Polydatin reverses oxidation low lipoprotein (oxLDL)-induced apoptosis of human umbilical vein endothelial cells via regulating the miR-26a-5p/BID axis

Atherosclerosis is a disease in which lipids and inflammatory factors accumulate on the walls of arteries, forming plaques that eventually block the flow of blood. Polydatin was derived from plant knotweed, which could play an important role in inhibiting the progression of atherosclerosis. However, the mechanism by which polydatin regulates the genesis and development of atherosclerosis remains unclear. To detect the function of polydatin in atherosclerosis, the proliferation, apoptosis and migration of human umbilical vein endothelial cells (HUVECs) was detected using 5-ethynyl-2’-deoxyuridine staining, flow cytometry and transwell assays, respectively. In addition, the branch points and capillary length of HUVECs were observed using a tube formation assay, and the lipid accumulation was tested by Oil-red O staining assay. Dual luciferase reporter assays were performed to confirm the association between microRNA (miR)-26a-5p and BH3 interacting domain death agonist (BID) in HUVECs. The data suggested oxidized low-density lipoprotein (oxLDL) notably inhibited the viability of HUVECs in a dose-dependent manner, and polydatin reversed the oxLDL-induced inhibition of HUVECs viability and proliferation. In addition, polydatin inhibited the apoptosis, migration and epithelial mesenchymal transition (EMT) process in oxLDL-treated HUVECs. Polydatin reversed oxLDL-induced lipid accumulation and angiogenesis inhibition in HUVECs. Furthermore, BID was targeted by miR-26a-5p, and polydatin reversed the oxLDL-induced apoptosis of HUVECs via regulating the miR-26a-5p/BID axis. In summary, polydatin reversed the oxLDL-induced apoptosis of HUVECs via regulating the miR-26a-5p/BID axis. Therefore, polydatin could act as a new agent for atherosclerosis treatment.Key words: Atherosclerosis, polydatin, miR-26a-5p, BH3 interacting domain death agonist     

Effects of highly selective sensory/motor nerve injury on bone metabolism and bone remodeling in rats

Objectives:This work aimed to investigate the mechanism of selective sensory/motor nerve injury in affecting bone metabolism and remodeling.Methods:The selective sensory/motor nerve injury rat model was constructed through posterior rhizotomy (PRG), anterior rhizotomy (ARG), or anterior combined with posterior rhizotomy (APRG) at the L_4-6 sensory/motor nerves on the right side of rats. Sham-operated (SOG) rats served as control. At 8 weeks after surgery, the sciatic nerves, spinal cord segments L₅ and tibial tissues were collected for analysis.Results:the integrity of trabecular bone was damaged, the number of trabecular bone was decreased and the number of osteoclasts were increased in ARG group. ARG activated NF-κβ and PPAR-γ pathways, and inhibited Wnt/β-catenin pathway. ARG group exhibited high turnover bone metabolism. In PRG group, the trabecular bone morphology became thinner, and the number of osteoclasts was increased. NF-κβ pathway was activated and OPG/RANKL ratio was decreased in PRG group. The activated osteoclasts, reduced osteoblasts activity and lower turnover bone metabolism were observed in PRG group. Additionally, the bone metabolism in APRG group was similar to ARG group.Conclusion:The posterior rhizotomy and anterior rhizotomy induced the different degree of osteoporosis in rats, which may attribute to regulate Wnt/β-catenin, NF-κβ and PPAR-γ signalling pathways.     

Endocytosis of Peptidase Inhibitor SerpinE2 promotes Myocardial Fibrosis through activating ERK1/2 and β-catenin Signaling Pathways

Cardiac fibrosis is one of the common pathological processes in many cardiovascular diseases characterized by excessive extracellular matrix deposition. SerpinE2 is a kind of protein that inhibits peptidase in extracellular matrix and up-regulated tremendously in mouse model of cardiac fibrosis induced by pressure-overloaded via transverse aortic constriction (TAC) surgery. However, its effect on cardiac fibroblasts (CFs), collagen secretion and the underlying mechanism remains unclear. In this study, DyLight® 488 green fluorescent dye or His-tagged proteins were used to label the exogenous serpinE2 protein. It was showed that extracellular serpinE2 translocated into CFs by low-density lipoprotein receptor-related protein 1 (LRP1) and urokinase plasminogen activator receptor (uPAR) of cell membrane through endocytosis. Knockdown of LRP1 or uPAR reduced the level of serpinE2 in CFs and down-regulated the collagen expression. Inhibition of the endocytosis of serpinE2 could inhibit ERK1/2 and β-catenin signaling pathways and subsequently attenuated collagen secretion. Knockdown of serpinE2 attenuates cardiac fibrosis in TAC mouse. We conclude that serpinE2 could be translocated into cardiac fibroblasts due to endocytosis through directly interact with the membrane protein LRP1 and uPAR, and this process activated the ERK1/2, β-catenin signaling pathways, consequently promoting collagen production.     

Establishment of a five‐enzalutamide‐resistance‐related‐gene‐based classifier for recurrence‐free survival predicting of prostate cancer

To identify prostate cancer (PCa) patients with a high risk of recurrence is critical before delivering adjuvant treatment. We developed a classifier based on the Enzalutamide treatment resistance‐related genes to assist the currently available staging system in predicting the recurrence‐free survival (RFS) prognosis of PCa patients. We overlapped the DEGs from two datasets to obtain a more convincing Enzalutamide‐resistance‐related‐gene (ERRG) cluster. The five‐ERRG‐based classifier obtained good predictive values in both the training and validation cohorts. The classifier precisely predicted RFS of patients in four cohorts, independent of patient age, pathological tumour stage, Gleason score and PSA levels. The classifier and the clinicopathological factors were combined to construct a nomogram, which had an increased predictive accuracy than that of each variable alone. Besides, we also compared the differences between high‐ and low‐risk subgroups and found their differences were enriched in cancer progression‐related pathways. The five‐ERRG‐based classifier is a practical and reliable predictor, which adds value to the existing staging system for predicting the RFS prognosis of PCa after radical prostatectomy, enabling physicians to make more informed treatment decisions concerning adjuvant therapy.     

