Review Articles

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    Leibniz Research Centre for Working Environment and Human Factors
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    The past and present of serum aminotransferases and the future of liver injury biomarkers
    (2016-12-15) McGill, Mitchell R.
    Laboratory testing is important in the diagnosis and monitoring of liver injury and disease. Current liver tests include plasma markers of injury (e.g. aminotransferases, Ī³-glutamyl transferase, and alkaline phosphatase), markers of function (e.g. prothrombin time, bilirubin), viral hepatitis serologies, and markers of proliferation (e.g. Ī±- fetoprotein). Among the injury markers, the alanine and aspartate aminotransferases (ALT and AST, respectively) are the most commonly used. However, interpretation of ALT and AST plasma levels can be complicated. Furthermore, both have poor prognostic utility in acute liver injury and liver failure. New biomarkers of liver injury are rapidly being developed, and the US Food and Drug Administration the European Medicines Agency have recently expressed support for use of some of these biomarkers in drug trials. The purpose of this paper is to review the history of liver biomarkers, to summarize mechanisms and interpretation of ALT and AST elevation in plasma in liver injury (particularly acute liver injury), and to discuss emerging liver injury biomarkers that may complement or even replace ALT and AST in the future.
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    Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors
    (2016-11-30) ChƔirez-Ramƭrez, M. H.; Moreno-JimƩnez, M. R.; GonzƔlez-Laredo, R. F.; Gallegos-Infante, J. A.; Rocha-GuzmƔn, N. E.
    In recent times, a great deal of interest has been motivated on plant derived compounds known as nutraceuticals. These compounds exert important beneficial activities that improve peopleā€™s health status when are consumed regularly, and now they appear as a viable option to explore their possible therapeutic effects against diseases like cancer. Particularly, lupane-type triterpenes have shown great ability to modulate multiple cancer-related signaling pathways and processes, including NF-ĪŗB, Wnt/Ī²-catenin, PI3K/Akt, apoptosis, and many other routes related to proliferation or cell death, which are uncontrolled in malignant tumors. These investigations have promoted in vitro and in vivo studies, searching their mechanisms of action; although more research is still needed to prove its potential in human clinical trials. This review focuses on the ability of betulin, betulinic acid and lupeol to show benefits against the most common types of malignant tumors, which are considered a major global threat for public health.
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    Efficacy of antioxidant in idiopathic pulmonary fibrosis
    (2016-11-07) Kandhare, Amit D.; Mukherjee, Anwesha; Ghosh, Pinaki; Bodhankar, Subhash L.
    Idiopathic pulmonary fibrosis (IPF) is a chronic oxido-inflammatory disorder of the lung. Oxidative stress is widely recognized as a central feature of IPF. Antioxidant therapy has been proposed as an effective treatment for IPF. An array of clinical trials describing the therapeutic impact of these drugs have been reporting albeit with conflicting evidence points. We performed a meta-analysis of trials in which efficacy of antioxidant therapy was compared with control in IPF. Systematic literature search was conducted in PubMed, EMBASE, the Cochrane Library, CPCI-S (Conference Proceedings Citation Index-Science), ICTRP (International Clinical Trials Registry Platform), and Google Scholar till June 2016 by two independent researchers. Various outcomes such as changes in pulmonary function tests (change in vital capacity [Ī”VC], change in forced vital capacity [Ī”FVC], change in percentage of predicted vital capacity [Ī”%VC], and change in percentage of predicted carbon monoxide diffusing capacity [Ī”%DLco]), changes in 6 minutes walking test distance (Ī”6MWT), rates of adverse events, and rates of death, were included. All statistical analyses were performed using RevMan V.5.3.Twelve studies (n = 1062) were identified that used antioxidants (N-acetylcysteine and lecithinized superoxide dismutase) as a treatment for IPF. Overall, there was no association of antioxidant therapy with Ī”FVC (SMD = 0.27, 95% CI:-0.07 to 0.61; P = 0.12), Ī”FVC (%) (SMD = -0.10, 95% CI:-0.56 to 0.36; P = 0.66) and 6MWT (SMD = -0.04, 95% CI:-0.11 to 0.20; P = 0.59) in IPF patients. However, combined antioxidant therapy was found to be associated with %VC (SMD = 0.37, 95% CI: 0.09 to 0.64; P = 0.008) and Ī”%DLco (SMD = 0.15, 95% CI: 0.00 to 0.29; P = 0.05) in IPF patients. Strong evidence was obtained that the antioxidants increased adverse effects adverse events (OR = 1.56, 95% CI: 0.75 to 3.24; P = 0.23) but it did not associate mortality (OR = 0.96, 95% CI: 0.44 to 2.11; P = 0.92). The use of significant clinical heterogeneity, low statistical power, high dropout rates, duration of follow-ups, and dosing regimens of antioxidant agents. Combined antioxidant therapy seems to be a safe and effective therapy for IPF patients which provides a more beneficial effect in terms of VC, and DLco rather than monotherapy. Further randomized controlled trials with homogeneous outcome measures are needed.
