5p/ATG10 axis in SK-N-SH cells.2020-08-05T00:00:00ZCytoprotective effects of fermented oyster extracts against oxidative stress-induced DNA damage and apoptosis through activation of the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblastsPark, CheolLee, HyesookHan, Min HoJeong, Jin-WooKim, Sung OkJeong, Soon-JeongLee, Bae‐JinKim, Gi‐YoungPark, Eui KyunJeon, You‐JinChoi, Yung Hyunhttp://hdl.handle.net/2003/398832020-12-15T02:40:54Z2020-08-04T00:00:00ZTitle: Cytoprotective effects of fermented oyster extracts against oxidative stress-induced DNA damage and apoptosis through activation of the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblasts
Authors: Park, Cheol; Lee, Hyesook; Han, Min Ho; Jeong, Jin-Woo; Kim, Sung Ok; Jeong, Soon-Jeong; Lee, Bae‐Jin; Kim, Gi‐Young; Park, Eui Kyun; Jeon, You‐Jin; Choi, Yung Hyun
Abstract: Osteoblast damage by oxidative stress has been recognized as a cause of bone-related disease, including osteoporosis. Recently, we reported that fermented Pacific oyster (Crassostrea gigas) extracts (FO) inhibited osteoclastogenesis and osteoporosis, while promoting osteogenesis. However, since the beneficial potential of FO on osteoblasts is not well known, in the present study, we investigated the cytoprotective effect of FO against oxidative stress in MC3T3-E1 osteoblasts. Our results demonstrated that FO inhibited hydrogen peroxide (H2O2)-induced DNA damage and cytotoxicity through the rescue of mitochondrial function by blocking abnormal ROS accumulation. FO also prevented apoptosis by suppressing loss of mitochondrial membrane potential and cytosolic release of cytochrome c, decreasing the rate of Bax/Bcl-2 expression and reducing the activity of caspase-9 and caspase-3 in H2O2-stimulated MC3T3-E1 osteoblasts, suggesting that FO protected MC3T3-E1 osteoblasts from the induction of caspase dependent- and mitochondria-mediated apoptosis by oxidative stress. In addition, FO markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression of heme oxygenase-1 (HO-1). However, inhibiting the expression of HO-1 by artificially blocking the expression of Nrf2 using siRNA significantly eliminated the protective effect of FO, indicating that FO activates the Nrf2/HO-1 signaling pathway in MC3T3-E1 osteoblasts to protect against oxidative stress. Based on the present data, FO is thought to be useful as a potential therapeutic agent for the inhibition of oxidative stress in osteoblasts.2020-08-04T00:00:00ZExosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion functionKeshtkar, SomayehKaviani, MaryamSarvestani, Fatemeh SabetGhahremani, Mohammad HosseinAghdaei, Mahdokht HosseinAl-Abdullah, Ismail H.Azarpira, Negarhttp://hdl.handle.net/2003/398822020-12-15T02:40:55Z2020-08-03T00:00:00ZTitle: Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function
Authors: Keshtkar, Somayeh; Kaviani, Maryam; Sarvestani, Fatemeh Sabet; Ghahremani, Mohammad Hossein; Aghdaei, Mahdokht Hossein; Al-Abdullah, Ismail H.; Azarpira, Negar
Abstract: Islet cell death and loss of function after isolation and before transplantation is considered a key barrier to successful islet transplantation outcomes. Mesenchymal stem cells (MSCs) have been used to protect isolated islets owing to their paracrine potential partially through the secretion of vascular endothelial growth factor (VEGF). The paracrine functions of MSCs are also mediated, at least in part, by the release of extracellular vesicles including exosomes. In the present study, we examined (i) the effect of exosomes from human MSCs on the survival and function of isolated mouse islets and (ii) whether exosomes contain VEGF and the potential impact of exosomal VEGF on the survival of mouse islets. Isolated mouse islets were cultured for three days with MSC-derived exosomes (MSC-Exo), MSCs, or MSC-conditioned media without exosomes (MSC-CM-without-Exo). We investigated the effects of the exosomes, MSCs, and conditioned media on islet viability, apoptosis and function. Besides the expression of apoptotic and pro-survival genes, the production of human and mouse VEGF proteins was evaluated. The MSCs and MSC-Exo, but not the MSC-CM-without-Exo, significantly decreased the percentage of apoptotic cells and increased islet viability following the downregulation of pro-apoptotic genes and the upregulation of pro-survival factors, as well as the promotion of insulin secretion. Human VEGF was observed in the isolated exosomes, and the gene expression and protein production of mouse VEGF significantly increased in islets cultured with MSC-Exo. MSC-derived exosomes are as efficient as parent MSCs for mitigating cell death and improving islet survival and function. This cytoprotective effect was probably mediated by VEGF transfer, suggesting a pivotal strategy for ameliorating islet transplantation outcomes.2020-08-03T00:00:00ZDevelopment of a novel in vitro assay to evaluate environmental water using an IL-8 reporter cell lineKimura, YutakaFujimura, ChizuImagawa, ToshifumiLupisan, Socorro P.Saito-Obata, MarikoSaito, MayukoOshitani, HitoshiAiba, Setsuyahttp://hdl.handle.net/2003/398812020-12-14T13:55:04Z2020-07-31T00:00:00ZTitle: Development of a novel in vitro assay to evaluate environmental water using an IL-8 reporter cell line
Authors: Kimura, Yutaka; Fujimura, Chizu; Imagawa, Toshifumi; Lupisan, Socorro P.; Saito-Obata, Mariko; Saito, Mayuko; Oshitani, Hitoshi; Aiba, Setsuya
