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    3-Aryl-1-phenyl-1H-pyrazole derivatives as new multitarget directed ligands for the treatment of Alzheimer's disease, with acetylcholinesterase and monoamine oxidase inhibitory properties
    (2013-12-13) Kumar, Ashwani; Jain, Sandeep; Parle, Milind; Jain, Neelam; Kumar, Parvin
    A series of 3-aryl-1-phenyl-1H-pyrazole derivatives was synthesized in good yield and assayed in vitro as inhibitors of the mice acetylcholinesterase (AChE) and two goat liver monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the compounds demonstrated a good AChE and selective MAO-B inhibitory activities in the nanomolar or low micromolar range. N-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) benzenamine (3e, pIC50 = 4.2) and N-((4-fluorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) methanamine (3f, pIC50 = 3.47) were the most potent AChE and highly selective MAO-B inhibitors respectively. Structure activity relationships showed that chloro derivatives were more effective AChE inhibitors as compared to fluoro derivatives while reverse trend was observed in MAO-B inhibitory activity. With the aid of modeling studies, potential binding orientations as well as interactions of the compounds in the AChE and MAO-B active sites were examined.
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    Changes in apoptotic factors in hypothalamus and hippocampus after acute and subchronic stress induction during conditioned place preference paradigm
    (2013-12-04) Haghparast, Abbas; Fatahi, Zahra; Zeighamy Alamdary, Shabnam; Khodagholi, Fariba
    The hypothalamus (HYP) and hippocampus (HIP) are important regions involved in stress responses. These areas are also associated with reward processing. In this study, the effects of acute and subchronic stress on the changes in apoptotic factors (Bax/Bcl-2 ratio, caspase-3 activation and PARP degradation) in the HYP and HIP during conditioned place preference (CPP) paradigm were evaluated. Male Wistar rats were divided into two saline- and morphine-reated supergroups. Each supergroup contained control, acute stress (AS) and subchronic stress (SS) groups. In all groups, CPP paradigm was done and thereinafter alterations of apoptotic factors were measured by western blot. The results revealed that in the HYP, all mentioned factors increased significantly in saline- or morphine-treated animals during AS and SS. On the other hand, in the HIP, Bax/Bcl-2 ratio in saline-treated animals increased significantly during AS and SS, while in morphine-treated animals this ratio did not have any significant alteration during AS and was decreased during SS compared with morphine-control group. Caspase-3 and PARP increased during AS and SS in saline- or morphine-treated animals. For example, caspase-3 increased during AS and SS in morphine-treated animals by 2.4 folds and PARP (89 KDa) increased by 3.1 and 3.5 folds, respectively. Interestingly, the increase of apoptotic factors in morphine-treated animals was more considerable than that of saline-treated animals. These results strongly implied that AS and SS trigger apoptotic events in the HYP and HIP of saline- and/or morphine-treated animals as well as morphine reinforces the effect of stress on the induction of apoptosis.
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    Selenoprotein M is expressed during bone development
    (2013-11-20) Grosch, Melanie; Fuchs, Jennifer; Bösl, Michael; Winterpacht, Andreas; Tagariello, Andreas
    25 selenoproteins that contain selenium, incorporated as selenocysteine (Sec), have been identified to date. Selenoprotein M (SELM) is one of seven endoplasmic reticulum (ER)-resident, Sec-containing proteins that may be involved in posttranslational processing of proteins and maintenance of ER function. Since SELM was overrepresented in a cartilage- and bone- specific expressed sequence tag (EST) library, we further investigated the expression pattern of Selm and its possible biological function in the skeleton. RNA in situ hybridization of Selm in chicken and mice of different developmental stages revealed prominent expression in bones, specifically in osteoblast, and in tendons. This result suggests that SELM functions during bone development, where it is possibly involved in the processing of secreted proteins.
