Background: Homocysteine is an important non-protein amino acid, very useful in all methylation reactions occurring in the body as the precursor of the sole methyl group donor S-Adenosyl-methionine (SAM). However, ele...Background: Homocysteine is an important non-protein amino acid, very useful in all methylation reactions occurring in the body as the precursor of the sole methyl group donor S-Adenosyl-methionine (SAM). However, elevated plasma homocysteine levels have been reported to contribute to epithelial damage leading to coronary artery disease and other metabolic syndromes. This study was aimed at evaluating the concentration of plasma homocysteine in diabetics and hypertensive patients in Port Harcourt, Nigeria. Methods: The study population included 60 Type II diabetes mellitus and Hypertensivesubjectsas group (I), 60 Type II diabetes mellitus and Normotensive subjects as group (II), 60 Hypertensive subjects as group (III), and 60 healthy subjects as control group within the age range of 30 - 70 years. An enzyme-linked immunosorbent assay (ELISA) method was used to quantitatively measure homocysteine in the serum sample, glycated haemoglobin were determined quantitatively using sandwich immunodetection and blood pressure was determined using mercury sphygnanometer. Statistics: The statistical analysis was done using GraphPad Prism version 9.4.1, and statistical significance was determined by a P Results: The results showed significantly higher plasma homocysteine levels in diabetics and hypertensive comorbidity patients when compared to healthy controls, P Conclusion: Our result shows an increase in plasma homocysteine levels in diabetics and hypertensives when compared to controls, and comorbidity instigates a higher increase in plasma levels when compared with the single morbidity.展开更多
This prospective case-control study aimed to assess the prevalence of hyperhomocysteinemia and explore its potential correlation with microangiopathic complications, specifically nephropathy and neuropathy, in a cohor...This prospective case-control study aimed to assess the prevalence of hyperhomocysteinemia and explore its potential correlation with microangiopathic complications, specifically nephropathy and neuropathy, in a cohort of both type 1 and type 2 diabetic patients. Conducted at the Marc Sankalé Center of Abass Ndao Hospital in Dakar from June to September 2018, the study enrolled a total of 106 diabetic patients, comprising 93 type 2 diabetics and 13 type 1 diabetics, who were matched with control subjects free from clinically detectable pathologies, based on sex and age ± 2 years. The mean age of type 1 and type 2 diabetic patients was 24.46 ± 8.41 years and 57.28 ± 11.28 years, respectively. Our findings revealed a statistically significant elevation in mean homocysteine levels among patients when compared to controls (12.63 vs. 9.88;p < 0.0001). Hyperhomocysteinemia was observed in 24.5% of the patients, exclusively among those with type 2 diabetes. Within the hyperhomocysteinemia subgroup, 58% were male, and 42% were female. The analysis of neuropathy and nephropathy frequencies among type 2 diabetic patients, stratified by homocysteine concentrations, demonstrated a notably higher prevalence of diabetic nephropathy in patients with hyperhomocysteinemia compared to those with normohomocysteinemia (23.07% vs. 8.75%;p = 0.052). Similarly, diabetic neuropathy exhibited a significantly greater frequency in patients with hyperhomocysteinemia as opposed to normohomocysteinemia (80.76% vs. 50%;p = 0.005). Furthermore, our results established a significant positive correlation between homocysteine concentrations and both age (r = 0.402;p < 0.0001) and creatinine levels (r = 0.461;p < 0.0001). Bivariate logistic regression analysis indicated that patients with hyperhomocysteinemia faced 3 times and 6 times higher risks of developing neuropathy (OR = 3.5;p = 0.061) and diabetic nephropathy (OR = 6.092;p = 0.014), respectively.展开更多
BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the ...BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization(MR).METHODS:A two-sample MR study was performed to infer the causal link.Genetically predicted plasma Hcy was selected as an instrumental variable(Ⅳ)from published genome-wide association study(GWAS)meta-analyses.COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses.The main MR analysis was performed using the inversevariance weighted(IVW)method.Additional analyses were further performed using Cochran’s Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.RESULTS:MR analysis showed no significant association between plasma Hcy and COPD.The results of the groups were consistent with the sensitivity analysis and repeated analysis,without heterogeneity or horizontal pleiotropy.The IVW results showed COPD hospital admissions(odds ratio[OR]1.06,95%confidence interval[CI]0.91-1.24,P=0.42),asthma/COPD(OR 0.97,95%CI0.89-1.06,P=0.55),COPD-related chronic infection(OR 1.50,95%CI 0.57-3.99,P=0.41),COPDI asthma/interstitial lung disease(ILD)-related pneumonia or pneumonia-derived septicemia(OR 0.93,95%CI 0.86-1.02,P=0.13),and COPD-related respiratory insufficiency(OR 1.00,95%CI 0.7-1.44,P=0.99).CONCLUSION:There is no direct causal relationship between plasma Hcy and COPD in our study.As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis,further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.展开更多
BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which ...BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.展开更多
