Triglyceride Glucose Index for the Detection of Diabetic Kidney Disease and Diabetic Peripheral Neuropathy in Hospitalized Patients with Type 2 Diabetes.

INTRODUCTION: The triglyceride-glucose index (TyG) has been identified as a dependable and simple indicator marker of insulin resistance (IR). Research has demonstrated a correlation between macrovascular complications and TyG. However, limited research exists regarding the relationship between TyG and diabetic microvascular complications. Consequently, the objective of this study is to investigate the association between TyG and diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN). METHODS: This is a cross-sectional, observational study. A total of 2048 patients from Tongren Hospital, Shanghai Jiao Tong University School of Medicine were enrolled. The primary outcomes are DKD and DPN. Quantile regression analysis was employed to investigate the implicit factors of TyG quartiles. Subsequently, based on implicit factors, logistic regression models were constructed to further examine the relationship between TyG and DKD and DPN. RESULTS: In the baseline, TyG exhibited higher values across patients with DKD, DPN, and co-existence of DKD and DPN (DKD + DPN) in type 2 diabetes (T2D). Univariate logistic regressions demonstrated a significant association between an elevated TyG and an increased risk of DKD (OR = 1.842, [95% CI] 1.317-2.578, P for trend < 0.01), DPN (OR = 1.516, [95% CI] 1.114-2.288, P for trend < 0.05), DKD + DPN (OR = 2.088, [95% CI] 1.429-3.052, P for trend < 0.05). Multivariable logistic regression models suggested a statistically significant increase in the risk of DKD (OR = 1.581, [95% CI] 1.031-2.424, p < 0.05), DKD + DPN (OR = 1.779, [95% CI] 1.091-2.903, p < 0.05) after adjusting the implicit factors of TyG quartiles. However, no significant relationship was observed between TyG and DPN in the multivariable regression analysis. CONCLUSIONS: Elevated TyG was significantly associated with an increased risk of DKD in T2D, but no significant relationship was shown with DPN. This finding provided further evidence for the clinical significance of integrating TyG into the initial assessment of diabetic microvascular complications.

Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy.

Diabetic patients often experience impaired wound healing. Human cathelicidin LL-37 possesses various biological functions, such as anti-microbial, anti-inflammatory, and pro-wound healing activities. Autophagy has important effects on skin wound healing. However, little is known about whether LL-37 accelerates diabetic wound healing by regulating autophagy. In the study, we aimed to investigate the role of autophagy in LL-37-induced wound healing and uncover the underlying mechanisms involved. A full-thickness wound closure model was established in diabetic mice to evaluate the effects of LL-37 and an autophagy inhibitor (3-MA) on wound healing. The roles of LL-37 and 3-MA in regulating keratinocyte migration were assessed using transwell migration and wound healing assays. The activation of transcription factor EB (TFEB) was measured using western blotting and immunofluorescence (IF) assays of its nuclear translocation. The results showed that LL-37 treatment improved wound healing in diabetic mice, whereas these effects were reversed by 3-MA. In vitro, 3-MA decreased the effects of LL-37 on promoting HaCat keratinocyte migration in the presence of high glucose (HG). Mechanistically, LL-37 promoted TFEB activation and resulted in subsequent activation of autophagy, as evidenced by increased nuclear translocation of TFEB and increased expression of ATG5, ATG7, and beclin 1 (BECN1), whereas these changes were blocked by TFEB knockdown. As expected, TFEB knockdown damaged the effects of LL-37 on promoting keratinocyte migration. Collectively, these results suggest that LL-37 accelerates wound healing in diabetic mice by activating TFEB-dependent autophagy, providing new insights into the mechanism by which LL-37 promotes diabetic wound healing.

Solution-grown millimeter-scale Mn-doped CsPbBr3/Cs4PbBr6 crystals with enhanced photoluminescence and stability for light-emitting applications.

