Higher expression of TSR2 aggravating hypertension via the PPAR signaling pathway.

Hypertension is a complex disease with unknown causes. Therefore, it's crucial to deeply study its molecular mechanism. The hypertension dataset was obtained from Gene Expression Omnibus data base (GEO), and miRNA regulating central hub genes was screened via weighted gene co-expression network (DEGs) and gene set enrichment (GSEA). Cell experiments validated TSR2's role and the PPAR signaling pathway through western blotting. 500 DEGs were identified for hypertension, mainly enriched in actin cross-linking, insulin signaling, PPAR signaling, and protein localization. Eight hub genes (SEC61G, SRP14, Liy AR, NIP7, SDAD1, POLR1D, DYNLL2, TSR2) were identified. Four hub genes (LYAR, SDAD1, POLR1D, TSR2) exhibited high expression levels in the hypertensive tissue samples, while showing low expression levels in the normal tissue samples. This led us to speculate that they may have relevant regulatory effects on hypertension. When TSR2 was knocked down in the hypertension peripheral blood mononuclear cells (PBMC) model, the critical proteins in the PPAR signaling pathway (FABP, PPAR, PLTP, ME1, SCD1, CYP27, FABP1, OLR1, CPT-1, PGAR, CAP, ADIPO, MMP1, UCP1, ILK, PDK1 UBC AQP7) were downregulated. This also occurred in the hypertension peripheral blood mononuclear cells (PBMC) + TSR2_ OV model. TSR2 is highly expressed in individuals with hypertension and may play a significant role in the development of hypertension through the PPAR signaling pathway. TSR2 could serve as a molecular target for the early diagnosis and precise treatment of hypertension, providing a valuable direction for the mechanism research of this condition.

HLA-B and TIMP1 as hub genes of the ventricular remodeling caused by hypertension.

RATIONALE: Myocardial fibrosis is an important pathological change that occurs during ventricular remodeling in patients with hypertension and is an important pathophysiological basis of cardiovascular disease. However, the molecular mechanism underlying this ventricular remodeling is unclear. METHODS: Bioinformatics analysis identified HLA-B and TIMP1 as hub genes in the process of myocardial fibrosis. Expression and correlation analyses of significant hub genes with ventricular remodeling were performed. Weighted gene co-expression network analysis (WGCNA) was performed to verify the role of HLA-B. ceRNA network was constructed to identify the candidate molecule drugs. Receiver operating characteristic (ROC) curves were analyzed. RESULTS: RT-qPCR was performed to verify the roles of HLA-B and TIMP1 in seven control individuals with hypertension and seven patients with hypertension and ventricular remodeling. The WGCNA showed that HLA-B was in the brown module and the correlation coefficient between HLA-B and ventricular remodeling was 0.67. Based on univariate logistic proportional regression analysis, HLA-B influences ventricular remodeling (P<0.05). RT-qPCR showed that the relative expression levels of HLA-B and TIMP1 were significantly higher in HLVR samples compared with their expression in the control group. CONCLUSIONS: HLA-B and TIMP1 might provide novel research targets for the diagnosis and treatment of HLVR.

Prevalence and factors associated with frailty and pre-frailty in the older adults in China: a national cross-sectional study.

Objective: Frailty increases poor clinical outcomes in older adults, the aim of this study was to investigate the prevalence and factors associated with frailty and pre-frailty in older adults in China. Research design and methods: Data were obtained from the Sample Survey of the Aged Population in Urban and Rural China in 2015, which was a cross-sectional study involving a nationally representative sample of older adults aged 60 years or older from 31 provinces/autonomous regions/municipalities in mainland China. The frailty index (FI) based on 33 potential deficits was used to classify individuals as robust (FI < 0.12), pre-frail (FI ≧0.12 and <0.25) and frail (FI ≥0.25). Results: A total of 208,386 older people were included in the study, and the age-sex standardised prevalence of frailty and pre-frailty among older adults in China was 9.5% (95% CI 9.4-9.7) and 46.1% (45.9-46.3) respectively. The prevalence of frailty and pre-frailty was higher in female than in male older adults, higher in rural than in urban older adults, and higher in northern China than in southern China. The multinomial analysis revealed similar risk factors for frailty and pre-frailty, including increased age, being female, living in a rural area, low educational attainment, poor marital status, living alone, difficult financial status, poor access to medical reimbursement, and living in northern China. Conclusion: Frailty and pre-frailty are very common among older adults in China and differ significantly between southern and northern China, men and women, and rural and urban areas. Appropriate public health prevention strategies should be developed based on identified risk factors in frail and pre-frail populations. The management of frailty and pre-frailty should be optimised according to regional and gender differences in prevalence and associated factors, such as strengthening the integrated management of chronic diseases, increasing reimbursement rates for medical costs, and focusing on vulnerable groups such as the disabled, economically disadvantaged, living alone and those with low literacy levels, in order to reduce the burden of frailty among older adults in China.

