Background Neutrophil gelatinase-associated lipocalin (NGAL) is not only a bone-derived factor involved in metabolism, but also a biomarker of kidney disease and cardiovascular pathophysiology. We conducted this cross-sectional observational study to explore relationships between plasma NGAL and thoracic aorta calcification (TAC) in maintenance hemodialysis (MHD) patients with and without diabetes. Methods Plasma NGAL was measured by ELISA, TAC was evaluated via computed tomography scan using a 3D quantification method or chest radiography aortic arch calcification score. Spearman correlation, Logistic regression and Partial correlation analysis were used to describe the correlations between NGAL and TAC. Results Plasma NGAL levels were lower in MHD patients with diabetes compared to those without diabetes (49.33(42.37, 55.48) vs 56.78(44.37, 674.13) ng/mL, P = 0.026). In MHD patients without diabetes, lg (NGAL) was positively correlated with ARC value( R = 0.612, P = 0.003) analyzed by Spearman correlation; for partial correlation analysis, lg (NGAL) was positively correlated with ARC value, after adjusting for age and sex ( R = 0.550, P = 0.015), adjusting for age, sex and CHD ( R = 0.565, P = 0.015), adjusting for age, sex, CHD and Alb ( R = 0.536, P = 0.027), or adjusting for age, sex, CHD, Alb, and dialyzer membrane (polysulfone) ( R = 0.590, P = 0.016); however, when adjusting for age, sex, CHD, Alb and Ca, the correlation between lg (NGAL) and ARC value disappeared. Positive correlation were found between NGAL and Ca ( R = 0.644, P < 0.001), Ca and ACR ( R = 0.534, P = 0.013) in Spearman coefficient analysis. Conclusion There were positive correlations among plasma NGAL, serum Ca and ARC in MHD patients without diabetes; which suggests that NGAL is possibly a participant in cardiovascular calcification, in non-diabetic MHD.

BackgroundIncreasing evidence has shown that elevated Thyroid stimulating hormone (TSH) levels are positively correlated with atherosclerosis (ATH) in patients with subclinical hypothyroidism (SCH). Some researchers found that the dysfunction of Endothelial Cells (ECs) in SCH plays an important role in the pathogenesis of ATH in SCH, but the association remains controversial. ObjectivesTo determine the expression profiles of serum microRNAs critical to the function of Endothelial cells (ECs) may help reanalyze the possible mechanism underlying ATH in SCH and the association between ATH and SCH. MethodsWe used qRT-PCR to perform microRNA profiling and analysis in normal control subjects (NC), patients with SCH alone (SCH), patients with SCH and ATH (SCH+ATH), and patients with ATH without SCH (ATH). ResultsBoth miR-221-3p and miR-222-3p showed a decreasing expression trend between the SCH and SCH+ATH groups. In addition, miR-126-3p and miR-150-5p showed a stepwise decrease from the NC to SCH groups and then to the SCH+ATH or ATH group. miR-21-5p was unregulated in the SCH, SCH+ATH, and ATH groups. Furthermore, elevated levels of miR-21-5p in SCH+ATH group were higher than SCH and ATH group. No differences were found in the levels of miR-150, miR-126, miR-221 and miR-222 between the ATH and the SCH+ATH subjects. ConclusionsmiR-21-5p may be involved in the atherosclerosis process in patients with SCH (SCH and SCH+ATH groups). miR-150-5p may be sensitive risk markers for predicting endothelial dysfunction in patients with ATH (ATH and SCH+ATH groups).