草地贪夜蛾幼虫在玉米和小麦上的取食和生长发育特性比较

【目的】评估草地贪夜蛾Spodoptera frugiperda转移至小麦上为害和暴发的风险。【方法】采用室内饲养观察与调查统计的方法,测定和比较了23℃下草地贪夜蛾在玉米和小麦上的取食和生长发育特性及种群生命表参数。【结果】草地贪夜蛾在小麦上可以完成世代,其3龄后幼虫取食小麦的取食量及体重指标显著地高于同处理后时间在玉米上取食的;而食物利用效率、幼虫存活率、幼虫发育历期、卵孵化率均显著低于取食玉米的。取食玉米和取食小麦的草地贪夜蛾的平均蛹重、产卵前期、单雌产卵量等指标间无显著差异。另外,生命表参数比较结果表明,取食玉米和取食小麦的草地贪夜蛾的平均世代周期(T)、内禀增长率(r_m)和周限增长率(λ)间均无显著差异,取食玉米的草地贪夜蛾的净增殖率(R₀)为303.55±2.04,显著高于取食小麦的。【结论】草地贪夜蛾取食小麦时,生长发育速度快,能够完成世代生活史,但其食物利用效率、种群繁殖能力等却均低于取食玉米时,说明草地贪夜蛾更适宜在玉米上取食为害,存在转移至小麦为害的风险,但考虑到虫源、自然温度等条件,草地贪夜蛾在小麦上暴发的风险较小。本研...     

Galectin-3 critically mediates the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling

We previously documented that M2-like macrophages exert a hepatoprotective effect in acute-on-chronic liver failure (ACLF) by inhibiting necroptosis signalling. Nevertheless, the molecular mechanism behind this hepatoprotection still needs to be further dissected. Galectin-3 (GAL3) has been reported to be critically involved in the pathogenesis of multiple liver diseases, whereas the potential role of GAL3 in ACLF remains to be explored. Herein, we hypothesised that GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting necroptosis. To test this hypothesis, we first assessed the expression of GAL3 in control and fibrotic mice with or without acute insult. Second, loss- and gain-of-function experiments of GAL3 were performed. Third, the correlation between GAL3 and M2-like macrophage activation was analysed, and the potential role of GAL3 in M2-like macrophage-conferred hepatoprotection was confirmed. Finally, the molecular mechanism underlying GAL3-mediated hepatoprotection was dissected. GAL3 was found to be obviously upregulated in fibrotic mice with or without acute insult but not in acutely injured mice. Depletion of GAL3 aggravated hepatic damage in fibrotic mice upon insult. Conversely, adoptive transfer of GAL3 provided normal mice enhanced resistance against acute insult. The expression of GAL3 is closely correlated with M2-like macrophage activation. Through adoptive transfer and depletion experiments, M2-like macrophages were verified to act as a major source of GAL3. Importantly, GAL3 was confirmed to hold a pivotal place in the hepatoprotection conferred by M2-like macrophages through loss- and gain-of-function experiments. Unexpectedly, the depletion and adoptive transfer of GAL3 resulted in significant differences in the expression levels of pyroptosis but not necroptosis signalling molecules. Taken together, GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling. Our findings provide novel insights into the pathogenesis and therapy of ACLF.Subject terms: Inflammasome, Necroptosis     

Multipartite symbioses in fungus-growing termites (Blattodea: Termitidae,Macrotermitinae) for the degradation of lignocellulose

Fungus-growing termites are among the most successful herbivorous animals and improve crop productivity and soil fertility. A range of symbiotic organisms can be found inside their nests. However, interactions of termites with these symbionts are poorly understood. This review provides detailed information on the role of multipartite symbioses (between termitophiles, termites, fungi, and bacteria) in fungus-growing termites for lignocellulose degradation. The specific functions of each component in the symbiotic system are also discussed. Based on previous studies, we argue that the enzymatic contribution from the host, fungus, and bacteria greatly facilitates the decomposition of complex polysaccharide plant materials. The host–termitophile interaction protects the termite nest from natural enemies and maintains the stability of the microenvironment inside the colony.     

Reconstruction of Surface Porous PEEK Decorated with Strontium-doped Calcium Phosphate Coatings for Enhancing Osteogenic Activity

The aim of this study was to reconstruct surface porous structure with hundreds of micrometers and then bio-mineralize Sr-doped Calcium Phosphate(Sr-doped CaP)o...     

A single dose of recombinant VSV-RABVG vaccine provides full protection against RABV challenge

Highlights:
1. A replication-competent recombinant VSV with RABV-G protein replacement was generated.
2. Single dose of VSV-RABVG immunization induce potent antigen-specific humoral immune response, especially the virus neutralizing antibodies.
3. Mice intranasally immunized with single dose of VSV-RABVG were 100% protected upon RABV challenge.     

薄荷化学成分及其药理作用研究进展

对国内外有关薄荷的化学成分和药理作用的研究进行了综述,为进一步研究和开发利用薄荷提供了依据。