Prevalence of frailty and pre-frailty and related factors in older adults with cardio-cerebral vascular disease in China: a national cross-sectional study.

Objective: Frailty increases adverse clinical outcomes in older patients with cardio-cerebral vascular disease (CCVD). The aim of this study was to investigate the prevalence of frailty and pre-frailty in older adults with CCVD in China and the factors associated with it. Research design and methods: In this cross-sectional study, we used data from the fourth Sample Survey of Aged Population in Urban and Rural China. We used the frailty index for frailty and pre-frailty assessment, and the diagnosis of CCVD in older adults was self-reported. Results: A total of 53,668 older patients with CCVD were enrolled in the study. The age-standardized prevalence of frailty and pre-frailty in older patients with CCVD was 22.6% (95% CI 22.3-23.0%) and 60.1% (95% CI 59.7-60.5%). Multinomial logistic regression analyses showed that being female, increasing age, rural residence, illiteracy, widowhood, ethnic minority, living alone, no health screening during the last year, hospitalization during the last year, difficult financial status, comorbid chronic conditions, and disability in activities of daily living were associated with frailty and pre-frailty in older patients with CCVD. Conclusion: CCVD is strongly associated with frailty and pre-frailty in older Chinese people, and assessment of frailty should become routine in the management of older CCVD patients. Appropriate public health prevention strategies should be developed based on identified risk factors for frailty in older CCVD patients, which can help prevent, ameliorate or reverse the development of frailty in CCVD in the older population.

Analysis of the status of social frailty in Chinese older adults with cardiovascular and cerebrovascular diseases: a national cross-sectional study.

Background: Social frailty is one type of frailty. Physical frailty with cardiovascular and cerebrovascular diseases (CCVD) have been studied a lot, but less research on social frailty. Objectives: To study the prevalence, related risk factors and regional differences of social frailty with CCVD in Chinese older adults. Methods: SSAPUR was a national cross-sectional survey. Participants aged 60 years or older were recruited in August 2015. Demographic data and information regarding family, health and medical conditions, living environment conditions, social participation, spiritual and cultural life, and health condition were obtained. Social frailty was assessed in five areas (HALFE Social Frailty Index) including inability to help others, limited social participation, loneliness, financial difficulty, and living alone. The prevalence of CCVD with social frailty, related risk factors and regional differences in CCVD with social frailty were studied. Results: A total of 222,179 participants were enrolled. 28.4% of them had CCVD history. The prevalence of social frailty in the CCVD group was 16.03%. In CCVD participants, compared with the group without social frailty, there were significant differences in gender, age, urban-rural distribution, ethnicity, marital status, and education levels in the social frailty group. Significant differences were also found in physical exercise participation, health status, cataract, hypertension, diabetes mellitus, hospitalization within 1 year, self-assessed health status, crutch or wheelchair usage, urinary and fecal incontinence, need for care from others, fall history, housing satisfaction, and self-assessed happiness in the social frailty group. Women with CCVD had a higher prevalence of social frailty than men. By age in CCVD with social frailty, the highest prevalence was found in participants 75-79 years old. The prevalence of CCVD was significant difference between social frailty in urban and rural group. The prevalence of social frailty with CCVD was significantly different in different regions. The highest prevalence was 20.4% in southwest area, and the lowest prevalence was 12.5% in northeast with area. Conclusion: The prevalence of social frailty among the CCVD older adults is high. Factors such as gender, age, region, urban-rural residence, and the state of the disease may be associated with social frailty.

The role of the microbiota-gut-brain axis and intestinal microbiome dysregulation in Parkinson's disease.