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    Flavonoids and its derivatives from Callistephus chinensis flowers and their inhibitory activities against alpha-glucosidase
    (2013-11-19) Zhang, Xiaoshu; Liu, Zhenting; Bi, Xiuli; Liu, Jingxin; Li, Wei; Zhao, Yuqing
    Inhibitors of carbohydrate-hydrolysing enzymes play an important role for the treatment of diabetes. One of the therapeutic methods for decreasing of postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate-hydrolysing enzymes, such as α-glucosidase, in the digestive organs. To investigate the therapeutic potential of compounds from natural sources, Callistephus chinensis flowers (CCF) were tested for inhibition of α-glucosidase, and acarboes was used as the positive control. The 70 % ethanol extract of CCF exhibited significant α-glucosidase inhibitory activities with IC50 value of 8.14 μg/ml. The stepwise polarity fractions of CCF were tested further for in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc) fraction exhibited the most significant inhibitory activity. Eight pure compounds, apigenin, apigenin-7-O-β-D-glucoside, kaempferol, hyperin, naringenin, quercetin, luteolin, and kaempferol-7-O-β-D-glucoside, were isolated (using enzyme assay-guide fractionation method) from the EtOAc fraction. Among these, quercetin was the most active one (IC50 values 2.04 μg/ml), and it appears that the inhibiting percentages are close to acarbose (IC50 values 2.24 μg/ml), the positive control, on α-glucosidase inhibition. HPLC/UV analysis indicated that the major components of CCF are kaempferol, hyperin and quercetin. The presented results revealed that CCF containing these eight flavonoids could be a useful natural source in the development of a novel α-glucosidase inhibitory agent against diabetic complications.
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    Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt
    (2013-11-11) Adel, Abdel-Moneim; Morsy, Basant M.; Mahmoud, Ayman M.; Abo-Seif, Mohamed A.; Zanaty, Mohamed I.
    Hepatitis C is a major global health burden and Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. The current study was designed to evaluate the beneficial therapeutic effects of ethanolic extracts of Nigella sativa, Zingiber officinale and their mixture in Egyptian HCV patients. Sixty volunteer patients with proven HCV and fifteen age matched healthy subjects were included in this study. Exclusion criteria included patients on interferon alpha (IFN-α) therapy, infection with hepatitis B virus, drug-induced liver diseases, advanced cirrhosis, hepatocellular carcinoma (HCC) or other malignancies, blood picture abnormalities and major severe illness. Liver function enzymes, albumin, total bilirubin, prothrombin time and concentration, international normalized ratio, alpha fetoprotein and viral load were all assessed at baseline and at the end of the study. Ethanolic extracts of Nigella sativa and Zingiber officinale were prepared and formulated into gelatinous capsules, each containing 500 mg of Nigella sativa and/or Zingiber officinale. Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. Both extracts as well as their mixture significantly ameliorated the altered viral load, alpha fetoprotein, liver function parameters; with more potent effect for the combined therapy. In conclusion, administration of Nigella sativa and/or Zingiber officinale ethanolic extracts to HCV patients exhibited potential therapeutic benefits via decreasing viral load and alleviating the altered liver function, with more potent effect offered by the mixture.
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    Chemical composition and anti-inflammatory effects of essential oil from Hallabong flower
    (2013-11-07) Kim, Min-Jin; Yang, Kyong-Wol; Kim, Sang Suk; Park, Suk Man; Park, Kyung Jin; Kim, Kwang Sik; Choi, Young Hun; Cho, Kwang Keun; Lee, Nam Ho; Hyun, Chang-Gu
    A number of essential oils derived from plants are claimed to have several medicinal functions, including anti-cancer and anti-inflammation effects. However, the chemical composition and biological activities of flower-derived components have not been sufficiently characterized. Therefore, we investigated the composition of essential oils from Hallabong flower [(Citrus unshiu Marcov × Citrus sinensis Osbeck) × Citrus reticulata Blanco] and their anti-inflammatory effects. Hydro-dist illed essential oils (HEOs) were analyzed using gas chromatography–mass spectrometry (GC–MS). In total, 21 components were identified, representing more than 98 % of the oils, with sabinene (34.75 %), linalool (14.77 %), β-ocimene (11.07 %), 4-terpineol (9.63 %), L-limonene (5.88 %), and γ-terpinene (4.67 %) as the main components. In the present study, we also investigated the anti-inflammatory effects of HEOs on lipopolysaccharide (LPS)-stimulated RAW 26 4.7 macrophage cells. HEOs were found to inhibit nitric oxide (NO) and prostaglandin E2 (PGE2) production and to suppress the LPS- induced expression of cyclooxygenase-2 (COX-2) protein. In addition, HEOs downregulated the production of the inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1 β(IC50 values are 0.05 %, 0.02 %, and 0.01 %, respectively). On the basis of these results, we suggest that HEOs can be consid ered potential anti-inflammatory candidates for therapeutic use in humans.
