Previous studies have shown that homocysteine (Hcy) is an important intestinal-derived uremic toxin. However, whether Hcy is involved in the epithelial barrier dysfunction observed in uremia remains unclear. This study aimed to investigate the effect of Hcy on intestinal permeability and intestinal barrier structure and function in adenine-induced uremic rats.Sprague-Dawley rats were divided into five groups: normal control (group NC), Hcy (group H), uremia (group U), uremia + Hcy (group UH), and uremia + Hcy + VSL#3 (group UHV). Experimental uremia was induced by intragastric adenine administration, and Hcy was injected subcutaneously. The animal models were assessed for renal function and pathological tissue staining. The pathological changes of intestinal tissue were observed by hematoxylin and eosin staining and electron microscopy. The serum and intestinal tissue levels of Hcy, interleukin (IL)-6, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), and malondialdehyde (MDA) as well as serum endotoxin and intestinal permeability were assessed. The levels of the tight junction proteins claudin-1, occludin, and zonula occludens-1 (ZO-1) were assessed by western blotting.Blood analyses and renal pathology indicated that experimental uremia was induced successfully. Pathological damage to intestinal structure was most obvious in group UH. Serum and tissue Hcy, serum endotoxin, and intestinal permeability were significantly elevated in group UH. The protein levels of claudin-1, occludin, and ZO-1 were decreased to various degrees in group UH compared with groups NC, H, and U. The serum and tissue levels of IL-6, TNF-α, and MDA were significantly increased, while SOD activity was markedly decreased. Supplementation with the probiotic VSL#3 improved these parameters to various degrees and up-regulated the abundance of tight junction proteins, which indicated a role for Hcy in the increase of intestinal permeability and destruction of the epithelial barrier in uremia.Hcy aggravates the increase of intestinal permeability and destruction of the epithelial barrier by stimulating inflammatory and oxidative damage. Probiotic administration can ameliorate this damage by reducing the levels of Hcy-induced inflammation and oxidation.
Introduction High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease. Whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. Methods A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xian Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus with kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline and kidney failure, was evaluated using Cox models. Results Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238-5.400, P = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783-0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756-0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95%CI, 1.791-14.944); P=0.002). Conclusion Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression.
To evaluate the in vivo and in vitro performance of a China-made dialysis machine (SWS-4000). This was a multi-center prospective controlled study consisting of both long-term in vitro evaluations and cross-over in vivo tests in 132 patients. The China-made SWS-4000 dialysis machine was compared with a German-made dialysis machine (Fresenius 4008) with regard to Kt/V values, URR values, and dialysis-related adverse reactions in patients on maintenance hemodialysis, as well as the ultrafiltration rate, the concentration of electrolytes in the proportioned dialysate, the rate of heparin injection, the flow rate of the blood pump, and the rate of malfunction. The Kt/V and URR values at the 1st and 4th weeks of dialysis as well as the incidence of adverse effects did not differ between the two groups in cross-over in vivo tests (P > 0.05). There were no significant differences between the two groups in the error values of the ultrafiltration rate, the rate of heparin injection or the concentrations of electrolytes in the proportioned dialysate at different time points under different parameter settings. At weeks 2 and 24, with the flow rate of the blood pump set at 300 mL/min, the actual error of the SWS-4000 dialysis machine was significantly higher than that of the Fresenius 4008 dialysis machine (P < 0.05), but there was no significant difference at other time points or under other settings (P > 0.05). The malfunction rate was higher in the SWS-4000 group than in the Fresenius 4008 group (P < 0.05). The in vivo performance of the SWS-4000 dialysis machine is roughly comparable to that of the Fresenius 4008 dialysis machine; however, the malfunction rate of the former is higher than that of the latter in in vitro tests. The stability and long-term accuracy of the SWS-4000 dialysis machine remain to be improved.
Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown.We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes.We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43.Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.
cification.The mechanism is presumably that VSMCs calcification is induced by influencing BMP-2 pathway, which may mediate the transdifferentiation of vascular smooth muscle cells.
Abstract The protection of hexafluoropropylene/air mixed gas for molten magnesium at temperatures from 670 °C to 800 °C has been investigated. The morphology and the composition of the protective film formed on the surface of the melt at 700 °C for holding time of 30 min and 60 min were investigated by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and X-ray diffraction (XRD). The results showed that the protective effect of the mixed gas on molten magnesium increased with the increasing of hexafluoropropylene concentration, the prolongation of holding time and the decrease of temperature. The protective film on the surface of the melt was uniform and continuous, and mainly composed of MgF 2 and small amount of MgO.
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