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Krogsgaard Mogensen posted an update 6 months ago
Background As one of the novel therapeutic drugs that targets Calcitonin gene-related peptide (CGRP), 75 mg rimegepant has been used for the acute management of migraine, which is one of the most common neurological diseases worldwide. Several clinical trials have been conducted to investigate the efficacy and safety of rimegepant for the acute management of migraine, but no systematic review of existing literature has been performed. We therefore performed a meta-analysis to investigate the efficacy and safety of rimegepant in treatment of patients with migraine. Method Pubmed, Embased, and Cochrane Library were searched from January 2001 to August 2019 for randomized controlled trials (RCTs). Four RCTs with 3,827 patients were finally included in our study. Result We pooled 3,827 patients from four RCTs, and the primary endpoints were freedom from pain, most bothersome symptom, and pain relief at 2 hr post dose. We found that 75 mg rimegepant led to significant freedom from pain (P less then 0.001), pain relief (P less then 0.001), and freedom from the most bothersome symptom (P less then 0.001) at 2 hr post dose compared with the placebo. In addition, there was no statistically significant increase in adverse events compared with the placebo. Conclusions 75 mg rimegepant had good efficacy and safety for acute treatment of migraine. Further studies are needed to compare the efficacy of rimegepant with traditional drugs for acute management of migraine. Copyright © 2020 Gao, Yang, Wang, Sun, Chen, Zhu and Wang.Introduction Diabetes is a metabolic disease with a high incidence and serious harm to human health. Islet β-cell function defects can occur in the late stage of type 1 diabetes and type 2 diabetes. Studies have shown that stem cell is a promising new approach in bioengineering regenerative medicine. In the study of stem cell differentiation, three-dimensional (3D) cell culture is more capable of mimicking the microenvironment of cell growth in vivo than two-dimensional (2D) cell culture. The natural contact between cells and cells, and cells and extracellular matrix can regulate the development process and promote the formation of the artificial regenerative organs and organization. Type IV, VI collagen and laminin are the most abundant extracellular matrix components in islets. Matrigel, a basement membrane matrix biomaterial rich in laminin and collagen IV. Materials and Methods We used Matrigel biomaterial to physically embed human dental pulp stem cells (hDPSCs) to provide vector and 3D culture conditioneptide from IPCs. Discussion Significant support is provided for obtaining a large number of functional IPCs for disease modeling and final cell therapy in regenerative medicine. Copyright © 2020 Xu, Fan, Zhao, Li, Wang, Wang, Wang, Guan and Niu.Two-dimensional (2D) nanosheets are characterized by their ultra-thin structure which sets them apart from their bulk materials. Due to this unique 2D structure, they have a high surface-to-volume ratio that can be beneficial for the delivery of various drugs including therapeutic DNAs and RNAs. In addition, various 2D materials exhibit excellent photothermal conversion efficiency when exposed to the near infrared (NIR) light. Therefore, this 2D nanosheet-based photonic nanomedicine has been gaining tremendous attention as both gene delivering vehicles and photothermal agents, which create synergistic effects in the treatment of different diseases. In this review, we briefly provide an overview of the following two parts regarding this type of photonic nanomedicine (1) mechanism and advantages of nanosheets in gene delivery and photothermal therapy, respectively. (2) mechanism of synergistic effects in nanosheet-mediated combined gene and photothermal therapies and their examples in a few representative nanosheets (e.g., graphene oxide, black phosphorus, and translational metal dichalcogenide). We also expect to provide some deep insights into the possible opportunities associated with the emerging 2D nanosheets for synergistic nanomedicine research. Copyright © 2020 Kim, Blake, De, Ouyang, Shi and Kong.The human voltage-sensitive K+ channel hERG plays a fundamental role in cardiac action potential repolarization, effectively controlling the QT interval of the electrocardiogram. Inherited loss- or gain-of-function mutations in hERG can result in dangerous “long” (LQTS) or “short” QT syndromes (SQTS), respectively, and the anomalous susceptibility of hERG to block by a diverse range of drugs underlies an acquired LQTS. A recent open channel cryo-EM structure of hERG should greatly advance understanding of the molecular basis of hERG channelopathies and drug-induced LQTS. Here we describe an update of recent research that addresses the nature of the particular gated state of hERG captured in the new structure, and the insight afforded by the structure into the molecular basis for high affinity drug block of hERG, the binding of hERG activators and the molecular basis of hERG’s peculiar gating properties. Interpretation of the pharmacology of natural SQTS mutants in the context of the structure is a promising approach to understanding the molecular basis of hERG inactivation, and the structure suggests how voltage-dependent changes in the membrane domain may be transmitted to an extracellular “turret” to effect inactivation through aromatic side chain motifs that are conserved throughout the KCNH family of channels. Copyright © 2020 Butler, Helliwell, Zhang, Hancox and Dempsey.In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still unclear. To explore this, we collected pre- and post-treatment serum samples of 85 FC patients from MZRW/Senna/placebo treatment groups for pharmacometabolomic analysis. An ultrahigh-performance liquid chromatography-mass spectrometer (UPLC-MS) was used for metabolic profiling and quantification. RVX-208 In vivo studies were conducted in constipated C57BL/6J mice to verify the effects and corresponding mechanism(s) of the action of MZRW. Pearson correlation analysis, paired t-test, one-way ANOVA analysis, χ2 test, and Student t-test were used to interpret the clinical and preclinical data.