Parkinson's disease (PD) is a complex progressive neurodegenerative disease associated with aging. Its main pathological feature is the degeneration and loss of dopaminergic neurons related to the misfolding and aggregation of α-synuclein. The pathogenesis of PD has not yet been fully elucidated, and its occurrence and development process are closely related to the microbiota-gut-brain axis. Dysregulation of intestinal microbiota may promote the damage of the intestinal epithelial barrier, intestinal inflammation, and the upward diffusion of phosphorylated α-synuclein from the enteric nervous system (ENS) to the brain in susceptible individuals and further lead to gastrointestinal dysfunction, neuroinflammation, and neurodegeneration of the central nervous system (CNS) through the disordered microbiota-gut-brain axis. The present review aimed to summarize recent advancements in studies focusing on the role of the microbiota-gut-brain axis in the pathogenesis of PD, especially the mechanism of intestinal microbiome dysregulation, intestinal inflammation, and gastrointestinal dysfunction in PD. Maintaining or restoring homeostasis in the gut microenvironment by targeting the gut microbiome may provide future direction for the development of new biomarkers for early diagnosis of PD and therapeutic strategies to slow disease progression.

Epidemiological status and associated factors of frailty and pre-frailty in older adults with asthma in China: A national cross-sectional study.

Objective: There are few studies on the prevalence and factors associated with frailty and pre-frailty in older adults with asthma worldwide. The aim of this study was to examine the epidemiological status and factors associated with frailty and pre-frailty in older adults with asthma in China. Research design and methods: Data were obtained from the Sample Survey of Aged Population in Urban and Rural China in 2015, a nationwide cross-sectional survey covering 224,142 older people aged 60 years or older in 31 provinces/autonomous regions/municipalities in mainland China. We performed frailty and pre-frailty assessments using the frailty index, and the diagnosis of asthma in the older adults was self-reported based on the history of the physician's diagnosis. Results: Nine thousand four hundred sixteen older adults with asthma were included in the study. The age-sex standardized prevalence of frailty and pre-frailty in Chinese older adults with asthma was 35.8% (95% CI 34.8%-36.7%) and 54.5% (95% CI 53.5%-55.5%). Multinomial logistic regression analysis showed that increased age, female, illiteracy, living alone, poor economic status, ADL disability, comorbid chronic diseases, previous hospitalization in the past year, and residence in northern China were associated with frailty and pre-frailty in older adults with asthma. Conclusion: The prevalence of frailty and pre-frailty in Chinese older adults with asthma is very high, and assessment of frailty should become routine in the management of older adults with asthma. Appropriate public health prevention strategies based on identified risk factors for frailty in older adults with asthma should be developed to reduce the burden of frailty in Chinese older adults with asthma.

PLK1 as one novel target for the poor prognosis of bladder cancer: An observational study.

Bladder cancer (BC) is one of the most common male malignant tumors and the most common urological tumor. However, the molecular mechanism and role of PLK1 on bladder cancer were unclear. Therefore, the study aims to explore the potential part of the overall survival of bladder cancer through bioinformatics analysis. GSE121711 and GSE130598, from the Gene Expression Omnibus database. The GEO2R screened differently expressed genes, and DAVID and Metascape were used for functional annotation. The cytoHubba made hub genes identification and expression. A total of 50 BC participants were recruited. After surgery, 50 BC tumor samples from BC patients and 50 adjacent standard bladder tissue samples were obtained. The RT-qPCR assay was performed to verify the expression of hub genes. The Kaplan-Meier Plotter analyzed the effect of hub gene expression for overall survival of BC. The compulsory module of Molecular Complex Detection tool analysis was shown, which included CDK1, TTK, AURKB, MELK, PLK1, and BUB1. And the six hub genes were up-regulated in the BC compared with the normal tissues. The relative expression levels of CDK1, TTK, AURKB, MELK, PLK1, and BUB1 were significantly higher in BC samples compared with the regular kidney tissue groups. The result demonstrated that CDK1, TTK, AURKB, MELK, PLK1, and BUB1 might be considered biomarkers for BC. Overall survival analysis showed that BC patients with high expression level of PLK1 had poorer overall survival times than those with low expression level (P < .05). The expression levels of CDK1, TTK, AURKB, MELK, and BUB1 was not related to the overall survival of BC patients (P > .05). The PLK1 gene might provide new ideas and evidence for bladder cancer research.

SGLT1/2 as the potential biomarkers of renal damage under Apoe-/- and chronic stress via the BP neural network model and support vector machine.

