Zobrazení zdroje stránky Paulsensutherland5141

Mitochondrial dysfunction has been thought to play roles in the pathogenesis of diabetic nephropathy (DN). However, precise mechanisms underlying mitochondrial dysfunction in DN remained unclear. Herein, mitochondria were isolated from renal tubular cells after exposure to normal glucose (5.5 mM glucose), high glucose (25 mM glucose), or osmotic control (5.5 mM glucose + 19.5 mM mannitol) for 96 h. Comparative proteomic analysis revealed six differentially expressed proteins among groups that were subsequently identified by tandem mass spectrometry (nanoLC-ESI-ETD MS/MS) and confirmed by Western blotting. Several various types of post-translational modifications (PTMs) were identified in all of these identified proteins. Interestingly, phosphorylation and oxidation were most abundant in mitochondrial proteins whose levels were exclusively increased in high glucose condition. The high glucose-induced increases in phosphorylation and oxidation of mitochondrial proteins were successfully confirmed by various assays including MS/MS analyses. Moreover, high glucose also increased levels of phosphorylated ezrin, intracellular ATP and ROS, all of which could be abolished by a p38 MAPK inhibitor (SB239063), implicating a role of p38 MAPK-mediated phosphorylation in high glucose-induced mitochondrial dysfunction. [https://www.selleckchem.com/products/Imatinib-Mesylate.html STI571] These data indicate that phosphorylation and oxidation of mitochondrial proteins are, at least in part, involved in mitochondrial dysfunction in renal tubular cells during DN.This study aimed to investigate the combined effects of two most potent probiotic bacteria Lactobacillus acidophilus and Lactobacillus plantarum on overall health and immune status of freshwater crayfish, marron under laboratory conditions. A total of 36 marron were distributed into six different tanks and two different feeding groups, control and probiotic-fed group. After acclimation, control group was fed with basal diet while probiotic group was fed 109 CFU/mL per kg of bacterial supplemented feed for 60 days. The results showed no significant differences in weight gain, however, probiotic feed significantly enhanced some hemolymph parameters and biochemical composition of tail muscle. Histology data revealed better hepatopancreas health and higher microvilli counts in the marron gut fed probiotic diet. The probiotic bacteria triggered significant shift of microbial communities at different taxa level, mostly those reported as beneficial for crayfish. The probiotic diet also enriched the metabolic functions and genes associated with innate immune response of crayfish. Further correlation analysis revealed significant association of some taxa with increased activity for hemolymph and immune genes. Therefore, dietary Lactobacillus supplementation can modulate the overall health and immunity as well as gut microbial composition and interaction network between gut microbiota and immune system in crayfish.There are still lot of controversies whether aberrant left hepatic artery (ALHA) originating from left gastric artery should be ligated or preserved during gastric cancer (GC) surgery. We aimed to investigate this issue. We reviewed ALHA cases who had laparoscopic gastrectomy for gastric cancer at Seoul National University Hospital (SNUH) from 2012 to 2016. Type of ALHA variants using Michel's classification of hepatic arterial anatomy and diameter of each vessel were evaluated by 2 radiologists. Postoperative hepatic function and surgical outcome were collected until 6 months after surgery. Results showed that if the diameter of ALHA was larger than 1.5 mm, a transient elevation of SGOT and SGPT on postoperative day 2 was observed in the ligated cases. No differences were observed in operation time, amount of blood loss, overall complication rate, hospital stay, and number of lymph nodes retrieved between the ligated and preserved replaced left hepatic artery (RLHA) and accessory left hepatic artery (acLHA) group. In this study, we conclude that ligation of ALHA seems to be safe as none of the patients suffered adverse outcome. A transient rise in postoperative SGOT and SGPT levels were seen after ligating ALHA &gt;1.5 mm in diameter regardless of subtype.Seagrass meadows are considered important natural carbon sinks due to their capacity to store organic carbon (Corg) in sediments. However, the spatial heterogeneity of carbon storage in seagrass sediments needs to be better understood to improve accuracy of Blue Carbon assessments, particularly when strong gradients are present. We performed an intensive coring study within a sub-tropical estuary to assess the spatial variability in sedimentary Corg associated with seagrasses, and to identify the key factors promoting this variability. We found a strong spatial pattern within the estuary, from 52.16 mg Corg cm-3 in seagrass meadows in the upper parts, declining to 1.06 mg Corg cm-3 in seagrass meadows at the estuary mouth, despite a general gradient of increasing seagrass cover and seagrass habitat extent in the opposite direction. The sedimentary Corg underneath seagrass meadows came principally from allochthonous (non-seagrass) sources (~70-90&nbsp;%), while the contribution of seagrasses was low (~10-30&nbsp;%) throughout the entire estuary. Our results showed that Corg stored in sediments of seagrass meadows can be highly variable within an estuary, attributed largely to accumulation of fine sediments and inputs of allochthonous sources. Local features and the existence of spatial gradients must be considered in Blue Carbon estimates in coastal ecosystems.Tumour vasculature supports the growth and progression