Granulosa cells (GCs) are regulated by various factors during ovarian development.However, there are few reports on the role of follicular fluid exosomes in ovarian GCs. In this study, porcine ovarian GCs were used to explore the effects of follicular fluid exosomes on GCs. GCs were treated with in vitro, and the changes in cell proliferation, steroid synthesis, and associated signal pathways were detected. The results showed that exosomes increased cell viability and altered the gene expression profile of GCs. Exosomes also increased the level of gene expression associated with both proliferation and progesterone synthesis, in which the MAPK/ERK and WNT/B-CATENIN pathways were involved. In addition, exosome-carried microR-NAs were identified by high-throughput sequencing, and exosomal miR-31-5p was found to promote the proliferation of GCs and progesterone synthesis via the WNT/ B-CATENIN pathway by targeting the SFRP4 follicle growth inhibitor. In conclusion, this study has demonstrated that exosomes are essential substances involved in regulating the physiological function of GCs.
Lifestyle choices, external environment, aging, and other factors influence the synthesis of melatonin. Although the physiological functions of melatonin have been widely studied in relation to specific organs, the systemic effects of endogenous melatonin reduction has not been reported. This study evaluates the systemic changes and possible pathogenic risks in an endogenous melatonin reduction (EMR) mouse model deficient in the rate limiting enzyme in melatonin production, arylalkylamine N-acetyltransferase (Aanat) gene. Using this model, we identified a new relationship between melatonin, Alzheimer’s disease (AD), and gut microbiota. Systematic changes were evaluated using multi-omics analysis. Fecal microbiota transplantation (FMT) was performed to examine the role of gut microbiota in the pathogenic risks of EMR. EMR mice exhibited a pan-metabolic disorder, with significant transcriptome changes in 11 organs, serum metabolome alterations as well as microbiota dysbiosis. Microbiota dysbiosis was accompanied by increased gut permeability along with gut and systemic inflammation. Correlation analysis revealed that systemic inflammation may be related to the increase of Ruminiclostridium_5 relative abundance. 8-month-old EMR mice had AD-like phenotypes, including Iba-1 activation, A β protein deposition and decreased spatial memory ability. Moreover, EMR mice showed decreased anti stress ability, under high-fat diet, EMR mice had greater body weight and more obvious hepatic steatosis compared with WT group. FMT improved gut permeability, systemic inflammation, and AD-related phenotypes, while reducing obesity in EMR mice. Our findings suggest EMR causes systemic changes mediated by gut microbiota dysbiosis, which may be a pathogenic factor for AD and obesity, we further proved the gut microbiota is a potential target for the prevention and treatment of AD and obesity.
The p75 neurotrophin receptor (p75NTR), a member of tumor necrosis factor receptor superfamily, involves in neuronal apoptosis after intracerebral hemorrhage (ICH). It has been previously demonstrated that phosphorylation of p35 is a crucial factor for fighting against the proapoptotic p25/CDK5 signaling in neuronal apoptosis. Then, in ICH models of rats and primary cortical neurons, we found that the expressions of p75NTR, p‐histone H1 (the kinase activity of CDK5), p25, Fas‐associated phosphatase‐1 (FAP‐1), and phosphorylated myocyte enhancer factor 2D (p‐MEF2D) were enhanced after ICH, whereas the expression of p35‐Thr(138) was attenuated. Coimmunoprecipitation analysis indicated several interactions as follows: p35/p25 and CKD5, p75NTR and p35, as well as p75NTR and FAP‐1. After p75NTR or FAP‐1 depletion with double‐stranded RNA interference in PC12 cells, the levels of p25 and p‐histone H1 were attenuated, whereas p35‐Thr(138) was elevated. Considering p75NTR has no effect of dephosphorylation, our results suggested that p75NTR might promote the dephosphorylation of p35‐Thr(138) via interaction with FAP‐1, and the p75NTR/p35 complex upregulated p25/CDK5 signaling to facilitate the neuronal apoptosis following ICH. So, in the study, we aimed to provide a theoretical and experimental basis that p75NTR could be regulated to reduce neuronal apoptosis following ICH for potential clinical treatment.