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    Changes of serum omentin-1 levels and relationship between omentin-1 and insulin resistance in chronic hepatitis C patients
    (2013-11-04) Nassif, Walaa Moustafa Hussein; Amin, Ashraf Ismail; Hassan, Zeinab Abdeltawab; Abdelaziz, Dalia Hussein Abdelhafiz
    Omentin-1 is a novel adipokine that has a pivotal role in modulating the insulin sensitivity, immunity and inflammation. The current study was conducted to evaluate the serum omentin-1 level in hepatitis C virus (HCV) infected patients, with or without type 2 diabetes, and to investigate its correlation with liver function parameters and insulin resistance. Methods: Eighty subjects were enrolled in this study divided into four groups: chronic HCV infected patients (n=20), chronic hepatitis C patients with concomitant type 2 diabetes (n=18), type 2 diabetic patients (n=22) and 20 healthy controls. Serum omentin-1 levels were assessed using enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose, insulin levels, and liver parameters including aminotrans ferases (ALT and AST) were determined. Results: Serum omentin-1 levels were significantly elevated in HCV infected patients compared to all other groups. Omentin-1 levels were positively correlated with AST and ALT levels (r =0.43, p< 0.001; r =0.423, p<0.001, respectively). Additionally, a significant negative correlation was found between omentin-1 and both fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.238, p< 0.05; r = -0.277, p<0.05, respectively). Furthermore, fasting blood glucose, HbA1c and HOMA-β were negatively correlated to serum omentin-1 levels however these correlations were not statistically significant. Conclusion: Serum omentin-1 level is elevated in HCV infected patients and is positively associated with liver enzymes AST and ALT. This suggested that omentin-1 may be implicated in the pathogenesis of hepatitis C and its metabolic complications. However its role needs to be elucidated by further studies.
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    The effect of opium addiction on serum adiponectin and leptin levels in male subjects
    (2013-10-30) Shahouzehi, Beydolah; Shokoohi, Mostafa; Najafipour, Hamid
    Serum adiponectin and leptin levels have been shown to be related to obesity, insulin resistance and cardiovascular diseases (CVD). Opium addiction has a positive association with endocrine system disorders. The relationship between adipokines and opium addiction is unclear. In the present study, we aimed to determine serum adiponectin and leptin levels in opium addicted subjects. Methods: 176 men, 88 opium addicts and 88 non-addicts were randomly selected from subjects who participated in Kerman Coronary Artery Disease Risk factors Study (KERCADRS); a population-based study. Serum adiponectin and leptin levels were measured using ELISA and compared between two groups. We adjusted the effect of some confounding factors such as the patients’ demographic, clinical and medical history in multivariate analysis model. Results: The serum level of adiponectin in opium addicts was significantly lower than control group (6.5±3.6 vs. 9.8±8.1 μg/ml, P<0.001). There was no significant difference in serum leptin level between two groups (11.8±10.3 ng/ml in control group vs. 11.5±10.8 ng/ml in opium addicts, p = 0.80). In the multivariate analysis, after adjusting for age, cigarette smoking, body mass index, type 2 diabetes, hypertension, cholesterol, triglyceride and high and low density lipoproteins, the negative association between opium addiction and decreased adiponectin level was still present (β = -0.144, P value = 0.005). Conclusions: The results showed that opium addiction reduces serum adiponectin level. Since adiponectin has been shown to have anti-diabetic and anti-atherogenic effects, its reduction may account for increase in the risk of metabolic disorders such as insulin resistance and CVD amongst opium addicted patients.