Objective: To investigate the application of cystatin C combined with homocysteine detection in AIDS and tuberculosis complicated with hypertension. Methods: 57 patients with AIDS complicated with hypertension and 52 ...Objective: To investigate the application of cystatin C combined with homocysteine detection in AIDS and tuberculosis complicated with hypertension. Methods: 57 patients with AIDS complicated with hypertension and 52 patients with tuberculosis complicated with hypertension from Guangxi Infectious Diseases Hospital Nanning Fourth People’s Hospital/Guangxi AIDS Clinical Treatment Center (Nanning) from October 2022 to March 2023, and 196 patients with simple hypertension from Guangxi Cardiovascular Diseases Hospital Nanning Third People’s Hospital were selected as research objects. And then the difference in the detection results of cystatin C and homocysteine among the three groups was compared. Results: The detection results of serum cystatin C and homocysteine in AIDS patients with hypertension and tuberculosis patients with hypertension were higher than those in the simple hypertension group, and the difference was statistically significant (P < 0.05). However, there was no significant difference in the detection results of cystatin C or homocysteine between the AIDS hypertension group and the tuberculosis hypertension group (P > 0.05). Conclusion: The detection of cystatin C combined with homocysteine has high clinical application value in AIDS with hypertension and tuberculosis with hypertension. When AIDS is combined with hypertension or tuberculosis is combined with hypertension, cystatin C and homocysteine are at a high level, while the concentration levels of cystatin C and homocysteine are relatively low in simple hypertension. Therefore, cystatin C combined with homocysteine detection can provide better laboratory evidence for clinical diagnosis and differential diagnosis, and is worth promoting and applying.展开更多
The incidence rate of breast cancer is the second highest of all cancers.Alterations to one's epigenome are among the most critical factors in breast cancer control.In breast cancer,nutrients can influence epigene...The incidence rate of breast cancer is the second highest of all cancers.Alterations to one's epigenome are among the most critical factors in breast cancer control.In breast cancer,nutrients can influence epigenetic pathways and homocysteine(Hcy)levels.Hcy has been related to cognitive decline,Alzheimer's disease,and cancer.Similar to how altered Hcy metabolism is strongly influenced by genetic,epigenetic,and environmental factors,it is significantly linked to cancer.This review aims to discuss the relationship between the levels of Hcy in breast cancer and the effects of nutrients on epigenetic processes.Dietary interventions have the ability to control epigenetic processes,and the Hcy levels are associated with both epigenetic mechanisms and nutritional supplements in breast cancer.Certain nutrients have been discovered to have an impact on these processes.Altered Hcy metabolism is influenced by genetic,epigenetic,and environmental factors and has a substantial link to the emergence of cancer.Nutrients,such as folic acid,vitamin B12 and many phytonutrients that have been found to affect the epigenetic processes in breast cancer may alter DNA methylation and histone modification,which in turn may affect how cancer cells behave.The review emphasizes the need for additional studies to fully comprehend nutrition's potential for the epigenetic mechanism and the relation between Hcy metabolism in breast cancer.展开更多
Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients wit...Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.展开更多
Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and...Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.展开更多
Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP...Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (<18 μmol/L and ≥18 μmol/L) and hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P<0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (>3 mg/L) compared with those with low tHcy (<18 μmol/L) and hsCRP (<1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (>3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.展开更多
Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population wit...Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.展开更多
AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were include...AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thrombo- embolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). Whenmultivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events.展开更多
The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that i...The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that in the controls. There was no correlation between plasma homocys- teine levels and hypertension, smoking, concentrations of blood glucose or hypertriglyceridesemia. It was suggested that hyperhomocysteinemia may be an independent risk factor for acute cerebral vascu- lar disease.展开更多
Elevated plasma or serum total homocysteine (tHcy) level has been established as a risk factor for cardiovascular disease[1], as well as dementia and cognitive decline[2]. Plasma or serum folate and vitamin B12 influe...Elevated plasma or serum total homocysteine (tHcy) level has been established as a risk factor for cardiovascular disease[1], as well as dementia and cognitive decline[2]. Plasma or serum folate and vitamin B12 influence homocysteine (Hcy) metabolism as a co-substrate and cofactor respectively, so that low concentrations of folate and vitamin B12 are also associated with high Hcy levels[1]. However, not much information is available describing serum tHcy, folate, and vitamin B12 status in Shanghai adults, especially in a healthy population. Therefore, we hypothesize that low serum folate and vitamin B12 is associated with high Hcy in healthy adults in Shanghai. The aim of this study was to determine the status of serum tHcy, folate, and vitamin B12, and the prevalence and factors contributing to HHcy, folate deficiency, and vitamin B12 deficiency among healthy adults in Shanghai, China.展开更多
Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical...Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.展开更多