Metal halide perovskites are particularly emerging for optoelectronic applications in light-emitting diodes, photodetectors, and solar cells due to their flourishing photophysical properties. However, the poor stability of three-dimensional (3D) lead halide perovskite nanocrystals (NCs) significantly hampers their optoelectronics and photovoltaics applications. Embedding 3D perovskites into zero-dimensional (0D) perovskite crystals and doping ions of appropriate elements into host lattices provide effective approaches to improve the stability and optical-electronic performance. In this study, millimeter-scale Mn-doped and undoped CsPbBr3/Cs4PbBr6 perovskite crystals were successfully fabricated by a one-step slow cooling method. We systematically investigated the effects of Mn2+ ion doping on the PL performance and stability of CsPbBr3/Cs4PbBr6 crystals. Compared with undoped crystals, the existence of Mn2+ ions not only blue-shifted the PL peak but also improved the luminescence performance and stability of the prepared millimeter-sized crystals. Moreover, doping Mn2+ ions can increase the proportion of radiative recombination at low temperature, which may be because Mn2+ ions can effectively accelerate the decay of a dark exciton by the magnetic mixing of bright and dark excitons. In addition, green LED devices with high efficiency packaged as-grown crystals are explored, which promises further application in display backlights.

Development of a counterselectable system for rapid and efficient CRISPR-based genome engineering in Zymomonas mobilis.

BACKGROUND: Zymomonas mobilis is an important industrial bacterium ideal for biorefinery and synthetic biology studies. High-throughput CRISPR-based genome editing technologies have been developed to enable targeted engineering of genes and hence metabolic pathways in the model ZM4 strain, expediting the exploitation of this biofuel-producing strain as a cell factory for sustainable chemicals, proteins and biofuels production. As these technologies mainly take plasmid-based strategies, their applications would be impeded due to the fact that curing of the extremely stable plasmids is laborious and inefficient. Whilst counterselection markers have been proven to be efficient for plasmid curing, hitherto only very few counterselection markers have been available for Z. mobilis. RESULTS: We constructed a conditional lethal mutant of the pheS gene of Z. mobilis ZM4, clmPheS, containing T263A and A318G substitutions and coding for a mutated alpha-subunit of phenylalanyl-tRNA synthetase to allow for the incorporation of a toxic analog of phenylalanine, p-chloro-phenylalanine (4-CP), into proteins, and hence leading to inhibition of cell growth. We demonstrated that expression of clmPheS driven by a strong Pgap promoter from a plasmid could render the Z. mobilis ZM4 cells sufficient sensitivity to 4-CP. The clmPheS-expressing cells were assayed to be extremely sensitive to 0.2 mM 4-CP. Subsequently, the clmPheS-assisted counterselection endowed fast curing of genome engineering plasmids immediately after obtaining the desired mutants, shortening the time of every two rounds of multiplex chromosome editing by at least 9 days, and enabled the development of a strategy for scarless modification of the native Z. mobilis ZM4 plasmids. CONCLUSIONS: This study developed a strategy, coupling an endogenous CRISPR-based genome editing toolkit with a counterselection marker created here, for rapid and efficient multi-round multiplex editing of the chromosome, as well as scarless modification of the native plasmids, providing an improved genome engineering toolkit for Z. mobilis and an important reference to develope similar genetic manipulation systems in other non-model organisms.

Comprehensive analysis of hub biomarkers associated with immune and oxidative stress in Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.

An Inferred Ancestral CotA Laccase with Improved Expression and Kinetic Efficiency.

Laccases are widely used in industrial production due to their broad substrate availability and environmentally friendly nature. However, the pursuit of laccases with superior stability and increased heterogeneous expression to meet industry demands appears to be an ongoing challenge. To address this challenge, we resurrected five ancestral sequences of laccase BsCotA and their homologues. All five variants were successfully expressed in soluble and functional forms with improved expression levels in Escherichia coli. Among the five variants, three exhibited higher catalytic rates, thermal stabilities, and acidic stabilities. Notably, AncCotA2, the best-performing variant, displayed a kcat/KM of 7.5 × 105 M-1·s-1, 5.2-fold higher than that of the wild-type BsCotA, an improved thermo- and acidic stability, and better dye decolorization ability. This study provides a laccase variant with high application potential and presents a new starting point for future enzyme engineering.

Chromic hydroxide-decorated palladium nanoparticles confined by amine-functionalized mesoporous silica for rapid dehydrogenation of formic acid.

