Application of Cystatin C Combined with Homocysteine Detection in AIDS and Tuberculosis Complicated with Hypertension

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.

Evaluation of Plasma Homocysteine Levels in Type II Diabetes and Hypertensive Patients Attending University of Port Harcourt Teaching Hospital, Nigeria

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.

Mendelian randomization study to investigate the causal relationship between plasma homocysteine and chronic obstructive pulmonary disease

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.

Association between Hyperhomocysteinemia and Microangiopathic Complications (Neuropathy and Nephropathy) in Subjects with Type 1 and Type 2 Diabetes

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.

Diagnostic and prognostic implications of non-high-density lipoprotein cholesterol and homocysteine levels for cognitive impairment in thalamic infarction

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.

The effects of smoking on blood lipids, C-reactive protein, and homocysteine in young patients with ischemic stroke

Objective:To investigate clinical significance of the effects of smoking on blood lipids, C-reactive protein,and homocysteine in young ischemic stroke patients.Methods:The clinical data of 423 young stroke patients in the department of neurology at Taihe Hospital in Shiyan City, China were retrospectively analyzed, including age,gender,drinking history,family history,and atrial fibrillation history. Patients were divided into two groups according to whether they smoked,and the blood lipids, C-reactive protein, and homocysteine were compared between groups.Results:The proportion of smokers was 41.83%.The levels of total cholesterol,triglycerides (TG), low density lipoprotein (LDL), and homocysteine were higher in patients who smoked than in those who did not(P < 0.05). High density lipoprotein (HDL) was lower in the smoking group (P < 0.05). C-reactive protein test results were divided into groups according to whether the levels exceeded the normal range or not, and no correlation was found between C-reactive protein levels and smoking(P>0.05). Conclusion:Total cholesterol, TG, LDL, HDL, and homocysteine were significantly different between stroke patients who smoked and those who did not. We therefore suggest that smoking cessation take place as soon as possible and that it be avoided entirely in order to reduce the incidence of atherosclerosis and stroke.

Latest advances in epigenetic mechanisms of nutrients in breast cancer and the relation of homocysteine mechanism

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.

Value of N-Terminal Pro B-Type Natriuretic Peptide,High-Sensitivity C-Reactive Protein,and Homocysteine Levels in Predicting Cardiovascular Events in Chronic Heart Failure Patients After Discharge

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.

Levels of serum homocysteine in depressive patients Self-correlation factor analysis and comparison with healthy subjects

BACKGROUND： Data indicate that the levels of serum homocysteine in depressive patients are higher than those in normal subjects. OBJECTIVE： To investigate the levels of serum homocysteine in patients with major depressive disorder, to determine whether serum homocysteine levels differ with sex, family history, or drug treatment, and to compare depressive patients with normal subjects. DESIGN： Non-randomized concurrent control trial. SETTING： Mental Heath Center of Shandong Province. PARTICIPANTS： Forty in-patients （23 males and 17 females, 18-63 years old） with major depressive disorder were selected from the Mental Health Center of Shandong Province from January to October 2006. All selected patients met the depressive diagnostic standard of Chinese Classification of Mental Disorder （3^rd Edition, CCMD-3）, and total scores evaluated by the 17-item Hamilton Rating Scale for Depression （HRSD） were ≥ 20. Meanwhile, 36 healthy subjects （20 males and 16 females, 18-60 years old） were enrolled as controls; their total 17-item HRSD scores were ≤ 7. All selected subjects provided consent, and the study was approved by the local ethics committee. METHODS： Fasting venous blood （3 mL） was drawn in both groups at 8：00 in the morning. The levels of serum homocysteine were determined by a fluorescence polarization immunoassay （FPIA）. The 17-item HRSD was also compiled from the patients when entering groups. The higher the scores were, the more severe the depression was. Enumeration data for both groups were compared by Chi-square test, measurement data were compared by t-test, and correlations were detected using Pearson and Spearman correlation analysis. MAIN OUTCOME MEASURES： ① Levels of serum homocysteine; ② incidence of hyperhomocysteinemia （HHcy）; ③ correlation between HRSD17 scores and levels of serum homocysteine in depressive patients. RESULTS： Forty depressive patients and 36 control subjects were included in the final analysis without any loss of participants. ① Levels of serum homocysteine and HHcy detection rate： the levels of serum homocysteine in the depressive patients were significantly higher than those in the control group （t = 4.377, P=0.000）. Hhcy detection rates were 42% （17/40） and 10% （4/36） in depressive group and control group, respectively. There was a significant difference between two groups （x^2 = 10.912, P = 0.001）. In the depressive group, there were no differences in serum homocysteine levels between males and females, before and after treatment, or between patients with positive or negative family histories of depression （t = 0.217-0.520, P 〉 0.05）. ② Correlation analysis： the HRSD17 scores in the depressive group were positively correlated with levels of serum homocysteine （r = 0.724, P = 0.000）. CONCLUSION： ① The increase in serum homocysteine levels may play an important role in the pathogenic mechanism of depressive disorder. ② The higher the levels of serum homocysteine are, the more severe the depressive disorder is. ③ There are no significant differences in serum homocysteine levels between patients of different sex or family history, or before and after drug treatment, among depressive patients.