Abstract: The IL-8 luciferase reporter cell line, THP-G8 cells, used in the in vitro sensitization test, OECD442E, can respond to a variety of stimuli other than haptens, such as lipopolysaccharide (LPS), other bacterial toxins, and detergents. Considering these characteristics, we examined the ability of the IL-8 luciferase assay using THP-G8 cells to evaluate water pollution. We first stimulated THP-G8 cell with various Toll-like receptor (TLR) agonists and nucleotide-binding oligomerization domain-like receptor (NLR) agonists, and found that TLR1, 2, 4, 5, 6 agonists and NOD 1, 2 agonists significantly augmented IL-8 luciferase activity (IL8LA). Then, we examined the detection threshold of LPS by THP-G8 cells, and found it 0.4 EU/ml. Next, we examined whether THP-G8 cells can differently respond to a variety of sources of environmental water around Sendai, Japan and Manila, Philippine and whether there is a correlation between the IL8LA of different sources of water and their level of endotoxin assessed by the LAL assay. There was a clear trend that the IL8LA was lower in the upper stream and higher in the downstream in both Japan and Philippine. Moreover, there was a strong correlation between the IL8LA of the environmental water and its endotoxin level. Finally, using N-acetyl-L-cysteine, an antioxidant/radical scavenger, and polymyxin B that neutralizes endotoxin, we demonstrated that there was a difference in the suppressive effects by them between the water from Japan and that from Philippine. These data suggest the potential of the IL-8 luciferase assay for evaluating environmental water pollution both quantitatively and qualitatively.2020-07-31T00:00:00ZAnalysis of natural killer cell functions in patients with hereditary hemochromatosisBönnemann, VivianClaus, MarenButzeck, BarbaraCollette, DanielaBröde, PeterGolka, KlausWatzl, Carstenhttp://hdl.handle.net/2003/398802020-12-14T13:57:12Z2020-03-25T00:00:00ZTitle: Analysis of natural killer cell functions in patients with hereditary hemochromatosis
Authors: Bönnemann, Vivian; Claus, Maren; Butzeck, Barbara; Collette, Daniela; Bröde, Peter; Golka, Klaus; Watzl, Carsten
Abstract: Hereditary hemochromatosis (HH) is an autosomal-recessive disorder of the iron metabolism. Patients are typically affected by dysregulated iron levels, which can lead to iron accumulation within essential organs, such as liver, heart and pancreas. Furthermore, many HH patients are also afflicted by several immune defects and increased occurrence of autoimmune diseases that are linked to human homeostatic iron regulator protein (HFE) in the immune response. Here we examined immune cell phenotype and function in 21 HH patients compared to 21 healthy controls with a focus on Natural Killer (NK) cells. We observed increased basal and stimulated production of pro-inflammatory cytokines such as IL-1β or IL-18 in HH patients compared to healthy controls. However, we did not find major changes in the phenotype, the amount or the cytotoxic function of NK cells in HH patients. Instead, our data show a general decrease in the total number of granulocytes in HH patients (2774 ± 958 per μl versus 3457 ± 1122 per μl in healthy controls). These data demonstrate that NK cells of HH patients are not significantly affected and that the patients’ treatment by regular phlebotomy is sufficient to avoid systemic iron overload and its consequences to the immune system.2020-03-25T00:00:00ZEffect of sodium butyrate on HDAC8 mRNA expression in colorectal cancer cell lines and molecular docking study of LHX1 - sodium butyrate interactionForouzesh, FloraGhiaghi, MahsaRahimi, Hamzehhttp://hdl.handle.net/2003/398792020-12-14T14:21:55Z2020-07-23T00:00:00ZTitle: Effect of sodium butyrate on HDAC8 mRNA expression in colorectal cancer cell lines and molecular docking study of LHX1 - sodium butyrate interaction
Authors: Forouzesh, Flora; Ghiaghi, Mahsa; Rahimi, Hamzeh
Abstract: Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer related death worldwide. Histone Deacetylase 8 (HDAC8) has a unique feature and is a good target for drug design. The LHX1 factor is an important transcription factor for this gene. The aim of this study was to investigate the effect of sodium butyrate (NaB) as a histone deacetylase inhibitors on the expression of the HDAC8 gene in the colorectal cancer cell line, and the molecular docking of LHX1 transcription factor with NaB. HCT-116 and HT-29 cell lines were treated with different concentrations of NaB (6.25mM to 150 mM) at 24, 48 and 72 hours. RNA was extracted from the treated and untreated cells and cDNA was synthesized. Quantitative Real-Time-PCR was done to investigate the mRNA expression of HDAC8. Molecular docking was performed to investigate NaB and LHX1 interaction. On the base of Real-time-PCR results, the concentration of 150 mM NaB after 24 hours in HT-29 and HCT-116 cell lines caused a significant reduction in mRNA expression of HDAC8 (P<0.05). In 48 hours of treatment, there was a significant decrease in the mRNA expression of HDAC8 at all concentrations (P<0.05). The docking results showed that LHX1 and NaB interacted the best way with the lowest energy levels. Our results showed that NaB bond to LHX1 strongly. Our results demonstrated that NaB bind to the LHX1 transcription factor and inhibited the function of this factor and subsequently the transcription from the HDAC8 gene was decreased and results in cell death. Future studies are needed to assess the molecular mechanisms of NaB on gene expression.2020-07-23T00:00:00ZThe therapeutic potential of losartan in lung metastasis of colorectal cancerHashemzehi, MiladNaghibzadeh, NiloufarAsgharzadeh, FereshtehMostafapour, AsmaHassanian, Seyed MahdiFerns, Gordon A.Cho, William C.Avan, AmirKhazaei, Majidhttp://hdl.handle.net/2003/398782020-12-12T02:41:00Z2020-06-29T00:00:00ZTitle: The therapeutic potential of losartan in lung metastasis of colorectal cancer
Authors: Hashemzehi, Milad; Naghibzadeh, Niloufar; Asgharzadeh, Fereshteh; Mostafapour, Asma; Hassanian, Seyed Mahdi; Ferns, Gordon A.; Cho, William C.; Avan, Amir; Khazaei, Majid