AIM: To investigate the effect of high homocysteine(Hcy) levels on apolipoprotein E(apoE) expression and the signaling pathways involved in this gene regulation.METHODS: Reverse transcriptase polymerase chain reaction...AIM: To investigate the effect of high homocysteine(Hcy) levels on apolipoprotein E(apoE) expression and the signaling pathways involved in this gene regulation.METHODS: Reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot were used to assess apo E expression in cells treated with various concentrations(50-500 μmol/L) of Hcy. Calcium phosphatetransient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2(ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcymediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKβ. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B(NF-κB), activator protein-1(AP-1) or nuclear factor of activated T cells(NFAT). Chromatin immunoprecipitation(ChI P)assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 μmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region-100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy(250-750 μmol/L) induced a 2-3 fold decrease in apoE m RNA levels in HEK-293 cells, while apo E gene expression was not significantly affected by treatment with lower concentrations of Hcy(100 μmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter activity, in the presence or absence of ME2, in a dose dependent manner, in both RAW 264.7 and HEK-293 cells, as revealed by transient transfection experiments. The downstream effectors of the signaling pathways of Hcy were also investigated. The inhibitory effect of Hcy on the apo E promoter activity was counteracted by MAPK/ERK kinase 1/2(MEK1/2) inhibitor U0126, suggesting that MEK1/2 is involved in the downregulation of apoE promoter activity by Hcy. Our data demonstrated that Hcy-induced inhibition of apoE took place through activation of NF-κB. Moreover, we demonstrated that Hcy activated a synthetic promoter containing three NF-κB binding sites, but did not affect promoters containing AP-1 or NFAT binding sites. ChI P experiments revealed that NF-κB p65 subunit is recruited to the apoE promoter following Hcy treatment of cells.CONCLUSION: Hcy-induced stress negatively modulates apoE expression via MEK1/2 and NF-κB activation. The decreased apo E expression in peripheral tissues may aggravate atherosclerosis, neurodegenerative diseases and renal dysfunctions.展开更多
Background and objectives Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine thiolactone (HcyT), one of the homocysteine metabolites in vivo, is toxic both in vivo and in vitro...Background and objectives Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine thiolactone (HcyT), one of the homocysteine metabolites in vivo, is toxic both in vivo and in vitro. The aim of this study was to investigate the effect of HcyT on apoptotic damage in human umbilical vein endothelial cells (HUVECs) and the role of antioxidants in the reduction of HcyT-induced apoptosis. Methods HUVECs were cultured in DMEM supplemented with 20% heat inactivated fetal bovine serum cell cultures were maintained in a humidified 5% CO2 atmosphere at 37 ℃. Cytotoxicity was determined by MTT assay,which consists of hypodiploid cells with propidium iodide labeling and intracellular reactive oxygen species levels using 2',7'-dichlorofluorescein diacetate as the probe by flow cytometry. Results HcyT (250-2000μM) induced HUVECs apoptosis in a time- and concentration-dependent manner. Reactive oxygen species levels rose in response to increasing HcyT concentrations at 24-h incubation.The reduction of cell apoptosis by N-acetylcysteine, vitamin E, or pyrrolidine dithiocarbamate, occurred simultaneously with a significant decrease in intracellular reactive oxygen species levels. Conclusion HcyT exerts its cytotoxic effects on endothelial cells through an apoptotic mechanism involving cellular reactive oxygen species production. The capacity of N-acetylcysteine, vitamin E, and pyrrolidine dithiocarbamate to scavenge HcyT-induced cellular reactive oxygen species correlates well with their efficiency to protect against HcyT-promoted apoptotic damage. The protective effect of pyrrolidine dithiocarbamate on cell apoptosis indicates HcyT-generated hydrogen peroxide may provoke cell apoptosis via activating nuclear factor-kappa binding protein.展开更多
AIM: To test for the association between genome-wide methylation and myopia in human and mice. METHODS: Long interspersed nucleotide element 1(LINE-1) methylation levels were used to surrogate genome-wide methylation...AIM: To test for the association between genome-wide methylation and myopia in human and mice. METHODS: Long interspersed nucleotide element 1(LINE-1) methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia(<-6 D) and LINE-1 methylation in leukocytes in 220 cases and 220 control subjects. Secondly, we validated the results of LINE-1 methylation in eyes from the form deprivation myopia(FDM) mice. Furthermore,we calculated the correlation of LINE-1 methylation levels between leukocyte DNA and ocular DNA in the mice. We also tested whether dopamine can alter LINE-1 methylation levels. RESULTS: The LINE-1 methylation level was significantly higher in the myopic human subjects than controls. The upper and middle tertiles of the methylation levels increased an approximately 2-fold(P≤0.002) risk for myopia than the lower tertile. Similarly, FDM mice had high LINE-1 methylation levels in the leukocyte, retina and sclera, and furthermore the methylation levels detected from these three tissues were significantly correlated. Immunohistochemical staining revealed higher levels of homocysteine and methionine in the rodent myopic eyes than normal eyes. Dopamine treatment to the cells reduced both LINE-1 methylation and DNA methyltransferase levels. CONCLUSION: LINE-1 hypermethylation may be associated with high myopia in human and mice. Homocysteine and methionine are accumulated in myopic eyes, which may provide excess methyl group for genome-wide methylation.展开更多