Formic acid (FA), one of the products of biomass conversion and CO2 reduction, has attracted much attention as a renewable liquid hydrogen carrier with a high hydrogen content (4.4 wt%). Searching for efficient catalysts to realize hydrogen evolution from FA are highly desired but challenging. Herein, ultrafine and mono-dispersed Pd-Cr(OH)3 nanoparticles (1.3 nm) loaded on amine-functionalized mesoporous silica (AFMS) have been prepared and applied as an effective catalyst for rapid hydrogen production from additive-free FA. The as-synthesized Pd-Cr(OH)3/AFMS catalysts exhibited efficient catalytic activity and 100% hydrogen selectivity and conversion toward FA dehydrogenation reaction without additives, giving an initial TOF value of 3112 h-1 at 323 K, which is comparable to most of the highly efficient heterogeneous catalysts reported so far under similar reaction conditions. This work provides a feasible idea for the design metal hydroxide-modified Pd-based efficient heterogeneous catalyst, which is expected to enhance the application of FA in fuel cells.

Circulating Ism1 Reduces the Risk of Type 2 Diabetes but not Diabetes-Associated NAFLD.

Purpose: To examine the association of serum Ism1, a new adipokine that can regulate glucose uptake, with type 2 diabetes (T2D) in a Chinese population. Considering high prevalence of Nonalcoholic Fatty Liver Disease in patients with type 2 diabetes and the regulating role of Ism1 on glucose uptake of peripheral tissues, we further explored the association between Ism1 and diabetes-associated nonalcoholic fatty liver disease. Methods: A total of 120 newly diagnosed T2D patients and 60 control subjects with normal glucose were recruited in the case-control study. Serum Ism1 concentrations were determined by ELISA. Multivariate logistic regression analysis was used to evaluate the independent association of serum Ism1 concentration with the risk of T2D. The 120 newly diagnosed T2D patients were divided into uncomplicated T2D group and diabetes-associated NAFLD group according to the FLI score. Results: The Ism1 level of normoglycemic controls was higher than that of T2D patients (3.91 ± 0.24 ng/ml vs 3.01 ± 0.16 ng/ml, P=0.001). Based on quartile analysis of Ism1 level, the proportion of high circulating Ism1 levels in the control group increased while T2D group decreased, and the distribution difference was statistically significant (P=0.015). Logistic regression analysis indicated that the serum Ism1 level was an independent protective factor of type 2 diabetes (OR=0.69, 95%CI: 0.54-0.89). The decrease of Ism1 level did not increase the risk of non-alcoholic fatty liver disease in diabetic patients by Binary logistic regression analysis (OR=1.08, 95% CI: 0.69-1.69). Conclusions: The increase of serum Ism1 was associated with a decreased risk of diabetes, and it did not reduce the risk of non-alcoholic fatty liver disease in diabetic patients.

The analysis of risk factors for diabetic kidney disease progression: a single-centre and cross-sectional experiment in Shanghai.

OBJECTIVE: To identify the risk factors for diabetic kidney disease (DKD) development, especially the difference between patients with different courses. PATIENTS AND METHODS: 791 patients were considered to be eligible and were enrolled in the cross-sectional study from Shanghai Tongren Hospital Inpatient Department. 36 variables were initially screened by univariate analysis. The risk factors affecting progression of DKD were determined by logistics regression analysis. Subgroups were grouped according to the course of diabetes disease, and multivariate logistics regression analysis was performed to find out the different risk factors in two subgroups. Finally, the receiver operating characteristics curve is used to verify the result. RESULTS: The logistic regression model indicated age (OR=1.020, p=0.017, 95% CI 1.004 to 1.040), systolic blood pressure (OR=1.013, p=0.006, 95% CI 1.004 to 1.022), waist circumference (OR=1.021, p=0.015, 95% CI 1.004 to 1.038), white blood cells (WBC, OR=1.185, p=0.001, 95% CI 1.085 to 1.295) and triglycerides (TG, OR=1.110, p=0.047, 95% CI 1.001 to 1.230) were risk factors for DKD, while free triiodothyronine (fT3, OR=0.711, p=0.011, 95% CI 0.547 to 0.926) was a protective factor for DKD in patients with type 2 diabetes mellitus (T2DM). Subgroup analysis revealed that in patients with a short duration of diabetes (<8 years), WBC (OR=1.306, p<0.001, 95% CI 1.157 to 1.475) and TG (OR=1.188, p=0.033, 95% CI 1.014 to 1.393) were risk factors for DKD,fT3 (OR=0.544, p=0.002, 95% CI 0.367 to 0.804) was a protective factor for DKD; whereas for patients with disease course more than 8 years, age (OR=1.026, Pp=0.012, 95%CI=95% CI[ 1.006- to 1.048]) was identified as the only risk factor for DKD and fT3 (OR=0.036, Pp=0.017, 95%CI=95% CI[ 0.439- to 0.922]) was a protective factor for DKD. CONCLUSION: The focus of attention should especially be on patients with a prolonged course of T2DM, and those with comorbid hypertension and hypertriglyceridaemia waist phenotype. More potential clinical indexes such as thyroid function and inflammatory indicators might be considered as early warning factors for DKD in T2DM. Women should pay attention to controlling inflammation and TGs, and men should strictly control blood pressure. Avoiding abdominal obesity in both men and women will bring great benefits.

