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Conclusion Our results yield further support the for the view that TNF-α inhibitors increase body weight and BMI as a potential side effect. Modulating cytokine signaling could be a future therapeutic mechanism to treat disorders associated with weight changes such as anorexia nervosa. Copyright © 2020 Patsalos, Dalton, Leppanen, Ibrahim and Himmerich.Mitophagy is a crucial process in controlling mitochondrial biogenesis. Balancing mitophagy and mitochondrial functions is required for maintaining cellular homeostasis. In this study, we found that Gerontoxanthone I (GeX1) and Macluraxanthone (McX), xanthone derivatives isolated from Garcinia bracteata C. Y. Wu ex Y. H. Li, induced Parkin puncta accumulation and promoted mitophagy. GeX1 and McX treatment induced the degradation of mitophagy-related proteins such as Tom20 and Tim23. GeX1 and McX directly stabilized PTEN-induced putative kinase 1 (PINK1) on the outer membrane of the mitochondria, and then recruited Parkin to mitochondria. This significantly induced phosphorylation and ubiquitination of Parkin, suggesting that GeX1 and McX mediate mitophagy through the PINK1-Parkin pathway. Transfecting ParkinS65A or pretreated MG132 abolished the induction effects of GeX1 and McX on mitophagy. Furthermore, GeX1 and McX treatment decreased cell death and the level of ROS in an ischemia/reperfusion (IR) injury model in H9c2 cells compared to a control group. Taken together, our data suggested that GeX1 and McX induce PINK1-Parkin-mediated mitophagy and attenuate myocardial IR injury in vitro. Copyright © 2020 Xiang, Wu, Zhang, Fu, Yang, Zhang, Zheng, Zhang, Lao and Xu.Breast cancer (BC) is one of the most prevalent types of cancer worldwide with high morbidity and mortality rates. Treatment modalities include systemic therapy, in which chemotherapy is a major component in many cases. Several chemotherapeutic agents are used in combinations or as single agents with many adverse events occurring in variable frequencies. These events can be a significant barrier in completing the treatment regimens. Germline genomic variants are thought of as potential determinants in chemotherapy response and the development of side effects. Some pharmacogenomic studies were designed to explore germline variants that can be used as biomarkers for predicting developing toxicity or adverse events during chemotherapy in BC. https://www.selleckchem.com/products/LY294002.html In this review, we reassess and summarize the major findings of pharmacogenomic studies of chemotherapy toxicity during BC management. In addition, deficiencies hampering utilizing these findings and the potential targets of future research are emphasized. Main insufficiencies in toxicity pharmacogenomics studies originate from study design, sample limitations, heterogeneity of selected genes, variants, and toxicity definitions. With the advent of high throughput genotyping techniques, researchers are expected to explore the identified as well as the potential genetic biomarkers of toxicity and efficacy to improve BC management. However, to achieve this, the limitations of previous work should be evaluated and avoided to reach more conclusive and translatable evidence for personalizing BC chemotherapy. Copyright © 2020 Al-Mahayri, Patrinos and Ali.Background Irrational use of antimicrobial agents for gastrointestinal diseases deserves attention, but corresponding antimicrobial stewardship programs (ASPs) are generally not a priority for managers. We conducted this study to evaluate the effectiveness of multifaceted pharmacist-led (MPL) interventions in the gastroenterology ward (GW) to provide evidence for the efficacy of ASPs in a non-priority department. Methods This was an interventional, retrospective study implemented in China. The MPL intervention lasting 1.5 years involved daily ward rounds with physicians, regular review of medical orders, monthly indicator feedback, frequent physician training, and necessary patient education. Data on all hospitalized adults receiving antibiotics was extracted from the hospital information system over a 36-month period from January 2016 to December 2018. Segmented regression analysis of interrupted time series was performed to evaluate the effect of the MPL interventions (started in July 2017) on antibiotic uss should actively practice MPL interventions by clinical pharmacists in ASPs in those departments that are not included in priority management. Copyright © 2020 Du, Li, Wang, Peng, Wang, He, Li, Wang, Yang and Zhang.Advances in immuno-oncology (IO) are making immunotherapy a powerful tool for cancer treatment. With the discovery of an increasing number of IO targets, many herbs or ingredients from traditional Chinese medicine (TCM) have shown immunomodulatory function and antitumor effects via targeting the immune system. However, knowledge of underlying mechanisms is limited due to the complexity of TCM, which has multiple ingredients acting on multiple targets. To address this issue, we present TCMIO, a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology, which can be used to explore the molecular mechanisms of TCM in modulating the cancer immune microenvironment. Over 120,000 small molecules against 400 IO targets were extracted from public databases and the literature. These ligands were further mapped to the chemical ingredients of TCM to identify herbs that interact with the IO targets. Furthermore, we applied a network inference-based approach to identify the potential IO targets of natural products in TCM. All of these data, along with cheminformatics and bioinformatics tools, were integrated into the publicly accessible database. Chemical structure mining