Objectives Regular consumption of moderate amounts of Chinese yellow wine is associated with a reduced risk of coronary disease. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation ha...Objectives Regular consumption of moderate amounts of Chinese yellow wine is associated with a reduced risk of coronary disease. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. The present research aimed to study the effects of Chinese yellow wine on the production of homocysteine-induced extracellular MMP-2 in cultured rats' vascular smooth muscle cells. Methods The effects of different homocysteine levels (0-1000 ?滋mol/l) on MMP-2 production, and the effects of Chinese yellow wine with low alcohol concentrations (12-19%) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells (VSMCs) were examined using gelatin zymography and western blotting. The changes of MMP-2 under various treatments for 12 h, 24 h and 48 h were further compared. Results Homocysteine (50-1000 ?滋mol/l) increased the production of MMP-2 significantly in a dose-dependent manner. Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added Chinese yellow wine. Production of MMP-2 under various treatments for 48 h increased more than 12 h and 24 h. Conclusions Extracellularly added Chinese yellow wine decreased homocysteine-induced MMP-2 secretion. The inhibitory effect of yellow wine on the activation of MMP-2 might contribute to their beneficial effects on the cardiovascular system.展开更多
Objective: To observe the influence of different concentrations of homocysteine(Hcy) and hydrogen sulfide(H2S) on the secretion and activation of matix metalloproteinase-2(MMP-2) in cardiocytes so as to search for new...Objective: To observe the influence of different concentrations of homocysteine(Hcy) and hydrogen sulfide(H2S) on the secretion and activation of matix metalloproteinase-2(MMP-2) in cardiocytes so as to search for new ways to fight against myocardial tissue fibrosis. Methods: Cardiocytes H9C2 was cultured in vitro and different concentrations of Hcy and H2 S were added for 6-h and 24-h cultivation. MTT cell proliferation assay was applied to test the activation change of cardiocytes H9C2 after affecting by different concentrations of Hcy and H2 S. ELISA and MTT were employed to detect the expression and enzymatic activity of MMP-2. Results: The H9C2 cell inhibition of activity was more significant with 1 000 μmol/L of Hcy as compared with other concentrations(P<0.001). With 2.5-100.0 μmol/L Hcy and 0.1, 1.0 and 10.0 mmol/L H2 S, the activity of H9C2 did not change significantly(P>0.05). Hcy with concentrations of 10, 50 and 100 μmol/L could increase the quantity of MMP-2 secreted by cardiocytes H9C2, and the interaction strength was concentration-dependent(P<0.05). After interacting with 100 μmol/L of Hcy for 6 h, the zymogen activation effect of MMP-2 was stronger than that of the 2.5-25 μmol/L group(P<0.05). After interacting with Hcy and H2S(1.0 mmol/L) for 6 h and 24 h, the activation effect of MMP-2 was stronger than those interacted with 10, 25, 50 and 100 μmol/L of Hcy(P<0.05). Conclusions: Hcy can increase the production of MMP-2 secreted by H9C2 cell and improve its zymogen activation. Besides, the interaction strength is concentration-dependent; while H2 S can up-regulate the activation of MMP-2 and co-promote the activation of MMP-2 with Hcy as well.展开更多
AIM: To evaluate the association between the levels of homocysteine(Hcy), folate, vitamin B12 in human immunodeficiency virus(HIV)-infected patients who were treated with antiretroviral therapy(ART) or not treated wit...AIM: To evaluate the association between the levels of homocysteine(Hcy), folate, vitamin B12 in human immunodeficiency virus(HIV)-infected patients who were treated with antiretroviral therapy(ART) or not treated with ART.METHODS: The Pub Med and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes(1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and;(2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevM an(version 5.2) was employed for data synthesis.RESULTS: A total of 12 studies were included in outcome 1(1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy(2.05 μmol/L; 95% CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations(-2.74 ng/m L; 95%CI:-5.18 to-0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis(1167 participants; 404 HIVinfected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to nonART HIV subjects(4.13 μmol/L; 95%CI: 1.34 to 6.92, P < 0.01).CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection.展开更多
文摘Background: Homocysteine is an important non-protein amino acid, very useful in all methylation reactions occurring in the body as the precursor of the sole methyl group donor S-Adenosyl-methionine (SAM). However, elevated plasma homocysteine levels have been reported to contribute to epithelial damage leading to coronary artery disease and other metabolic syndromes. This study was aimed at evaluating the concentration of plasma homocysteine in diabetics and hypertensive patients in Port Harcourt, Nigeria. Methods: The study population included 60 Type II diabetes mellitus and Hypertensivesubjectsas group (I), 60 Type II diabetes mellitus and Normotensive subjects as group (II), 60 Hypertensive subjects as group (III), and 60 healthy subjects as control group within the age range of 30 - 70 years. An enzyme-linked immunosorbent assay (ELISA) method was used to quantitatively measure homocysteine in the serum sample, glycated haemoglobin were determined quantitatively using sandwich immunodetection and blood pressure was determined using mercury sphygnanometer. Statistics: The statistical analysis was done using GraphPad Prism version 9.4.1, and statistical significance was determined by a P Results: The results showed significantly higher plasma homocysteine levels in diabetics and hypertensive comorbidity patients when compared to healthy controls, P Conclusion: Our result shows an increase in plasma homocysteine levels in diabetics and hypertensives when compared to controls, and comorbidity instigates a higher increase in plasma levels when compared with the single morbidity.