Abstract: Colorectal cancer (CRC) is a common cancer with a high incidence rate. Components of the renin-angiotensin system (RAS) have been reported to be dysregulated in several malignancies including CRC. Here, we have explored the potential anti-metastatic effects of a RAS inhibitor, losartan, in an experimental model of lung metastasis in CRC. A murine model of lung metastasis of CRC was used, which involved the intravenous injection of CT26 cells via a tail vein. Four experimental groups comprised: an untreated group; a group that received 5-FU which was administered intraperitoneally; a losartan group that received a combination group that received 5-FU plus losartan . We evaluated the anti-inflammatory effects of losartan by histopathological method, and the measurement of oxidative or antioxidant markers including malondialdehyde (MDA) and total-thiols (T-SH) tissue levels, superoxide-dismutase (SOD) and catalase activity. We found that losartan inhibited lung metastasis of CRC and there was a reduction of the IL-6 expression level in the tissue sample. It was also associated with reduced levels of the anti-angiogenic factor Vascular endothelial growth factor (VEGF). Furthermore, we found that losartan induced oxidative stress as assessed by an elevation of MDA level, reduction of T-SH, SOD and catalase activities in lung tissue. Our findings demonstrated that losartan ameliorates angiogenesis, inflammation and the induction of oxidative stress via Angiotensin II type I receptor (AT1R). This may shine some lights on targeting the RAS pathway as a potential therapeutic approach in the treatment of metastatic CRC patients.2020-06-29T00:00:00ZInduction and repression effects on CYP and transporter protein abundance by azole mixture uptake in rat liverHammer, HelenSchmidt, FlaviaHeise, TanjaKnebel, ConstanzeDabrowski, AlexanderPlanatscher, HannesKneuer, CarstenMarx-Stoelting, PhilipPötz, Oliverhttp://hdl.handle.net/2003/398772020-12-12T02:41:00Z2020-06-26T00:00:00ZTitle: Induction and repression effects on CYP and transporter protein abundance by azole mixture uptake in rat liver
Authors: Hammer, Helen; Schmidt, Flavia; Heise, Tanja; Knebel, Constanze; Dabrowski, Alexander; Planatscher, Hannes; Kneuer, Carsten; Marx-Stoelting, Philip; Pötz, Oliver
Abstract: Detection of mixture effects is a major challenge in current experimental and regulatory toxicology. Robust markers are needed that are easy to quantify and responsive to chemical stressors in a broad dose range. Several hepatic enzymes and proteins related to drug metabolism like cytochrome-P-450 (CYP) enzymes and transporters have been shown to be responsive to pesticide active substances in a broad dose range and are therefore good candidates to be used as markers for mixture toxicity. Even though they can be well quantified at the mRNA level, quantification on the protein level is challenging because most of these proteins are membrane bound. Here we report the development of mass spectrometry-based assays using triple-x-proteomics (TXP) antibodies in combination with targeted selected ion monitoring (tSIM) to quantify changes of protein levels due to exposure to mixtures of pesticide active substances. Our results indicate that changes on the protein level of CYP1A1, ABCB2, ABCC3 are in line with observations on the mRNA and enzyme activity level and are indicative of mixture effects. Therefore, the tests are promising to reveal effects by chemical mixture effects in toxicological studies in rats.2020-06-26T00:00:00ZProteomics profiling asthma induced-lysine acetylationSu, Xin-mingRen, YuanLi, Meng-luBai, Shi-yaoYu, NaKong, Ling-feiKang, Jianhttp://hdl.handle.net/2003/398762020-12-12T02:40:58Z2020-06-04T00:00:00ZTitle: Proteomics profiling asthma induced-lysine acetylation
Authors: Su, Xin-ming; Ren, Yuan; Li, Meng-lu; Bai, Shi-yao; Yu, Na; Kong, Ling-fei; Kang, Jian
Abstract: Asthma is a chronic inflammatory disease that has been extensively studied for many years. However, finding a complete cure remains a significant challenge. Protein acetylation, especially histone acetylation, plays a significant role in the anti-asthma process. Histone deacetylation inhibitors (HDACi) have been shown to have a curative effect on asthma in clinical practice. An asthmatic mouse model was created by ovalbumin induction. Proteome and acetylproteome analysis were performed on lung tissues. HDACi were tested in the asthmatic mice. A total of 5346 proteins and 581 acetylation sites were identified, among which 154 proteins and 68 acetylation peptides were significantly altered by asthma. Many activated and deactivated processes, pathways, and protein groups were identified through bioinformatics analysis. Sequence motif preference analysis gave rise to a novel Kac-related core histone region, -KAXXK-, which was postulated as a key regulatory unit of histone acetylation. Asthma involves a variety of proteome dynamics and is controlled by protein lysine acetylation through the core motif -KAXXK-. These findings provide novel avenues to target and treat asthma.2020-06-04T00:00:00ZMicrobiological and virulence aspects of Rhodotorula mucilaginosaJarros, Isabele CarrilhoVeiga, Flávia FrancoCorrêa, Jakeline LuizBarros, Isabella Letícia EstevesGadelha, Marina CristinaVoidaleski, Morgana F.Pieralisi, NeliPedroso, Raissa BocchiVicente, Vânia A.Negri, MelyssaSvidzinski, Terezinha Inez Estivalethttp://hdl.handle.net/2003/398752020-12-12T02:40:58Z2020-05-27T00:00:00ZTitle: Microbiological and virulence aspects of Rhodotorula mucilaginosa
Authors: Jarros, Isabele Carrilho; Veiga, Flávia Franco; Corrêa, Jakeline Luiz; Barros, Isabella Letícia Esteves; Gadelha, Marina Cristina; Voidaleski, Morgana F.; Pieralisi, Neli; Pedroso, Raissa Bocchi; Vicente, Vânia A.; Negri, Melyssa; Svidzinski, Terezinha Inez Estivalet
