LncRNA H19 rs4929984 Variant is Associated with Coronary Artery Disease Susceptibility in Han Chinese Female Population

Biochemical Genetics - Long non-coding RNAs (lncRNAs) have been reported to play an important role in cardiovascular diseases. The present study aimed to investigate the levels of lncRNA H19 in...     

Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system

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Protective Effect of Piceatannol Against Cerebral Ischaemia–Reperfusion Injury Via Regulating Nrf2/HO-1 Pathway In Vivo and Vitro

Neurochemical Research - Piceatannol is a natural plant-derived compound with protective effects against cardiovascular diseases. However, its effect on cerebral ischaemia–reperfusion injury...     

WormFarm: a quantitative control and measurement device toward automated Caenorhabditis elegans aging analysis

Caenorhabditis elegans is a leading model organism for studying the basic mechanisms of aging. Progress has been limited, however, by the lack of an automated system for quantitative analysis of longevity and mean lifespan. To address this barrier, we developed ‘WormFarm’, an integrated microfluidic device for culturing nematodes. Cohorts of 30–50 animals are maintained throughout their lifespan in each of eight separate chambers on a single WormFarm polydimethylsiloxane chip. Design features allow for automated removal of progeny and efficient control of environmental conditions. In addition, we have developed computational algorithms for automated analysis of video footage to quantitate survival and other phenotypes, such as body size and motility. As proof‐of‐principle, we show here that WormFarm successfully recapitulates survival data obtained from a standard plate‐based assay for both RNAi‐mediated and dietary‐induced changes in lifespan. Further, using a fluorescent reporter in conjunction with WormFarm, we report an age‐associated decrease in fluorescent intensity of GFP in transgenic worms expressing GFP tagged with a mitochondrial import signal under the control of the myo‐3 promoter. This marker may therefore serve as a useful biomarker of biological age and aging rate.     

Antitumour effects of pentapeptide derived from donkey serum albumin both in vitro and in vivo

AimsAntitumour effects of pentapeptide (LH) derived from donkey serum albumin hydrolysates were tested against tumour cells both in vitro and in vivo. The mechanism of LH induced tumour cell apoptosis was investigated.Main methodsHuman promyelocytic leukaemia cells (HL 60) were cultured to observe inhibition in vitro. Two animal models, a solid tumour and a non-entity myeloid leukaemia tumour, were used to determine the effect of LH in vivo. The former, fifty BALB/c nude mice were transplanted with HL 60 cells. The tumours were isolated completely and weighed after treatment. The latter, fifty BALB/c mice were injected intravenously with transplantable erythroblastic leukaemia cells (EL9611 cells). The survival time of mice was recorded and organs were used for histological study. The mechanism about tumour cell apoptosis was evaluated using fluorescence-activated cell sorting and transmission electron microscope for morphological assays.Key findingsThe LH inhibited tumour cell proliferation and the inhibitions were dependent on both the concentration and the dose; the best inhibition rate was up to 70% of the untreated control in vitro.It markedly inhibited the growth of a transplanted tumour with HL 60 cells in an immune-deficient nude mouse model. LH was also able to prolong the survival time of leukaemia mice with transplanted EL9611 cells and prevent the infiltration of leukaemia cells to the main internal organs.SignificanceThe LH peptide is an excellent inhibitor of tumour cell growth. These data provide the experimental foundation to use the LH peptide as a candidate for antitumour drugs in the future.     

Structure-based design of HSPA5 inhibitors: From peptide to small molecule inhibitors

We identified nine small-molecule hit compounds of Heat shock 70 kDa protein 5 (HSPA5) from cascade in silico screening based on the binding modes of the tetrapeptides derived from the peptide substrate or inhibitors of Escherichia coli HSP70. Two compounds exhibit promising inhibition activities from cancer cell viability and tumor inhibition assays. The binding modes of the hit compounds provide a platform for development of selective small molecule inhibitors of HSPA5.     

Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8⁺/IFN-γ⁺ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.     

Genetic Analysis of Population Structure and Reproductive Mode of the Termite Reticulitermes chinensis Snyder

The subterranean termite Reticulitermes chinensis Snyder is an important pest of trees and buildings in China. Here, we characterized genetic structure and reproductive modes of R. chinensis from China for the first time. A total of 1,875 workers from 75 collection sites in Huanggang, Changsha and Chongqing cities were genotyped at eight microsatellite loci. Analysis of genetic clusters showed two subpopulations in Chongqing city. The Huanggang population showed a uniform genetic pattern and was separated from the other populations by the largest genetic distances (F _ST: 0.17–0.20). In contrast, smaller genetic distances (F _ST: 0.05–0.12) separated Changsha, Chongqing-1 and Chongqing-2 populations. Chongqing-1 was the only population showing a genetic bottleneck. Isolation by distance among colonies in the Huanggang population indicated limited alate dispersal or colony budding. Lack of isolation by distance among colonies within the populations of Changsha, Chongqing-1 and Chongqing-2, suggested long-range dispersal by alates and/or human-mediated transport. Overall, extended family colonies (73.91%) were predominant in all four populations, followed by simple (20.29%), and mixed family colonies (5.80%). Most simple families were headed by inbred related reproductive pairs in the Changsha population, while most simple families in the Chongqing-1 population were headed by outbred unrelated pairs. Simple families in the Huanggang population were a mixture of colonies headed by outbred or inbred reproductive pairs. The sample size of simple families in the Chongqing-2 population was too small to yield significant results. Extended families in all four populations were headed on the average by ≤10 neotenics. Mixed families likely originated from pleometrosis. Presence of heterozygote genotypes showed that all neotenic reproductives collected in addition from five field colonies in Wuhan city were sexually produced, suggesting that these colonies did not undergo parthenogenesis. This study contributes to better understanding of the variance of genetic structure and reproductive mode in the genus Reticulitermes.     

Ribosomal Protein S27-Like in Colorectal Cancer: A Candidate for Predicting Prognoses

Background

The development and progression of colorectal cancer (CRC) involve a complex process of multiple genetic changes. Tumor suppressor p53 is capable of determining the fate of CRC cells. However, the role of a p53-inducible modulator, ribosomal protein S27-like (RPS27L), in CRC is unknown.

Methods

Here, the differential expression of RPS27L was examined in the feces and colonic tissues of CRC patients, to explore its possible correlation with patient survival and to investigate the cellular mechanisms underlying their clinical outcomes. Eighty intermediate-stage CRC patients (42 at stage II and 38 at stage III) were divided into two groups according to their fecal RPS27L mRNA levels. The survival probabilities of the groups were estimated using the Kaplan–Meier method. The RPS27L protein in the colonic tissues of stage III patients with different prognoses was further examined immunohistochemically. RPS27L expression in LoVo cells was manipulated to examine the possible cellular responses in vitro.

Results

Elevated RPS27L expression, in either feces or tissues, was related to a better prognosis. In vitro, RPS27L-expressing LoVo cells ceased DNA synthesis and apoptotic activity while the expression of their DNA repair molecules was upregulated.

Conclusions

Elevated RPS27L may improve the prognoses of certain CRC patients by enhancing the DNA repair capacity of their colonic cells, and can be determined in feces. By integrating clinical, molecular, and cellular data, our study demonstrates that fecal RPS27L may be a useful index for predicting prognoses and guiding personalized therapeutic strategies, especially in patients with intermediate-stage CRC.