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.

High expression of CASP1 induces atherosclerosis.

Atherosclerosis is a chronic, progressive vascular disease. The relationship between CASP1 gene expression and atherosclerosis remains unclear. The atherosclerosis dataset GSE132651 and GSE202625 profiles were downloaded from gene expression omnibus. Differentially expressed genes (DEGs) were screened. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis, and Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEG. 47 DEGs were identified. According to gene ontology analysis, they were mainly enriched in the regulation of stimulus response, response to organic matter, extracellular region, extracellular region, and the same protein binding. Kyoto Encyclopedia of Gene and Genome analysis results showed that the target cells were mainly enriched in the PI3K-Akt signaling pathway, Ras signaling pathway, and PPAR signaling pathway. In the enrichment project of Metascape, vascular development, regulation of body fluid levels, and positive regulation of cell motility can be seen in the gene ontology enrichment project. Eleven core genes (CASP1, NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A) were obtained. IRS1, PPARG, APOE, FGF2, CCR2, and HIF1A genes are identified as core genes. Gene expression heatmap showed that CASP1 was highly expressed in atherosclerosis samples and low expressed in normal samples. NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A were low expressed in atherosclerosis samples. CTD analysis showed that 5 genes (CASP1, NLRP3, CCR2, ICAM1, HIF1A) were found to be associated with pneumonia, inflammation, cardiac enlargement, and tumor invasiveness. CASP1 gene is highly expressed in atherosclerosis. The higher the CASP1 gene, the worse the prognosis.

Influence of loneliness burden on cardio-cerebral vascular disease among the Chinese older adult: a national cohort study.

Background: Adverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult. Methods: A total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017-2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018-2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD. Results: Among participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096-1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62-72 years or in those with diabetes. Conclusion: The cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term.

Adrenal SGLT1 or SGLT2 as predictors of atherosclerosis under chronic stress based on a computer algorithm.

Background: Chronic stress promotes the development of atherosclerosis, causing disruptions in the body's hormone levels and changes in the structural function of organs. Objective: The purpose of this study was to investigate the pathological changes in the adrenal gland in a model of atherosclerosis under chronic stress and to verify the expression levels of Sodium-glucose cotransporter (SGLT) 1 and SGLT2 in the adrenal gland and their significance in the changes of adrenal gland. Methods: The model mice were constructed by chronic unpredictable stress, high-fat diet, and Apoe-/- knockout, and they were tested behaviorally at 0, 4, 8 and 12 weeks. The state of the abdominal artery was examined by ultrasound, and the pathological changes of the aorta and adrenal glands were observed by histological methods, and the expression levels and distribution of SGLT1 and SGLT2 in the adrenal gland were observed and analyzed by immunofluorescence and immunohistochemistry. The predictive value of SGLT1 and SGLT2 expression levels on intima-media thickness, internal diameter and adrenal abnormalities were verified by receiver operating characteristic (ROC) curves, support vector machine (SVM) and back-propagation (BP) neural network. Results: The results showed that chronic stress mice had elevated expression levels of SGLT1 and SGLT2. The model mice developed thickening intima-media and smaller internal diameter in the aorta, and edema, reticular fiber rupture, increased adrenal glycogen content in the adrenal glands. More importantly, analysis of ROC, SVM and BP showed that SGLT1 and SGLT2 expression levels in the adrenal glands could predict the above changes in the aorta and were also sensitive and specific predictors of adrenal abnormalities. Conclusion: SGLT1 and SGLT2 could be potential biomarkers of adrenal injury in atherosclerosis under chronic stress.

Prevalence of social frailty and its associated factors in the older Chinese population: a national cross-sectional study.