Enabling Efficient Genetic Manipulations in a Rare Actinomycete Pseudonocardia alni Shahu.

Pseudonocardia species are emerging as important microorganisms of global concern with unique and increasingly significant ecological roles and represent a prominent source of bioactive natural products, but genetic engineering of these organisms for biotechnological applications is greatly hindered due to the limitation of efficient genetic manipulation tools. In this regard, we report here the establishment of an efficient genetic manipulation system for a newly isolated strain, Pseudonocardia alni Shahu, based on plasmid conjugal transfer from Escherichia coli to Pseudonocardia. Conjugants were yielded upon determining the optimal ratio between the donor and recipient cells, and designed genome modifications were efficiently accomplished, including exogenous gene integration based on an integrative plasmid and chromosomal stretch removal by homologous recombination using a suicidal non-replicating vector. Collectively, this work has made the P. alni Shahu accessible for genetic engineering, and provided an important reference for developing genetic manipulation methods in other rare actinomycetes.

Double nicking by RNA-directed Cascade-nCas3 for high-efficiency large-scale genome engineering.

New CRISPR-based genome editing technologies are developed to continually drive advances in life sciences, which, however, are predominantly derived from systems of Type II CRISPR-Cas9 and Type V CRISPR-Cas12a for eukaryotes. Here we report a novel CRISPR-n(nickase)Cas3 genome editing tool established upon a Type I-F system. We demonstrate that nCas3 variants can be created by alanine-substituting any catalytic residue of the Cas3 helicase domain. While nCas3 overproduction via plasmid shows severe cytotoxicity, an in situ nCas3 introduces targeted double-strand breaks, facilitating genome editing without visible cell killing. By harnessing this CRISPR-nCas3 in situ gene insertion, nucleotide substitution and deletion of genes or genomic DNA stretches can be consistently accomplished with near-100% efficiencies, including simultaneous removal of two large genomic fragments. Our work describes the first establishment of a CRISPR-nCas3-based genome editing technology, thereby offering a simple, yet useful approach to convert the naturally most abundantly occurring Type I systems into advanced genome editing tools to facilitate high-throughput prokaryotic engineering.

Circular RNA circEIF4G2 aggravates renal fibrosis in diabetic nephropathy by sponging miR-218.

Circular RNAs play essential roles in the development of various human diseases. However, how circRNAs are involved in diabetic nephropathy (DN) are not fully understood. Our study aimed to investigate the effects of circRNA circEIF4G2 on DN. Experiments were performed in the db/db mouse model of type 2 diabetes and NRK-52E cells. We found that circEIF4G2 was significantly up-regulated in the kidneys of db/db mice and NRK-52E cells stimulated by high glucose. circEIF4G2 knockdown inhibited the expressions of TGF-ß1, Collagen I and Fibronectin in high glucose-stimulated NRK-52E cells, which could be rescued by miR-218 inhibitor. Knockdown of SERBP1 reduced the expression of TGF-ß1, Collagen I and Fibronectin in HG-stimulated NRK-52E cells. In summary, our findings suggested that circEIF4G2 promotes renal tubular epithelial cell fibrosis via the miR-218/SERBP1 pathway, presenting a novel insight for DN treatment.

Metabolic remodeling of glycerophospholipids acts as a signature of dulaglutide and liraglutide treatment in recent-onset type 2 diabetes mellitus.