Elevated Homocysteine and C-reactive Protein Levels Independently Predict Worsening Prognosis after Stroke in Chinese Patients

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.

Increased levels of homocysteine in patients with ulcerative colitis

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.

Plasma Homocysteine and Gene Polymorphisms Associated with the Risk of Hyperlipidemia in Northern Chinese Subjects

Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.

Association between Serum Homocysteine and Oxidative Stress in Elderly Patients with Obstructive Sleep Apnea/hypopnea Syndrome

Objective Elderly patients with obstructive sleep apnea/hypopnea syndrome （OSAHS） has a higher risk of cardiovascular and cerebrovascular disease. However, changes of homocysteine （Hey） as markers of cardiovascular and eerebrovascular disease associated with OSAHS and their mechanism have not been elucidated so far. This study aims to investigate the changes of both serum Hcy and oxidative stress and their possible links with OSAHS in elderly patients. Methods Based on polysomnogram （PSG） and age, 83 patients with OSAHS were recruited and divided into elderly-OSAHS （n=32） and non-elderly OSAHS groups （n=51）. Fifty two subjects without OSAHS were divided into elderly control （n=29） and non-elderly control groups （n-23）. A total of 135 subjects were included in the present study. All subjects were recorded for PSG variables and the contents of homocysteine （Hcy）, malonaldehyde （MDA）, and glutathione （GSH） which were detected after sleep. Serum homocysteine was measured by cyclophorase. MDA and GSH were measured by speetrophotometer. Results （1） The serum levels of Hcy showed significant difference among the four groups （P〈0.05）. The concentrations of Hcy in elderly OSAHS patients were higher than in other groups, while those in the elderly control group were higher than in the non-elderly control; the concentrations in the non-elderly OSAHS group were higher than in the non-elderly control. （2） The concentrations of MDA and GSH changed at an equal pace with Hcy in the four groups. （3） Multielement linearity regression analysis indicated a statistically significant relationship between Hcy concentration and age, MDA, GSH, and apnea hypopnea index （AHI）. Conclusions （1） The concentrations of Hcy and oxidative stress have increased with advancing age. （2） The concentrations of Hcy and oxidative stress have further increased in the elderly patients with OSAHS. （3） Oxidative stress might cause high-level serum Hcy in the elderly patients with OSAHS.

Study on the Relationship between Plasma Homocysteine and Acute Cerebral Vascular Disease

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.

Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL receptor-deficient mice

Background Hyperhomocysteine is an independent risk factor of coronary heart disease （CHD）. However, whether hyperhomocys teine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the forma tion of atherosclerosis in low-density lipoprotein receptor-deficient （LDLr ） mice. Methods Forty-eight 7-week-old LDLr/ mice were assigned to the following groups： mice fed a standard rodent diet （control group）, mice fed a high-methionine diet （high-methionine group）, mice fed a high-fat diet （high-fat group）, and mice fed a diet high in both methionine and fat （high-methionine and high-fat group）. At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. Results At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group （P 〈 0.001）. Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. Conclusions Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLrmice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.

Genome-wide DNA hypermethylation and homocysteine increase a risk for myopia

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.

Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension

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.

Association between serum homocysteine and arterial stiffness in elderly： a community-based study

Background Arterial stiffness and homocysteine are both powerful predictors of cardiovascular disease, especially in older popula tions. Previous studies have investigated the association of homocysteine with arterial stiffness in human subjects, while the relationship between homocysteine and arterial stiffness in the elderly is still indefinite. The current study examined the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. Methods We related serum levels of homocysteine to two measures of arte- rial stiffness （carotid-femoral pulse wave velocity （PWV） and carotid-radial PWV） in 780 participants （46.3% men, mean age 71.9 years （ranging 65-96 years old）） from two communities of Beijing, China. Arterial stiffness were measured within two days of the time of bio- marker measurement. Results In multiple-adjusted models, homocysteine levels was strongly associated with the carotid-femoral PWV （standardized 13 = 0.13, P 〈 0.001）, even after adjustment for classical risk factors of cardiovascular disease. The association is also stronger when the carotid-femoral PWV is elevated above normal, whereas no significant association with homocysteine was observed for ca-rotid-radial PWV. Conclusions In Chinese elderly persons, serum homocysteine levels are associated with alterations of aortic stiffness.

Factors influencing ischemic cerebrovascular disease complicated by hyperhomocysteinemia

BACKGROUND： Hyperhomocysteinemia, as an important risk factor for ischemic cerebrovascular disease is receiving increasing attention. OBJECTIVE： To analyze whether differences of gender, age, cerebrovascular disease typing, and disease conditions exist when ischemic cerebrovascular disease occurs together with hyperhomocysteinemia. DESIGN： A controlled observation. SETTING： Department of Neurology, Tianjin Huanhu Hospital. PARTICIPANTS： A total of 601 acute ischemic cerebrovascular disease inpatients, comprising 386 males and 215 females, aged 33-90 years old, were admitted to the Department of Stroke, Tianjin Huanhu Hospital between August 2005 and April 2007, and were recruited for this study. All included patients consisted of 342 aged patients （≥ 60 years old） and 92 middle-aged and young patients （〈 60 years old）. Among these patients, 48 suffered from transient cerebral ischemic attack, 138 from lacunar cerebral infarction, 273 from atherosclerotic stroke, 38 from cardiogenic cerebral infarction, 44 from agnogenic ischemic stroke, and 6 from other factor-induced ischemic strokes. All included inpatients corresponded to the diagnosis criteria of acute ischemic cerebrovascular disease, formulated in the 4^th National Working Conference of Cerebrovascular Disease, and were confirmed as acute ischemic cerebral infarction by CT and/or MRI examinations. Informed consents of laboratory measurements were obtained from all subjects, and this study was approved by the Hospital＇s Ethics Committee. METHODS： Following admission, 2 mL venous blood was collected from each fasting patient on the third morning. Plasma homocysteine level was measured by an enzymatic cycling assay with a CX5 reader （Beckman, USA）. Plasma homocysteine levels ≥ 16μ mol/L were defined as hyperhomocysteinemia. Clinical neurological function deficit scoring was also performed for each ischemic stroke patient using Chinese stroke scales. Scores ranged from 0 45 （0-15： mild neurological function deficits, 16-30： moderate neurological deficits, and 31-45： severe neurological deficits）. The scores positively correlated with severity of stroke. MAIN OUTCOME MEASURES： Incidence of ischemic cerebrovascular disease patients complicated by hyperhomocysteinemia and the effects of patient age and gender; plasma homocysteine levels of each type of ischemic cerebrovascular disease; and effects of ischemic cerebrovascular disease conditions on plasma homocysteine levels. RESULTS： All 601 inpatients with acute ischemic cerebrovascular disease were included in the final analysis. The detection rate of homocysteine was significantly higher in aged patients than in middle-aged and young patients （ x^2 = 5.353 0, P 〈 0.05）. The incidence of hyperhomocysteinemia was significantly higher in male patients than in female patients （ x^2 = 9.484 4, P 〈 0.05）. There was no significant difference in the incidence of hyperhomocysteinemia among various types of ischemic cerebrovascular diseases （P 〉 0.05）. No significant difference in incidence of hyperhomocysteinemia existed between mild, moderate, and severe cerebrovascular disease patients （P 〉 0.05）. CONCLUSION： There is a greater chance of ischemic cerebrovascular disease complicated by hyperhomocysteinemia in older, male patients.

