The receptor activator of NF- κ B ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF- κ B pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF- κ B pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF- κ B pathway.
Abstract Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51+ SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51+ SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51+ cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro. As a specific cytotoxin that eliminates Leydig cells (LCs) in adult rats, ethane dimethanesulfonate (EDS) was used to ablate LCs before the SLC transplantation. After being transplanted into the testes of EDS-treated rats, the CD51+ cells differentiated into mature LCs, and the recipient rats showed a partial recovery of testosterone production and spermatogenesis. Notably, a testosterone analysis revealed a circadian rhythm of testosterone secretion in cell-transplanted rats, and these testosterone secretions could be suppressed by decapeptyl (a luteinizing hormone-releasing hormone agonist), suggesting that the transplanted cells might be regulated by the HPG axis. This study is the first to demonstrate that CD51+ SLCs can restore the neuroendocrine regulation of testicular function by physiologically recovering the expected episodic changes in diurnal testosterone serum levels and that SLC transplantation may provide a new tool for the studies of testosterone deficiency treatment.
To explore the relationship of ascitic bacterial DNA and plasma endotoxin, intestinal permeability, gut flora in cirrhotic patients.Fifty-five decompensated cirrhotic patients with ascites were included in the study. A paracentesis was performed for every patient at admission and ascites fluid was collected for bacterial DNA isolation and amplification, plus other routine studies and cultured for aerobic and anaerobic bacteria. Plasma endotoxin, intestinal permeability, and gut flora were studied on the day following admission. Blood from the patients was obtained for routine hematologic, biochemical, and coagulation studies. Thirty healthy subjects were studied as normal controls.No bacteria were found in the ascites cultures in the 55 patients, but bacterial DNA was found in 19 (34.55%). Compared with the bacterial DNA negative group, the bacterial DNA positive group showed a significantly lower level of PTA (t= -3.184, P=0.002), a higher Child-Pugh score (t=3.224, P=0.002) and a higher quantity of WBC in their ascitic fluid (t=4.088, P=0.001). Compared with normal controls, cirrhotic patients showed significantly higher levels of plasma endotoxin (t=13.705, P=0.000), lactulose/mannitol (L/M, t=28.568, P=0.000) in urine, and the quantity of enteric bacilli (t=2.912, P=0.005); the quantity of their intestinal bifidobacteria was significantly lower (t= -3.669, P=0.000). The variables correlative with the presence of bacterial DNA were the quantities of enteric bacilli (P=0.007) and PTA (P=0.011).Intestinal bacterial overgrowth plays a key role in the pathogenesis of ascitic bacterial translocation (ABT) in cirrhotic patients. ABT is correlated with the degrees of the liver disease.
The integration of grapes into canned food processing not only effectively extends their shelf life but also preserves their rich nutrition and delightful flavor. This marks a significant advancement toward value-added products and sustainability in the grape industry. This study aims to evaluate the appropriateness of different grape varieties for canned grape production, with a focus on peeling characteristics, sensory quality, and storage properties. Our findings reveal that Kyoho, Takatsuma, and Zuijinxiang grapes stand out as promising candidates, characterized by their ease of peeling, minimal peeling loss, and efficient peeling time. Subsequently, a fuzzy mathematical sensory evaluation approach was employed to assess the taste, flavor, texture, appearance, and size of the peeled grapes from nine grape varieties. Notably, Kyoho (3.87), Takatsuma (3.70), and Zuijinxiang (3.57) grapes exhibited superior sensory scores compared with the other varieties. Regarding storage quality, after 180 days of storage, Kyoho grapes exhibited lower color difference by 12.97–23.50%, higher brittleness by 13.77–19.17%, total phenolic content by 15.73–29.29%, total flavonoid content by 28.54–39.31%, anthocyanin content by 23.81–35.66%, and stronger antioxidant capacity (IC50 DPPH: 24.42–69.55%; IC50 ABTS: 13.27–57.43%) compared with Takatsuma and Zuijinxiang grapes. This comprehensive assessment highlights Kyoho grapes as the most suitable variety for canned grape production, followed by Takatsuma and Zuijinxiang grapes. Their exceptional peeling characteristics, sensory qualities, and notable storage resilience position them as promising candidates for commercialization, presenting substantial potential for widespread acceptance among consumers.
Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow‐up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9–34.1 μmol/L) was 0.75 (95% CI, 0.59–0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5–24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60–0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89–2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76–2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.
Objective To explore the method for early diagnosis of Sjgren's syndrome complicated by Pneumocystis pneumonia(PCP).Method The clinical data of one case of Sjgren's syndrome complicated by Pneumocystis pneumonia were retrospective analyzed.Results The patient with Sjgren's syndrome went on to develop fever of undetermined origin,hacking cough and dyspnea on exertion after received immunosuppressive agents treatment for 2 months.Diagnosis of PCP was based on the clinical features,chest X-rays,CT findings,sputum Pneumocystis jiroveci Grocott's methenamine silver(GMS) staining and polymerase chain reaction(PCR).The Pneumocystis jiroveci DNA burden in sputum sample was decreased form 104 / ml to 102 / ml after receiving clindamycin(sulfa drugs hypersensitive) and caspofugin treatment for 6 days.The DNA burden was further decreased to 101 / ml at 12 days after the treatment.After caspofugin treatment for 21 days,the patient was cured and discharged.Conclusions Although the specificity of GMS stain for sputum samples was high,the sensitivity of this staining method was low.The highly sensitive PCR method can be used not only for the clinical screening of PCP and but also for the monitoring therapeutic effect after the treatment.
Background: Few studies have directly compared clinical efficacy and safety among Chinese herb injections (CHIs) for gastric cancer (GC). The present study aimed to compare CHIs combined with FOLFOX regimens for GC to show which provides the best CHIs results. Materials and Methods: 9 electronic databases and 6 gray literature databases were comprehensive searched in April 20, 2013. According to inclusion and exclusion criteria, two reviewers independently selected and assessed the included trials. The risk of bias tool described in the Cochrane Handbook version 5.1.0 and CONSORT statement were used to assess the quality of the trials. All calculations and graphs were performed and produced using ADDIS 1.16.5 software. Results: A total of 541 records were searched and 38 RCTs met the inclusion criteria (2,761 participants), involving 10 CHIs. The results of network meta-analysis showed that compared with FOLFOX alone, combinations with Kanglaite, Astragalus polysaccharides, Cinobufacini, or Yadanziyouru injections could furthest strengthen ORR, improve the quality of life, reduce nausea and vomiting, and reduce the incidence of leukopenia (III-IV). Conclusions: Kanglaite injection, Astragalus polysaccharides injection, Yadanziyouru injection were superior to other CHIs in clinical efficacy and safety for GC. The conclusions now need to be confirmed by large sample size direct head-to-head studies.
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