BACKGROUND: Social frailty has not been comprehensively studied in China. Our objective is to investigate the prevalence of social frailty among the older population in China, as well as identify relevant factors and urban-rural differences. METHODS: We obtained data from the Fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) database. The study employed a multistage, stratified, cluster-sampling method, recruiting a total of 224,142 adults aged 60 years or older. Participants were interviewed to gather demographic data and information on family, health and medical conditions, health care service status, living environment conditions, social participation, protected rights status, spiritual and cultural life, and health. Social frailty was assessed using the HALFE Social Frailty Index. A score of three or above indicated social frailty. RESULTS: We analyzed a total of 222,179 cases, and the overall prevalence of social frailty was found to be 15.2%. The highest prevalence was observed among participants aged 75-79 years (18.0%). The prevalence of social frailty was higher in rural older populations compared to urban older populations (19.9% in rural vs. 10.9% in urban, P < 0.0001). In urban areas, women had a higher prevalence than men (11.7% in women vs. 9.9% in men, P < 0.0001), while in rural areas, men had a higher prevalence than women (20.6% in men vs. 19.2% in women, P < 0.0001). Multivariate regression analysis revealed that living in a rural/urban environment (OR 1.789, 95% CI 1.742-1.837), absence of a spouse/spousal presence (OR 4.874, 95% CI 4.743-5.009), self-assessed unhealthy/health status (OR 1.696, 95% CI 1.633-1.761), and housing dissatisfaction/satisfaction (OR 2.303, 95% CI 2.233-2.376) were all significantly associated with social frailty. CONCLUSIONS: Using the HALFE social frailty index, we found a prevalence of 15.2% among older people in China, with the highest prevalence observed in the 75-79 age group. Social frailty was more prevalent in rural areas than in urban areas. Various factors, including spousal presence, housing satisfaction, health status, and urban-rural residential differences, were significantly associated with social frailty. These findings highlight the modifiable and non-modifiable factors that contribute to social frailty among older individuals in China.

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.

Targeting WDxR motif reprograms immune microenvironment and inhibits hepatocellular carcinoma progression.

The WD-repeat (WDR) family affects carcinogenesis, but its role in the immune microenvironment is poorly characterized. Although functional loss or gain of WDR6 does not markedly change in vitro proliferative and invasive capacity of HCC cells, its deficiency in hepa1-6 cells drastically inhibits the growth and lung metastasis of orthotopically implanted tumors in immune-competent C57BL/6J mice. Mechanistically, WDR6 targets tumor suppressor UVRAG to the CUL4A-DDB1-ROC1 E3 ubiquitin ligase complex through a unique WDxR motif and promotes its degradation. This upregulates chromatin accessibility at the TNFα locus by blocking autophagic degradation of p65, elevates intratumoral myeloid-derived suppressor cell (MDSC) number, and reduces CD8+ T cell infiltration, thereby promoting HCC progression. These immunosuppressive effects are reversed by TNFα blockade. TNFα recruits NF-κB to activate the transcription of WDR6, establishing a WDR6-TNFα loop. Clinically, the WDR6/UVRAG/NF-κB pathway is hyperactivated in HCC, predicting a poor prognosis. Importantly, a WDxR-like peptide disrupts the WDR6/UVRAG complex and enhances the efficiency of anti-PD-L1 against HCC with WDR6 dysregulation.

Self-reported prevalence and potential factors influencing cardio-cerebral vascular disease among the Chinese elderly: A national cross-sectional study.

