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1.
J Cell Mol Med ; 26(12): 3557-3567, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35607269

RESUMO

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.


Assuntos
Fibrilação Atrial , MicroRNAs , Proteínas Adaptadoras de Transdução de Sinal/genética , Fibrilação Atrial/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Inflamação/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Transcriptoma
2.
Clin Exp Rheumatol ; 39(1): 21-31, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32083545

RESUMO

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.


Assuntos
Fibromialgia , MicroRNAs , Idoso , Biologia Computacional , Feminino , Fibromialgia/genética , Fibromialgia/terapia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Mapas de Interação de Proteínas
3.
Lipids Health Dis ; 18(1): 107, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043156

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) refers to a series of diseases caused by atherosclerosis (AS). It is one of the most important causes of death worldwide. According to the inflammatory response theory, macrophages play a critical role in AS. However, the potential targets associated with macrophages in the development of AS are still obscure. This study aimed to use bioinformatics tools for screening and identifying molecular targets in AS macrophages. METHODS: Two expression profiling datasets (GSE7074 and GSE9874) were obtained from the Gene Expression Omnibus dataset, and differentially expressed genes (DEGs) between non-AS macrophages and AS macrophages were identified. Functional annotation of the DEGs was performed by analyzing the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. STRING and Cytoscape were employed for constructing a protein-protein interaction network and analyzing hub genes. RESULTS: A total of 98 DEGs were distinguished between non-AS macrophages and AS macrophages. The functional variations in DEGs were mainly enriched in response to hypoxia, respiratory gaseous exchange, protein binding, and intracellular, ciliary tip, early endosome membrane, and Lys63-specific deubiquitinase activities. Three genes were identified as hub genes, including KDELR3, CD55, and DYNC2H1. CONCLUSION: Hub genes and DEGs identified by using microarray techniques can be used as diagnostic and therapeutic biomarkers for AS.


Assuntos
Aterosclerose/genética , Biomarcadores/metabolismo , Macrófagos/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Análise por Conglomerados , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Anotação de Sequência Molecular , Mapas de Interação de Proteínas/genética
4.
Lipids Health Dis ; 17(1): 143, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921279

RESUMO

BACKGROUND: The mortality of atherosclerotic cerebrovascular disease is on the rise, and changes in intimal and media thickness are a leading cause of cerebral ischemia-related death. Levels of low density lipoprotein cholesterol (LDLC), total cholesterol (TC), and chronic stress (CS) are all recognized risk factors for atherosclerosis (AS). However, the leading independent risk factor is indistinct. This study explored the effects of chronic stress, LDLC, and TC on AS and intimal and media thickness, preliminarily explored the main risk factor of AS, and analyzed the related histocyte mechanisms for macrophages and endothelial cells. METHODS: Conditions include normal, high-fat diet (HF), and HF plus CS. The correlations between intimal and media thickness and general risk factors were analyzed using χ2, Spearman's rho test, and multiple linear regression. Univariate Cox regression was used to identify potential factors that affect the non-depression time (NDT). We performed a ROC curve to determine the ability of this condition to predict the thickness. Immunohistochemistry was implemented to detect macrophagocytes and endotheliocytes. RESULTS: Based on χ2 and Spearman's rho test, LDLC, TC, and CS are all related with intimal and media thickness (P < 0.05). However, in multiple linear regression, CS is still a risk factor of thickness (P < 0.05) but LDLC and TC are not. High levels of LDLC, TC, and CS were correlated with poor NDT (P < 0.05). This condition can predict the thickness sensitively. The endarterium is richest in macrophagocytes, and the arrangement of endotheliocytes is disordered and cracked under CS. CONCLUSION: CS is the main independent risk factor for AS and intimal (and media) thickness, rather than LDLC or TC.


Assuntos
Aterosclerose/diagnóstico , LDL-Colesterol/sangue , Dieta Hiperlipídica , Hipercolesterolemia/sangue , Estresse Psicológico/complicações , Animais , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/análise , Doença Crônica , Feminino , Metabolismo dos Lipídeos , Masculino , Curva ROC , Coelhos , Fatores de Risco , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Túnica Íntima/patologia
5.
Aging (Albany NY) ; 16(9): 8260-8278, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38728374

RESUMO

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.


Assuntos
Antígenos HLA-B , Hipertensão , Inibidor Tecidual de Metaloproteinase-1 , Remodelação Ventricular , Humanos , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Remodelação Ventricular/genética , Antígenos HLA-B/genética , Hipertensão/genética , Masculino , Feminino , Pessoa de Meia-Idade , Redes Reguladoras de Genes , Biologia Computacional , Idoso , Fibrose/genética
6.
Aging (Albany NY) ; 16(10): 8980-8997, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38814181

RESUMO

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.


