Abstract. The aim of the present study was to investigate the renoprotective effects of isorhamnetin (ISO) in type 2 diabetic rats and its effects on the nuclear factor-κB (NF-κB) signaling pathway, which is associated with diabetic nephropathy. The type 2 diabetic rat model was established by a high-fat diet plus streptozocin injection and the rats were subsequently treated with two dosages of ISO, respectively. The levels of blood glucose were determined. Urinary osteopontin, kidney injury molecule-1 (KIM-1) and albumin were measured to evaluate the renal function of the rats. Renal NF-κB signaling activity was assessed by measuring the levels of NF-κB p65, phospho-NF-κB p65, inhibitor of NF-κB (IκBα) and phospho-IκBα, and the NF-κB p65 DNA-binding activity. Downstream inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1)] of the NF-κB signaling pathway were investigated to evaluate the renal inflammatory response. Renal levels of malondialdehyde and total superoxide dismutase were detected to access the oxidative stress. Furthermore, glomerular mesangial cells (GMCs) were treated with lipopolysaccharide and ISO. In the cellular experiment, the NF-κB signaling activity, levels of TNF-α, IL-1β, IL-6, ICAM-1 and TGF-β1, and oxidative stress were also investigated. The results showed that ISO decreased the levels of urinary osteopontin, KIM-1 and albumin. ISO also inhibited the NF-κB signaling activity, decreased the production of inflammatory mediators and attenuated oxidative stress in diabetic rats and GMCs. The present investigations revealed that ISO had ameliorative effects on diabetes-induced renal damage and the activity may be associated with the negative regulation of NF-κB signaling pathway.

Renal ischemia/reperfusion injury is a main cause of acute kidney injury (AKI) triggering an inflammatory response associated with infiltrating macrophages. Lipocalin-2 (Lcn2) levels correlate positively and protect against renal ischemia/reperfusion injury. However, the mechanisms remain unclear. The aim of study was to investigate the protective mechanisms of Lcn2 on renal ischemia/reperfusion injury. We found that Lcn2 deficiency significantly aggravated renal injury as evidenced by higher serum creatinine, more severe morphological injury, and increased tubular epithelial cell death in mice. We also observed that attenuated autophagy in Lcn2 mice, as autophagy markers LC3 II level was significantly decreased and p62 was increased in the Lcn2 mice after I/R, compared with that of wild type. Mechanistically, we found that recombinant Lcn2 attenuated hypoxia-induced apoptosis in proximal tubule epithelial cells in vitro, and downregulation of HIF-1α blunted Lcn2-induced autophagy and enhanced apoptosis. In addition, the Lcn2 attenuated NF-κb subunit p65 activation under hypoxia conditions. Thus, our findings provide a better understanding of the protective role of Lcn2 in kidney ischemia/reperfusion injury and suggest that Lcn2 may be a promising therapeutic target for treating patients with AKI.

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<b><i>Background:</i></b> Although the protective effects of alcohol consumption against future cardiovascular disease have been published, the effects of alcohol on stroke risk remain controversial. <b><i>Method:</i></b> We assessed the effects of alcohol consumption on stroke risk in a poorly educated, low-income population in rural China. Between 1991 and 2018, a population-based cohort study was conducted in rural Tianjin, China, to examine stroke risk. All registered stroke events were clinically verified using available computed tomography or MRI scans. The stroke risk was analyzed, according to the extent of alcohol consumption, using Cox regression analyses. <b><i>Results:</i></b> We identified 352 incident stroke events among male participants during the study period. The stroke incidences (per 100,000 person-years) were 965.3 overall, 575.9 for ischemic stroke events, 208.4 for hemorrhagic stroke events, and 181.0 for undefined stroke events. Overall, alcohol consumption provided a 32% reduction in the total stroke risk. Low-dose alcohol consumption (≤12 g/day) showed a negative association with total (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46–0.88; <i>p</i> = 0.008) and ischemic (HR, 0.66; 95% CI, 0.44–0.98; <i>p</i> = 0.039) strokes. Alcohol consumption was not significantly associated with hemorrhagic strokes. After age stratification, alcohol consumption was protective against total and ischemic strokes in men aged ≥55 years old, with the risk of each stroke type decreasing by 46 and 49%, respectively. Low-dose alcohol consumption was inversely associated with both total and ischemic stroke risks, with the risks decreasing by 56 and 65%, respectively. Alcohol consumption was not significantly associated with strokes among men aged &#x3c;55 years old. <b><i>Conclusions:</i></b> These findings suggest that low-dose alcohol consumption may decrease the risk of ischemic strokes among men. Even so, the adverse effects of alcohol on the liver and pancreas cannot be ignored. Additionally, the effects of alcohol consumption on stroke risk vary with age, protecting against ischemic and total strokes among males ≥55 years old. Nevertheless, recommending light drinking and its potential health benefits should not be generalized to men of all ages.