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mice in estrus. Compared to estrus-stage mice and E-treated OVX mice, DMPA-treated ovary-intact mice and OVX mice also exhibited significantly reduced genital epithelial barrier function, greater susceptibility to genital herpes simplex virus type 2 infection, and delayed clearance of genital Chlamydia trachomatis infection. Current studies thus identify analogous loss of genital epithelial integrity in OVX mice and menopausal and postmenopausal women. By showing that loss of genital epithelial integrity is associated with increased mouse susceptibility to bacterial and viral pathogens, our findings also prioritize the need to resolve if reduced genital epithelial integrity in postmenopausal women is a significant risk factor for genital infection.
Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations.
This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models.
Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2-0.4,
< .001), a decrease in serum calcium of 0.06 mg/dL (95% CI, -0.11 to -0.01,
= .01), an increase in iPTH of 5.4% (95% CI, 1.4-9.3,
= .01), and an increase in iFGF23 of 5.0% (95% CI, 2.0-8.0,
= .001). Dietary phosphorus intake was not related to cFGF23.
Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.
Increased dietary phosphorus intake acutely increases serum phosphate, iPTH, and iFGF23 levels and decreases serum calcium levels, highlighting the important role of daily fluctuations of dietary habits in disturbed mineral homeostasis in hemodialysis patients.BackgroundLigneous conjunctivitis (LC) is a rare disease characterized by the development of a wood-like pseudomembrane on the tarsal conjunctiva secondary to type I plasminogen deficiency. Here we reported on a Chinese patient with LC in a consanguineous family and performed a literature review of all reported mutations for this disease. Methods A 13-month-old girl diagnosed with LC and her parents were included in this study. Hematoxylin and eosin staining was used to perform histopathology examination. The plasminogen activity was determined by chromogenic assay. Sanger sequencing was performed to screen the mutation site for the disease. IOX1 price In silico analysis was applied to predict the pathogenesis of the identified mutation. In addition, we reviewed the literatures on PLG mutations of LC. Results Histopathology examination revealed the infiltration of inflammatory cells on membranous lesions. Plasma plasminogen activity was severely decreased in the patient and moderately decreased in her parents (patient plasminogen activity, 2.50%; father plasminogen activity, 41.02%; mother plasminogen activity, 54.07%). Co-segregation analysis indicated that the patient was homozygous for the c.763 G > A (p.Glu255Lys) mutation in plasminogen gene (PLG). Bioinformatics analysis strongly suggested that the mutation was damaging for the disease. The model analysis indicated the mutation might cause abnormal spatial structure and low stability, thus affecting functional activity. A literature review of the LC mutations indicated a strong genetic heterogeneity of the disease. Conclusions LC exhibited strong genetic heterogeneity, and our study identified a novel homozygous missense mutation of plasminogen (c.763 G > A, p.Glu255Lys) in one Chinese patient with LC.Diabetic nephropathy (DN) is a common complication of diabetes. Yishen capsule, composed of Chinese herbs, improves the clinical outcome in DN patients. However, its therapeutic potential and underlying mechanisms require further elucidation. Hence, our study aimed to investigate the underlying mechanisms and therapeutic potential of Yishen capsule in DN. Streptozotocin-induced DN rats were treated with Yishen capsules (1.25 g/kg/day) for 8 weeks. Then, blood glucose and urine protein levels were measured. Hematoxylin and eosin staining and western blot assays were used to examine the histologic changes and gene expression, respectively, in kidney samples. Mouse podocytes were treated with rat serum containing Yishen capsule and transmission electron microscopy was used to examine autophagosome formation. Cell counting kit-8 assay was performed to examine cell proliferation. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to detect changes in gene expression. The localization of SIRT1 was examined in the podocytes using immunocytofluorescence assay. We found that Yishen capsule relieved pathological changes, decreased urine protein, increased SIRT1, LC3-II, and Beclin-1 expression, and reduced acetylated NF-κB p65 expression in vivo. In addition, rat serum containing Yishen capsule showed improved podocyte proliferation, promoted the mRNA and protein levels of LC3-II and Beclin-1, and induced nuclear translocation of SIRT1. Furthermore, it increased SIRT1 expression and decreased mRNA level of NF-κB in the serum. SIRT1 inhibitor increased the mRNA level of NF-κB. Our data suggests that Yishen capsule improves DN by promoting podocyte autophagy via the SIRT1/NF-κB pathway.
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