The gut microbiome and metabolome in kidney transplant recipients with normal and moderately decreased kidney function.

BACKGROUND: The kidney transplant recipients (KTRs) were diagnosed with Chronic Kidney Disease after transplantation (CKD-T). CKD-T can be affected by the microbial composition and metabolites. The present study integrates the analysis of gut microbiome and metabolites to further identify the characteristics of CKD-T. METHODS: We collected 100 fecal samples of KTRs and divided them into two groups according to the stage progression of CKD-T. Among them, 55 samples were analyzed by Hiseq sequencing, and 100 samples were used for non-targeted metabolomics analysis. The gut microbiome and metabolomics of KTRs were comprehensively characterized. RESULTS: As well as significant differences in gut microbiome diversity between the CKD G1-2T group and CKD G3T group. Eight flora including Akkermansia were found to be enriched in CKD G3T group. As compared with CKD G1-2T group, the relative abundance of some amino acid metabolism, glycerophospholipid metabolism, amino acid biosynthesis, carbohydrate metabolism and purine metabolism in CKD G3T group were differential expressed significantly. In addition, fecal metabolome analysis indicated that CKD G3T group had a unique metabolite distribution characteristic. Two differentially expressed metabolites, N-acetylornithine and 5-deoxy-5'-(Methylthio) Adenosine, were highly correlated with serum creatinine, eGFR and cystatin C. The enrichment of gut microbial function in CKD-T is correlated with the expression of gut metabolites. CONCLUSION: Gut microbiome and metabolites in the progression of CKD-T display some unique distribution and expression characteristics. The composition of the gut microbiome and their metabolites appears to be different between patients with CKD G3T and those with CKD G1-2T.

Parameters of MR perfusion-weighted imaging predict the response and prognosis to high-dose methotrexate-based chemotherapy in immunocompetent patients with primary central nervous system lymphoma.

To investigate the effectiveness of dynamic susceptibility contrast-perfusion weighted imaging (DSCPWI) in predicting the progression-free survival (PFS) and chemotherapeutic responsiveness of primary central nervous system lymphoma (PCNSL) before high-dose methotrexate-based chemotherapy. DSCPWI was used to analyze 35 patients who had pathology-confirmed PCNSL. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and relative time to peak (rTTP) were measured on parameter maps. The 5th, 50th and 95th percentile values of every parameter were recorded for enhanced tumors and compared with the parameters of the normally contralateral hemisphere. The ratio of each PWI parameter (rrCBV, rrCBF, rrMTT, rrTTP) was obtained. The influence of parameters on responsiveness and PFS was investigated by univariate Kaplan-Meier analysis and logistic regression and Cox regression for multivariate analysis with a stepwise method. Differences in PWI parameters between the higher and lower vascular endothelial growth factor (VEGF) groups were assessed by the Mann-Whitney U test. Eighteen patients achieved a complete response (CRi) after four initial cycles of chemotherapy. Patients with lower age (p = 0.011), higher VEGF (p < 0.001), higher Karnofsky Performance Status (KPS) (p < 0.001), higher rrCBV95% (p < 0.001), higher rrCBV50% (p = 0.016), higher rrCBF95% (p < 0.001), higher rrCBF50% (p = 0.002) showed better PFS; there was difference on age(p = 0.044), KPS (p < 0.001), VEGF (p < 0.001), rrCBV95% (p = 0.018), rrCBF95% (p = 0.018), rrCBF50% (p = 0.007) between CRi and nonCRi. Multivariate analysis demonstrated that rrCBF95% (p = 0.037, 95% confidence interval: 1.065-7.206) was significantly associated with PFS. rCBV and rCBF may be used to assess the responsiveness and prognosis of PCNSL, and rCBF95% may be a better predictor.

Mesoporous ZnMn2O4 Microtubules Derived from a Biomorphic Strategy for High-Performance Lithium/Sodium Ion Batteries.