Abstract: We aimed to characterize microbiologically clinical isolates of R. mucilaginosa isolated from colonization of a patient with chronic renal disease (CKD), as well as to evaluate their phylogeny, antifungal susceptibility, virulence, and pathogenicity in order to infer the potential to become a possible infective agent. For this study, two isolates of R. mucilaginosa from oral colonization of a CKD patient were isolated, identified and characterized by classical (genotypic and phenotypic) methods. Susceptibility to conventional antifungals was evaluated, followed by biofilm production, measured by different techniques (total biomass, metabolic activity, colony forming units and extracellular matrix quantification). Finally, the pathogenicity of yeast was evaluated by infection of Tenebrio molitor larvae. All isolates were resistant to azole and sensitive to polyenes and they were able to adhere and form biofilm on the abiotic surface of polystyrene. In general, similar profiles among isolates were observed over the observed periods (2, 24, 48 and 72 hours). Regarding extracellular matrix components of biofilms at different maturation ages, R. mucilaginosa was able to produce eDNA, eRNA, proteins, and polysaccharides that varied according to time and the strain. The death curve in vivo model showed a large reduction in the survival percentage of the larvae was observed in the first 24 hours, with only 40 % survival at the end of the evaluation. We infer that colonization of chronic renal patients by R. mucilaginosa offers a high risk of serious infection. And also emphasize that the correct identification of yeast is the main means for an efficient treatment.2020-05-27T00:00:00ZBioinformatics and experimental studies of anti-leukemic activity from 6-gingerol demonstrate its role in p53 mediated apoptosis pathwayChatupheeraphat, ChawalitNantasenamat, ChaninDeesrisak, KamolchanokRoytrakul, SittirukAnurathapan, UsanaratTanyong, Dalinahttp://hdl.handle.net/2003/398742020-12-12T02:41:01Z2020-05-06T00:00:00ZTitle: Bioinformatics and experimental studies of anti-leukemic activity from 6-gingerol demonstrate its role in p53 mediated apoptosis pathway
Authors: Chatupheeraphat, Chawalit; Nantasenamat, Chanin; Deesrisak, Kamolchanok; Roytrakul, Sittiruk; Anurathapan, Usanarat; Tanyong, Dalina
Abstract: 6-gingerol is a traditional medicine that possesses anti-cancer activity against several types of cancer. However, the mechanism of action still remains unclear. Therefore, this study explored the effects of 6-gingerol on anti-leukemic mechanisms in NB4, MOLT4, and Raji leukemic cell. Results indicated that 6-gingerol inhibited cell proliferation and induced cell apoptosis in these 3 cell lines. Moreover, 6-gingerol was shown to increase the mRNA expression of the caspase family thereby suggesting that 6-gingerol induced apoptosis through the caspase-dependent pathway. To explore the signaling pathway regulating 6-gingerol induced apoptosis, we utilized and integrated the network pharmacology approach together with experimental investigations. Targets of 6-gingerol were identified from ChEMBL and STITCH databases, which were used for constructing the protein-protein interaction (PPI) network. Results from the PPI network indicated that p53 was a key regulator. Moreover, it was found that 6-gingerol could increase the levels of p53 mRNA in all leukemic cell lines. Thus, 6-gingerol has shown to have anti-cancer activity. In addition, p53, BAX and BCL2 could be involved in the apoptosis pathway of these leukemic cells. This study is anticipated to be useful for the development of 6-gingerol as an anti-leukemic drug in the future.2020-05-06T00:00:00ZToxoplasma gondiiZaki, LeilaGhaffarifar, FatemehSharifi, ZohrehHorton, JohnSadraei, Javidhttp://hdl.handle.net/2003/398732020-12-12T02:41:01Z2020-04-20T00:00:00ZTitle: Toxoplasma gondii
Authors: Zaki, Leila; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Horton, John; Sadraei, Javid
Abstract: Common medicines for the treatment of toxoplasmosis have limited efficacy and unwanted side effects. Opiates can effect both innate and cell-mediated immunity and stimulate the immune responses in different parasitic infections. In this work, preventive and therapeutic effects of morphine were evaluated on the tachyzoites of Toxoplasma gondii and infected macrophages in vitro and in a murine model. Different concentrations of morphine (0.1 and 0.01 μg/ml) were evaluated on mortality rate of T. gondii by direct counting after 3 and 24 hours. The cytotoxic and apoptotic effects of these drugs were measured by the MTT assays and flow cytometry analysis, respectively. The same procedures were assessed in T. gondii-infected macrophages. The parasite loads were determined using quantitative polymerase chain reaction (qPCR). For in vivo assessment, BALB/c mice treated with morphine before or after infection with tachyzoites. The survival rate of animals, parasite load in the spleen, and the IFN-γ and IL-4 cytokines levels were measured. Morphine was effective on tachyzoites of T. gondii and had a reverse relationship with its concentration. The results of flow cytometry showed that the toxic effects of morphine on tachyzoites after 3 hours was not statistically significant (p<0.05). Also, apoptosis in infected MQs rose with a decreasing concentration of morphine. The parasitic load in MQs treated with morphine before infection was lower than that in cells treated after infection and the differences were statistically significant (p<0.01). In mice that received morphine before infection, survival rate, parasite load and the IFN-γ level were significantly lower than in mice treated after infection (p<0.01). The results of this study have shown that morphine in the pre-treatment group had higher anti-Toxoplasma activity than morphine in post-treatment in vitro and in murine model.2020-04-20T00:00:00ZThe neural basis of hazard perception differences between novice and experienced driversGharib, SeifollahZare-Sadeghi, ArashZakerian, Seyed AbolfazlHaidari, Mohsen Rezahttp://hdl.handle.net/2003/398722020-12-12T02:41:02Z2020-05-04T00:00:00ZTitle: The neural basis of hazard perception differences between novice and experienced drivers
Authors: Gharib, Seifollah; Zare-Sadeghi, Arash; Zakerian, Seyed Abolfazl; Haidari, Mohsen Reza