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    Biochemical aspirin resistance in stroke patients - a cross-sectional single centre study
    (2013-10-29) Azmin, Shahrul; Sahathevan, Ramesh; Rabani, Remli; Nafisah, Wan Y.; Tan, Hui J.; Raymond, Azman A.; Hamidon, Basri B; Shamsu, Azhar S; Norlinah, Mohamed Ibrahim
    Aspirin use is known to reduce the recurrence of stroke. However, the clinical response to aspirin has been mixed. The rate of stroke recurrence whilst on aspirin treatment is still unacceptably high. A plausible explanation for this may be resistance to the effects of aspirin. The causes of aspirin resistance are manifold and multi-factorial. We conducted a study to investigate the prevalence rate of biochemical aspirin resistance in a cohort of aspirin-naïve stroke patients. We also sought to determine the inherent factors that may predispose towards the development of aspirin resistance. Method: This was a cross-sectional, observational study conducted on patients admitted to our centre with an acute stroke who were aspirin-naïve. The diagnosis of an acute stroke was confirmed by clinical history and brain imaging. Fifty consecutive patients were prospectively enrolled. Socio-demographic data were collected and baseline blood investigations were performed. Patients were tested for biochemical aspirin resistance using Multiplate® platelet analyser (Dynabyte, Munich, Germany) after 5 doses of aspirin, corresponding to a total dose of 900 mg. Results: The median age of patients was 65.5 years and 54 % of patients were female. There were 11 smokers; of these 10 were male. Twenty-six (52 %) patients were Chinese, 21 (41 %) were Malay and 3 (6.0 %) were Indian. Aspirin resistance was present in 14 % of our patients. There was an inverse relationship between the presence of aspirin resistance and plasma HDL levels (r = -0.394; p = 0.005). There was no relationship observed between aspirin resistance and total cholesterol, triglycerides, LDL, HbA1c, ALT, ALP, urea and creatinine levels. There were no significant differences in demographic profiles or smoking status between the aspirin resistant and non-aspirin resistant groups. We did not find any link between ethnicity and aspirin resistance. Conclusions: Our results indicate that a lower HDL level is associated with biochemical aspirin resistance. This may increase platelet aggregation and consequently increase the risk of a recurrent stroke. The clinical implications for aspirin resistance are far reaching. Any evidence that correctable factors may negatively influence the action of aspirin warrants further investigation. The prevalence rate of biochemical aspirin resistance in our study is comparable to the findings in other studies performed in an Asian population. Further research is required to determine how our findings translate into clinical aspirin resistance and stroke recurrence.
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    Chrysen-2-ol derivative from West Indian wood nettle Laportea aestuans (L.) Chew inhibits oxidation and microbial growth in vitro
    (2013-10-18) Oloyede, Ganiyat K.; Oyelola, Martha S.