Background: Chronic stress (CS) could produce negative emotions. The molecular mechanism of SGLT1 and SGLT2 in kidney injury caused by chronic stress combined with atherosclerosis remains unclear. Methods: In total, 60 C57BL/6J mice were randomly divided into four groups, namely, control (CON, n = 15), control diet + chronic stress (CON+CS, n = 15), high-fat diet + Apoe-/- (HF + Apoe-/-, n = 15), and high-fat diet + Apoe-/- + chronic stress (HF+Apoe-/- + CS, n = 15) groups. The elevated plus maze and open field tests were performed to examine the effect of chronic stress. The expression of SGLT1 and SGLT2 in the kidney was detected. The support vector machine (SVM) and back propagation (BP) neural network model were constructed to explore the predictive value of the expression of SGLT1/2 on the renal pathological changes. The receiver operating characteristic (ROC) curve analysis was used. Results: A chronic stress model and atherosclerosis model were constructed successfully. Edema, broken reticular fiber, and increased glycogen in the kidney would be obvious in the HF + Apoe-/- + CS group. Compared with the CON group, the expression of SGLT1/2 in the kidney was upregulated in the HF + Apoe-/- + CS group (P < 0.05). There existed positive correlations among edema, glycogen, reticular fiber, expression of SGLT1/2 in the kidney. There were higher sensitivity and specificity of diagnosis of SGLT1/2 for edema, reticular fiber, and glycogen in the kidney. The result of the SVM and BP neural network model showed better predictive values of SGLT1 and SGLT2 for edema and glycogen in the kidney. Conclusion: In conclusion, SGLT1/2 might be potential biomarkers of renal damage under Apoe-/- and chronic stress, which provided a potential research direction for future related explorations into this mechanism.

CXCR4 and TYROBP mediate the development of atrial fibrillation via inflammation.

Atrial fibrillation (AF) is a rapid supraventricular arrhythmia. However, the pathogenesis of atrial fibrillation remains controversial. We obtained transcriptome expression profiles GSE41177, GSE115574 and GSE79768 from GEO database. WGCNA was performed, DEGs were screened, PPI network was constructed using STRING database. CTD database was used to identify the reference score of hub genes associated with cardiovascular diseases. Prediction of miRNAs of hub genes was performed by TargetScan. DIANA-miRPath v3.0 was applied to make functional annotation of miRNA. The animal model of atrial fibrillation was constructed, RT-PCR was used to verify the expression of hub genes. Immunofluorescence assay for THBS2 and VCAN was made to identify molecular. Design of BP neural network was made to explore the prediction relationship of CXCR4 and TYROBP on AF. The merged datasets contained 104 up-regulated and 34 down-regulated genes. GO and KEGG enrichment analysis results of DEGs showed they were mainly enriched in 'regulation of release of sequestered calcium ion into cytosol', 'actin cytoskeleton organization' and 'focal adhesion'. The hub genes were CXCR4, SNAI2, S100A4, IGFBP3, CSNK2A1, CHGB, VCAN, APOE, C1QC and TYROBP, which were up-regulated expression in the AF compared with control tissues. There was strong correlation among the CXCR4, TYROBP and AF based on the BP neural network. Through training, best training performance is 9.6474e-05 at epoch 14, and the relativity was 0.99998. CXCR4 and TYROBP might be involved in the development of atrial fibrillation by affecting inflammation-related signalling pathways and may serve as targets for early diagnosis and preventive treatment.

A Potential Target for Clinical Atherosclerosis: A Novel Insight Derived from TPM2.

Atherosclerosis (AS) is a potential inducer of numerous cardio-cerebrovascular diseases. However, little research has investigated the expression of TPM2 in human atherosclerosis samples. A total of 34 clinical samples were obtained, including 17 atherosclerosis and 17 normal artery samples, between January 2018 and April 2021. Bioinformatics analysis was applied to explore the potential role of TPM2 in atherosclerosis. Immunohistochemistry, immunofluorescence, and western blotting assays were used to detect the expression of TPM2 and α-SMA proteins. The mRNA expression levels of TPM2 and α-SMA were detected using RT-qPCR. A neural network and intima-media thickness model were constructed. A strong relationship existed between the intima-media thickness and relative protein expression of TPM2 (P<0.001, R=-0.579). The expression of TPM2 was lower in atherosclerosis than normal artery (P<0.05). Univariate logistic regression showed that TPM2 (OR=0.150, 95% CI: 0.026-0.868, P=0.034) had clear correlations with atherosclerosis. A neural network model was successfully constructed with a relativity of 0.94434. TPM2 might be an independent protective factor for arteries, and one novel biomarker of atherosclerosis.