文摘This prospective case-control study aimed to assess the prevalence of hyperhomocysteinemia and explore its potential correlation with microangiopathic complications, specifically nephropathy and neuropathy, in a cohort of both type 1 and type 2 diabetic patients. Conducted at the Marc Sankalé Center of Abass Ndao Hospital in Dakar from June to September 2018, the study enrolled a total of 106 diabetic patients, comprising 93 type 2 diabetics and 13 type 1 diabetics, who were matched with control subjects free from clinically detectable pathologies, based on sex and age ± 2 years. The mean age of type 1 and type 2 diabetic patients was 24.46 ± 8.41 years and 57.28 ± 11.28 years, respectively. Our findings revealed a statistically significant elevation in mean homocysteine levels among patients when compared to controls (12.63 vs. 9.88;p < 0.0001). Hyperhomocysteinemia was observed in 24.5% of the patients, exclusively among those with type 2 diabetes. Within the hyperhomocysteinemia subgroup, 58% were male, and 42% were female. The analysis of neuropathy and nephropathy frequencies among type 2 diabetic patients, stratified by homocysteine concentrations, demonstrated a notably higher prevalence of diabetic nephropathy in patients with hyperhomocysteinemia compared to those with normohomocysteinemia (23.07% vs. 8.75%;p = 0.052). Similarly, diabetic neuropathy exhibited a significantly greater frequency in patients with hyperhomocysteinemia as opposed to normohomocysteinemia (80.76% vs. 50%;p = 0.005). Furthermore, our results established a significant positive correlation between homocysteine concentrations and both age (r = 0.402;p < 0.0001) and creatinine levels (r = 0.461;p < 0.0001). Bivariate logistic regression analysis indicated that patients with hyperhomocysteinemia faced 3 times and 6 times higher risks of developing neuropathy (OR = 3.5;p = 0.061) and diabetic nephropathy (OR = 6.092;p = 0.014), respectively.
基金supported by grants from Hainan Provincial Natural Science Foundation of China(821RC557,2019RC232)National Natural Science Foundation of China(81871611,82160647)+1 种基金Finance Science and Technology Program of Sichuan Province(2022YFS0602)Hainan Clinical Medical Research Center Project(LCYX202310)。
文摘BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization(MR).METHODS:A two-sample MR study was performed to infer the causal link.Genetically predicted plasma Hcy was selected as an instrumental variable(Ⅳ)from published genome-wide association study(GWAS)meta-analyses.COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses.The main MR analysis was performed using the inversevariance weighted(IVW)method.Additional analyses were further performed using Cochran’s Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.RESULTS:MR analysis showed no significant association between plasma Hcy and COPD.The results of the groups were consistent with the sensitivity analysis and repeated analysis,without heterogeneity or horizontal pleiotropy.The IVW results showed COPD hospital admissions(odds ratio[OR]1.06,95%confidence interval[CI]0.91-1.24,P=0.42),asthma/COPD(OR 0.97,95%CI0.89-1.06,P=0.55),COPD-related chronic infection(OR 1.50,95%CI 0.57-3.99,P=0.41),COPDI asthma/interstitial lung disease(ILD)-related pneumonia or pneumonia-derived septicemia(OR 0.93,95%CI 0.86-1.02,P=0.13),and COPD-related respiratory insufficiency(OR 1.00,95%CI 0.7-1.44,P=0.99).CONCLUSION:There is no direct causal relationship between plasma Hcy and COPD in our study.As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis,further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.
基金The study was reviewed and approved by the Institutional Review Board of Chaohu Hospital Affiliated to AnhuiMedical University,Approval No.KYXM-202208-011.
文摘BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.
文摘Objective: To investigate the application of cystatin C combined with homocysteine detection in AIDS and tuberculosis complicated with hypertension. Methods: 57 patients with AIDS complicated with hypertension and 52 patients with tuberculosis complicated with hypertension from Guangxi Infectious Diseases Hospital Nanning Fourth People’s Hospital/Guangxi AIDS Clinical Treatment Center (Nanning) from October 2022 to March 2023, and 196 patients with simple hypertension from Guangxi Cardiovascular Diseases Hospital Nanning Third People’s Hospital were selected as research objects. And then the difference in the detection results of cystatin C and homocysteine among the three groups was compared. Results: The detection results of serum cystatin C and homocysteine in AIDS patients with hypertension and tuberculosis patients with hypertension were higher than those in the simple hypertension group, and the difference was statistically significant (P < 0.05). However, there was no significant difference in the detection results of cystatin C or homocysteine between the AIDS hypertension group and the tuberculosis hypertension group (P > 0.05). Conclusion: The detection of cystatin C combined with homocysteine has high clinical application value in AIDS with hypertension and tuberculosis with hypertension. When AIDS is combined with hypertension or tuberculosis is combined with hypertension, cystatin C and homocysteine are at a high level, while the concentration levels of cystatin C and homocysteine are relatively low in simple hypertension. Therefore, cystatin C combined with homocysteine detection can provide better laboratory evidence for clinical diagnosis and differential diagnosis, and is worth promoting and applying.
