Baicalein alleviates osteoarthritis by protecting subchondral bone,inhibiting angiogenesis and synovial proliferation

Osteoarthritis (OA) is one of the most frequent chronic joint diseases with the increasing life expectancy. The main characteristics of the disease are loss of articular cartilage, subchondral bone sclerosis and synovium inflammation. Physical measures, drug therapy and surgery are the mainstay of treatments for OA, whereas drug therapies are mainly limited to analgesics, glucocorticoids, hyaluronic acids and some alternative therapies because of single therapeutic target of OA joints. Baicalein, a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been widely used in anti-inflammatory therapies. Previous studies revealed that baicalein could alleviate cartilage degeneration effectively by acting on articular chondrocytes. However, the mechanisms involved in baicalein-mediated protection of the OA are not completely understood in consideration of integrality of arthrosis. In this study, we found that intra-articular injection of baicalein ameliorated subchondral bone remodelling. Further studies showed that baicalein could decrease the number of differentiated osteoblasts by inhibiting pre-osteoblasts proliferation and promoting pre-osteoblasts apoptosis. In addition, baicalein impaired angiogenesis of endothelial cells and inhibited proliferation of synovial cells. Taken together, these results implicated that baicalein might be an effective medicine for treating OA by regulating multiple targets.     

Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus

Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.     

Phytochemical Constituents and Biological Activities of Plants from the Genus Cissampelos

Cissampelos is a significant genus comprising of approximately 21 species of the medicinal plants (Menispermaceae). The plants of this genus are used in traditional medicine for the treatment of various ailments such as asthma, arthritis, dysentery, hyperglycemia, cardiopathy, hypertension and other related problems. These plants are rich in bioactive dibenzylisoquinoline and aborphine as well as small amounts of other ingredients. In recent years, the chemical constituents and pharmacological activities of Cissampelos genus have been paid more and more attention due to their diversity. Herein, we compile the chemical constituents and biological activities on this genus, and summarize the ¹³C-NMR data of the main bioactive ingredients. All information comes from scientific databases such as Google Scholar, PubMed, Sci-Finder, ScienceDirect, Web of Science and CNKI. It provides valuable data for the future research and development of Cissampelos genus.     

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.     

中西部幼儿肠道菌群与膳食关系的比较

目的探究中部和西部地区幼儿肠道菌群的结构差异与膳食的关系,为幼儿营养健康状况监测和营养改善工作提供有效的营养干预。方法选择“贫困地区儿童营养改善项目”河南汝阳和贵州福泉,随机抽取107名汉族健康幼儿为调查对象,食物摄入采用24 h消费调查方法。应用高通量测序技术对肠道菌群进行测序和生物信息分析,研究两县幼儿肠道菌群差异。结果两县幼儿肠道菌群组成结构较为一致,但Alpha多样性分析表明,贵州福泉县幼儿肠道物种丰富度和多样性高于河南汝阳县。细菌属水平分析中,两县幼儿肠道内均以拟杆菌属、普雷沃菌、柔嫩梭菌和双歧杆菌属为主导的菌群结构,但河南汝阳县幼儿肠道双歧杆菌属和乳杆菌属丰度显著高于贵州福泉县(12.36% vs. 7.44%;0.19% vs. 0.03%)。结论中西部地区幼儿肠道菌群结构差异不大,但有益菌含量存在显著差异,这为研究肠道菌群与膳食及营养健康状况之间的关系提供了依据。     

Floral fungal-bacterial community structure and co-occurrence patterns in four sympatric island plant species

Flowers’ fungal and bacterial communities can exert great impacts on host plant wellness and reproductive success—both directly and indirectly through species interactions. However, information about community structure and co-occurrence patterns in floral microbiome remains scarce. Here, using culture-independent methods, we investigated fungal and bacterial communities associated with stamens and pistils of four plant species (Scaevola taccada, Ipomoea cairica, Ipomoea pes-caprae, and Mussaenda kwangtungensis) growing together under the same environment conditions in an island located in South China. Plant species identity significantly influenced community composition of floral fungi but not bacteria. Stamen and pistil microbiomes did not differ in community composition, but differed in co-occurrence network topological features. Compared with the stamen network, pistil counterpart had fewer links between bacteria and fungi and showed more modular but less concentrated and connected structure. In addition, degree distribution of microbial network in each host species and each microhabitat (stamen or pistil) followed a significant power-law pattern. These results enhance our understanding in the assembly principles and ecological interactions of floral microbial communities.     

LncRNA PDCD4-AS1 alleviates triple negative breast cancer by increasing expression of IQGAP2 via miR-10b-5p

ObjectiveMounting evidence demonstrates that long non-coding RNA (lncRNA) is dysregulated in breast cancers. This study was designed to detect the influences and regulatory mechanism of lncRNA PDCD4-AS1 in triple-negative breast cancer (TNBC).MethodsqRT-PCR and Western blot were utilized to investigate the expression levels of PDCD4-AS1, miR-10b-5p and IQGAP2 in TNBC tissues and cells. Online software and luciferase reporter gene system were employed to testify the interactions among these molecules. Loss and gain of function of PDCD4-AS1, miR-10b-5p or IQGAP2 were performed before MTT and colony formation assay, TUNEL staining in addition to Transwell and scratch assays were applied to measure the cell biological functions.ResultsIn this work, PDCD4-AS1 and IQGAP2 were lowly expressed while miR-10b-5p was strongly expressed in TNBC tissues and cells. PDCD4-AS1 or IQGAP2 overexpression effectively attenuated TNBC cell proliferation, migration and invasion, and increased the apoptosis rate, while this effect was abandoned in response to miR-10b-5p mimics transfection. miR-10b-5p bound to IQGAP2 and acted as a downstream target of PDCD4-AS1.ConclusionOur findings identified lncRNA PDCD4-AS1 as a tumor suppressor in TNBC by regulating IQGAP2 expression via miR-10b-5p, giving a novel insight into the regulatory mechanism of PDCD4-AS1 in the pathogenesis of TNBC.