Recent Progress of Chronic Stress in the Development of Atherosclerosis.

With the development of the times, cardiovascular diseases have become the biggest cause of death in the global aging society, causing a serious social burden. Atherosclerosis is a chronic inflammatory disease, which can occur in large and medium-sized blood vessels in the whole body. It takes atherosclerotic plaque as the typical pathological change and endothelial injury as the core pathophysiological mechanism. It is the pathological basis of coronary heart disease, peripheral artery disease, cerebrovascular disease, and other diseases. Recent studies have shown that chronic stress plays an important role in the occurrence and development of atherosclerosis, endothelial injury, lipid metabolism, and chronic inflammation. This process involves a large number of molecular targets. It is usually the cause of atherosclerotic cardiovascular and cerebrovascular diseases. If chronic stress factors exist for a long time, patients have genetic susceptibility, and the combination of environmental factors triggers the pathogenesis, which may eventually lead to complete blockage of the blood vessels, unstable rupture of plaques, and serious adverse cardiovascular events. This paper reviews the role of chronic stress in the occurrence and development of atherosclerosis, focusing on the pathophysiological mechanism.

A study on the prevalence and related factors of frailty and pre-frailty in the older population with hypertension in China: A national cross-sectional study.

Objective: To explore the prevalence and factors associated with frailty and pre-frailty in elderly Chinese patients with hypertension. Background: In China, there have been few national studies into the prevalence and factors associated with frailty and pre-frailty in elderly patients with hypertension. Methods: Through the 4th Sample Survey of Aged Population in Urban and Rural China (SSAPUR) in 2015, the situation of hypertension subjects aged 60 years or older in 31 provinces, autonomous regions, and municipalities in mainland China was obtained. And the frailty index was constructed based on 33 potential defects, elderly hypertensive patients are classified as robust, frailty, and pre-frailty. Results: A total of 76,801 elderly patients with hypertension were enrolled in the study. The age-sex standardized prevalence of frailty and pre-frailty in hypertensive elderly in China was 16.1% (95%CI 15.8-16.3%), 58.1% (95%CI 57.7-58.4%). There were significant geographical differences in the prevalence of frailty and pre-frailty in elderly hypertensive patients. Multinomial logistic regression analysis showed that poor economic status, activities of daily living disability, and comorbid chronic diseases were related to frailty and pre-frailty. Conclusion: Frailty and pre-frailty are very common in elderly Chinese patients with hypertension and have similar risk factors. Prevention strategies should be developed to stop or delay the onset of frailty by targeting established risk factors in the pre-frailty population of elderly hypertension. It is also crucial to optimize the management of frailty in elderly Chinese patients with hypertension.

Screening and Identification of Key Biomarkers of Gastric Cancer: Three Genes Jointly Predict Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers all over the world, causing high mortality. Gastric cancer screening is one of the effective strategies used to reduce mortality. We expect that good biomarkers can be discovered to diagnose and treat gastric cancer as early as possible. METHODS: We download four gene expression profiling datasets of gastric cancer (GSE118916, GSE54129, GSE103236, GSE112369), which were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between gastric cancer and adjacent normal tissues were detected to explore biomarkers that may play an important role in gastric cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of overlap genes were conducted by the Metascape online database; the protein-protein interaction (PPI) network was constructed by the STRING online database, and we screened the hub genes of the PPI network using the Cytoscape software. The survival curve analysis was conducted by km-plotter and the stage plots of hub genes were created by the GEPIA online database. PCR, WB, and immunohistochemistry were used to verify the expression of hub genes. A neural network model was established to quantify the predictors of gastric cancer. RESULTS: The relative expression level of cadherin-3 (CDH3), lymphoid enhancer-binding factor 1 (LEF1), and matrix metallopeptidase 7 (MMP7) were significantly higher in gastric samples, compared with the normal groups (p<0.05). Receiver operator characteristic (ROC) curves were constructed to determine the effect of the three genes' expression on gastric cancer, and the AUC was used to determine the degree of confidence: CDH3 (AUC = 0.800, P<0.05, 95% CI =0.857-0.895), LEF1 (AUC=0.620, P<0.05, 95%CI=0.632-0.714), and MMP7 (AUC=0.914, P<0.05, 95%CI=0.714-0.947). The high-risk warning indicator of gastric cancer contained 8

Citrate Synthase and OGDH as Potential Biomarkers of Atherosclerosis under Chronic Stress.