Abstract: The neural mechanisms underlying hazard perception are poorly understood as to how experience affects it in drivers. In this study we used functional magnetic resonance imaging (fMRI) to examine experienced-related changes in brain activation of a hazard perception skill between novice and aged drivers. Additionally, region of interest (ROI) and seed-to-voxel analysis were conducted to examine experienced-related functional connectivity changes in visual attention and saliency networks between novice (n=15, age 22.13± 3.38 years years) and experienced (n=16, age 41.44± 5.83 years) drivers. Experienced drivers had significantly lower hazard perception reaction time (1.32 ± 1.09 s) and miss rates (11.42 ± 8.36 %) compared to the novice (3.58± 1.45 s and 39.67 ± 15.72 %, respectively). Blood oxygen level dependent (BOLD) activation increased in occipital, parietal and frontal areas when executing hazard perception task in the both the groups. During task execution, experienced drivers showed, in general, greater activation in occipital lobe, Supramarginal Gyrus (SMG), right insular cortex, and anterior cingulate cortex (ACC) and cerebellar regions compared to the novice drivers indicating more efficient visual attention and decision-making processing in hazard perception skill. Seed based functional analyses in the task revealed greater connectivity between the ACC and the entire salience network (visual attention network) in the experienced group. Additionally, ACC had higher functional connectivity with right frontal eye field (FEF) and, bilateral Intraparietal Sulcus (IPS) and lateral occipital areas in the experienced group. Our results suggest that the hazard perception ability in experienced drivers is due to increase in the activation of executive attention regions, and better functional connectivity between bilateral occipital cortices and salience network. Better hazard perception performance is highly dependent on emotional awareness and attention to the velocity of motion.2020-05-04T00:00:00ZAssociation between HIC1 promoter methylation and solid tumorZhao, TieAfrifa, JusticeWang, DongYu, Jingcuihttp://hdl.handle.net/2003/398712020-12-12T02:40:59Z2020-04-07T00:00:00ZTitle: Association between HIC1 promoter methylation and solid tumor
Authors: Zhao, Tie; Afrifa, Justice; Wang, Dong; Yu, Jingcui
Abstract: The epigenetic silencing of tumor suppressor genes by promoter methylation plays an increasingly important role in cancer research. A number of studies have reported the contribution of HIC1 promoter methylation towards the occurrence and development of solid tumors, even though HIC1 promoter methylation has also been found in normal and benign tissue samples. We sought to perform a more accurate and comprehensive meta-analysis to assess the association between HIC1 promoter methylation and cancer risk. We searched and retrieved all published studies on HIC1 promoter methylation in PubMed, Google Scholar, Embase, Cochrane Library, and Web of Science databases. After two reviewers checked the studies and extracted the necessary data independently, the meta-analysis was performed using STATA 12.0 software. A total of 14 case-control studies (949 cancer patients, 282 benign, and 371 normal controls) were included in our study. We report a significantly elevated HIC1 promoter methylation in tumor samples compared to normal (OR = 7.02, 95 % CI 3.12-15.78, P < 0.001) and benign controls (OR = 2.69, 95 % CI 1.13-6.42, P = 0.025). Subgroup analysis stratified by ethnicity showed a significantly reduced heterogeneity among North American (I2 = 0.0 %, P = 0.502) and European (I2 = 33.7 %, P = 0.183) samples. In addition, heterogeneity was significantly reduced among MSP based detection method (I2= 36.4 %, P = 0.139) when samples were stratified based on the methylation detection methods. The overall outcome demonstrated that HIC1 promoter methylation may be involved in the occurrence and development of solid tumors and has the potential to serve as an epigenetic maker in various specific tumors.2020-04-07T00:00:00ZQSAR-driven rational design of novel DNA methyltransferase 1 inhibitorsPhanus-umporn, ChuleepornPrachayasittikul, VedaNantasenamat, ChaninPrachayasittikul, SupalukPrachayasittikul, Viraponghttp://hdl.handle.net/2003/398702020-12-12T02:41:02Z2020-04-02T00:00:00ZTitle: QSAR-driven rational design of novel DNA methyltransferase 1 inhibitors
Authors: Phanus-umporn, Chuleeporn; Prachayasittikul, Veda; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Prachayasittikul, Virapong
Abstract: DNA methylation, an epigenetic modification, is mediated by DNA methyltransferases (DNMTs), a family of enzymes. Inhibitions of these enzymes are considered a promising strategy for the treatment of several diseases. In this study, a quantitative structure-activity relationship (QSAR) modeling was employed to understand the structure-activity relationship (SAR) of currently available non-nucleoside DNMT1 inhibitors (i.e., indole and oxazoline/1,2-oxazole scaffolds). Two QSAR models were successfully constructed using multiple linear regression (MLR) and provided good predictive performance (R2Tr = 0.850-0.988 and R2CV = 0.672-0.869). Bond information content index (BIC1) and electronegativity (R6e+) are the most influential descriptors governing the activity of compounds. The constructed QSAR models were further applied for guiding a rational design of novel inhibitors. A novel set of 153 structurally modified compounds were designed in silico according to the important descriptors deduced from the QSAR finding, and their DNMT1 inhibitory activities were predicted. This result demonstrated that 86 newly designed inhibitors were predicted to elicit enhanced DNMT1 inhibitory activity when compared to their parent compounds. Finally, a set of promising compounds as potent DNMT1 inhibitors were highlighted to be further developed. The key SAR findings may also be beneficial for structural optimization to improve properties of the known inhibitors.2020-04-02T00:00:00ZHygrophorus eburneus, edible mushroom, a promising natural bioactive agentKosanić, Marijana M.Šeklić, Dragana S.Jovanović, Milena M.Petrović, Nevena N.Marković, Snežana D.http://hdl.handle.net/2003/398692020-12-12T02:41:01Z2020-03-31T00:00:00ZTitle: Hygrophorus eburneus, edible mushroom, a promising natural bioactive agent
Authors: Kosanić, Marijana M.; Šeklić, Dragana S.; Jovanović, Milena M.; Petrović, Nevena N.; Marković, Snežana D.