    Bio-active compounds present in West Indian Wood Nettle Laportea aestuans (L.) Chew (Urticaceae), used in ethno medicine as antioxidant and antimicrobial were studied. The aim of this research work was to isolate and characterize the bio-active compounds in the n-hexane fraction of L. aestuans, determine the toxicity and subject it to in-vitro antimicrobial and free radical scavenging activities. The chemical constituents were isolated by gradient elution column chromatographic technique and Ultra Violet/visible (UV), Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectroscopies were used for structural elucidation. The free radical scavenging activity of the isolate was assessed using three methods; scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), hydroxyl radical generated from hydrogen peroxide and ferric thiocynate method. Antimicrobial screening was done by agar well diffusion method while toxicity was determined by Brine shrimp lethality test. Structures were proposed for the white crystalline solids isolated; (4E)-3,6-dimethylhep-4-en-3-ol (AB) and 1,2,3,4,4a,4b,5,6,6a,7,8,9,10,10a,10b,11-hexadecahydro-1,1,6a,10b-tetramethyl-7-((E)-4,7-dimethyloct-5-enyl) chrysen-2-ol (AC). Percentage yield of AC was 91.2 and was non-toxic with LC50 (μg/ml) value of 1581233000.0. AC significantly scavenged free radical at 0.0625 mg/ml in the DPPH (64.73 %) and hydrogen peroxide (99.22 %) tests. It also showed 65.23 % inhibition at 1.0 mg/ml in the ferric thiocyanate test. AC also inhibited microbial growth significantly when compared with gentamicin and tioconazole which are antibacterial and antifungal standards respectively. The presence of Chrysen-2-ol derivative in L. aestuans which was non-toxic and possessed significant antimicrobial and antioxidant activities supports its ethno medicinal application.
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    Machine learning approaches for discerning intercorrelation of hematological parameters and glucose level for identification of diabetes mellitus
    (2013-10-21) Worachartcheewan, Apilak; Nantasenamat, Chanin; Prasertsrithong, Pisit; Amranan, Jakraphob; Monnor, Teerawat; Chaisatit, Tassaneya; Nuchpramool, Wilairat; Prachayasittikul, Virapong
    The aim of this study is to explore the relationship between hematological parameters and glycemic status in the establishment of quantitative population-health relationship (QPHR) model for identifying individuals with or without diabetes mellitus (DM). Methods: A cross-sectional investigation of 190 participants residing in Nakhon Pathom, Thailand in January-March, 2013 was used in this study. Individuals were classified into 3 groups based on their blood glucose levels (normal, Pre-DM and DM). Hematological (white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb) and hematocrite (Hct)) and glucose parameters were used as input variables while the glycemic status was used as output variable. Support vector machine (SVM) and artificial neural network (ANN) are machine learning approaches that were employed for identifying the glycemic status while association analysis (AA) was utilized in discovery of health parameters that frequently occur together. Results: Relationship amongst hematological parameters and glucose level indicated that the glycemic status (normal, Pre-DM and DM) was well correlated with WBC, RBC, Hb and Hct. SVM and ANN achieved accuracy of more than 98 % in classifying the glycemic status. Furthermore, AA analysis provided association rules for defining individuals with or without DM. Interestingly, rules for the Pre-DM group are associated with high levels of WBC, RBC,Hb and Hct. Conclusion: This study presents the utilization of machine learning approaches for identification of DM status as well as in the discovery of frequently occurring parameters. Such predictive models provided high classification accuracy as well as pertinent rules in defining DM.
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    DNA and chromosomal damage in coronary artery disease patients
    (2013-10-08) Bhat, Mohd Akbar; Mahajan, Naresh; Gandhi, Gursatej
    DNA and chromosomal damage in peripheral blood leukocytes of patients with coronary artery disease (CAD) were investigated by using the single cell gel electrophoresis assay /comet and cytokinesis- block micronucleus (CBMN) assays, respectively. The case-control study comprised patients with CAD (n = 46; average age 53.0 ± 1.27 y) undergoing treatment at local hospitals, and healthy age-and sex-matched controls (n = 19; average age 54.21 ± 0.91 y) from the general population. The results of the comet assay revealed that the mean values of DNA damage were significantly (p < 0.001) higher in CAD patients than in controls (Tail DNA% 11.55 ± 0.38 vs. 5.31 ± 0.44; Tail moment 6.17 ± 0.31 vs. 2.93 ± 0.21 AU; Olive tail moment 3.52 ± 0.23 vs. 1.25 ± 0.11 AU). The mean values of chromosomal damage were also significantly higher (p < 0.001) in CAD patients than in controls (Binucleated cells with MN-28.15 ± 1.18 vs. 18.16 ± 2.59; micronuclei 29.52 ± 1.21 vs. 18.68 ± 2.64, respectively) while nuclear division index (1.48 ± 0.01 vs. 1.63 ± 0.01) was significantly higher (p < 0.001) in controls. The results of the present study indicate that coronary artery disease patients had increased levels of both, unrepaired (DNA) and repaired (chromosomal) genetic damage which may be a pathological consequence of the disease and/or the drug-treatment. This accumulation of DNA/chromosomal damage is of concern as it can lead to the development of cancer with increased chances of morbidity and mortality in the CAD patients.