文摘The incidence rate of breast cancer is the second highest of all cancers.Alterations to one's epigenome are among the most critical factors in breast cancer control.In breast cancer,nutrients can influence epigenetic pathways and homocysteine(Hcy)levels.Hcy has been related to cognitive decline,Alzheimer's disease,and cancer.Similar to how altered Hcy metabolism is strongly influenced by genetic,epigenetic,and environmental factors,it is significantly linked to cancer.This review aims to discuss the relationship between the levels of Hcy in breast cancer and the effects of nutrients on epigenetic processes.Dietary interventions have the ability to control epigenetic processes,and the Hcy levels are associated with both epigenetic mechanisms and nutritional supplements in breast cancer.Certain nutrients have been discovered to have an impact on these processes.Altered Hcy metabolism is influenced by genetic,epigenetic,and environmental factors and has a substantial link to the emergence of cancer.Nutrients,such as folic acid,vitamin B12 and many phytonutrients that have been found to affect the epigenetic processes in breast cancer may alter DNA methylation and histone modification,which in turn may affect how cancer cells behave.The review emphasizes the need for additional studies to fully comprehend nutrition's potential for the epigenetic mechanism and the relation between Hcy metabolism in breast cancer.
基金supported by the Project of Baoding Science and Technology Bureau(Project number:2241ZF343).
文摘Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.
文摘Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.
基金supported in part by funds from a national research project of China (Program 863) (No.2006-AA02A406)a project of the Ministry of Education of China+1 种基金a project of the National Natural Sciences Foundation of China (No.30540087)a national basic research program of China (Program 973) (No.2007CB512004)
文摘Increased plasma total homocysteine (tHcy) and high sensitivity C-reactive protein (hsCRP) levels are independent risk factors for cardiovascular disease.However, the predictive value of tHcy in combination with hsCRP in patients with stroke is not known.To determine the relationship between tHcy and hsCRP, we enrolled 291 patients with first-onset stroke (196 ischemic and 95 hemorrhagic).Plasma tHcy and hsCRP levels were measured and subsequent vascular events and deaths were determined over a 5-year period.Using the arbitrary cutoff for tHcy (<18 μmol/L and ≥18 μmol/L) and hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L), the patients were divided into 6 groups.Survival analysis showed that the probability of death or new vascular events during a 5-year follow-up increased according to tHcy and hsCRP levels (P<0.01).The relative risk (RR) of death or new vascular events was 4.67 (95% CI, 1.96 to 11.14, P=0.001) in patients with high tHcy (≥18 μmol/L) and hsCRP (>3 mg/L) compared with those with low tHcy (<18 μmol/L) and hsCRP (<1 mg/L).The increased tHcy level (≥18 μmol/L) combined with increased hsCRP level (>3 mg/L) was still significantly associated with the risk of death or new vascular events (RR, 4.10, 95% CI, 1.61 to 10.45, P=0.003) even when adjusted for other risk factors at inclusion.The combination of increased tHcy and hsCRP levels had a stronger predictive value than increased hsCRP alone or increased tHcy level alone.Further studies are required to evaluate the potential decrease in risks associated with lowering both Hcy and hsCRP levels in patients that present with both increased tHcy and hsCRP.
基金the National Key Development Plan for Precision Medicine Research(2017YFC0910004)Jinan Science Project(201602171),and Jinan Science and Technology Plan Project(201503009).
文摘Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.
文摘AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thrombo- embolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). Whenmultivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events.
文摘The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that in the controls. There was no correlation between plasma homocys- teine levels and hypertension, smoking, concentrations of blood glucose or hypertriglyceridesemia. It was suggested that hyperhomocysteinemia may be an independent risk factor for acute cerebral vascu- lar disease.
文摘Elevated plasma or serum total homocysteine (tHcy) level has been established as a risk factor for cardiovascular disease[1], as well as dementia and cognitive decline[2]. Plasma or serum folate and vitamin B12 influence homocysteine (Hcy) metabolism as a co-substrate and cofactor respectively, so that low concentrations of folate and vitamin B12 are also associated with high Hcy levels[1]. However, not much information is available describing serum tHcy, folate, and vitamin B12 status in Shanghai adults, especially in a healthy population. Therefore, we hypothesize that low serum folate and vitamin B12 is associated with high Hcy in healthy adults in Shanghai. The aim of this study was to determine the status of serum tHcy, folate, and vitamin B12, and the prevalence and factors contributing to HHcy, folate deficiency, and vitamin B12 deficiency among healthy adults in Shanghai, China.
基金supported by the Beijing Natural Science Foundation Program(Grant number:5102040)the Open Foundation of the Beijing Key Laboratory of Hypertension Research(Grant number:2015GXYB01)
文摘Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.
