Elevated whole blood arsenic level is associated with type 2 diabetes in coal-burning areas in Guizhou.

The potential association between coal-burning arsenic exposure and type 2 diabetes (T2D) was examined through a case control study, conducted in coal-burning arsenic poisoning areas in the Guizhou Province. This study included patients diagnosed with type 2 diabetes. Control subjects without type 2 diabetes were recruited randomly after gender and age 1:1 matching. All subjects completed questionnaire surveys and underwent physical examination and whole blood arsenic level testing. The whole blood arsenic level was associated with a significant increase in the risk of type 2 diabetes (75th versus 25th, adjusted OR = 1.76, 95% CI: 1.03-3.01). However, a nonlinear relationship was observed between the blood arsenic level and type 2 diabetes. The risk of type 2 diabetes increased with blood arsenic levels above 3.69 µg/L (Log As ≥0.57). The subgroup analysis revealed that blood arsenic levels were associated with significantly increased risk of type 2 diabetes in people who ever smoked (P < .05), particularly those who smoked ≥15 years (adjusted OR = 3.15, 95% CI: 1.9-7.28). Therefore, prolonged arsenic exposure, even at a low level, is associated with a higher prevalence of type 2 diabetes in a nonlinear pattern. Blood arsenic levels less than 3.69 µg/L may be considered safe with respect to the risk of T2D. However, smoking, particularly smoking ≥15 years, may be associated with the development of diabetes in patients with arsenic exposure.

Naringin Protects Against Interleukin 1ß (IL-1ß)-Induced Human Nucleus Pulposus Cells Degeneration via Downregulation Nuclear Factor kappa B (NF-κB) Pathway and p53 Expression.

BACKGROUND Low back pain (LBP) is regarded as a frequent disease that causes disability. We aimed to explore the effect of naringin on intervertebral disc degeneration (IDD) in IL-1ß-induced human nucleus pulposus (NP) cells and its corresponding molecular mechanisms. MATERIAL AND METHODS Human NP cells were identified by toluidine blue and Safranin O staining. Cell viability was determined by MTT assay. The expression levels of matrix metalloproteinases (MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, collagen II, aggrecan), inflammatory genes (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6), kappa B kinase alpha (IkappaBalpha), p65 and p53 were determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Immunofluorescence study was performed to detect the position and expression of p65 protein in IL-1ß-induced human NP cells. RESULTS Human NP cells were successfully separated from intervertebral disc tissue. We found that naringin could significantly reduce the expressions of matrix metalloproteinases (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and inflammatory genes in IL-1ß-stimulated human NP cells, while collagen II and aggrecan were increased at mRNA and protein level. Immunofluorescence showed that naringin pretreatment decreased the p65 protein expression in the nucleus and suppressed the phosphorylation of IkappaBalpha and p65. CONCLUSIONS These results demonstrated that naringin could attenuate matrix metalloproteinase catabolism and inflammation in IL-1ß-treated human nucleus pulposus cells via downregulating NF-kappaB pathway and p53 expression, suggesting that naringin has the potential to prevent and treat IDD.

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury.

Spinal cord injury (SCI) is a devastating traumatic condition. METTL14-mediated m6A modification is associated with SCI. This study was intended to investigate the functional mechanism of RNA methyltransferase METTL14 in spinal cord neuron apoptosis during SCI. The SCI rat model was established, followed by evaluation of pathological conditions, apoptosis, and viability of spinal cord neurons. The neuronal function of primary cultured spinal motoneurons of rats was assessed after hypoxia/reoxygenation treatment. Expressions of EEF1A2, Akt/mTOR pathway-related proteins, inflammatory cytokines, and apoptosis-related proteins were detected. EEF1A2 was weakly expressed and Akt/mTOR pathway was inhibited in SCI rat models. Hypoxia/Reoxygenation decreased the viability of spinal cord neurons, promoted LDH release and neuronal apoptosis. EEF1A2 overexpression promoted the viability of spinal cord neurons, inhibited neuronal apoptosis, and decreased inflammatory cytokine levels. Silencing METTL14 inhibited m6A modification of EEF1A2 and increased EEF1A2 expression while METTL14 overexpression showed reverse results. EEF1A2 overexpression promoted viability and inhibited apoptosis of spinal cord neurons and inflammation by activating the Akt/mTOR pathway. In conclusion, silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated SCI by inhibiting m6A modification of EEF1A2 and activating the Akt/mTOR pathway.