BACKGROUND: Pathological changes of the adrenal gland and the possible underlying molecular mechanisms are currently unclear in the case of atherosclerosis (AS) combined with chronic stress (CS). METHODS: New Zealand white rabbits were used to construct a CS and AS animal model. Proteomics and bioinformatics were employed to identify hub proteins in the adrenal gland related to CS and AS. Hub proteins were detected using immunohistochemistry, immunofluorescence assays, and Western blotting. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression of genes. In addition, a neural network model was constructed. The quantitative relationships were inferred by cubic spline interpolation. Enzymatic activity of mitochondrial citrate synthase and OGDH was detected by the enzymatic assay kit. Function of citrate synthase and OGDH with knockdown experiments in the adrenal cell lines was performed. Furthermore, target genes-TF-miRNA regulatory network was constructed. Coimmunoprecipitation (IP) assay and molecular docking study were used to detect the interaction between citrate synthase and OGDH. RESULTS: Two most significant hub proteins (citrate synthase and OGDH) that were related to CS and AS were identified in the adrenal gland using numerous bioinformatic methods. The hub proteins were mainly enriched in mitochondrial proton transport ATP synthase complex, ATPase activation, and the AMPK signaling pathway. Compared with the control group, the adrenal glands were larger and more disordered, irregular, and necrotic in the AS+CS group. The expression of citrate synthase and OGDH was higher in the AS+CS group than in the control group, both at the protein and mRNA levels (P < 0.05). There were strong correlations among the cross-sectional areas of adrenal glands, citrate synthase, and OGDH (P < 0.05) via Spearman's rho analysis, receiver operating characteristic curves, a neural network model, and cubic spline interpolation. Enzymatic activity of citrate synthase and OGDH increased under the situation of atherosclerosis and chronic stress. Through the CCK8 assay, the adrenal cell viability was downregulated significantly after the knockdown experiment of citrate synthase and OGDH. Target genes-TF-miRNA regulatory network presented the close interrelations among the predicted microRNA, citrate synthase and OGDH. After Coimmunoprecipitation (IP) assay, the result manifested that the citrate synthase and OGDH were coexpressed in the adrenal gland. The molecular docking study showed that the docking score of optimal complex conformation between citrate synthase and OGDH was -6.15 kcal/mol. CONCLUSION: AS combined with CS plays a significant role on the hypothalamic-pituitary-adrenal (HPA) axis, promotes adrenomegaly, increases the release of glucocorticoid (GC), and might enhance ATP synthesis and energy metabolism in the body through citrate synthase and OGDH gene targets, providing a potential research direction for future related explorations into this mechanism.

Bioinformatics analysis and verification of gene targets for renal clear cell carcinoma.

BACKGROUND: It is estimated that there are 338,000 new renal-cell carcinoma releases every year in the world. Renal cell carcinoma (RCC) is a heterogeneous tumor, of which more than 70% is clear cell renal cell carcinoma (ccRCC). It is estimated that about 30% of new renal-cell carcinoma patients have metastases at the time of diagnosis. However, the pathogenesis of renal clear cell carcinoma has not been elucidated. Therefore, it is necessary to further study the pathogenesis of ccRCC. METHODS: Two expression profiling datasets (GSE68417, GSE71963) were downloaded from the GEO database. Differentially expressed genes (DEGs) between ccRCC and normal tissue samples were identified by GEO2R. Functional enrichment analysis was made by the DAVID tool. Protein-protein interaction (PPI) network was constructed. The hub genes were excavated. The clustering analysis of expression level of hub genes was performed by UCSC (University of California Santa Cruz) Xena database. The hub gene on overall survival rate (OS) in patients with ccRCC was performed by Kaplan-Meier Plotter. Finally, we used the ccRCC renal tissue samples to verify the hub genes. RESULTS: 1182 common DEGs between the two datasets were identified. The results of GO and KEGG analysis revealed that variations in were predominantly enriched in intracellular signaling cascade, oxidation reduction, intrinsic to membrane, integral to membrane, nucleoside binding, purine nucleoside binding, pathways in cancer, focal adhesion, cell adhesion molecules. 10 hub genes ITGAX, CD86, LY86, TLR2, TYROBP, FCGR2A, FCGR2B, PTPRC, ITGB2, ITGAM were identified. FCGR2B and TYROBP were negatively correlated with the overall survival rate in patients with ccRCC (P < 0.05). RT-qPCR analysis showed that the relative expression levels of CD86, FCGR2A, FCGR2B, TYROBP, LY86, and TLR2 were significantly higher in ccRCC samples, compared with the adjacent renal tissue groups. CONCLUSIONS: In summary, bioinformatics technology could be a useful tool to predict the progression of ccRCC. In addition, there are DEGs between ccRCC tumor tissue and normal renal tissue, and these DEGs might be considered as biomarkers for ccRCC.

