A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice

Virologica Sinica - SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines....     

聚多曲霉菌原生质体和液泡的制备及优化

原生质体的大量制备是研究原生质体转化、诱变、融合等技术的关键,液泡的制备对研究液泡中分解、转运有机物的特性具有重要意义,但目前分离技术还不够成熟.本研究从聚多曲霉菌菌丝中分离原生质体和液泡并对分离条件进行优化,以聚多曲霉菌DJ515-2菌丝为材料,探索不同因素对原生质体和液泡制备分离效果的影响.结果表明,聚多曲霉菌DJ515-2在菌龄42 h,以3％纤维素酶、1％蜗牛酶和3％的溶壁酶组成复合酶液,25℃下酶解4 h,原生质体达到最大产量,为5.167×105个/mL.同时,在此基础上裂解液泡的最优条件为pH7.5、1.0mol/L KCl、0.020％Triton X-10,其产量达2.63×105个/mL,产率为原生质体的50.8％,相比采用多元碱化合物诱导真菌原生质体裂解释放液泡的产率增加了 40％～45％.本研究为真菌和植物的各种原生质体技术及基于亚细胞层面的研究提供了材料基础.     

氧化甾醇结合蛋白相关蛋白家族的研究进展

膜脂是细胞膜的主要组分, 也是参与信号转导的重要信号分子。不同脂质分子在细胞膜上的不均等分布需要特殊类型的通道蛋白和运输蛋白来实现。氧化甾醇结合蛋白相关蛋白(ORPs)是一类非常保守的蛋白分子, 能够对磷脂酰肌醇和固醇等脂类分子进行识别并转运, 参与细胞中的许多生理过程, 包括信号转导、囊泡运输、脂类代谢和非囊泡运输等, 对于个体的生长发育具有重要作用。近几年, 关于ORPs在哺乳动物和酵母(Saccharomyces cerevisiae)中结构和功能的研究取得了一系列重要进展, 但在植物中相关研究尚少。该文综述了ORPs及其相关蛋白在哺乳动物、酵母和植物中的研究进展, 探讨了植物ORPs的结构及其与哺乳动物和酵母同源蛋白之间的进化关系, 并对植物ORPs未来的研究方向进行了展望。     

Expression profiles and potential roles of transfer RNA-derived small RNAs in atherosclerosis

Knowledge regarding the relationship between the molecular mechanisms underlying atherosclerosis (AS) and transfer RNA-derived small RNAs (tsRNAs) is limited. This study illustrated the expression profile of tsRNAs, thus exploring its roles in AS pathogenesis. Small RNA sequencing was performed with four atherosclerotic arterial and four healthy subject samples. Using bioinformatics, the protein-protein interaction network and cellular experiments were constructed to predict the enriched signalling pathways and regulatory roles of tsRNAs in AS. Of the total 315 tsRNAs identified to be dysregulated in the AS group, 131 and 184 were up-regulated and down-regulated, respectively. Interestingly, the pathway of the differentiated expression of tsRNAs in cell adhesion molecules (CAMs) was implicated to be closely associated with AS. Particularly, tRF-Gly-GCC might participate in AS pathogenesis via regulating cell adhesion, proliferation, migration and phenotypic transformation in HUVECs and VSMCs. In conclusion, tsRNAs might help understand the molecular mechanisms of AS better. tRF-Gly-GCC may be a promising target for suppressing abnormal vessels functions, suggesting a novel strategy for preventing the progression of atherosclerosis.     

Protective Effects of Pidotimod Against Salmonella Infections

International Journal of Peptide Research and Therapeutics - Pidotimod has been shown to exhibit immunomodulatory activities and exert protective effects against bacterial infections. This study...     

Hypoxic bone marrow mesenchymal cell-extracellular vesicles containing miR-328-3p promote lung cancer progression via the NF2-mediated Hippo axis

Lung cancer is the most aggressive tumour afflicting patients on a global scale. Extracellular vesicle (EV)-delivered microRNAs (miRs) have been reported to play critical roles in cancer development. The current study aimed to investigate the role of hypoxic bone marrow mesenchymal cell (BMSC)-derived EVs containing miR-328-3p in lung cancer. miR-328-3p expression was determined in a set of lung cancer tissues by RT-qPCR. BMSCs were infected with lentivirus-mediated miR-328-3p knock-down and then cultured in normoxic or hypoxic conditions, followed by isolation of EVs. Following ectopic expression and depletion experiments in lung cancer cells, the biological functions of miR-328-3p were analysed using CCK-8 assay, flow cytometry and Transwell assay. Xenograft in nude mice was performed to test the in vivo effects of miR-328-3p delivered by hypoxic BMSC-derived EVs on tumour growth of lung cancer. Finally, the expression of circulating miR-328-3p was detected in the serum of lung cancer patients. miR-328-3p was highly expressed in EVs derived from hypoxic BMSCs. miR-328-3p was delivered to lung cancer cells by hypoxic BMSC-derived EVs, thereby promoting lung cancer cell proliferation, invasion, migration and epithelial-mesenchymal transition. miR-328-3p targeted NF2 to inactivate the Hippo pathway. Moreover, EV-delivered miR-328-3p increased tumour growth in vivo. Additionally, circulating miR-328-3p was bioactive in the serum of lung cancer patients. Taken together, our results demonstrated that hypoxic BMSC-derived EVs could deliver miR-328-3p to lung cancer cells and that miR-328-3p targets the NF2 gene, thereby inhibiting the Hippo pathway to ultimately promote the occurrence and progression of lung cancer.     

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.     

TGF-β isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners

Transforming growth factor beta (TGF-β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-β isoforms, including TGF-β1, TGF-β2 and TGF-β3, remain unclear. Here, we demonstrated that all of the three TGF-β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-β/SMAD signalling pathway–dependent and TGF-β/SMAD signalling pathway–independent manners. TGF-β isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-β1 and TGF-β2, not TGF-β3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-β isoforms in the HCV-related liver disease progression.