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    Current trends in the treatment of hepatitis C
    (2016-10-14) Saleem, Ammara; Akhtar, Muhammad Furqan; Mushtaq, Muhammed Fahd; Saleem, Muhammad; Muhammad, Syed Taqi; Akhtar, Bushra; Sharif, Ali; Peerzada, Sohaib
    Viral hepatitis, an inflammatory liver disease, is caused by various genotypes of hepatitis C viruses (HCV). Hepatitis C slowly sprouts into fibrosis, which progresses to cirrhosis. Over a prolonged period of time compensated cirrhosis can advance to decompensated cirrhosis culminating in hepatic failure and death. Conventional treatment of HCV involves the administration of interferons. However, association of interferon with the adverse drug reactions led to the development of novel anti-HCV drugs given as monotherapy or in combination with the other drugs. Advances in drug delivery systems (DDS) improved the pharmacokinetic profile and stability of drugs, ameliorated tissue damages on extravasation and increased the targeting of affected sites. Liposomes and lipid based vehicles have been employed with polyethylene glycol (PEG) so as to stabilize the formulations as PEG drug complex. Sofosbuvir, a novel anti-HCV drug, is administered as monotherapy or in combination with daclatasvir, ledipasivir, protease inhibitors, ribavirin and interferon for the treatment of HCV genotypes 1, 2 and 3. These drug combinations are highly effective in eradicating the interferon resistance, recurrent HCV infection in liver transplant, concurrent HIV infection and preventing interferon related adverse effects. Further investigations to improve drug targeting and identification of new drug targets are highly warranted due to the rapid emergence of drug resistance in HCV.
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    Nutrients as novel therapeutic approaches for metabolic disturbances in polycystic ovary syndrome
    (2016-09-05) Mansour, Asieh; Hosseini, Saeed; Larijani, Bagher; Mohajeri-Tehrani, Mohammad Reza
    Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women. This disease is characterized by infertility, menstrual dysfunction, and hyperandrogenism. Also, PCOS is often associated with hyperlipidemia and impaired glucose tolerance, conditions that are associated with cardiovascular disorder, type 2 diabetes, cancer and hypertension. Evidence supports that some nutrients may affect the hormonal and metabolic disturbances of PCOS. Here in this study, we aimed to review the available literature that assessed the nutrients such as inostol, isoflavonids, resveratrol, vitamin D, and PUFA (polyunsaturated fatty acids), known to influence the hormonal and metabolic disturbances of PCOS, along with the strategies and future directions of nutrient supplementations in such patients.
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    Connexins and pannexins in liver damage
    (2016-02-25) Crespo Yanguas, Sara; Willebrords, Joost; Maes, Michaƫl; da Silva, Tereza Cristina; Veloso Alves Pereira, Isabel; Cogliati, Bruno; Zaidan Dagli, Maria Lucia; Vinken, Mathieu
    Connexins and pannexins are key players in the control of cellular communication and thus in the maintenance of tissue homeostasis. Inherent to this function these proteins are frequently involved in pathological processes. The present paper reviews the role of connexins and pannexins in liver toxicity and disease. As they act both as sensors and effectors in these deleterious events connexins and pannexins could represent a set of novel clinical diagnostic biomarkers and drug targets.
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    Homing in hematopoietic stem cells: focus on regulatory role of CXCR7 on SDF1a/CXCR4 axis
    (2016-02-15) Asri, Amir; Sabour, Javid; Atashi, Amir; Soleimani, Masoud
    Hematopoietic stem cells (HSCs) form a rare population of multipotent stem cells, which give rise to all hematopoietic lineages. HSCs home to bone marrow niches and circulate between blood and bone marrow. Many factors, especially SDF1a, affect the circulation of HSCs, but these have not been fully recognized. SDF1a has been shown to bind CXCR7 in addition to CXCR4 and can also function as SDF1a/CXCR4 modulator. CXCR7 plays a role in HSCs homing via SDF1a gradient and is a mediator of CXCR4/SDF1a axis. This review describes the current concepts and questions concerning CXCR7/CXCR4/SDF1a axis as an important key in hematopoietic stem cells homing with particular emphasis on CXCR7 receptor. Homing of HSCs is an essential step for successful hematopoietic stem cell transplantation.