Background: Aging is an essential national condition throughout China in the 21st century. Cardio-cerebral vascular disease (CCVD) is a common chronic vascular disease in the elderly. Despite aging becoming an increasingly pressing issue, there has been no comprehensive national investigation into the risk factors, prevalence, and management of CCVD among the elderly population in China. Materials and methods: Through the 4th Survey of the Aged Population in Urban and Rural China (SSAPUR), a nationally representative sample of 224,142 adults aged more than 60 years was surveyed using a multistage, stratified sampling method. The 4th SSAPUR was used to investigate CCVD in the elderly. Univariate and multivariate logistic proportional regression analyses explored the risk factors. These risk factors were then entered into a multivariate linear regression model to identify independent predictive factors for CCVD. Disease management was assessed from the self-reported history of physician diagnosis, treatments, and hospital visits among individuals with CCVD. Results: After excluding samples with missing information, 215,041 individuals were included in the analysis. The overall prevalence of CCVD was 26%. Living in a rural area, being older, being female, having low literacy, smoking, getting little sleep, losing a spouse, being single, not getting enough exercise, having a bad financial situation, and not taking part in public welfare programs were the main risk factors for CCVD among the elderly in China (P < 0.05). In the multivariate linear regression model, holding all other variables at any fixed value, CCVD remained associated with "urban and rural" (ß = 0.012, P < 0.001), "age" (ß = -0.003, P < 0.001), "sex" (ß = -0.022, P < 0.001), "education level" (ß = -0.017, P < 0.001), "marriage" (ß = 0.004, P = 0.047), "smoking" (ß = 0.012, P = 0.003), "drinking" (ß = -0.015, P = 0.001), and "sleep" (ß = 0.008, P = 0.005). There were no collinearity problems among these factors. Conclusion: Major risk factors for prevalent CCVD among the elderly in China include the following: rural residence, female, low literacy level, poor sleep quality, bereavement, non-marriage, living alone, lack of exercise, poor financial situation, and non-participation in public welfare activities. Chinese national policies for preventing, controlling, and managing risk factors for CCVD in the elderly must be urgently developed.

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

Objective: To investigate the prevalence of frailty and pre-frailty and its associated factors in Chinese older adults with diabetes through a nationwide cross-sectional study. Research design and methods: The data were obtained from the Sample Survey of the Aged Population in Urban and Rural China (SSAPUR), conducted in 2015, which was a cross-sectional study involving a nationally representative sample of older adults aged 60 years or more from 31 provinces, autonomous regions, and municipalities in mainland China. Subjects with diabetes were included in this study. Frailty index (FI), based on 33 potential deficits, was used to categorize individuals as robust, pre-frail, or frail. Results: A total of 18,010 older adults with diabetes were included in this study. The weighted prevalence of frailty and pre-frailty in older adults with diabetes in China was 22.7% (95% CI 22.1-23.3%) and 58.5% (95% CI 57.8-59.2%), respectively. The prevalence of frailty and pre-frailty among older adults with diabetes from different provinces/municipalities/autonomous regions was significantly different. Multinomial logistic regression analysis showed living alone, poor economic status, ADL disability, and comorbidities were strongly correlated with frailty and pre-frailty in older adults with diabetes. Conclusion: Frailty and pre-frailty are common in older adults with diabetes in China, and exhibit sociodemographic and geographic differences. In the clinical setting of older adults with diabetes, there is a need to increase awareness of frailty and to advance the early diagnosis and intervention of frailty.

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.

A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies.

Ischemic stroke is a life-threatening condition that also frequently results in long-term disability. Currently, intravenous thrombolysis with tissue plasminogen activator and mechanical thrombectomy is the most popular treatment. However, the narrow time window and related complications limit the treatment benefits. Exosomes have recently emerged as ideal therapeutic candidates for ischemic stroke with the ability to pass through the blood_brain barrier and mediate intercellular communication, in addition, exosomes and their contents can be bioengineered to implement targeted delivery. In the last two decades, exosomes and exosomal noncoding RNAs have been found to be involved in the pathophysiological progression of ischemic stroke, including atherosclerosis, apoptosis, inflammation, oxidative stress, and neurovascular remodeling. In this review, we describe the latest progress regarding the role of exosomal long noncoding RNAs and circular RNAs in the occurrence, progression, and recovery of ischemic stroke. Exploration of exosomal noncoding RNAs and their correlated effects in ischemic stroke may facilitate accurate diagnosis, and they may serve as new therapeutic targets for the disease.

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.