Ammonia is one of the major toxic components of metabolites in blood and tissues of high-producing dairy cows and could affect the health of bovine mammary glands. Bovine mammary epithelial cells are sensitive to oxidative stress induced by intensive cell metabolism. In our previous study, we found that ammonia could induce oxidative stress, apoptosis and inflammatory responses in bovine mammary epithelial cells. In the present study, the cytoprotective effects of astragaloside IV against ammonia in vitro were explored. The results demonstrated that pretreatment of MAC-T cells with astragaloside IV could potently suppress the increase in the level of intracellular reactive oxygen species (ROS) and the rate of cell apoptosis, inhibit the ammonia-induced inflammatory responses, and rescue the decrease of cell viability. Astragaloside IV prevented ammonia-induced endoplasmic reticulum stress. Astragaloside IV also significantly suppressed the levels of BAX, caspase 3 and p53 phosphorylation in ammonia-induced MAC-T cells. Nuclear factor erythroid 2-related factor 2(Nrf2) was essential for cytoprotective effects of astragaloside IV in MAC-T cells, as knockdown of Nrf2 dramatically abolished the prosurvival effects of astragaloside IV on treated cells. Furthermore, the PI3K/AKT and ERK/MAPK pathways were responsible for the induction of Nrf2 by astragaloside IV. In conclusion, astragaloside IV played a beneficial role against ammonia-induced damage of MAC-T cells. This provides a cue for future study to use astragaloside IV as a protective and curative agent against ammonia exposure of mammary glands in dairy cows.
Giant pandas represent one of the most endangered species worldwide, and their reproductive capacity is extremely low. They have a relatively long gestational period, mainly because embryo implantation is delayed. Giant panda cubs comprise only a small proportion of the mother's body weight, making it difficult to determine whether a giant panda is pregnant. Timely determination of pregnancy contributes to the efficient breeding and management of giant pandas. Meanwhile, metabolomics studies the metabolic composition of biological samples, which can reflect metabolic functions in cells, tissues, and organisms. This work explored the urinary metabolites of giant pandas during pregnancy. A sample of 8 female pandas was selected. Differences in metabolite levels in giant panda urine samples were analyzed via ultrahigh-performance liquid chromatography/mass spectrometry comparing pregnancy to anoestrus. Pattern recognition techniques, including partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis, were used to analyze multiple parameters of the data. Compared with the results during anoestrus, multivariate statistical analysis of results obtained from the same pandas being pregnant identified 16 differential metabolites in the positive-ion mode and 43 differential metabolites in the negative-ion mode. The levels of tryptophan, choline, kynurenic acid, uric acid, indole-3-acetaldehyde, taurine, and betaine were higher in samples during pregnancy, whereas those of xanthurenic acid and S-adenosylhomocysteine were lower. Amino acid metabolism, lipid metabolism, and organic acid production differed significantly between anoestrus and pregnancy. Our results provide new insights into metabolic changes in the urine of giant pandas during pregnancy, and the differential levels of metabolites in urine provide a basis for determining pregnancy in giant pandas. Understanding these metabolic changes could be helpful for managing pregnant pandas to provide proper nutrients to their fetuses.
Vaccaria segetalis is a dry mature seed of Vaccaria hispanica (Mill.) Rauschert, which belongs to the genus V. segetalis (Neck.) Garcke. There are multiple medicinal parts of V. segetalis, according to the records, including roots, stems, leaves, flowers, and seeds, which should be used together. Currently, V. segetalis is most frequently used in the treatment of menstruation, dysmenorrhea, breast milk stoppages, and chylorrhea. Numerous studies present historical evidence of the use of V. segetalis to treat several diseases and describe its beneficial effects including prolactin- (PRL-) like, estrogen-like, antitumor, antiangiogenesis, and antioxidant activity. We summarized the period from January 1980 to December 2019 regarding V. segetalis. This review paper indicates that V. segetalis has promising clinical applications. The main active ingredients of the plant have been elucidated in recent years. We summarized the previously and newly discovered pharmacological effects of V. segetalis in addition to its active ingredients, ethnopharmacological uses, and toxicological properties, and provided a focus for future research.
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