Assuntos
Proteínas Reguladoras de Apoptose , Hipertensão , Receptores Ativados por Proliferador de Peroxissomo , Transdução de Sinais , Humanos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Hipertensão/genética , Hipertensão/metabolismo , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Transdução de Sinais/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo
7.
J Cardiothorac Surg ; 19(1): 321, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845009

RESUMO

BACKGROUND: Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS) are complex disorders with unclear origins, underscoring the need for in-depth molecular investigations into their mechanisms. The main aim of this study is to identify the shared key genes between LQTS and BWS, shedding light on potential common molecular pathways underlying these syndromes. METHODS: The LQTS and BWS datasets are available for download from the GEO database. Differential expression genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was used to detect significant modules and central genes. Gene enrichment analysis was performed. CIBERSORT was used for immune cell infiltration analysis. The predictive protein interaction (PPI) network of core genes was constructed using STRING, and miRNAs regulating central genes were screened using TargetScan. RESULTS: Five hundred DEGs associated with Long QT Syndrome and Beckwith-Wiedemann Syndrome were identified. GSEA analysis revealed enrichment in pathways such as T cell receptor signaling, MAPK signaling, and adrenergic signaling in cardiac myocytes. Immune cell infiltration indicated higher levels of memory B cells and naive CD4 T cells. Four core genes (CD8A, ICOS, CTLA4, LCK) were identified, with CD8A and ICOS showing low expression in the syndromes and high expression in normal samples, suggesting potential inverse regulatory roles. CONCLUSION: The expression of CD8A and ICOS is low in long QT syndrome and Beckwith-Wiedemann syndrome, indicating their potential as key genes in the pathogenesis of these syndromes. The identification of shared key genes between LQTS and BWS provides insights into common molecular mechanisms underlying these disorders, potentially facilitating the development of targeted therapeutic strategies.


Assuntos
Síndrome de Beckwith-Wiedemann , Antígenos CD8 , Proteína Coestimuladora de Linfócitos T Induzíveis , Síndrome do QT Longo , Humanos , Síndrome de Beckwith-Wiedemann/genética , Antígenos CD8/genética , Antígenos CD8/metabolismo , Perfilação da Expressão Gênica/métodos , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Síndrome do QT Longo/genética
8.
Front Neurol ; 14: 1185375, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305758

RESUMO

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.

9.
Front Public Health ; 11: 1022208, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293616

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Transtornos Cerebrovasculares , Fragilidade , Masculino , Humanos , Feminino , Idoso , Fragilidade/epidemiologia , Estudos Transversais , População do Leste Asiático , Transtornos Cerebrovasculares/epidemiologia , Doenças Cardiovasculares/epidemiologia
10.
Front Public Health ; 11: 1136135, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935664

RESUMO

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.


Assuntos
Asma , Fragilidade , Humanos , Feminino , Idoso , Fragilidade/epidemiologia , Estudos Transversais , Asma/epidemiologia , China/epidemiologia , Fatores de Risco
11.
Front Public Health ; 11: 1110648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554734

RESUMO

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.


Assuntos
Fragilidade , Idoso , Humanos , Masculino , Feminino , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos Transversais , Prevalência , China/epidemiologia
12.
Front Public Health ; 11: 1168792, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397753

RESUMO

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.


Assuntos
Fragilidade , Doenças Vasculares , Idoso , Humanos , Feminino , Masculino , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos Transversais , Atividades Cotidianas , Prevalência , Etnicidade , Grupos Minoritários , China/epidemiologia
13.
Oxid Med Cell Longev ; 2022: 4121173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300174

RESUMO

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.


Assuntos
Aterosclerose/metabolismo , Estresse Fisiológico , Animais , Aterosclerose/etiologia , Humanos
14.
Front Cardiovasc Med ; 9: 948909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035950

RESUMO

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.

15.
Medicine (Baltimore) ; 101(39): e30723, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181054

RESUMO

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.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Neoplasias da Bexiga Urinária/genética , Quinase 1 Polo-Like
16.
Aging Dis ; 13(2): 373-378, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35371599

RESUMO

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.

17.
Front Cardiovasc Med ; 9: 1057361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36712273

RESUMO

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.

18.
Front Cardiovasc Med ; 8: 738654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34988123

RESUMO

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.

19.
Front Oncol ; 11: 591893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485109

RESUMO

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

20.
Comput Biol Chem ; 92: 107453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33636636

RESUMO

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.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Biologia Computacional , Neoplasias Renais/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos
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