BackgroundSystemic inflammation and immune response are involved in the pathogenesis of diabetic nephropathy (DN). However, the specific immune-associated signature during DN development is unclear. Our study aimed to reveal the roles of immune-related genes during DN progression.MethodsThe GSE30529 and GSE30528 datasets were acquired from the Gene Expression Omnibus (GEO) database. Then, the intersection between differentially expressed genes (DEGs) and immune score-related genes (ISRGs) was screened. Subsequently, functional enrichment analyses were performed. The different immune phenotype-related subgroups were finally divided using unsupervised clustering. The core genes were identified by WGCNA and the protein-protein interaction (PPI) network. xCell algorithm was applied to assess the proportion of immune cell infiltration.Results92 immune score-related DEGs (ISRDEGs) were identified, and these genes were enriched in inflammation- and immune-associated pathways. Furthermore, two distinct immune-associated subgroups (C1 and C2) were identified, and the C1 subgroup exhibited activated immune pathways and a higher percentage of immune cells compared to the C2 subgroup. Two core genes (LCK and HCK) were identified and all up-regulated in DN, and the expressions were verified using GSE30122, GSE142025, and GSE104954 datasets. GSEA indicated the core genes were mainly enriched in immune-related pathways. Correlation analysis indicated LCK and HCK expressions were positively correlated with aDC, CD4+ Tem, CD8+T cells, CD8+ Tem, and mast cells.ConclusionsWe identified two immune-related genes and two immune-associated subgroups, which might help to design more precise tailored immunotherapy for DN patients.

Subclinical hypothyroidism (SCH) is associated with increased risks of endothelial dysfunction and atherosclerosis, but the mechanisms remain unclear. In our previous study, microRNA-126-3p was downregulated in SCH, but the role and regulatory mechanism of miR-126 in SCH has not been investigated. A SCH mouse model was established by feeding mice methimazole. Both primary endothelial cells (ECs) and HUVECs were cultured. The expression levels of key molecules were detected via quantitative RT-PCR, western blotting, and immunofluorescence. Wire myography was used to analyze the changes in vascular tones. A dual-luciferase assay was used to investigate the relationship between lncRNAs, microRNAs and target genes. In detail, it was shown that the expression levels of miR-126-3p were significantly decreased in both the SCH vasculature and HUVECs. MiR-126 supplementation suppressed HUVEC apoptosis and improved vascular function. Moreover, miR-126 could bind to the 3′-untranslated region of TRAF7, thus, regulating the C-FLIP pathway and endothelial apoptosis. Furthermore, lncRNA NEAT1 was upregulated upon TSH treatment and could function as a ceRNA and bind to miR-126, thus, modulating its expression level and vascular function. Finally, the NEAT1/miR-126/TRAF7 axis functions in response to TSH and regulates endothelial functions in SCH in vitro and in vivo. In conclusion, dysregulation of the NEAT1/miR-126/TRAF7 axis is responsible for impaired endothelial functions in SCH. Targeting this axis might become a promising treatment strategy or improving endothelial functions in SCH.

Diabetic kidney disease (DKD) is a complication associated with diabetes and is a major public health problem in modern society. Podocyte injury is the central target of the development of DKD, and the loss or dysregulation of nephrin, a key structural and signalling molecule located in the podocyte slit diaphragm (SD), initiates potentially catastrophic downstream events within podocytes. IQGAP1, a scaffold protein containing multiple protein-binding domains that regulates endocytosis, can interact with nephrin in podocytes. It is hypothesized that IQGAP1 contributes to nephrin endocytosis and may participate in the pathogenesis of DKD. The dramatically increased histo-nephrin granularity score in DKD glomeruli showed a significant positive correlation with increased IQGAP1-nephrin interaction without changes in the total protein content of nephrin and IQGAP1. In cultured human podocytes, hyperglycaemia induced the intracellular translocation of IQGAP1 from the cytosol to the vicinity of the cytomembrane, reinforced the IQGAP1-nephrin interaction, and augmented nephrin endocytosis. Moreover, impaired podocyte function, such as migration, extensibility and permeability, were further aggravated by wild-type IQGAP1 plasmid transfection, and these effects were partially restored by siRNA-mediated IQGAP1 downregulation. Collectively, these findings show that IQGAP1, an intracellular partner of nephrin, is involved in nephrin endocytosis and the functional regulation of podocytes in DKD.