The aggregation of α-synuclein (α-syn) promotes neuroinflammation and neuronal apoptosis, which eventually contribute to the pathogenesis of Parkinson’s disease (PD). Our microarray analysis and experimental data indicated a significant expression difference of the long noncoding RNA IL6ST-AS and its anti-sense strand, IL6ST, in α-synuclein-induced microglia, compared with unstimulated microglia. IL6ST is a key component of the IL6R/IL6ST complex in the microglial membrane, which recognizes extracellular inflammatory factors, such as IL6. Studies have shown that the binding of IL6 to the IL6R/IL6ST complex could activate the JAK2-STAT3 pathway and promote an excessive immune response in glia cells. Meanwhile, the phosphorylation and activation of STAT3 could increase the transcription of HIF1A, encoding a hypoxia-inducible factor related to cytotoxic damage. Our results indicated that the overexpression of IL6ST-AS induced by exogenous α-synuclein could inhibit the expression of IL6ST and the activation of JAK2-STAT3 pathway in HMC3 cells. In addition, a reduction in STAT3 resulted in the transcription inhibition of HIF1A and the acceleration of oxidative stress injury in SH-SY5Y cells co-cultured with α-synuclein-induced HMC3 cells. Our findings indicate that IL6ST-AS is an important factor that regulates microglia activation and neuronal necrosis in the progression of PD. In the HMC3 and SH-SY5Y cell co-culture system, the overexpression of IL6ST-AS led to microglial dysfunction and neurotoxicology through the IL6ST-AS/STAT3/HIF-1α axis. Our research revealed the relationships among α-synuclein, IL6ST, STAT3, and HIF-1α in the pathological process of PD and provided a new inflammation hypothesis for the pathogenesis of PD.

Background: Malnutrition’s prognostic impact in patients with severe stroke requiring ICU admission is not well known. This study aimed to assess the nutritional status of severe stroke patients using the geriatric nutritional risk index (GNRI) and examine the association of GNRI with mortality in that population. Methods: We identified 1145 severe stroke patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-III) database and divided them into low GNRI (≤98) or high GNRI (>98) groups. We used a propensity score matching (PSM) method to reduce confounding. Cox proportional hazards regression and restricted cubic splines were used to elucidate the association between GNRI and mortality. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: A total of 397 (35%) patients were in the low GNRI group (at risk of malnutrition). After PSM, patients in the low GNRI group still suffered higher mortality compared with the high GNRI group at 28 days (27.9 vs. 20.8%), 90 days (35.5 vs. 25.7%), and 1 year (43.4 vs. 30.9%) (p < 0.05). A low GNRI was significantly associated with an increased mortality (HR: 1.38, 95% CI 1.03–1.86 in 28 days; HR: 1.45, 95% CI 1.11–1.89 in 90 days; HR: 1.51, 95% CI 1.19–1.92 in 1 year). Sensitivity analyses yielded consistent results. Restricted cubic splines showed a progressively decreasing risk of mortality with increasing GNRI scores up to 110, approximately. Conclusion: Severe stroke patients with malnutrition experienced an increased risk of death compared to those without malnutrition. GNRI, as a simple and practical nutritional screening tool, can be used as a routine approach to the nutritional status of stroke patients.