滋阴药延缓衰老机制的研究进展＊

当代社会，老年人口比例呈现不断上升的趋势，老龄化问题日益严峻。因此，如何有效地延缓衰老不仅成为了世界医学研究的热点，也成为了全球亟待解决的问题。中医药在延缓衰老方面经验丰富，而滋阴药在此类研究中效果显著。本文通过整理滋阴药抗衰老作用机制的若干文献，对滋阴复方六味地黄丸、二至丸、左归丸及其他滋阴中药延缓衰老的机制研究进展进行综述。     

Population Genetics Identifies Challenges in Analyzing Rare Variants

Geneticists have, for years, understood the nature of genome‐wide association studies using common genomic variants. Recently, however, focus has shifted to the analysis of rare variants. This presents potential problems for researchers, as rare variants do not always behave in the same way common variants do, sometimes rendering decades of solid intuition moot. In this paper, we present examples of the differences between common and rare variants. We show why one must be significantly more careful about the origin of rare variants, and how failing to do so can lead to highly inflated type I error. We then explain how to best avoid such concerns with careful understanding and study design. Additionally, we demonstrate that a seemingly low error rate in next‐generation sequencing can dramatically impact the false‐positive rate for rare variants. This is due to the fact that rare variants are, by definition, seen infrequently, making it hard to distinguish between errors and real variants. Compounding this problem is the fact that the proportion of errors is likely to get worse, not better, with increasing sample size. One cannot simply scale their way up in order to solve this problem. Understanding these potential pitfalls is a key step in successfully identifying true associations between rare variants and diseases.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis

Background and aimThis network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors.Methods and resultsLiterature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central). Inclusion criteria: Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26–70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: −0.14 mmol/L, 95%–CI: −0.28, −0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: −2.99 to −2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: −0.68, 95%–CI: −1.31, −0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75).ConclusionsHP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.     

Chalcone hybrids and their antimalarial activity

Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed.     

Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products

Phytonutrients extracted from natural resources are receiving much attention among researchers due to their highly antioxidative characteristics which prevent several degenerative diseases including cardiovascular diseases and cancers. These nutraceutical compounds can be used in food, pharmaceutical and cosmetic products as natural antioxidants, preservatives, colourants and functional foods. Huge volume of food wastes are generated from the processing industry and these low-value food residues are rich in various phytonutrients worth recovering. This approach of valorisation reduces the generation of food wastes and is cost-effective considering the cheap feedstock, reduced waste management expenses and high market value of extracted compounds. In light of the health and safety risks posed by commonly used organic extraction solvents derived from the petrochemical industry, there is a need to recover the phytonutrients using green, sustainable and efficient solvents that are safe for human consumption. This work discusses ethyl lactate as a safe, green, efficient and potentially cheap solvent to recover phytonutrients from fruit and vegetable by-products. Ethyl lactate is compared with other organic solvents commonly used from the aspects of safety, environmental impacts and efficiency. Current challenges when employing ethyl lactate are also discussed.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

《医用有机化学》课程中进行德育渗透

教学与德育有机融会贯通,是当前教育领域的共识。医学本科生秉承"以德载医"的精神,肩负"治病救人"的重任,因此德育教育在整个医学教学中占有重要的地位。《医用有机化学》教材中含有丰富的德育内容,高校教师传授专业知识的同时,在教学过程中巧妙的穿插辩证唯物主义、爱国主义和社会责任感的思政教育,可以帮助学生们树立正确的世界观和人生观。文章以医用有机化学课程为例,主要从教师的自身道德素养、德育在教学过程中的具体实践和德育实施过程中需要注意的问题三方面进行阐述,充分将新时代新理念融入大纲、教案和课堂中,化"知识"为"智慧",变"文化"为"品格",充分发挥医用有机化学课程的德育功能。