基金Supported by The grant of the Romanian National Authority for Scientific Research,National Research Council-Executive Agency for Higher Education,Research,Development and Innovation Funding,No.PN-II-ID-PCE-2011-3-0591(grant awarded to Gafencu AV)the Romanian Academy,and the strategic grant financed by the European Social Found within the Sectorial Operational Program Human Resources Development 2007-2013,No.POSDRU/159/1.5/S/133391(Fenyo IM and Trusca VG)
文摘AIM: To investigate the effect of high homocysteine(Hcy) levels on apolipoprotein E(apoE) expression and the signaling pathways involved in this gene regulation.METHODS: Reverse transcriptase polymerase chain reaction(RT-PCR) and Western blot were used to assess apo E expression in cells treated with various concentrations(50-500 μmol/L) of Hcy. Calcium phosphatetransient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2(ME2)]. To this aim, plasmids containing the proximal apoE promoter [(-500/+73)apoE construct] alone or in the presence of ME2 [ME2/(-500/+73)apoE construct] to drive the expression of the reporter luciferase gene were used. Co-transfection experiments were carried out to investigate the downstream effectors of Hcymediated regulation of apoE promoter by using specific inhibitors or a dominant negative form of IKβ. In other co-transfections, the luciferase reporter was under the control of synthetic promoters containing multiple specific binding sites for nuclear factor kappa B(NF-κB), activator protein-1(AP-1) or nuclear factor of activated T cells(NFAT). Chromatin immunoprecipitation(ChI P)assay was accomplished to detect the binding of NF-κB p65 subunit to the apoE promoter in HEK-293 treated with 500 μmol/L Hcy. As control, cells were incubated with similar concentration of cysteine. NF-κB p65 proteins bound to DNA were immunoprecipitated with anti-p65 antibodies and DNA was identified by PCR using primers amplifying the region-100/+4 of the apoE gene. RESULTS: RT-PCR revealed that high levels of Hcy(250-750 μmol/L) induced a 2-3 fold decrease in apoE m RNA levels in HEK-293 cells, while apo E gene expression was not significantly affected by treatment with lower concentrations of Hcy(100 μmol/L). Immunoblotting data provided additional evidence for the negative role of Hcy in apoE expression. Hcy decreased apoE promoter activity, in the presence or absence of ME2, in a dose dependent manner, in both RAW 264.7 and HEK-293 cells, as revealed by transient transfection experiments. The downstream effectors of the signaling pathways of Hcy were also investigated. The inhibitory effect of Hcy on the apo E promoter activity was counteracted by MAPK/ERK kinase 1/2(MEK1/2) inhibitor U0126, suggesting that MEK1/2 is involved in the downregulation of apoE promoter activity by Hcy. Our data demonstrated that Hcy-induced inhibition of apoE took place through activation of NF-κB. Moreover, we demonstrated that Hcy activated a synthetic promoter containing three NF-κB binding sites, but did not affect promoters containing AP-1 or NFAT binding sites. ChI P experiments revealed that NF-κB p65 subunit is recruited to the apoE promoter following Hcy treatment of cells.CONCLUSION: Hcy-induced stress negatively modulates apoE expression via MEK1/2 and NF-κB activation. The decreased apo E expression in peripheral tissues may aggravate atherosclerosis, neurodegenerative diseases and renal dysfunctions.
文摘Background and objectives Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine thiolactone (HcyT), one of the homocysteine metabolites in vivo, is toxic both in vivo and in vitro. The aim of this study was to investigate the effect of HcyT on apoptotic damage in human umbilical vein endothelial cells (HUVECs) and the role of antioxidants in the reduction of HcyT-induced apoptosis. Methods HUVECs were cultured in DMEM supplemented with 20% heat inactivated fetal bovine serum cell cultures were maintained in a humidified 5% CO2 atmosphere at 37 ℃. Cytotoxicity was determined by MTT assay,which consists of hypodiploid cells with propidium iodide labeling and intracellular reactive oxygen species levels using 2',7'-dichlorofluorescein diacetate as the probe by flow cytometry. Results HcyT (250-2000μM) induced HUVECs apoptosis in a time- and concentration-dependent manner. Reactive oxygen species levels rose in response to increasing HcyT concentrations at 24-h incubation.The reduction of cell apoptosis by N-acetylcysteine, vitamin E, or pyrrolidine dithiocarbamate, occurred simultaneously with a significant decrease in intracellular reactive oxygen species levels. Conclusion HcyT exerts its cytotoxic effects on endothelial cells through an apoptotic mechanism involving cellular reactive oxygen species production. The capacity of N-acetylcysteine, vitamin E, and pyrrolidine dithiocarbamate to scavenge HcyT-induced cellular reactive oxygen species correlates well with their efficiency to protect against HcyT-promoted apoptotic damage. The protective effect of pyrrolidine dithiocarbamate on cell apoptosis indicates HcyT-generated hydrogen peroxide may provoke cell apoptosis via activating nuclear factor-kappa binding protein.
基金Supported by the grants from the Taiwan Ministry of Science and Technology(MOST 104-2622-B-037-005)Taiwan Ministry of Health and Welfare Clinical Trial Centre(MOHW107-TDU-B-212-123004)Drug Development Center,China Medical University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan
文摘AIM: To test for the association between genome-wide methylation and myopia in human and mice. METHODS: Long interspersed nucleotide element 1(LINE-1) methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia(<-6 D) and LINE-1 methylation in leukocytes in 220 cases and 220 control subjects. Secondly, we validated the results of LINE-1 methylation in eyes from the form deprivation myopia(FDM) mice. Furthermore,we calculated the correlation of LINE-1 methylation levels between leukocyte DNA and ocular DNA in the mice. We also tested whether dopamine can alter LINE-1 methylation levels. RESULTS: The LINE-1 methylation level was significantly higher in the myopic human subjects than controls. The upper and middle tertiles of the methylation levels increased an approximately 2-fold(P≤0.002) risk for myopia than the lower tertile. Similarly, FDM mice had high LINE-1 methylation levels in the leukocyte, retina and sclera, and furthermore the methylation levels detected from these three tissues were significantly correlated. Immunohistochemical staining revealed higher levels of homocysteine and methionine in the rodent myopic eyes than normal eyes. Dopamine treatment to the cells reduced both LINE-1 methylation and DNA methyltransferase levels. CONCLUSION: LINE-1 hypermethylation may be associated with high myopia in human and mice. Homocysteine and methionine are accumulated in myopic eyes, which may provide excess methyl group for genome-wide methylation.