Abstract: It is known that many edible mushrooms have important medicinal properties, including effects on different types of cancers. This is the first report regarding the neuroprotective, antimicrobial, antioxidative and anticancer activities of the acetone extract of edible mushroom Hygrophorus eburneus. Neuroprotective potential was evaluated by measuring the capacity of the extract to inhibit acetylcholinesterase. In this assay, the tested extract showed activity against acetylcholinesterase in a dose-dependent manner where the percentage of inhibition ranged from 13.19 to 46.44 %. The antimicrobial potential was determined by the microdilution method against five species of bacteria and eight species of fungi and the results of this method exhibited moderate antimicrobial activity of H. eburneus with MIC values ranging from 6.25 to 25 mg/mL. Antioxidant activity was evaluated by measuring the scavenging capacity of the tested sample on DPPH and superoxide anion radicals, by the reducing power assay and by measuring the amounts of total phenolics in extract. As a result of the study, H. eburneus extract showed a potent antioxidant activity (IC50 were 102.93 μg/mL for DPPH radical scavenging activity and 123.27 μg/mL for superoxide anion radicals scavenging) while absorbances for reducing power assay were from 0.0235 to 0.1161. The total phenolic content in the extract was 9.27 µg PE/mg. Finally, anticancer effects were evaluated by MTT test for cytotoxicity, acridine orange/ethidium bromide staining for detection of the type of cell death and wound healing assay for antimigratory effects on human colorectal cancer cell line (HCT-116) and human breast cancer cell line (MDA-MB-231). The results for cytotoxicity and apoptosis were measured after 24 and 72 h and for anti-migratory effect after 12 and 24 h. The tested H. eburneus mushroom extract expressed cell selectivity, with notable cytotoxic effects observed on HCT-116 cells, with a strong proapoptotic potential. The migration of HCT-116 cells was significantly inhibited, while MDA-MB-231 cells were less sensitive to the treatment. The results of this study revealed that the tested extract had relatively strong neuroprotective, antimicrobial, antioxidant, and anticancer effects. It suggests that this mushroom can be proposed as a novel source of nutraceuticals and pharmaceuticals.2020-03-31T00:00:00ZThe small chain fatty acid butyrate antagonizes the TCR-stimulation-induced metabolic shift in murine epidermal γδ T cellsHäselbarth, LukasOuwens, D. MargrietTeichweyde, NadineHochrath, KatrinMerches, KatjaEsser, Charlottehttp://hdl.handle.net/2003/398682020-12-12T02:41:00Z2020-03-09T00:00:00ZTitle: The small chain fatty acid butyrate antagonizes the TCR-stimulation-induced metabolic shift in murine epidermal γδ T cells
Authors: Häselbarth, Lukas; Ouwens, D. Margriet; Teichweyde, Nadine; Hochrath, Katrin; Merches, Katja; Esser, Charlotte
Abstract: The metabolic requirements change during cell proliferation and differentiation. Upon antigen-stimulation, effector T cells switch from adenosine-triphospate (ATP)-production by oxidative phosphorylation in the mitochondria to glycolysis. In the gut it was shown that short chain fatty acids (SCFA), fermentation products of the microbiota in colon, ameliorate inflammatory reactions by supporting the differentiation of regulatory T cells. SCFA are a major energy source, but they are also anabolic metabolites, histone-deacetylase-inhibitors and activators of G protein receptors. Recently, it was reported that a topical application of the SCFA butyrate promotes regulatory T cells in the skin. Here we ask if the SCFA butyrate, propionate and acetate affect the energy metabolism and inflammatory potential of dendritic epidermal T cells (DETC), the innate resident skin γδ T cell population. Using the Seahorse™ technology, we measured glycolysis and oxidative phosphorylation (OXPHOS) in a murine DETC cell line, 7-17, upon TCR-stimulation by CD3/CD28 crosslinking, with or without SCFA addition. TCR engagement resulted in a change of the ratio glycolysis/OXPHOS. A similar metabolic shift has been described for activated CD4 T cells. Addition of 5 mM SCFA, in particular butyrate, antagonized the effect. Stimulated DETC secrete cytokines, e.g. the pro-inflammatory cytokine interferon-gamma (IFNγ), and thereby regulate skin homeostasis. Addition of butyrate and propionate to the cultures at non-toxic concentrations decreased secretion of IFNγ by DETC and increased the expression of the immunoregulatory surface receptor CD69. We hypothesize that SCFA can dampen the inflammatory activity of DETC.2020-03-09T00:00:00ZPossible involvement of the opioidergic system in the modulation of body temperature, jumping behavior and memory process in cholestatic and addicted miceZarrindast, Mohammad-RezaIssazadeh, YasamanRezaei, NiloofarKhakpai, Fatemehhttp://hdl.handle.net/2003/398662020-12-12T02:40:59Z2020-03-04T00:00:00ZTitle: Possible involvement of the opioidergic system in the modulation of body temperature, jumping behavior and memory process in cholestatic and addicted mice
