Long non-coding RNAs (LncRNAs) are a class of endogenous RNA molecules, which have a transcribing length of over 200 nt, lack a complete functional open reading frame (ORF), and rarely encode a functional short peptide. Recent studies have revealed that disruption of LncRNAs levels correlates with several human diseases, including diabetes mellitus (DM), a complex multifactorial metabolic disorder affecting more than 400 million people worldwide. LncRNAs are emerging as pivotal regulators in various biological processes, in the progression of DM and its associated complications, involving pancreatic β-cell disorder, insulin resistance, and epigenetic regulation, etc. Further investigation into the mechanisms of action of LncRNAs in DM will be of great value in the thorough understanding of pathogenesis. However, prior to successful application of LncRNAs, further search for molecular biomarkers and drug targets to provide a new strategy for DM prevention, early diagnosis, and therapy is warranted.

Platelet-activating factor (PAF), protein kinase C (PKC)βI, transforming growth factor (TGF)-β1 and aberrant extracellular matrix (ECM) deposition have been associated with diabetic nephropathy (DN). However, the mechanistic basis underlying this association remains to be elucidated. The present study investigated the association among the aforementioned factors in a DN model consisting of human mesangial cells (HMCs) exposed to high glucose (HG) and lysophosphatidylcholine (LPC) treatments. HMCs were divided into the following treatment groups: Control; PAF; PAF+PKCβI inhibitor LY333531; HG + LPC; PAF + HG + LPC; and PAF + HG + LPC + LY333531. Cells were cultured for 24 h, and PKCβI and TGF-β1 expression was determined using the reverse transcription-quantitative polymerase chain reaction and western blotting. The expression levels of the ECM-associated molecules collagen IV and fibronectin in the supernatant were detected using ELISA analysis. Subcellular localization of PKCβI was assessed using immunocytochemistry. PKCβI and TGF-β1 expression was increased in the PAF + HG + LPC group compared with the other groups (P<0.05); however, this effect was abolished in the presence of LY333531 (P<0.05). Supernatant fibronectin and collagen IV levels were increased in the PAF + HG + LPC group compared with the others (P<0.05); this was reversed by treatment with LY333531 (P<0.05). In cells treated with PAF, HG and LPC, PKCβI was translocated from the cytosol to the nucleus, an effect which was blocked when PKCβI expression was inhibited (P<0.05). The findings of the present study demonstrated that PAF stimulated ECM deposition in HMCs via activation of the PKC-TGF-β1 axis in a DN model.

Dipeptidyl peptidase-4 (DPP4) has been proven to exert its functions by both enzymatic and nonenzymatic pathways. The nonenzymatic function of DPP4 in diabetesassociated cognitive impairment remains unexplored. We determined DPP4 protein concentrations or its enzymatic activity in type 2 diabetic patients and db/db mice and tested the impact of the non-enzymatic function of DPP4 on mitochondrial dysfunction and cognitive impairment both in vivo and in vitro. The results show that increased DPP4 activity was an independent risk factor for incident mild cognitive impairment (MCI) in type 2 diabetic patients. In addition, DPP4 was highly expressed in the hippocampus of db/db mice and contributed to mitochondria dysfunction and cognitive impairment. Mechanistically, DPP4 might bind to PAR2 in the hippocampus and trigger GSK-3β activation, which downregulates peroxisome proliferator-activated receptor gamma coactivator 1 alpha expression and leads to mitochondria dysfunction, thereby promoting cognitive impairment in diabetes. Our findings indicate that the nonenzymatic function of DPP4 might promote mitochondrial dysfunction and cognitive impairment in diabetes.

Background The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg–/HBcAb+ is still inconsistent. Methods We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg−/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included. Results We included 26 studies of 2252 HBsAg−/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01−0.04; I 2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) were 9.0% (95% CI: 0.04−0.15; I 2 = 61%, p = .03), 6.0% (95% CI: 0.01−0.13; I 2 = 40%, p = .19), 1.0% (95% CI: 0.00−0.03; I 2 = 41%, p = .19), 0.0% (95% CI: 0.00−0.02; I 2 = 0%, p = .43), 0.0% (95% CI: 0.00−0.01; I 2 = 0%, p = .87), respectively. While HBsAb‐ patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45−8.48; I 2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35−21.94; I 2 = 0%, p = .46). Conclusions This meta‐analysis demonstrates the highest potential risk of HBV reactivation in HBsAg−/HBcAb+ RA patients receiving RTX treatment, especially HBsAb− patients. Our study furthers the understanding of the prophylactic use of anti‐HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL‐6, TNF‐α, and JAK in these patients.

Platelet-activating factor (PAF) promotes glomerular extracellular matrix (ECM) deposition, primarily through activation of the protein kinase C (PKC) pathway. The present study was designed to investigate whether atorvastatin, which mediates a protective effect against glomerular ECM deposition and diabetic neuropathy, may interfere with the PKC-transforming growth factor-β1 (TGF-β1) pathway in a model of human mesangial cells (HMCs) exposed to a high glucose (HG) and lysophosphatidylcholine (LPC) environment. HMCs were divided into three treatment groups: Control, high glucose and lysophosphatidylcholine (HG+LPC), and HG+LPC+atorvastatin. Cells were cultured for 24 h. The levels of the ECM-associated molecules collagen IV (Col IV) and fibronectin (Fn) in the supernatant were detected using an ELISA kit. PKC-β1, TGF-β1 and PAF-receptor gene expression was detected by reverse transcription-quantitative polymerase chain reaction. PKC-β1 and TGF-β1 protein expression was detected by western blotting, and the subcellular localization of PKC-β1 was assessed using immunofluorescence. The results indicated that atorvastatin may reduce the secretion of ECM components (Fn and Col IV) in HMCs in a HG and LPC environment, by inhibiting the increase in PAF secretion and the activation of the PKC-TGF-β1 signaling pathway.