Membranous nephropathy (MN) is the major cause of nephrotic syndrome with special pathological features, caused by the formation of immune complexes in the space between podocytes and the glomerular basement membrane. In idiopathic membranous nephropathy (IMN) the immune complexes are formed by circulating antibodies binding mainly to one of two naturally-expressed podocyte antigens: the M-type receptor for secretory phospholipase A2 (PLA2R1) and the Thrombospondin type-1 domain-containing 7A (THSD7A). Formation of antibodies against PLA2R1 is much more common, accounting for 70–80% of IMN. However, the mechanism of anti-podocyte antibody production in IMN is still unclear. In this review, we emphasize that the exposure of PLA2R1 is critical for triggering the pathogenesis of PLA2R1-associated MN, and propose the potential association between inflammation, pollution and PLA2R1. Our review aims to clarify the current research of these precipitating factors in a way that may suggest future directions for discovering the pathogenesis of MN, leading to additional therapeutic targets and strategies for the prevention and early treatment of MN.
Follicular regulatory T (Tfr) cell can effectively regulate humoral immunity, but its function and mechanism in antibody-mediated rejection (AMR) after organ transplantation remains unclear. Here we detected follicular helper T (Tfh) cell subsets in 88 renal transplant patients with chronic renal allograft dysfunction (40 with AMR and 48 without AMR). The ratio of Tfr cells in renal graft tissues and peripheral blood of AMR patients significantly decreased, while the ratio of IL-21-producing Tfh cells (Tfh2 and Tfh17) significantly increased, compared to non-AMR patients. When tested in functional assays, Tfr cells from both AMR and non-AMR patients exerted equivalent inhibitory function. Tfr cell transplantation or CTLA-4 virus transfection could significantly inhibit IL-21 secretion from Tfh cells of these patients, further suppress the proliferation and differentiation of B cells. CTLA-4 blocking, IL-10 and TGF-β neutralization could partially weaken such inhibitory effect of Tfr cells. Besides, our study found that sirolimus reduced the ratio of Tfr cells, while cyclosporine and tacrolimus had no significant effect on Tfr cells. In a word, renal transplant patients with AMR have low proportion of Tfr cells but these cell exerted normal function.
Baicalin is an important flavonoid compound THaT is isolated from the Scutellaria baicalensis Georgi chinese herb and plays a critical role in anti-oxidative, anti-inflammatory, anti-infection and anti-tumor functions. although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin (BLM)-induced pulmonary fibrosis remain to be elucidated. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Hematoxylin and eosin (H&E) and Masson staining were used to measure the morphology of pulmonary fibrosis, ELIASA kits were used to test the ROS and inflammation, and western blotting and Tunel were performed to study the apoptosis proteins. In vitro, MTT assay, flow cytometry, western blotting and immunofluorescence were performed to investigate the effects of baicalin on proliferation of fibroblasts. The most significantly fibrotic changes were identified in the lungs of model rats at day 28. Baicalin (50 mg/kg) attenuated the degree of pulmonary fibrosis, and the hydroxyproline content of the lung tissues was decreased in the baicalin group, compared with the BLM group. Further investigation revealed that baicalin significantly increased glutathione peroxidase (GSH-px), total-superoxide dismutase (T-Sod) and glutathione (GSH) levels, whilst decreasing that of serum malondialdehyde (MDA). TUNEL-positive cells were significantly decreased in rats treated with baicalin group, compared with the model group. Furthermore, it was found that BLM promoted fibroblasts viability in a dose-dependent manner in vivo, which was restricted following treatment with different concentrations of baicalin. Moreover, BLM promoted the expression levels of cyclin a, d and e, proliferating cell nuclear antigen, phosphorylated (p)-AKT and p-calcium/calmodulin-dependent protein kinase type. BLM also promoted the transition of cells from the G 0 /G 1 phase to the G 2 /M and S phases, and increased the intracellular ca 2+ concentration, which was subsequently suppressed by baicalin. Collectively, the results of the present study suggested that baicalin exerted a suppressive effect on BLM-induced pulmonary fibrosis and fibroblast proliferation.
