RESUMO
Observational studies suggest that cardiovascular disease (CVD) increases the risk of developing Alzheimer's disease (AD). However, the causal relationship between the two is not clear. This study applied a two-sample bidirectional Mendelian randomization method to explore the causal relationship between CVD and AD. Genome-wide association study (GWAS) data from 46 datasets of European populations (21,982 cases of AD and 41,944 controls) were utilized to obtain genetic instrumental variables for AD. In addition, genetic instrumental variables for atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), coronary heart disease (CHD), angina pectoris (AP), and ischemic stroke (IS) (including large-artery atherosclerotic stroke [LAS] and cardioembolic stroke [CES]) were selected from GWAS data of European populations (P < 5E-8). The inverse variance weighting method was employed as the major Mendelian randomization analysis method. Genetically predicted AD odds ratios (OR) (1.06) (95% CI: 1.02-1.10, P = 0.003) were linked to higher AP analysis. A higher genetically predicted OR for CES (0.9) (95% CI 0.82-0.99, P = 0.02) was linked to a decreased AD risk. This Mendelian randomized study identified AD as a risk factor for AP. In addition, CES was related to a reduced incidence of AD. Therefore, these modifiable risk factors are crucial targets for preventing and treating AD.
Assuntos
Doença de Alzheimer , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Análise da Randomização Mendeliana , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Causalidade , Angina PectorisRESUMO
As diabetic macroangiopathy is becoming increasingly prevalent, it is urgent to explore preventive and therapeutic drugs and study the mechanism. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ)for five consecutive days. Diabetic mice were divided into diabetic and allicin groups. After sacrifice, frozen aortic root sections were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammation cytokine-tumor necrosis factor α (TNF-α), and the remaining aortic tissues were analyzed by Western blot for the expression of proinflammation genes. In vitro, Nrf2 and inflammatory relative protein expression levels in Human Umbilical Vein Endothelial Cells (HUVECs) were examined. HUVECs proliferation and apoptosis were measured. TNF-α expression was increased in diabetic group compared to that in control group; this effect was alleviated in allicin-treated mice. Inflammation relative protein expression of Vascular Cell Adhesion Molecule 1(VCAM-1), Matrix metalloproteinase 2 (MMP-2), Inducible Nitric Oxide Synthase (iNOS), and monocyte chemotactic protein 1 (MCP-1) was higher in the diabetic group than in the control group; however, allicin treatment inhibited these diabetes-induced increase. In vitro, allicin treatment reversed the hyperglycemia-induced reduction in proliferation, and decreased the apoptosis induced by high glucose. Inflammation relative protein expression was consistent with that in vivo. Additionally, the expression of nuclear factor kappa-B (NF-κB)and Nrf2 was increased in both DM mice and HUVECs; allicin treatment induced a significant reduction in NF-κB level and improvement in Nrf2 level. Allicin alleviates inflammation caused by diabetic macroangiopathy, and the mechanism may occur via increasing Nrf2 and decreasing NF-κB.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ácidos Sulfínicos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/análise , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Angiopatias Diabéticas/imunologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Dissulfetos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação , Masculino , Camundongos Endogâmicos C57BL , Estreptozocina , Ácidos Sulfínicos/administração & dosagemRESUMO
OBJECTIVES: Lower serum uric acid (UA) levels are considered to be related to the risk to develop many neurodegenerative disorders. However, the association between serum UA level and multiple system atrophy (MSA) remains controversial. The aim of this meta-analysis was to evaluate the relationship between serum UA level and MSA. PATIENTS AND METHODS: PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched for eligible studies. Standardized mean difference (SMD) and 95% confidence intervals (95% CI) were calculated in a fixed-effects model or a random-effects model when appropriate. Subgroup analyses were carried out based on gender. A total of 6 eligible studies involving 547 MSA patients and 637 healthy individuals were identified. RESULTS: Meta-analysis results revealed that individuals with MSA had lower sera levels of UA as compared with healthy controls (pooled SMD is -0.51, 95%CI: -0.88 to -0.14; pâ¯=â¯0.006). The subgroup analysis to detect sex differences showed that the pooled SMD was -0.61 (95% CI: -0.82 to -0.40; pâ¯<â¯0.0001) for males and -0.22 (95% CI: -0.55 to 0.10; pâ¯=â¯0.18) for females compared with healthy controls. CONCLUSION: Our meta-analysis revealed that lower serum level of UA is associated with an increased risk of MSA and the relationship is significant in men but not in women.
Assuntos
Atrofia de Múltiplos Sistemas/sangue , Atrofia de Múltiplos Sistemas/epidemiologia , Ácido Úrico/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Atrofia de Múltiplos Sistemas/diagnóstico , Fatores SexuaisRESUMO
Paeonol (Pae) is an herbal extract that has attracted extensive attention for its anticancer effects demonstrated by a number of studies, which have predominantly demonstrated inhibition of cell proliferation and induction of apoptosis. The influence of Pae on cancer cell metastasis has been less widely reported. The present study aimed to investigate the underreported effects of Pae on the growth, invasion and migration of poorly differentiated BGC823 gastric cancer cells with strong invasive and metastatic abilities. The antiproliferative and proapoptotic effects of Pae on BGC823 cells were verified by Cell Counting kit8 and Annexin Vfluorescein isothiocyanate/propidium iodide assays. Cell scratchwound healing and Transwell methods were applied, and it was demonstrated that Pae could exert inhibitory activities on the invasion and migration of BGC823 cells. Furthermore, it was indicated by western blot analysis that Pae could downregulate the protein expression levels of matrix metalloproteinase (MMP)2 and 9 in a concentrationdependent manner, which may support a novel potential mechanism accounting for its anticancer effects on gastric cancer.