Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7.

INTRODUCTION: Transforming growth factor-ß (TGF-ß), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. OBJECTIVE: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. METHODS: HK-2 cells were induced with 5 ng/mL TGF-ß1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-ß1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-ß1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. RESULTS: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-ß1-induced cells. CONCLUSION: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.

Role of Artificial Intelligence in Kidney Disease.

Artificial intelligence (AI), as an advanced science technology, has been widely used in medical fields to promote medical development, mainly applied to early detections, disease diagnoses, and management. Owing to the huge number of patients, kidney disease remains a global health problem. Challenges remain in its diagnosis and treatment. AI could take individual conditions into account, produce suitable decisions and promise to make great strides in kidney disease management. Here, we review the current studies of AI applications in kidney disease in alerting systems, diagnostic assistance, guiding treatment and evaluating prognosis. Although the number of studies related to AI applications in kidney disease is small, the potential of AI in the management of kidney disease is well recognized by clinicians; AI will greatly enhance clinicians' capacity in their clinical practice in the future.

Distribution of selenium and cadmium in soil-rice system of selenium-rich area in Hainan, China.

Rice, which is the staple food in East Asia, is a source of Selenium (Se) and Cadmium (Cd). The distribution of Se and Cd in soil-rice system is significant to human nutrition and public health. This study is to explore the distribution of Se and Cd in arable land soils and their distribution in polished rice and stalks of Se-rich area. A total of 63 soil samples and 126 rice samples (63 groups of rice grains and stalk samples) were collected from West Hainan Island to determine Se and Cd concentrations. The results suggested the concentration of Se in soil was higher than average level in China, and Cd content was lower than the agricultural land-use threshold of China. The distribution of Se and Cd in arable land soil was primarily determined by diagenesis and mineralization. Se and Cd were more inclined to accumulate in stalks than rice grains, and the contents in polished rice were correlated with that in stalk. Acidification of arable land soil will threaten human nutrition and health for the bioaccumulation factor of Se in polished rice decreased significantly with the decrease of soil pH, while that of Cd in polished rice increased significantly. Therefore, application of lime or alkaline fertilizers in arable land soil of Se-rich area can promote the accumulation of Se in polished rice but reduced the intake of Cd in rice crops.

Long Non-coding RNA ENST00000453774.1 Confers an Inhibitory Effect on Renal Fibrosis by Inhibiting miR-324-3p to Promote NRG1 Expression.

Progressive or chronic renal diseases arise from a process of destructive renal fibrosis. Therefore, the molecular basis of renal fibrosis has attracted increasing attention. In this investigation, we set out to elucidate the potential interaction among long non-coding RNA ENST00000453774.1 (lncRNA 74.1), microRNA-324-3p (miR-324-3p), and NRG1, and to investigate their roles in the context of cellular autophagy and renal fibrosis. We collected 30 renal fibrosis tissue samples for analysis. In other studies, HK-2 cells were stimulated with TGF-ß1 to induce a cell model of renal fibrosis, followed by alteration on the expression of lncRNA 74.1, miR-324-3p, or NRG1, or by the addition of AKT activator SC79 in the HK-2 cells. The expression levels of lncRNA 74.1, miR-324-3p, NRG1, autophagy-related proteins (ATG5, ATG7, LC3II/I, and P62), and the corresponding fibrosis markers (Collagen I, Fibronectin, and α-SMA) were subsequently determined using various assay methods. In addition, the proportion of LC3 positive cells and number of autophagosomes were recorded. Results revealed that lncRNA 74.1 and NRG1 were poorly expressed and miR-324-3p was highly expressed in renal fibrosis tissues and modeled cells. LncRNA 74.1 could bind to miR-324-3p, which led to upregulated NRG1 expression and inhibition of the PI3K/AKT signaling pathway. Meanwhile, overexpression of lncRNA 74.1 or down-regulation of miR-324-3p increased the levels of ATG5, ATG7, LC3II, and LC3I, and decreased levels of P62, Collagen I, Fibronectin, and α-SMA, accompanied by elevated proportions of LC3 positive cells and autophagosomes. Findings concur in showing that lncRNA 74.1 could induce cellular autophagy and alleviate renal fibrosis by regulating the miR-324-3p-mediated NRG1/PI3K/AKT axis. This axis may thus present a potential molecular target in renal fibrosis treatment.

Ferroptosis and kidney diseases.

Ferroptosis is a form of iron-dependent, non-apoptotic regulated cell death, which is characterized by the accumulation of lipid hydroperoxides to lethal levels. Ferroptosis recently has been shown to have implications in diverse kidney diseases, such as acute kidney injury, polycystic kidney disease and renal cell carcinoma. This review summarizes current research on ferroptosis, its underlying mechanisms and its role in the progression of different kidney diseases to provide more information regarding treatment and prevention of these destructive diseases.

Identification of C3 as a therapeutic target for diabetic nephropathy by bioinformatics analysis.

The pathogenesis of diabetic nephropathy is not completely understood, and the effects of existing treatments are not satisfactory. Various public platforms already contain extensive data for deeper bioinformatics analysis. From the GSE30529 dataset based on diabetic nephropathy tubular samples, we identified 345 genes through differential expression analysis and weighted gene coexpression correlation network analysis. GO annotations mainly included neutrophil activation, regulation of immune effector process, positive regulation of cytokine production and neutrophil-mediated immunity. KEGG pathways mostly included phagosome, complement and coagulation cascades, cell adhesion molecules and the AGE-RAGE signalling pathway in diabetic complications. Additional datasets were analysed to understand the mechanisms of differential gene expression from an epigenetic perspective. Differentially expressed miRNAs were obtained to construct a miRNA-mRNA network from the miRNA profiles in the GSE57674 dataset. The miR-1237-3p/SH2B3, miR-1238-5p/ZNF652 and miR-766-3p/TGFBI axes may be involved in diabetic nephropathy. The methylation levels of the 345 genes were also tested based on the gene methylation profiles of the GSE121820 dataset. The top 20 hub genes in the PPI network were discerned using the CytoHubba tool. Correlation analysis with GFR showed that SYK, CXCL1, LYN, VWF, ANXA1, C3, HLA-E, RHOA, SERPING1, EGF and KNG1 may be involved in diabetic nephropathy. Eight small molecule compounds were identified as potential therapeutic drugs using Connectivity Map.

Photoelectric and flexible poly(styrene-b-ethylene/butylene-b-styrene)-zinc porphyrin-graphene hybrid composite: synthesis, performance, and mechanism.

Stretchable and flexible photoelectric materials are highly desirable for the development of artificial intelligence products. However, it remains a challenge to fabricate a stable, processable, and cost-efficient material with both high photoelectric sensitivity and remarkable deformability. Herein, a new kind of photoelectric sensitive, highly stretchable and environmentally adaptive materials was developed through in situ synthesis and π-π conjugation design. Specifically, a photoelectric elastomer zinc porphyrin SEBS(Zn-PorSEBS) was synthesized by introducing porphyrin to SEBS chain via a one-pot method. Then, graphene/zinc porphyrin SEBS (G/Zn-PorSEBS) composites were obtained by combing the elastomer with graphene sheets through solution blending. Notably, the resultant flexible composites were capable of capturing light changes with illumination on or off, and the maximum photocurrent density reached 0.13 µA cm-2. Moreover, the photoelectric composites exhibited a dramatic elongation (more than 1000%) and an excellent tensile strength about 20 MPa. This proposed strategy represents a general approach to manufacture photoelectric and flexible materials.