Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

BACKGROUND AND AIMS: An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH AND RESULTS: This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3ß HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3ß HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3ß HCA and hepatic lipid homeostasis.

Integrated machine learning methods identify FNDC3B as a potential prognostic biomarker and correlated with immune infiltrates in glioma.

Background: Recent discoveries have revealed that fibronectin type III domain containing 3B (FNDC3B) acts as an oncogene in various cancers; however, its role in glioma remains unclear. Methods: In this study, we comprehensively investigated the expression, prognostic value, and immune significance of FNDC3B in glioma using several databases and a variety of machine learning algorithms. RNA expression data and clinical information of 529 patients from the Cancer Genome Atlas (TCGA) and 1319 patients from Chinese Glioma Genome Atlas (CGGA) databases were downloaded for further investigation. To evaluate whether FNDC3B expression can predict clinical prognosis of glioma, we constructed a clinical nomogram to estimate long-term survival probabilities. The predicted nomogram was validated by CGGA cohorts. Differentially expressed genes (DEGs) were detected by the Wilcoxon test based on the TCGA-LGG dataset and the weighted gene co-expression network analysis (WGCNA) was implemented to identify the significant module associated with the expression level of FNDC3B. Furthermore, we investigated the correlation between FNDC3B with cancer immune infiltrates using TISIDB, ESTIMATE, and CIBERSORTx. Results: Higher FNDC3B expression displayed a remarkably worse overall survival and the expression level of FNDC3B was an independent prognostic indicator for patients with glioma. Based on TCGA LGG dataset, a co-expression network was established and the hub genes were identified. FNDC3B expression was positively correlated to the tumor-infiltrating lymphocytes and immune infiltration score, and high FNDC3B expression was accompanied by the increased expression of B7-H3, PD-L1, TIM-3, PD-1, and CTLA-4. Moreover, expression of FNDC3B was significantly associated with infiltrating levels of several types of immune cells and most of their gene markers in glioma. Conclusion: This study demonstrated that FNDC3B may be involved in the occurrence and development of glioma and can be regarded as a promising prognostic and immunotherapeutic biomarker for the treatment of glioma.

High-Quality Nursing Care for the Elderly in the Department of Otolaryngology.

ENT patients have different types of diseases and clinical symptoms, and generally, patients have a low level of understanding of their professional knowledge about their ENT diseases. In this paper, quality nursing interventions in otorhinolaryngology require nursing staff to implement relevant nursing interventions in the process of implementing relevant nursing care, which should be based on patients' needs, and guide patients to perform rehabilitation exercises according to their individual conditions, in addition to establishing continuous nursing interventions with patients at the time of discharge with the help of modern technology. By comparing the nursing satisfaction of patients in the observation group and the control group, it was found that the nursing satisfaction of patients in the observation group who received humanistic nursing was higher, and the difference was statistically significant compared with that of the control group (P < 0.05). The SCL-90 scale scores of patients in both groups were not significantly different on the day of admission as verified by t values, and the SCL-90 scale scores of patients in both groups changed to a certain extent after hospitalization. The difference between the two groups was verified by t value.

DNA methylation suppresses liver Hamp expression in response to iron deficiency after bariatric surgery.

BACKGROUND: Iron deficiency is extremely common after bariatric surgery. HEPCIDIN, encoded by Hamp, is a hormone that negatively regulates iron homeostasis. OBJECTIVES: We aimed to investigate the alteration of Hamp expression and related regulatory factors to explore the probable role of DNA methylation in modulating Hamp expression in the context of iron deficiency after bariatric surgery. SETTING: Laboratories of Diabetes Institute. METHODS: RNA-seq was performed using rat liver tissue after either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy surgery to identify differentially expressed genes between the bariatric surgery and sham group. Hamp expression were measured by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The DNA methylation level was determined using MassARRAY EpiTYPER. Iron status, erythrocyte parameters, and inflammation factors were assessed. RESULTS: RNA-seq data showed that liver Hamp expression changed most dramatically in RYGB-operated rats. Both the mRNA expression of Hamp and the abundance of its protein product HEPCIDIN-25 decreased markedly after bariatric surgery compared with sham, while sleeve gastrectomy-operated rats showed marginally higher Hamp expression than RYGB-operated rats. The DNA methylation level of the Hamp promoter region was significant higher in RYGB-operated rats than sham, while sleeve gastrectomy rats increased slightly in DNA methylation. Consistent with the change of HEPCIDIN-25, serum iron was significantly lower for both bariatric groups than sham and particularly low in RYGB. CONCLUSIONS: Our data demonstrate that elevated DNA methylation of the Hamp promoter region suppresses its expression, this epigenetic modification likely occurs in reaction to iron deficiency after bariatric surgery, helping to maintain system iron homeostasis.