of solid cancers with both angiogenesis (endothelial cell proliferation) and vasculogenic mimicry (VM, the formation of vascular structures by cancer cells themselves) predictors of poor patient outcomes. Increased circulating platelet counts also predict poor outcome for cancer patients but the influence of platelets on tumour vasculature is incompletely understood. Herein, we show with in vitro assays that platelets did not influence angiogenesis but did actively inhibit VM formation by cancer cell lines. Both platelet sized beads and the releasates from platelets were partially effective at inhibiting VM formation suggesting that direct contact maximises the effect. Platelets also promoted cancer cell invasion in vitro. B16F10 melanomas in Bcl-xPlt20/Plt20 thrombocytopenic mice showed a higher content of VM than their wildtype counterparts while angiogenesis did not differ. In a xenograft mouse model of breast cancer with low-dose aspirin to inactivate the platelets, the burden of MDA-MB-231-LM2 breast cancer cells was reduced and the gene expression profile of the cancer cells was altered; but no effect on tumour vasculature was observed. Taken together, this study provides new insights into the action of platelets on VM formation and their involvement in cancer progression.Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction. Previous studies have shown that natural killer (NK) cells may play an important role in the pathogenesis of RA. Interleukin (IL)-15, a pro-inflammatory cytokine which induces proliferation and differentiation of NK cells, is overexpressed in RA. In this present study, we examine various NKRs and adhesion molecule expression on NK cells from RA patients and their response to IL-15 stimulation. We also sought to study cytokine-induced memory-like (CIML) NK cells in RA patients. We established that 1. RA patients had higher NK cell percentages in peripheral blood and their serum IL-15 levels were higher compared to healthy volunteers; 2. NK cells from RA patients showed lower NKp46 expression and an impaired CD69 response to IL-15; 3. NK cells from RA patients showed higher CD158b and CD158e expression but lower CD62L expression; 4. exogenous IL-15 up-regulated CD69, CD158b, CD158e but down-regulated NKp46 and CD62L expression in RA; 5. As to CIML NK cells, restimulation - induced NK cytotoxicity and IFN-γ production was impaired in RA patients, 6. Reduced NKp46, perforin, and granzyme B expression on NK cells was found in RA patients with bone deformity and erosion, 7. RA disease activity (DAS28) showed inverse correlation with the percentages of CD56+CD3- NK cells, and NKp46 and perforin expression on NK cells, respectively. Taken together, our study demonstrated differential expression of various NK receptors in RA patients. link2 NKp46, CD158e, and perforin expression on NK cells may serve as markers of RA severity.Peripheral CD4+CD8+ double positive (DP) T cells are a phenotypically and functionally heterogeneous population depending on their origin and pathologic context. We previously identified among tumour infiltrating lymphocytes in melanoma, a tumour-reactive MHC class-I restricted CD4lowCD8high DP αβ T-cell subpopulation with CD4-like function. In this study, we used an in-depth comparative transriptomic analysis of intra-melanoma DP T cells and CD4 and CD8 single positive (SP) T cells, to better comprehend the origin of this DP phenotype, and define the transcriptomic signature of activated DP T cells. We observed that intra-melanoma DP T cells were transcriptome-wise closer to their CD8 SP T-cell counterparts in terms of number of genes differentially expressed (97 in common with CD8 SP T cells and 15 with CD4 SP T cells) but presented hallmarks of a transition to a CD4-like functional profile (CD40LG) with a decreased cytotoxic signature (KLRC1) in favour of an increased cytokine-receptor interaction signature (IL4, IL24, IL17A…). link3 This unleashed CD4-like program could be the results of the observed unbalanced expression of the THPOK/Runx3 transcription factors in DP T cells. Overall, this study allow us to speculate that intra-melanoma DP T cells arise from CD8 SP T cells being reprogrammed to a helper function.Arsenic (As) exposure adversely affects neurodevelopment in children. Accumulation of misfolded proteins in cells exposed to&nbsp;As&nbsp;leads to endoplasmic reticulum (ER) stress response, which,&nbsp;if not relieved, results in&nbsp;cell death. Despite the potential role of ER stress for As-induced neurotoxicity, the underlying mechanisms remain poorly understood. Here we aimed to investigate&nbsp;the roles of microRNA(miR)-124, a novel ER stress suppressor, in As-induced ER stress response and cytotoxicity in neural cells. We further aimed to link these in vitro findings to neurodevelopmental outcomes in children who were exposed to As. Using Quantitative RT-PCR and Cyquant assay, we showed that miR-124 protects against As-induced cytotoxicity in neural cells with concomitant suppression of As-induced ER stress. In addition, As-induced cytotoxicity was exacerbated in miR-124 knockout cells&nbsp;generated by CRISPR-based gene editing compared scramble control. Furthermore, we identified two miR-124 SNPs rs67543816 (p = 0.0003) and rs35418153 (p = 0.0004) that are significantly associated with a mental composite score calculated from the Bayley Scales of Infant Development III in Bangladesh children. Our study&nbsp;reveals As-induced ER stress as a crucial mechanism underlying&nbsp;the toxic&nbsp;effects of As on neural cell function and neurodevelopment and identifies miR-124 as a potential preventative and therapeutic target against detrimental effects of As exposure in children.