Yi Lu

Diabetes has been associated with an elevated risk of Parkinson’s disease (PD), yet the relationship between prediabetes (PreD) and the incidence of PD in the adult population remains unclear. Therefore, a systematic review and meta-analysis was conducted to evaluate if PreD is also associated with a higher risk of PD. We conducted comprehensive searches of the PubMed, Embase, and Web of Science databases to identify relevant observational studies with longitudinal follow-up. The random-effects model was employed to synthesize the data, mitigating the potential impact of study heterogeneity on the outcomes. Our analysis incorporated seven datasets from five cohort studies, encompassing 18,170,592 adult participants without a PD diagnosis at baseline. Among them, 2,432,148 (13.3%) had PreD. During the follow-up, a total of 46,682 patients were diagnosed with PD. The pooled results indicated that PreD was associated with an increased incidence of PD (risk ratio [RR] 1.09, 95% confidence interval [CI] 1.02 - 1.16; P = 0.02; I2 = 52%), after adjusting for potential confounding factors such as age, sex, body mass index (BMI), and smoking. Subsequent pilot subgroup analyses suggested that the association between PreD and PD might not be significantly influenced by the country of the study, its design, age or sex of the participants, definition of PreD, or the quality scores of the study (P for subgroup difference all > 0.05). In conclusion, adult population with PreD may have a mildly increased risk of developing PD compared to those with normoglycemia.

To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Naringenin significantly ameliorated OGD/R-induced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1β, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.