Berberine has significant antibacterial and antipyretic effects and is a commonly used drug for treating infectious diarrhoea. The current research data show that the pharmacological effects of berberine are numerous and complex, and researchers have been enthusiastic about this field. To allow researchers to quickly understand the field and to provide references for the direction of research, using bibliometrics, we analysed 1426 articles, dating from 1985 to 2018, in the field of berberine pharmacology. The research articles we found came from 69 countries/regions, 1381 institutions, 5675 authors, and 325 journals; they contained 3794 key words; they were written in 7 languages; and they were of 2 article types. This study summarizes and discusses the evolution of the historical themes of berberine pharmacology as well as the status quo and the future development directions from a holistic perspective.
Placentas associated with preeclampsia are characterized by extensive apoptosis in trophoblast lineages. Syncytin-1 (HERVWE1) mediates the fusion of cytotrophoblasts to form syncytiotrophoblasts, which assume the placental barrier, fetal-maternal exchange and endocrine functions. While decreased syncytin-1 expression has been observed in preeclamptic placentas, it is not clear if this alteration is involved in trophoblast apoptosis. In the current study we found that siRNA-mediated knockdown of syncytin-1 led to apoptosis in choriocarcinoma BeWo, a cell line of trophoblastic origin. Characterization of the apoptotic pathways indicated that this effect does not rely on the activation of caspases. Rather, decreased syncytin-1 levels activated the AIF apoptotic pathway by inducing the expression, cleavage, and nuclear translocation of AIF. Moreover, calpain1, the cysteine protease capable of cleaving AIF, was upregulated by syncytin-1 knockdown. Furthermore, treatment with calpain1 inhibitor MDL28170 effectively reversed AIF cleavage, AIF nuclear translocation, and cell apoptosis triggered by syncytin-1 downregulation, verifying the specific action of calpain1-AIF pathway in trophoblast apoptosis. We confirmed that preeclamptic placentas express lower levels of syncytin-1 than normal placentas, and observed an inverse correlation between syncytin-1 and AIF/calpain1 mRNA levels, a result consistent with the in vitro findings. Immunohistochemistry analyses indicated decreased syncytin-1, increased AIF and calpain1 protein levels in apoptotic cells of preeclamptic placentas. These findings have for the first time revealed that decreased levels of syncytin-1 can trigger the AIF-mediated apoptosis pathway in BeWo cells. This novel mechanism may contribute to the structural and functional deficiencies of syncytium frequently observed in preeclamptic placentas.
ObjectiveThis study aims to explore the necessity and safety of digestive endoscopy during the epidemic of coronavirus disease 2019.MethodsA retrospective cohort study method was used to collect patients’ data from the endoscopy center of the Civil Aviation General Hospital of China from February 1 to May 31, 2020, as the observation group. The patients’ data of endoscopic diagnosis and treatment during the same period in 2019 were used as a control group, to compare the differences in the number of diagnosis and treatment and the detection rate of gastrointestinal diseases in the two groups. At the same time, patients and related staff were followed up for the situation of new infection.ResultsDuring the epidemic, our endoscopy center conducted a total of 1,808 cases of endoscopic operations and 5,903 cases in the control group. The amount of endoscopic work during the epidemic period was 30.63% in the same period last year. During the epidemic, 26 patients underwent endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) treatment, 26 patients underwent ERCP, and 18 patients underwent gastrointestinal stent implantation. In the control group, 273 patients underwent EMR/ESD, 17 underwent ERCP, and 16 underwent gastrointestinal stenting. During COVID-19, compared with the same period last year, the detection rates of peptic ulcer, esophageal cancer, gastric cancer, colon cancer, and rectal cancer were significantly higher (χ2 = 4.482, P = 0.034; χ2 = 5.223, P = 0.006; χ2 = 2.329, P = 0.041; χ2 = 8.755, P = 0.003; and χ2 = 5.136, P = 0.023). Through telephone follow-up, novel coronavirus nucleic acid detection and blood antibody detection, no patients or medical staff were infected with the novel coronavirus.ConclusionDuring COVID-19, the number of digestive endoscopic operations decreased significantly compared with the same period last year, but the detection rate of various diseases of the digestive tract increased significantly. On the basis of strict prevention and control, orderly recovery of endoscopic work is essential.
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