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    Embelia ribes extract reduces high fat diet and low dose streptozotocin-induced diabetic nephrotoxicity in rats
    (2013-09-24) Chaudhari, Hemantkumar Somabhai; Bhandari, Uma; Khanna, Geetika
    Nephropathy associated with type 2 diabetes is the single most common cause of end-stage renal disease. The aim of the present study was to evaluate the preventive effect of ethanolic extract of Embelia ribes fruit (EER) against high fat diet (HFD) and low dose streptozotocin (STZ)-induced diabetic nephrotoxicity in Wistar rats. HFD-fed and low dose STZ (35 mg/kg, i.p)-induced diabetic rats were treated with EER (100 and 200 mg/kg/day) for 21 days while continuing on HFD. Preventive effects of EER were demonstrated by significant reduction (p< 0.01) in body weight gain, fasting blood glucose, blood pressure, serum lactate dehydrogenase (LDH), creatinine, alkaline phosphatase (ALP), total cholesterol and triglyceride levels, while elevation in serum albumin and total protein levels. Insulin sensitizing effects were seen during oral glucose tolerance testing. Further, EER treatment significantly (p< 0.01) decreased the kidney thiobarbituric acid-reactive substance (TBARS) levels, while increasing the superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in diabetic rats. Histological studies of kidney also supported the experimental findings. Taken together, our data suggest that EER attenuates renal injury in type 2 diabetic rats, possibly by improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, blood pressure lowering, and inhibition of lipid peroxidation process.
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    A simple click by click protocol to perform docking
    (2013-09-23) Rizvi, Syed Mohd. Danish; Shakil, Shazi; Haneef, Mohd.
    Recently, bioinformatics has advanced to the level that it allows almost accurate prediction of molecular interactions that hold together a protein and a ligand in the bound state. For instance, the program AutoDock has been developed to provide a procedure for predicting the interaction of small molecules with macromolecular targets which can easily separate compounds with micromolar and nanomolar binding constants from those with millimolar binding constants and can often rank molecules with finer differences in affinity. AutoDock can be used to screen a variety of possible compounds, searching for new compounds with specific binding properties or testing a range of modifications of an existing compound. The present work is a detailed outline of the protocol to use AutoDock in a more user-friendly manner. The first step is to retrieve required Ligand and Target.pdb files from major databases. The second step is preparing PDBQT format files for Target and Ligand (Target.pdbqt, Ligand.pdbqt) and Grid and Docking Parameter file (a.gpf and a.dpf) using AutoDock 4.2. The third step is to perform molecular docking using Cygwin and finally the results are analyzed. With due confidence, this is our humble claim that a researcher with no previous background in bioinformatics research would be able to perform molecular docking using AutoDock 4.2 program by following stepwise guide lines given in this article.
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    COX-2 inhibitors from stem bark of Bauhinia rufescens Lam. (Fabaceae)
    (2013-09-13) Muhammad, Aminu; Sirat, Hasnah Mohd
    Chemical investigation of the stem bark of Bauhinia rufescens resulted in the isolation of a new cyanoglucoside and menisdaurin from methanol extract and oxepin from petroleum ether extract. The isolated compounds were tested for their anti-inflammatory potentials based on the cyclooxygenase-2 enzyme (COX-2) model. Cyanoglucoside exhibited the highest activity among the compounds with an inhibition activity of 49.34 % at 100 μM (IC50 0.46 μM) compared to the positive control, indomethacin (79.20 %, IC50 0.24 μM).