Authors: Zarrindast, Mohammad-Reza; Issazadeh, Yasaman; Rezaei, Niloofar; Khakpai, Fatemeh
Abstract: Cholestasis is related to an increased plasma level of endogenous opioid levels. Naloxone-induced withdrawal syndrome has been reported in a mouse model of cholestasis. Moreover, studies revealed that the memory process is affected by cholestasis. Thus, we aimed at determining whether pharmacological manipulation of the opioidergic system is involved in signs of cholestasis disease such as hypothermia and withdrawal behaviors such as jumping behavior as well as memory process in mice. Cholestasis was induced by bile duct resection in mice and physical dependence was induced by administration of morphine and/or tramadol three times daily (8, 12 and 16 h) at the doses of 25, 50 and 75 mg/kg during three consecutive days. The memory process was assessed by a step-down passive avoidance test. Our results indicated that cholestatic mice showed hypothermia whereas cholestatic- and drug dependent mice indicated hyperthermia. Moreover, administration of morphine (50 mg/kg) and/or tramadol (50 mg/kg) on the 4th day, 2 h before naloxone injection significantly decreased latency to first jumping but increased the number of jumping and rearing behavior as well as locomotor activity in BDL-vs. sham-operated mice. In addition, the latency time of the step-down test decreased in BDL-vs. sham-operated group, showing impairment of memory in BDL mice. The results of this study support the evidence that (1) the opioidergic system involved in thermoregulation of cholestasis mice, (2) μ-opioid receptors play an important role in withdrawal behaviors, and (3) memory process is affected by cholestasis and addiction in mice.2020-03-04T00:00:00ZRole of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptorOrtega, Joseph ThomasSerrano, Maria LuisaPujol, Flor HeleneRangel, Hector Rafaelhttp://hdl.handle.net/2003/398642020-12-11T02:40:55Z2020-03-18T00:00:00ZTitle: Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor
Authors: Ortega, Joseph Thomas; Serrano, Maria Luisa; Pujol, Flor Helene; Rangel, Hector Rafael
Abstract: Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans.2020-03-18T00:00:00ZAntitrypanosomal butanolides from Aiouea trinervisNunes, Felipe Oliveirade Almeida, Júlio MentaFerreira, Alda Maria Teixeirada Cruz, Letícia AlvesJacob, Camila Mareti BoninGarcez, Walmir SilvaGarcez, Fernanda Rodrigueshttp://hdl.handle.net/2003/398622020-12-11T02:40:54Z2020-03-06T00:00:00ZTitle: Antitrypanosomal butanolides from Aiouea trinervis
Authors: Nunes, Felipe Oliveira; de Almeida, Júlio Menta; Ferreira, Alda Maria Teixeira; da Cruz, Letícia Alves; Jacob, Camila Mareti Bonin; Garcez, Walmir Silva; Garcez, Fernanda Rodrigues
Abstract: In a search for new antitrypanosomal agents in the Brazilian flora, the ethanol extract of the xylopodium from Aiouea trinervis (Lauraceae) exhibited in vitro activity against the epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. Bioassay-guided chromatographic fractionation of the ethanol extract afforded three butanolides, isoobtusilactone A (1), epilitsenolide C2 (2), and epilitsenolide C1 (3). Butanolides 1 and 3 were more active against T. cruzi epimastigotes than the reference drug benznidazole (by 8.9-fold and 3.2-fold, respectively), while 2 proved inactive. Compounds 1 and 3 showed low cytotoxicity in mammalian Vero cells (CC50> 156 μmol L-1) and high selectivity index (SI) values for epimastigotes (SI = 56.8 and 28.6, respectively), and 1 was more selective than benznidazole (SI = 46.5). Butanolide 1 at 24 μmol L-1 also led to cell cycle alterations in epimastigote forms, and inhibited the growth of amastigote cells in more than 70 %. In silico ADMET properties of 1 were also analyzed and predicted favorable drug-like characteristics. This butanolide also complied with Lipinski’s rule of five and was not predicted as interference compound (PAINS). This is the first report on the isolation of these bioactive butanolides under the guidance of in vitro trypanocidal activity against T. cruzi.2020-03-06T00:00:00ZRoles of kininogen-1, basement membrane specific heparan sulfate proteoglycan core protein, and roundabout homolog 4 as potential urinary protein biomarkers in diabetic nephropathyNa Nakorn, PiyadaPannengpetch, SupitchaIsarankura-Na-Ayudhya, PatchareeThippakorn, ChadineeLawung, RatanaSathirapongsasuti, NuankanyaKitiyakara, ChagriyaSritara, PiyamitrVathesatogkit, PrinIsarankura-Na-Ayudhya, Chartchalermhttp://hdl.handle.net/2003/398582020-12-08T02:40:50Z2020-06-24T00:00:00ZTitle: Roles of kininogen-1, basement membrane specific heparan sulfate proteoglycan core protein, and roundabout homolog 4 as potential urinary protein biomarkers in diabetic nephropathy
Authors: Na Nakorn, Piyada; Pannengpetch, Supitcha; Isarankura-Na-Ayudhya, Patcharee; Thippakorn, Chadinee; Lawung, Ratana; Sathirapongsasuti, Nuankanya; Kitiyakara, Chagriya; Sritara, Piyamitr; Vathesatogkit, Prin; Isarankura-Na-Ayudhya, Chartchalerm
