Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics.

The incidence of premature ovarian insufficiency (POI) is increasing worldwide, particularly among younger women, posing a significant challenge to fertility. In addition to menopausal symptoms, POI leads to several complications that profoundly affect female reproductive function and overall health. Unfortunately, current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes. These approaches typically involve hormone replacement therapy combined with psychological support. Recently, mesenchymal stem cell (MSC) therapies for POI have garnered considerable attention in global research. MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms, including controlling differentiation, promoting angiogenesis, regulating ovarian fibrosis, inhibiting apoptosis, enhancing autocrine and paracrine effects, suppressing inflammation, modulating the immune system, and genetic regulation. This editorial offers a succinct summary of the application of MSC therapy in the context of POI, providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

Background: The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019. Methods: This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed. Results: From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China. Conclusion: Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.

Generation and Characterization of a Nanobody Against SARS-CoV.

The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has caused global panic in 2003, and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available; thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain (RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensin-converting enzyme 2 (ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.

Expression and localization of GPR143 in sheep skin.

G-protein coupled receptor143 (GPR143) plays an important role in melanogenesis. In this study, we investigated the expression pattern and localization of GPR143 in skin of sheep with different coat colors and explored the correlation between GPR143 gene and coat color. The mRNA level and protein level of GPR143 in skin of sheep with different coat colors were detected by qRT-PCR and immunoblotting separately while the localization of GPR143 in sheep skin was detected by immunofluorescence assay following optical density analysis. The qRT-PCR results showed that the relative expression level of GPR143 mRNA in black sheep skin was 7.84 times of that in white sheep skin (P<0.01). Immunoblotting results demonstrated that the expression level of GPR143 protein in black sheep skin was 1.30 times of that in white sheep skin (P<0.05). Immunofluorescence assay revealed that GPR143 was primarily expressed in the outer root sheath of hair follicles and epidermal skin tissue. Optical density analysis showed that expression levels of GPR143 in the outer root sheath and epidermis of black sheep skin were significantly higher than that of white sheep skin. Our studies demonstrated that GPR143 is expressed in skin of sheep with different coat colors. However, the mRNA and protein levels of GPR143 in black sheep skin are significantly higher than that in white sheep skin, indicating that GPR143 mRNA and protein levels are upregulated in skin of black sheep while downregulated in skin of white sheep. GPR143 may participate in the formation of coat color by regulating the level of MITF and the number, size, motility and maturation of the melanosome.

Study on the chromosomal karyotype and G-banding of Alpacas (Lama pacos).

Blood samples from 23 Huacaya alpacas, 3 males and 20 females, were used to study chromosomes and karyotypes, so as to provide some effective cytogenetic bases for the selection, improvement by crossing, disease diagnosis of alpacas, and genetic mechanisms of sex determination. Peripheral blood lymphocyte culture was used to prepare chromosome. A method of trypase-EDTA was used for G-banding. The results showed as follows: The number of diploid chromosomes was 2n=74, with the karyotype 74, XY and 74, XX for males and females respectively. Thirty-six homologous pairs of chromosomes were autosomes, in which chromosomes pairs No.1 to No.20 were acrocentric-subterminal and No.21 to No.36 metacentric-submetacentric. And X chromosome was metacentric, Y chromosome telocentric. The analysis of G-bands showed that bright and dark bands appeared by turn. It showed different bands. And every pair of chromosomes had its distinct band, and the longer the chromosomes, the more the number of bands, and the more clear the bands.