Aims: As metabolic remodeling is a pathological characteristic in type 2 diabetes (T2D), we investigate the roles of newly developed long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as dulaglutide and liraglutide on metabolic remodeling in patients with recent-onset T2D. Methods: We recruited 52 cases of T2D and 28 control cases in this study. In the patient with T2D, 39 cases received treatment with dulaglutide and 13 cases received treatment with liraglutide. Using untargeted metabolomics analysis with broad-spectrum LC-MS, we tracked serum metabolic changes of the patients from the beginning to the end of follow-up (12th week). Results: We identified 198 metabolites that were differentially expressed in the patients with T2D, compared to the control group, in which 23 metabolites were significantly associated with fasting plasma glucose. Compared to pre-treatment, a total of 46 and 45 differentially regulated metabolites were identified after treatments with dulaglutide and liraglutide, respectively, in which the most differentially regulated metabolites belong to glycerophospholipids. Furthermore, a longitudinal integration analysis concurrent with diabetes case-control status revealed that metabolic pathways, such as the insulin resistance pathway and type 2 diabetes mellitus, were enriched after dulaglutide and liraglutide treatments. Proteins such as GLP-1R, GNAS, and GCG were speculated as potential targets of dulaglutide and liraglutide. Conclusions: In total, a metabolic change in lipids existed in the early stage of T2D was ameliorated after the treatments of GLP-1RAs. In addition to similar effects on improving glycemic control, remodeling of glycerophospholipid metabolism was identified as a signature of dulaglutide and liraglutide treatments.

A Broad-Specificity Chitinase from Penicillium oxalicum k10 Exhibits Antifungal Activity and Biodegradation Properties of Chitin.

Penicillium oxalicum k10 isolated from soil revealed the hydrolyzing ability of shrimp chitin and antifungal activity against Sclerotinia sclerotiorum. The k10 chitinase was produced from a powder chitin-containing medium and purified by ammonium sulfate precipitation and column chromatography. The purified chitinase showed maximal activity toward colloidal chitin at pH 5 and 40 °C. The enzymatic activity was enhanced by potassium and zinc, and it was inhibited by silver, iron, and copper. The chitinase could convert colloidal chitin to N-acetylglucosamine (GlcNAc), (GlcNAc)2, and (GlcNAc)3, showing that this enzyme had endocleavage and exocleavage activities. In addition, the chitinase prevented the mycelial growth of the phytopathogenic fungi S. sclerotiorum and Mucor circinelloides. These results indicate that k10 is a potential candidate for producing chitinase that could be useful for generating chitooligosaccharides from chitinous waste and functions as a fungicide.

Vof16-miR-205-Gnb3 axis regulates hippocampal neuron functions in cognitively impaired diabetic rats.

BACKGROUND: Diabetes is a chronic metabolic disease and an independent risk factor for cognitive damage. Non-protein coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are involved in various pathophysiological conditions. METHODS: In this study, cognitive impairment was induced in diabetics rats by streptozotocin (STZ) injection, and the differential lncRNAs and mRNAs in rat hippocampal tissue between control and STZ-treated groups were analyzed with microarray. RESULTS: In the hippocampus of STZ-treated diabetic rats, lncRNA Vof-16, and Gnb3 mRNA were significantly upregulated and silicon analysis showed that Vof-16 and miR-205 share the same miRNA response element (MRE). In addition, the overexpression of Vof-16 in primary hippocampal neurons inhibited the expression of miR-205, and vice versa. Dual luciferase assay verified the binding between Vof-16 and miR-205, and Vof-16 was seen to promote the proliferation of primary hippocampal neurons via sponging miR-205. Silicon analysis predicted that miR-205 could bind with Gnb3, which was verified with dual luciferase assay, and the overexpression of miR-205 could inhibit the protein level of Gnb3, which could be rescued by co-expression with Vof-16. In conclusion, lncRNA Vof-16 regulated Gnb3 expression by competitively binding to miR-205. CONCLUSIONS: These results provided a novel regulation axis for the pathogenesis of STZ-induced diabetes.

Metabolic engineering of Pichia pastoris for malic acid production from methanol.