Abstract: Diabetic nephropathy, a major complication of diabetes mellitus (DM), is increasing worldwide and the large majority of patients have type 2 DM. Microalbuminuria has been used as a diagnostic marker of diabetic nephropathy. But owing to its insufficient sensitivity and specificity, other biomarkers are being sought. In addition, the pathophysiology of diabetic nephropathy is not fully understood and declines in renal function occur even without microalbuminuria. In this study, we investigated urinary proteins from three study groups (controls, and type 2 diabetic subjects with or without microalbuminuria). Non-targeted label-free Nano-LC QTOF analysis was conducted to discover underlying mechanisms and protein networks, and targeted label-free Nano-LC QTOF with SWATH was performed to qualify discovered protein candidates. Twenty-eight proteins were identified as candidates and functionally analyzed via String DB, gene ontology and pathway analysis. Four predictive mechanisms were analyzed: i) response to stimulus, ii) platelet activation, signaling and aggregation, iii) ECM-receptor interaction, and iv) angiogenesis. These mechanisms can provoke kidney dysfunction in type 2 diabetic patients via endothelial cell damage and glomerulus structural alteration. Based on these analyses, three proteins (kininogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, and roundabout homolog 4) were proposed for further study as potential biomarkers. Our findings provide insights that may improve methods for both prevention and diagnosis of diabetic nephropathy.2020-06-24T00:00:00ZMolecular mechanism and health effects of 1,2-NaphtoquinoneSoares, Antonio GarciaMuscara, Marcelo N.Costa, Soraia K. P.http://hdl.handle.net/2003/398572020-12-08T02:40:51Z2020-06-03T00:00:00ZTitle: Molecular mechanism and health effects of 1,2-Naphtoquinone
Authors: Soares, Antonio Garcia; Muscara, Marcelo N.; Costa, Soraia K. P.
Abstract: Extensive literature regarding the health side effects of ambient pollutants (AP) are available, such as diesel exhaust particles (DEPs), but limited studies are available on their electrophilic contaminant 1,2-Naphthoquinone (1,2-NQ), enzymatically derived from naphthalene. This review summarizes relevant toxicologic and biological properties of 1,2-NQ as an environmental pollutant or to a lesser degree as a backbone in drug development to treat infectious diseases. It presents evidence of 1,2-NQ-mediated genotoxicity, neurogenic inflammation, and cytotoxicity due to several mechanistic properties, including the production of reactive oxygen species (ROS), that promote cell damage, carcinogenesis, and cell death. Many signal transduction pathways act as a vulnerable target for 1,2-NQ, including kappaB kinase b (IKKbeta) and protein tyrosine phosphatase 1B (PTP1B). Antioxidant molecules act in defense against ROS/RNS-mediated 1,2-NQ responses to injury. Nonetheless, its inhibitory effects at PTP1B, altering the insulin signaling pathway, represents a new therapeutic target to treat diabetes type 2. Questions exist whether exposure to 1,2-NQ may promote arylation of the Keap1 factor, a negative regulator of Nrf2, as well as acting on the sepiapterin reductase activity, an NADPH-dependent enzyme which catalyzes the formation of critical cofactors in aromatic amino acid metabolism and nitric oxide biosynthesis. Exposure to 1,2-NQ is linked to neurologic, behavioral, and developmental disturbances as well as increased susceptibility to asthma. Limited new knowledge exists on molecular modeling of quinones molecules as antitumoral and anti-microorganism agents. Altogether, these studies suggest that 1,2-NQ and its intermediate compounds can initiate a number of pathological pathways as AP in living organisms but it can be used to better understand molecular pathways.2020-06-03T00:00:00ZTumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinomaYu, Qing-JiangLiang, Yi-ZhiMei, Xiao-PingFang, Tai-Yonghttp://hdl.handle.net/2003/398562020-12-08T02:40:51Z2020-06-22T00:00:00ZTitle: Tumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinoma
Authors: Yu, Qing-Jiang; Liang, Yi-Zhi; Mei, Xiao-Ping; Fang, Tai-Yong
Abstract: Tumor mutation burden (TMB) is associated with immunogenic responses and the survival of cancer patients. This study demonstrates how TMB levels impact the immune-related cells, genes, and miRNAs, and how miRNA/gene interactions respond to variations in the survival rate of patients with liver hepatocellular carcinoma (LIHC). LIHC patients were divided into two groups, either a low TMB (< median) or a high TMB (≥ median) group. We found that high TMB plays a positive role in immune-mediated infiltration, generating more CD4 T-cells and memory B cells. Among the 21 immune genes that altered significantly, only C9orf24 and CYP1A1 were expected to up-regulate in LIHC patients with high TMB. A total of 19 miRNAs, which regulate various functional pathways, were significantly altered in patients with LIHC. One of the miRNA/gene pair, hsa-miR-33a/ALDH1A3 was significantly associated with the survival rate of LIHC patients. Our results suggest that LIHC patients with high TMB can be treated more effectively with immunotherapy.2020-06-22T00:00:00Z