Objectives: The study is performed to analyze the relationship between immune-related long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We constructed a prognostic model and explored the immune characteristics of different risk groups.Methods: We downloaded the gene expression profiles and clinical data of 227 patients from The Cancer Genome Atlas database and extracted immune-related lncRNAs. Cox regression analysis was used to pick out the predictive lncRNAs. The risk score of each patient was calculated based on the expression level of lncRNAs and regression coefficient (β), and a prognostic model was constructed. The overall survival (OS) of different risk groups was analyzed and compared by the Kaplan–Meier method. To analyze the distribution of immune-related genes in each group, principal component analysis and Gene set enrichment analysis were carried out. Estimation of STromal and Immune cells in MAlignant Tumors using Expression data was performed to explore the immune microenvironment.Results: Patients were divided into training set and validation set. Five immune-related lncRNAs (H1FX-AS1, AL441992.1, USP30-AS1, AP001527.2, and AL031123.2) were selected for the construction of the prognostic model. Patients in the training set were divided into high-risk group with shorter OS and low-risk group with longer OS (p = 0.004); meanwhile, similar result were found in validation set (p = 0.013), combination set (p < 0.001) and patients with different tumor stages. This model was further confirmed in 56 cervical cancer tissues by Q-PCR. The distribution of immune-related genes was significantly different in each group. In addition, the immune score and the programmed death-ligand 1 expression of the low-risk group was higher.Conclusions: The prognostic model based on immune-related lncRNAs could predict the prognosis and immune status of cervical cancer patients which is conducive to clinical prognosis judgment and individual treatment.

Nitric oxide (NO) has a variety of physiological roles, including acting as a key mediator in various phases of tendon healing, but its importance as a modulator of gene expression during tendon healing has not been well studied. The current study used microarray analysis to elucidate global gene expression after transfection with inducible nitric oxide synthase (iNOS) in tenocytes isolated from the injured rotator cuff tendons of human patients. We show that the expression of a wide range of genes is affected by NO, with many activated genes having known roles in healing. Of particular significance is that NOS overexpression stimulates the transcription and translation of a range of extracellular matrix genes important to the structure of connective tissues such as tendons, including collagen Iα1, collagen IIIα1, collagen IVα5, biglycan, decorin, laminin, and matrix metalloproteinase 10 (MMP10). These genes were also shown to respond to stimulation by the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) in a dose-dependant manner. We further show that varying levels of NO significantly affect cellular adhesion in tenocytes, a critical process during tendon repair. These findings will be of use when optimizing the dose of NO delivery in further work investigating NO as potential treatment of tendon injuries. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Background: Studies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach. Methods: Potential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran’s Q test, the MR–Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis. Results: According to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001–1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914–0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010–0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567–0.912; P = 0.006). Conclusion: The study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

Background: Childhood obesity has become a huge challenge to childhood health, and there is a lack of understanding about the relationship between dietary inflammatory index (DII) and childhood obesity. The main objective of this study was to analyze the potential link between DII and obesity among children and adolescents residing in the United States. Methods: A cross-sectional analysis was performed using data obtained from the National Health and Nutrition Examination Survey between 2009 and 2018. In total, 12,454 participants were included in the analysis. DII was calculated based on dietary data from the first day of the 24-hour dietary recall. Logistic regression was used to analyze the association between DII and obesity, as well as central obesity defined by the waist-to-height ratio of 0.5 or higher or waist circumference ≥ 90th percentile for age and sex. Results: The mean dietary inflammation index was 2.05 (SE = 0.02), with higher levels in children than in adolescents (P = 0.01). According to our findings, the prevalence of central obesity was higher among adolescents (38.0%) than among children (31.4%). The adolescents in the third quartile of DII have a higher risk of overweight/obesity (OR = 1.46, 95% CI: 1.24–1.71) after adjusting for age, sex, and race. This positive association remained significant even after physical activity was added to the model. Concerning central obesity, the adolescents in the highest quartile of DII have a higher risk, independent of demographic characteristics and physical activity. However, no significant association was observed among children. Conclusions: The dietary inflammation index was positively associated with overweight/obesity and central obesity among adolescents in the United States after adjusting for confounding factors. These findings highlight the importance of promoting anti-inflammatory diets in adolescents to prevent obesity and its associated complications.

Kawasaki disease (KD) is an immune-response disorder with unknown etiology. KD is an acute systemic immune vasculitis caused by infectious factors that can be complicated by coronary artery lesions. Innate immune cells are closely associated with KD onset, but we know little regarding the expression of immunity-related genes (IRGs) and the possible immune regulatory mechanisms involved in KD. In this study, we analyzed public single-cell RNA sequencing (scRNA-seq) and microarray data of peripheral blood mononuclear cells from normal controls and KD patients. The results of scRNA-seq revealed myeloid cells, T cells, B cells, NK cells, erythrocytes, platelets, plasma cells, hematopoietic stem cells, and progenitor cells in the peripheral blood of patients with KD. In particular, myeloid cells were expanded and heterogeneous. Further analysis of the myeloid cell population revealed that monocytes in KD exhibited higher expression of the inflammatory genes S100A8, S100A9, and S100A12; furthermore, CD14CD16 monocyte clusters were associated with inflammatory responses. Microarray data revealed that activation of the innate immune response contributed to KD development and progression. Differential expression and weighted gene coexpression network analysis identified 48 differentially expressed IRGs associated with response to intravenous immunoglobulin, currently the most effective treatment of KD, although numerous patients are resistant. Proteinprotein interaction analysis identified ten hub genes (IL1R1, SOCS3, IL1R2, TLR8, IL1RN, CCR1, IL1B, IL4R, IL10RB, and IFNGR1) among the IRGs. In addition, the expressions of IL1R1, SOCS3, CCR1, IL1B, and IL10RB were validated in Chinese KD patients using the real-time reverse transcriptase-polymerase chain reaction. Finally, we found that the neutrophil/lymphocyte ratio could be used as a biomarker to predict responsiveness to intravenous immunoglobulin in KD. In conclusion, our data highlight the importance of innate immunity in KD pathogenesis and its potential in predicting treatment response.

Annexin A6 (ANXA6), a calcium-dependent phospholipid protein, is closely related to the prognosis of a variety of tumors. However, the function and its regulatory mechanism in tumors is largely unknown. Here, we found that tumor microenvironment ANXA6 expression was associated with unfavorable prognosis of patients with cervical cancer. Downregulation of ANXA6 in cervical cancer cells suppressed tumor cell migration, colony formation and promoted tumor cell death. Furthermore, we identified ANXA6 co-localized with cGAS and function as an inhibitor of the cGAS-STING signaling pathway by promoting the ubiquitination of cGAS. Inhibiting ANXA6 expression resulted in increase of cGAS and activation of the cGAS-STING signaling pathway, leading to elevated expression of phosphorylated TBK1, IRF3, and type I IFN stimulated gene MX1, ISG15, ISG56. In addition, downregulation of ANXA6 in cervical cancer cells impedes the K63-linked ubiquitination process of cGAS protein, resulting in an upregulation of cGAS expression. This subsequently facilitates the activation of the cGAS-STING signaling pathway, leading to increased production of reactive oxygen species and lipid peroxides in cervical cancer cells. Ultimately, these events induce ferroptosis in tumor cells. Therefore, our findings revealed that inhibiting ANXA6 can promote tumor cell ferroptosis by activating the cGAS-STING pathway, thereby provide potential strategies that enhancing the efficacy of anti-tumor immunotherapy in cervical cancer.