Chronic Stress A Potential Suspect Zero of Atherosclerosis: A Systematic Review.

Atherosclerosis (AS) is a chronic vascular inflammatory disease, in which the lipid accumulation in the intima of the arteries shows yellow atheromatous appearance, which is the pathological basis of many diseases, such as coronary artery disease, peripheral artery disease and cerebrovascular disease. In recent years, it has become the main cause of death in the global aging society, which seriously endangers human health. As a result, research on AS is increasing. Lesions of atherosclerosis contain macrophages, T cells and other cells of the immune response, together with cholesterol that infiltrates from the blood. Recent studies have shown that chronic stress plays an important role in the occurrence and development of AS. From the etiology of disease, social, environmental and genetic factors jointly determine the occurrence of disease. Atherosclerotic cardio-cerebrovascular disease (ASCVD) is often caused by chronic stress (CS). If it cannot be effectively prevented, there will be biological changes in the body environment successively, and then the morphological changes of the corresponding organs. If the patient has a genetic predisposition and a combination of environmental factors triggers the pathogenesis, then chronic stress can eventually lead to AS. Therefore, this paper discusses the influence of chronic stress on AS in the aspects of inflammation, lipid metabolism, endothelial dysfunction, hemodynamics and blood pressure, plaque stability, autophagy, ferroptosis, and cholesterol efflux.

Bioinformatics analysis of gene and microRNA targets for fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is the most common chronic pain disease in middle-aged women. Patients may also complain of migraine, irritable bowel syndrome and depression, which seriously affect their work and life, causing huge economic losses to society. However, the pathogenesis of FM is still controversial and the effect of the current treatment is far from satisfactory. METHODS: Differentially expressed genes (DEGs) and miRNAs (DEMs) were found between FM and normal blood samples. The pathway and process enrichment analysis of the genes were performed. Protein-protein interaction network were constructed. Hub genes were found and analysed in The Comparative Toxicogenomics Database. RESULTS: A total of 102 genes were up-regulated and 46 down-regulated, 206 miRNAs down-regulated, and 15 up-regulated in FM. CD38, GATM, HDC, FOS were found as canditate genes. These genes were significantly associated with musculoskeletal disease, mental disorder, immune system disease. There was partial overlap between metformin therapy-related genes and FM-related genes. CONCLUSIONS: We found DEGs and DEMs in FM patients through bioinformatics analysis, which may be involved in the occurrence and development of FM and serve as potential targets for diagnosis and treatment.

Identification of Potential Hub Genes of Atherosclerosis Through Bioinformatic Analysis.

Cardiovascular and cerebrovascular diseases, which mainly consist of atherosclerosis (AS), are major causes of death. A great deal of research has been carried out to clarify the molecular mechanisms of AS. However, the etiology of AS remains poorly understood. To screen the potential genes of AS occurrence and development, GSE43292 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database in this study for bioinformatic analysis. First, GEO2R was used to identify differentially expressed genes (DEGs) and the functional annotation of DEGs was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Search Tool for the Retrieval of Interacting Genes (STRING) tool was used to construct the protein-protein interaction network and the most important modules and core genes were mined. The results show that a total of 211 DEGs are identified. The functional changes of DEGs are mainly associated with the cellular process, catalytic activity, and protein binding. Eighteen genes were identified as core genes. Bioinformatic analysis showed that the core genes are mainly enriched in numerous processes related to actin. In conclusion, the DEGs and hub genes identified in this study may help us understand the potential etiology of the occurrence and development of AS.