Beneficial Effect of Edoxaban on Preventing Atrial Fibrillation and Coagulation by Reducing Inflammation via HBG1/HBD Biomarkers.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The effectiveness and mechanism of edoxaban in preventing stroke after atrial fibrillation remain unclear. Methods: The expressions of HBG1 and HBD in red blood cells were tested in AF. Sixty C57B/6J mice were randomly divided into the following groups: the control (CON) group, atrial fibrillation (AF) group, AF + edoxaban group, and AF + rivaroxaban group. H&E staining assay and reticular fiber staining were performed. Myocardial fibrosis was evaluated by the Masson staining assay, Sirius red staining assay, and immunohistochemical assay for the expressions of α-SMA and COL1A1. ELISA and RT-PCR assay were performed for the detection of inflammatory parameters (TNF-α, IL-1ß, IL-6, and IL-10). Blood lipids were detected by using the Beckman automatic biochemical analyzer. Furthermore, four items of coagulation were detected, and molecular docking among HBG1, HBD, and MASP1 (Xa) was performed by PyMOL 2.1 software. The BP neural network model, cubic spline interpolation, and support vector machine model were constructed to predict prothrombin time based on HBG1 and HBD expressions. COIP assay was performed to construct the interaction between HBG1 and HBD. The functional enrichment analysis was performed by DAVID and Metascape tools. Results: The expressions of HBG1 and HBD in red blood cells of the patients with atrial fibrillation were decreased. The results showed a lower level of hemoglobin in red blood cells with HBG1-siRNA and HBG1-siRNA. Compared with the AF group, the collagen fiber percentage in the AF + edoxaban group was decreased (p < 0.05). After using edoxaban, the expressions of TNF-α, IL-1ß, IL-6, and IL-10 were significantly decreased (p < 0.05). The LDL-C, TC, and TG levels were downregulated in the AF + edoxaban group. The PT and APTT levels in the AF + edoxaban group were more increasing than in the AF mice (p < 0.05). Compared with the AF group, the expressions of HBG1 and HBD were downregulated in the AF + edoxaban group (p < 0.05). HBG1 protein matched well with HBD and MASP1(Xa) protein surfaces. There exists a significant interaction between HBG1, HBD, and PT via the BP neural network and support vector machine. Enrichment analysis showed that HBG1 and HBD were mainly enriched in blood coagulation. Conclusion: Edoxaban could prevent atrial fibrillation and coagulation by reducing inflammation, lipids, and fibrosis via HBG1/HBD biomarkers effectively, and the effect was superior to that of rivaroxaban.

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.

Identification of ITGAX and CCR1 as potential biomarkers of atherosclerosis via Gene Set Enrichment Analysis.

OBJECTIVE: Atherosclerosis (AS) is a life-threatening disease in aging populations worldwide. However, the molecular and gene regulation mechanisms of AS are still unclear. This study aimed to identify gene expression differences between atheroma plaques and normal tissues in humans. METHODS: The expression profiling dataset GSE43292 was obtained from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were identified between the atheroma plaques and normal tissues via GEO2R, and functional annotation of the DEGs was performed by GSEA. STRING and MCODE plug-in of Cytoscape were used to construct a protein-protein interaction (PPI) network and analyze hub genes. Finally, quantitative polymerase chain reaction (qPCR) was performed to verify the hub genes. RESULTS: Overall, 134 DEGs were screened. Functional annotation demonstrated that these DEGs were mainly enriched in sphingolipid metabolism, apoptosis, lysosome, and more. Six hub genes were identified from the PPI network: ITGAX, CCR1, IL1RN, CXCL10, CD163, and MMP9. qPCR analysis suggested that the relative expression levels of the six hub genes were significantly higher in AS samples. CONCLUSIONS: We used bioinformatics to identify six hub genes: ITGAX, CCR1, IL1RN, CXCL10, CD163, and MMP9. These hub genes are potential promising diagnostic and therapeutic targets for AS.