Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke.

Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse.

Normal weight obesity and the risk of diabetes in Chinese people: a 9-year population-based cohort study.

We evaluated the risk of developing diabetes in Chinese individuals with normal weight obesity (NWO). This 9-year population-based cohort study was based on the China National Diabetes and Metabolic Disorders Survey. A total of 1128 subjects without diabetes were included. Body fat percentage (BF%) was assessed by electrical bioimpedance. NWO was defined as subjects with a normal BMI (< 24 kg/m2) and an excess BF% (≥ 24% in men; ≥ 33% in women). Of 1128 individuals, 528 individuals were normal weight non-obese (NWNO), 118 (10.5%) were normal weight obese (NWO), 63 were overweight non-obese (OWNO), and 419 were overweight obese (OWO). During a follow-up of 9.0 years (interquartile range: 8.9-9.3), 113 (10.0%) individuals developed diabetes. The incidence rates of diabetes in NWNO, NWO, OWNO and OWO people were 5.69 (27 cases), 11.30 (12 cases), 3.53 (2 cases) and 19.09 (72 cases) per 1000 person-years, respectively. Cox regression analyses indicated multivariate-adjusted hazard ratios of diabetes in NWO, OWNO and OWO people were 2.110 (95% CI 1.026-4.337, p = 0.025), 0.441 (95% CI 0.101-1.928, p = 0.232) and 3.465 (95% CI 2.163-5.551, p < 0.001), respectively, relative to NWNO people. Chinese people with NWO are at increased risk of developing diabetes. We strongly suggest the incorporation of BF% measurement into the regular physical examination in Chinese medical practice.

Insulin resistance is not independently associated with chronic kidney disease in Chinese population: A population-based cross-sectional study.

BACKGROUND: Metabolic syndrome (MS) may modify the association of insulin resistance (IR) with chronic kidney disease (CKD), but the relevant studies were not enough. We evaluated whether IR is independently associated with CKD in Chinese population. METHODS: The data were from 2007-2008 China National Diabetes and Metabolic Disorders Study. CKD was defined as an estimated glomerular filtration rate <60ml/min/1.73m(2). IR was evaluated by using the homeostatic model assessment (HOMA-IR). RESULTS: A total of 11,143 individuals were included. Participants in the higher quartiles of HOMA-IR tended to have higher prevalence of CKD in general population (P<0.001). However, there was no significant difference among the quartiles of HOMA-IR in population without MS (P=0.288). In general population, the adjusted odds ratio of CKD was 1.183 (95% CI: 0.838-1.670), 1.543 (95% CI: 1.103-2.158), and 1.549 (95% CI: 1.079-2.223) in the second, third and fourth quartile of HOMA-IR relative to the lowest quartile, while the odds ratios in population without MS showed no significance in all higher quartiles. CONCLUSIONS: IR was not an independently significant predictor of CKD in Chinese population, and MS may contribute greatly to the association between IR and CKD.