tools are provided to explore the chemical ingredients and ligands against IO targets. Herb-ingredient-target networks can be generated online, and pathway enrichment analysis for TCM or prescription is available. This database is functional for chemical ingredient structure mining and network analysis for TCM. We believe that this database provides a comprehensive resource for further research on the exploration of the mechanisms of TCM in cancer immunity and TCM-inspired identification of novel drug leads for cancer immunotherapy. TCMIO can be publicly accessed at http//tcmio.xielab.net. Copyright © 2020 Liu, Cai, Du, Liu, Cui, Fan, Wu, Fang and Xie.Background As a traditional Chinese medicine (TCM) prescription for acute stroke, Liangxue Tongyu formula (LXTYF) was widely used as auxiliary treatment measure in some clinical practice. This study aimed to evaluate the clinical efficacy and safety of LXTYF combined western conventional medicine (WCM) with WCM only for acute intracerebral hemorrhage (ICH). Methods We systematically searched PubMed, Embase, Cochrane Library, CMB (Chinese biomedicine database), CNKI (China National Knowledge Infrastructure), WanFang, and VIP until August 2019 to confirm relevant randomized controlled trials (RCTs) compared the combination of LXTYF and WCM with WCM alone for the treatment of acute ICH. Two investigators independently assessed the risk of bias, and extracted and analyzed the data from the identified studies using RevMan 5.3.0 software following Cochrane's standard and PRISMA guidelines. The herbal compositions of LXTYF were also assessed. Results 15 RCTs were identified, totally recruiting 1648 patients with acute intracerebral hemorrhage. Compared with the WCM alone, the combination therapy of LXTYF with WCM could improve the clinical effective rate (RR, 1.21; 95% CI, 1.15-1.25, P less then 0.05) and ADL score (MD, 18.09; 95% CI, 12.11-24.07; P less then 0.05), and reduce syndrome scores of the TCM (MD, -4.11; 95% CI, -4.69 to -3.53; P less then 0.05) and the Glasgow outcome score(GOS) (MD=0.43, 95%CI 0.06 to 0.79, P=0.02) Moreover, there was no sufficient evidence to indicate the adverse effects would increase compared with WCM alone. Conclusion Based on current evidence, we concluded that the combined therapy had some benefits in treating acute intracerebral hemorrhage. However, considering the potential biases and limitations of our study, additional large, high-quality RCTs are required in the future to confirm or refute the effects of LFTYF combined with WCM in acute stroke. Copyright © 2020 Jiang, Yang, Dong and Li.Background The use of quinolones has been associated with the development of serious and persistent adverse drug reaction (ADR) mainly affecting muscles, joints and the nervous system. This risk has led the European Medicines Agency (EMA) to endorse some restrictions on the use of this class of antibiotic. Therefore, we performed a study to primary estimate the reporting probability of musculoskeletal, neurological, and psychiatric ADRs among quinolone generations using national data. Methods We retrieved Individual Case Safety Reports (ICSRs) with a quinolone as suspected drug among those reported through the Campania spontaneous reporting system from January 1st, 2001 to April 30th 2019. Moreover, we retrieved national aggregated safety data from the online public report system (RAM system) for the period from January 1st, 2002 to March 31st, 2019. Risk factors were classified as "age greater than 60 years," "therapeutic indication," "renal failure," "organ transplantation," "use of corticosteroid," and "hihird-generation quinolones were always associated with a higher reporting probability of musculoskeletal, neurological, and psychiatric ADRs compared to the second generation ones. Moreover, we described risk factors in more than half of our cases suggesting that the inappropriate use of quinolones is a phenomenon that may frequently predispose patients to the occurrence of these ADRs. Copyright © 2020 Scavone, Mascolo, Ruggiero, Sportiello, Rafaniello, Berrino and Capuano.The aim of this research is to investigate the potential neuro-protective effect of kaempferol which with anti-oxidant, anti-inflammatory, and immune modulatory properties, and understand the effect of kaempferol on reducing cerebral ischemia reperfusion (I/R) injury in vivo. Male adult Sprague Dawley (SD) rats were pretreated with kaempferol for one week via gavage before cerebral I/R injury operation. We found that kaempferol treatment can reduce the cerebral infarct volume and neurological score after cerebral I/R. Rats were sacrificed after 24 h reperfusion. We observed that kaempferol improved the arrangement, distribution, and morphological structure of neurons, as well as attenuated cell apoptosis in brain tissue via hematoxylin and eosin (H&E) staining, Nissl staining and TUNEL staining. Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH) kit analysis, enzyme-linked immunosorbent (ELISA) assay, real-time PCR, Western blot, and immunohistochemical examination indicated that kaempferol mitigated oxidative and inflammatory stress via regulating the expression of proteins, p-Akt, p-GSK-3β, nuclear factor erythroid2-related factor 2 (Nrf-2), and p-NF-κB during cerebral I/R, thus increasing the activity of SOD and GSH, meanwhile decreasing the content of MDA in serum and brain tissue, as well as restoring the expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in vivo. Taken together, this study suggested that kaempferol protects against cerebral I/R induced brain damage. The possible mechanism is related with inhibiting oxidative and inflammatory stress induced apoptosis. Copyright © 2020 Wang, Mao, Wang, Li, Wu and Yuan.