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    Chemical composition, antioxidant and antigenotoxic activities of different fractions of Gentiana asclepiadea L. roots extract
    (2013-09-12) Mihailović, Vladimir; Matić, Sanja; Mišić, Danijela; Solujić, Slavica; Stanić, Snežana; Katanić, Jelena; Mladenović, Milan; Stanković, Nevena
    The aim of this study was to evaluate the antioxidant and antigenotoxic activities of chloroform, ethyl acetate and n-butanol fractions obtained from Gentiana asclepiadea L. roots methanolic extract. The main secondary metabolites sweroside, swertiamarin and gentiopicrine were quantified in G. asclepiadea root extracts using HPLC-DAD analysis. Amount of total phenols, flavonoids, flavonols and gallotannins was also determined. The antigenotoxic potential of extracts from roots of G. asclepiadea was assessed using the standard in vivo procedure for the detection of sex linked recessive lethal mutations in Drosophila melanogaster males treated with ethyl methanesulfonate (EMS). The results showed that the most abundant secoiridoid in G. asclepiadea roots was gentiopicrine and its content in the n-butanol fraction (442.89 mg/g) was the highest. Among all extracts, ethyl acetate fraction showed the highest antioxidant activity, as well as total phenolics (146.64 GAE/g), flavonoids (44.62 RUE/g), flavonols (22.71 RUE/g) and gallotannins (0.99 mg GAE/g) content. All the fractions showed antioxidant activity using in vitro model systems and the results have been correlated with total phenolics, flavonoids, flavonols and gallotannins content. In addition to antioxidant activity, G. asclepiadea root extract fractions possess an antigenotoxic effect against DNA damage induced by alkylation with EMS. The antioxidant activity exhibited by G. asclepiadea depended on the phenolic compounds content of the tested extracts, while there was no significant difference in the antigenotoxic potential between fractions.
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    Nicotine exposure caused significant transgenerational heritable behavioral changes in Caenorhabditis elegans
    (2013-09-10) Taki, Faten A.; Pan, Xiaoping; Zhang, Baohong
    Passive and active exposure to tobacco smoking among youth is directly associated with immediate as well as long-term health deterioration. Despite all public health policies and efforts, the percentage of teenage smokers is still relatively high, especially in developing countries. Very few, if any, studies have been done on the transgenerational effect of nicotine exposed during the more sensitive, early developmental stages. We employed C. elegans as a biological model to study the multigenerational impact of chronic nicotine exposure. Nicotine treatment was limited to N2 hermaphrodites of the F0 generation. Exposure was limited to the larval period L1-L4 (~31 hours) after which worms were transferred to a fresh NGM plate. N2 hermaphrodites at L4 developmental stage were used for behavioral analysis across three generations: F0, F1, and F2. Our results show that nicotine was associated with changes in sinusoidal locomotion, speed, and body bends in L4 larvae in all three tested generations. These behavioral alterations were not restricted to F0, but were observed in F1 and F2 generations which were never exposed to nicotine. Our study is the first to reveal that nicotine addiction is heritable using C. elegans as a model organism. These results underscored the sensitivity of early development stages, with hope to spread more awareness to encourage the avoidance of nicotine exposure, especially at a young age.
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    Heme oxygenase effect on mesenchymal stem cells action on experimental Alzheimer's disease
    (2013-09-03) Abdel Aziz, M. T.; Atta, H. M.; Samer, H.; Ahmed, H. H.; Rashed, L. A.; Sabry, D.; Abdel Raouf, E. R.; ALKaffas, M. A.