文摘Objectives Regular consumption of moderate amounts of Chinese yellow wine is associated with a reduced risk of coronary disease. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. The present research aimed to study the effects of Chinese yellow wine on the production of homocysteine-induced extracellular MMP-2 in cultured rats' vascular smooth muscle cells. Methods The effects of different homocysteine levels (0-1000 ?滋mol/l) on MMP-2 production, and the effects of Chinese yellow wine with low alcohol concentrations (12-19%) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells (VSMCs) were examined using gelatin zymography and western blotting. The changes of MMP-2 under various treatments for 12 h, 24 h and 48 h were further compared. Results Homocysteine (50-1000 ?滋mol/l) increased the production of MMP-2 significantly in a dose-dependent manner. Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added Chinese yellow wine. Production of MMP-2 under various treatments for 48 h increased more than 12 h and 24 h. Conclusions Extracellularly added Chinese yellow wine decreased homocysteine-induced MMP-2 secretion. The inhibitory effect of yellow wine on the activation of MMP-2 might contribute to their beneficial effects on the cardiovascular system.
基金supported by the Natural Science Foundation of Guangdong Province(Grant No.06033503)
文摘Objective: To observe the influence of different concentrations of homocysteine(Hcy) and hydrogen sulfide(H2S) on the secretion and activation of matix metalloproteinase-2(MMP-2) in cardiocytes so as to search for new ways to fight against myocardial tissue fibrosis. Methods: Cardiocytes H9C2 was cultured in vitro and different concentrations of Hcy and H2 S were added for 6-h and 24-h cultivation. MTT cell proliferation assay was applied to test the activation change of cardiocytes H9C2 after affecting by different concentrations of Hcy and H2 S. ELISA and MTT were employed to detect the expression and enzymatic activity of MMP-2. Results: The H9C2 cell inhibition of activity was more significant with 1 000 μmol/L of Hcy as compared with other concentrations(P<0.001). With 2.5-100.0 μmol/L Hcy and 0.1, 1.0 and 10.0 mmol/L H2 S, the activity of H9C2 did not change significantly(P>0.05). Hcy with concentrations of 10, 50 and 100 μmol/L could increase the quantity of MMP-2 secreted by cardiocytes H9C2, and the interaction strength was concentration-dependent(P<0.05). After interacting with 100 μmol/L of Hcy for 6 h, the zymogen activation effect of MMP-2 was stronger than that of the 2.5-25 μmol/L group(P<0.05). After interacting with Hcy and H2S(1.0 mmol/L) for 6 h and 24 h, the activation effect of MMP-2 was stronger than those interacted with 10, 25, 50 and 100 μmol/L of Hcy(P<0.05). Conclusions: Hcy can increase the production of MMP-2 secreted by H9C2 cell and improve its zymogen activation. Besides, the interaction strength is concentration-dependent; while H2 S can up-regulate the activation of MMP-2 and co-promote the activation of MMP-2 with Hcy as well.
基金Supported by Rafael Deminice is supported by Brazilian grants SETI-PR (Programa Universidade sem Fronteiras,Secretaria da Ciência,Tecnologia e Ensino Superior)
文摘AIM: To evaluate the association between the levels of homocysteine(Hcy), folate, vitamin B12 in human immunodeficiency virus(HIV)-infected patients who were treated with antiretroviral therapy(ART) or not treated with ART.METHODS: The Pub Med and Scielo databases were searched. Eligible studies regarding plasma Hcy level in HIV-infected patients were firstly identified. After careful analysis by two independent researches, the identified articles were included in the review according to two outcomes(1) Hcy, folate and vitamin B12 blood concentration in HIV-infected subjects vs health controls and;(2) Hcy blood concentration in HIV-infected subjects under ART vs not treated with ART. RevM an(version 5.2) was employed for data synthesis.RESULTS: A total of 12 studies were included in outcome 1(1649 participants, 932 cases and 717 controls). Outcome 1 meta-analysis demonstrated higher plasma Hcy(2.05 μmol/L; 95% CI: 0.10 to 4.00, P < 0.01) and decreased plasma folate concentrations(-2.74 ng/m L; 95%CI:-5.18 to-0.29, P < 0.01) in HIV-infected patients compared to healthy controls. No changes in vitamin B12 plasma concentration were observed between groups. All studies included in the outcome 2 meta-analysis(1167 participants; 404 HIVinfected exposed to ART and 757 HIV-infected non-ART patients) demonstrated higher mean Hcy concentration in subjects HIV-infected under ART compared to nonART HIV subjects(4.13 μmol/L; 95%CI: 1.34 to 6.92, P < 0.01).CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate, but not vitamin B12, were associated with HIV infection. In addition, Hcy levels were higher in HIV-infected patients who were under ART compared to HIV-infected patients who were not exposed to ART. Our results suggest that hyperhomocysteinemia should be included among the several important metabolic disturbances that are associated with ART in patients with HIV infection.