Serum haptoglobin levels are associated with renal function decline in type 2 diabetes mellitus patients in a Chinese Han population.

AIMS: We investigated whether serum haptoglobin (Hp) levels play a role in the development and progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in a Chinese Han population, which has not been previously investigated. METHODS: We recruited 233 participants who had suffered from T2DM for more than 10 years, including 118 subjects with DKD (case) and 115 subjects without DKD (control). Serum Hp levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Serum Hp levels were significantly higher (P = 0.0258) in case group (2.74 (1.77, 3.48) g/L) than control (2.29 (0.98, 3.48) g/L). The serum Hp level was significantly positively associated with both logarithmically transformed (log-transformed) serum creatinine (r = 0.1663, P = 0.011) and albuminuria levels (r = 0.1793, P = 0.0062) and was negatively associated with the log-transformed estimated glomerular filtration rate (r = -0.1482, P = 0.0237). Multiple linear regression analysis revealed that serum Hp levels were significantly correlated with serum creatinine levels (P = 0.0088) after adjusting for confounding risk factors. CONCLUSIONS: Our findings suggest that serum Hp levels may be used as a potential biomarker for the early diagnosis and monitoring of DKD in T2DM patients.

Resveratrol reduces intracellular reactive oxygen species levels by inducing autophagy through the AMPK-mTOR pathway.

Oxidative stress induced by free fatty acid aggravates endothelial injury, which leads to diabetic cardiovascular complications. Reduction of intracellular oxidative stress may attenuate these pathogenic processes. The dietary polyphenol resveratrol reportedly exerts potential protective effects against endothelial injury. This study determined whether resveratrol can reduce the palmitic acid (PA)-induced generation of reactive oxygen species (ROS) and further explored the underlying molecular mechanisms. We found that resveratrol significantly reduced the PA-induced endothelial ROS levels in human aortic endothelial cells. Resveratrol also induced endothelial cell autophagy, which mediated the effect of resveratrol on ROS reduction. Resveratrol stimulated autophagy via the AMP-activated protein kinase (AMPK)-mTOR pathway. Taken together, these data suggest that resveratrol prevents PA-induced intracellular ROS by autophagy regulation via the AMPK-mTOR pathway. Thus, the induction of autophagy by resveratrol may provide a novel therapeutic candidate for cardioprotection in metabolic syndrome.

Causal Association of Overall Obesity and Abdominal Obesity with Type 2 Diabetes: A Mendelian Randomization Analysis.

OBJECTIVE: This study aimed to compare the causal effect of overall obesity and abdominal obesity on type 2 diabetes among Chinese Han individuals. METHODS: The causal relationship of BMI and waist-to-hip ratio (WHR) with the risk of glucose deterioration and glycemic traits was compared using two different genetic instruments based on 30 BMI loci and 6 WHR loci with Mendelian randomization (MR) in three prospective cohorts (n = 6,476). RESULTS: Each 1-SD genetically instrumented higher WHR was associated with a 65.7% higher risk of glucose deterioration (95% CI = 1.069-2.569, P = 0.024), whereas no significant association of BMI with glucose deterioration was observed. Furthermore, a causal relationship was found only between BMI and homeostatic model assessment ß-cell function (HOMA-B) (ß = 0.143, P = 0.001), and there was a nominal association with Stumvoll second-phase insulin secretion traits (ß = 0.074, P = 0.022). The significance level did not persist in sensitivity analyses, except in the causal estimate of WHR on the Gutt index in MR-Egger (ß = -0.379, P = 0.022) and the causal estimate of BMI on homeostatic model assessment ß-cell function in weighted median MR (ß = 0.128, P = 0.017). CONCLUSIONS: The data from this study support the potential causal relationship between abdominal obesity and hyperglycemia, which may be driven by aggravated insulin resistance, in contrast with the potential causal relationship between overall obesity and insulin secretion.