The application of rational design in reallocating metabolic flux to accumulate desired chemicals is always restricted by the native regulatory network. In this study, recombinant Pichia pastoris was constructed for malic acid production from sole methanol through rational redistribution of metabolic flux. Different malic acid accumulation modules were systematically evaluated and optimized in P. pastoris. The recombinant PP-CM301 could produce 8.55 g/L malic acid from glucose, which showed a 3.45-fold increase compared to the parent strain. To improve the efficiency of site-directed gene knockout, NHEJ-related protein Ku70 was destroyed, whereas leading to the silencing of heterogenous genes. Hence, genes related to by-product generation were deleted via a specially designed FRT/FLP system, which successfully reduced succinic acid and ethanol production. Furthermore, a key node in the methanol assimilation pathway, glucose-6-phosphate isomerase was knocked out to liberate metabolic fluxes trapped in the XuMP cycle, which finally enabled 2.79 g/L malic acid accumulation from sole methanol feeding with nitrogen source optimization. These results will provide guidance and reference for the metabolic engineering of P. pastoris to produce value-added chemicals from methanol.

circ_0037128/miR-17-3p/AKT3 axis promotes the development of diabetic nephropathy.

Circular RNAs (circRNAs) play vital roles in the development of diabetic nephropathy (DN). In this study, we investigated the function of circ_0037128 and molecular mechanism via which it regulates diabetic nephropathy development. It was found that expression of circ_0037128 was significantly increased in mouse DN model and high glucose treated mesangial cells (MCs), and circ_0037128 loss-of-function led to reduced cell proliferation and fibrosis in vitro. Moreover, miR-17-3p acts as competitive endogenous RNA (ceRNA) that directly interacts with circ_0037128 through its miRNA response elements (MREs). Consistently, expression of miR-17-3p was remarkably down-regulated in DN model, and negatively regulated cell proliferation and fibrosis. Further investigations revealed that AKT3 was the putative target of miR-17-3p, whose expression was elevated in DN model. In conclusion, we have characterized the function of a novel circ_0037128 and illustrated the significance of circ_0037128-miR-17-3p-AKT3 axis in DN pathogenesis.

Long non-coding RNA Dlx6os1 serves as a potential treatment target for diabetic nephropathy via regulation of apoptosis and inflammation.

The present study investigated the effect of long non-coding RNA (lncRNA) Dlx6os1 silencing on cell proliferation, apoptosis and fibrosis, and further explored its influence on the mRNA expression profile in mouse mesangial cells (MMCs) of a diabetic nephropathy (DN) cellular model. A DN cellular model was constructed in SV40 MES13 MMCs under high glucose conditions (30 mmol/l glucose culture). lncRNA Dlx6os1 short hairpin (sh)RNA plasmids and negative control (NC) shRNA plasmids were transfected into the MMCs of the DN cellular model as the sh-lncRNA group and sh-NC group respectively. The mRNA expression profile was determined in the sh-lncRNA and sh-NC groups. Compared with the sh-NC group, the cell proliferation, mRNA and protein expression levels of proliferative markers (cyclin D1 and proliferating cell nuclear antigen) as well as fibrosis markers (fibronectin and collagen I) were suppressed, whereas cell apoptosis was promoted in the sh-lncRNA group. The mRNA expression profile identified 423 upregulated mRNAs and 438 downregulated mRNAs in the sh-lncRNA group compared with the sh-NC group. Additionally, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the differentially expressed mRNAs were enriched in apoptosis and inflammation-related pathways. Further gene-set enrichment analysis of apoptosis and inflammation revealed that lncRNA Dlx6os1 inhibition promoted apoptosis and suppressed inflammation in MMCs of the DN cellular model. In conclusion, lncRNA Dlx6os1 may serve as a potential treatment target for DN via regulation of multiple apoptosis- and inflammation-related pathways.

Circular RNA Circ_0000064 promotes the proliferation and fibrosis of mesangial cells via miR-143 in diabetic nephropathy.

Diabetic nephropathy (DN) as one of the most frequent microvascular complications of diabetic patients causes chronic renal failure and end-stage renal disease. Noncoding RNAs including circular RNAs (circRNAs) and micro RNAs (miRNAs) were widely reported to play a critical role in numerous human diseases including DN. This research was designed to investigate the role of circ_0000064 in diabetic nephropathy progression. The results showed that circ_0000064 significantly promoted mesangial cells proliferation and aggravated fibrosis in DN. In the subsequent mechanism investigation, we found that circ_0000064 was involved in this process by targeting micro RNA miR-143. The inhibition of miR-143 significantly reverses the effect of circ_0000064 silencing on DN. In conclusion, we demonstrated the regulatory role of circ_0000064 in DN and clarified that circ_0000064 play a role in DN via targeting miR-143. Circ_0000064 and miR-143 also showed the potential as a biomarker for DN.