    The objective is to evaluate the effect of heme oxygenase-1 (HO-1) enzyme inducer and inhibitor on Mesenchymal Stem Cells (MSCs) in Alzheimer disease. Materials and Methods: 70 female albino rats were divided equally into 7 groups as follows: group 1: healthy control; group 2: Aluminium chloride induced Alzheimer disease; group 3: induced Alzheimer rats that received intravenous injection of MSCs; group 4: induced Alzheimer rats that received MSCs and HO inducer cobalt protoporphyrin; group 5: induced Alzheimer rats that received MSCs and HO inhibitor zinc protoporphyrin; group 6: induced Alzheimer rats that received HO inducer; group7: induced Alzheimer rats that received HO inhibitor. Brain tissue was collected for HO-1, seladin-1 gene expression by real time polymerase chain reaction, heme oxygenase activity, cholesterol estimation and histopathological examination. Results: MSCs decreased the plaque lesions, heme oxygenase induction with stem cells also decreased plaque lesions however there was hemorrhage in the brain. Both heme oxygenase inducer alone or with stem cells increased seladin-1 expression and decreased cholesterol level. Conclusion: MSCs alone or with HO-1 induction exert a therapeutic effect against the brain lesion in Alzheimer’s disease possibly through decreasing the brain cholesterol level and increasing seladin-1 gene expression.
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    Protective effect of ginseng against gamma-irradiation-induced oxidative stress and endothelial dysfunction in rats
    (2013-08-30) Mansour, Heba Hosny
    This study investigated the potential protective effects of ginseng on gamma-irradiation-induced oxidative stress and endothelial dysfunction in rats. Twenty four male albino rats were divided into four groups. In the control group, rats were administered vehicle by tube for 7 consecutive days. The second group was administered ginseng extract (100 mg/kg, by gavage) for 7 consecutive days. Animals in the third group were administered vehicle by tube for 7 consecutive days, then exposed to single dose gamma-irradiation (6 Gy). The Fourth group received ginseng extract for 7 consecutive days, one hour later rats were exposed to gamma-irradiation. Oral administration of ginseng extract prior to irradiation produced a significant protection which was evidenced by a significant reduction in serum creatine kinase (CPK) and lactate dehydrogenase (LDH) activities and asymmetric dimethylarginine (ADMA), urea and creatinine levels with significant increase in serum total nitrate/nitrite (NO(x)) level. Moreover, ginseng significantly increased cardiac and renal superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities, and reduced glutathione (GSH) content, associated with a significant depletion in malondialdehyde (MDA) and NO(x) levels compared to irradiated group. This study suggests that ginseng may serve as a potential protective agent against gamma-irradiation-induced cardio-nephrotoxicity via enhancing the antioxidant activity and inhibition of endothelial dysfunction.
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    Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases
    (2013-08-29) Inoue, Sumito; Shibata, Yoko; Takabatake, Noriaki; Igarashi, Akira; Abe, Shuichi; Kubota, Isao
    Annual influenza vaccination is strongly recommended for patients with chronic pulmonary diseases, such as bronchial asthma, chronic obstructive pulmonary disease (COPD), and interstitial pulmonary diseases. However, many of these patients regularly receive systemic and/or inhaled corticosteroid therapy, and the impact of corticosteroid therapy on influenza vaccine efficacy and safety is unclear. Patients with chronic pulmonary diseases were enrolled in the study and divided into three groups based on their maintenance therapy: (A) without corticosteroid therapy (17 males, three females; mean age, 72.3 ± 7.9), (B) oral corticosteroid therapy (four males, seven females; mean age, 66.1 ± 10.6), and (C) inhaled corticosteroid therapy (eight males, nine females; mean age, 62.4 ± 16.0). All patients received influenza vaccine, and serum hemagglutination inhibition (HI) antibodies against influenza strains A/H1N1, A/H3N2, and B were measured at baseline (before vaccination) and 4-6 weeks after vaccination. Sufficient antibody titers or significant increases were observed after vaccination compared with titers before vaccination in all three groups. No systemic reactions were reported. Long-term oral/inhaled corticosteroid therapy was not associated with vaccination side effects and did not affect the immune response to the influenza vaccine.