ZnMn2O4 microtubules (ZMO-MTs) with a mesoporous structure are fabricated by a novel yet effective biomorphic approach employing cotton fiber as a biotemplate. The fabricated ZMO-MT has approximately an inner diameter of 8.5 µm and wall thickness of 1.5 µm. Further, the sample of ZMO-MT displays a large specific surface area of 48.5 m2 g-1. When evaluated as a negative material for Li-ion batteries, ZMO-MT demonstrates an improved cyclic performance with discharge capacities of 750.4 and 535.2 mA h g-1 after 300 cycles, under current densities of 200 and 500 mA g-1, respectively. Meanwhile, ZMO-MT exhibits superior rate performances with high reversible discharge capacities of 614.7 and 465.2 mA h g-1 under high rates of 1000 and 2000 mA g-1, respectively. In sodium ion batteries applications, ZMO-MT delivers excellent high discharge capacities of 102 and 71.4 mA h g-1 after 300 cycles under 100 and 200 mA g-1, respectively. An excellent rate capability of 58.2 mA h g-1 under the current density of 2000 mA g-1 can also be achieved. The promising cycling performance and rate capability could be benefited from the unique one-dimensional mesoporous microtubular architecture of ZMO-MT, which offers a large electrolyte/electrode accessible contact area and short diffusion distance for both of ions and electrons, buffering the volume variation originated from the repeated ion intercalation/deintercalation processes.

Diabetogenic agent alloxan is a proteasome inhibitor.

Alloxan has been used as a diabetogenic agent to induce diabetes. It selectively induces pancreatic ß-cell death. The specific toxicity, however, is not fully understood. In this study, we observed the effect of alloxan on proteasome function. We found that alloxan caused the accumulation of ubiquitinated proteins in NRK cells through the inhibition of the proteolytic activities of the proteasome. Biochemistry experiments with purified 26S and 20S proteasomes revealed that alloxan directly acts on the chymotrypsin- and trypsin-like peptidase activities. These results demonstrate that alloxan is a proteasome inhibitor, which suggests that its specific toxicity toward ß-cell is at least in part through proteasome inhibition.

Co-cultured hBMSCs and HUVECs on human bio-derived bone scaffolds provide support for the long-term ex vivo culture of HSC/HPCs.

In order to closely mimic a multi-cell state in hematopoietic stem/progenitor cells (HSC/HPCs) vascular niche, we co-cultured human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) without any cytokines as feeder cells and applied bio-derived bone from human femoral metaphyseal portion as scaffold to develop a new HSC/HPCs three-dimensional culture system (named 3D-Mix cultures). Scanning electron and fluorescent microscopy showed excellent biocompatibility of bio-derived bone to hBMSCs and HUVECs in vitro. Flow cytometry analysis and quantitative real-time polymerase chain reaction (qPCR) assay of p21 expression demonstrated that 3D-Mix could promote self-renewal and ex vivo expansion of HSCs/HPCs significantly higher than 3D-hMSC and 3D-HUVEC. Long-term culture initiating cell (LTC-IC) confirmed that 3D-Mix had the most powerful activity of maintaining multipotent differentiation of primitive cell subpopulation in HSCs. The nonobese diabetic/severe combined immunodeficiency (NOD/SCID) repopulating cell (SRC) assay demonstrated that 3D-Mix promoted the expansion of long-term primitive transplantable HSCs. qPCR of alkaline phosphatase (ALP) and osteocalcin (OC) demonstrated that HUVECs enhanced the early osteogenic differentiation of BMSCs. Western blot and qPCR revealed that HUVECs activated Wnt/ß-catenin signaling in hBMSCs inducing Notch signal activation in HSCs. Our study indicated that interaction between hMSCs and HUVECs may have a critical role in to influent on HSCs/HPCs fate in vitro. These results demonstrated that the 3D-Mix have the ability to support the maintenance and proliferation of HSCs/HPCs in vitro.