Homocysteine aggravates cerebral hemorrhage in rats: Correlation with oxygen-free radical production and cell apoptosis in tissue surrounding hematoma

BACKGROUND： Previous studies have demonstrated that homocysteine is an independent risk factor for ischemic stroke, as determined by detection of apoptosis and oxygen-free radical scavengers following cerebral ischemia. However, the mechanisms of homocysteine remain unclear Several reports have addressed the effects of homocysteine on ischemic stroke. OBJECTIVE： To analyze the effects of homocysteine on apoptosis, intracellular superoxide dismutase （SOD） activity, and malondialdehyde content in tissue surrounding hematoma in rats with cerebral hemorrhage, and to determine the action pathway of malondialdehyde following cerebral hemorrhage. DESIGN, TIME AND SETTING： The randomized, controlled, animal experiment was performed at the Laboratory of Molecular Biology, Hospital Affiliated to Luzhou Medical College, China from April 2007 to April 2008. MATERIALS： In situ apoptosis detection kit （Roche, Mannheim, Germany）, SOD detection kit and malondialdehyde detection kit （Nanjing Jiancheng Bioengineering Institute, China）, and homocysteine （Sigma, St Louis, MO, USA） were used in the present study. METHODS： A total of 75 Sprague Dawley rats were equally and randomly assigned to sham surgery model, and homocysteine groups. Autologous blood was infused into the caudate putamen of rats to establish models of cerebral hemorrhage in model and homocysteine groups. Homocysteine was injected directly into the brain through the skull at the hematoma hemisphere at 30 minutes after model induction in the homocysteine group. MAIN OUTCOME MEASURES： At 6, 12, 24, and 72 hours, as well as 1 week, post-surgery, neurological deficits were observed in each group. Brain water content was measured using the dry-wet weight method. Cell apoptosis in tissue surrounding the hematoma was detected utilizing terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. SOD activity and malondialdehyde content in tissue surrounding the hematoma were respectively measured using the xanthine oxidase and thiobarbituric acid methods. RESULTS： Neurological function was similar between model and homocysteine groups following cerebral hemorrhage （P 〉 0.05）. Brain water content was increased at 12 hours post-surgery, peaked at 3 days, and remained unchanged at 7 days in the model group. Brain edema was not significantly aggravated following homocysteine intervention （P 〉 0.05）, but SOD activity significantly decreased and malondialdehyde content significantly increased （P 〈 0.05）. The number of apoptotic cells increased in rats with cerebral hemorrhage at 12 hours （P 〈 0.05）, and numbers peaked at 72 hours following model establishment （P〈 0.05）. The time of peak value was identical between model and homocysteine groups. Brain water content was negatively associated with SOD activity （rmodel group =-0.448, P 〈 0.05; rhomocysteine group =-0.612, P 〈 0.05）, but was positively associated with malondialdehyde content （rmodel group = 0.542, P 〈 0.05; rhomocysteine group = 0.684, P 〈 0.05） in brain tissues surrounding the hematoma following surgery in model and homocysteine groups. CONCLUSION： Homocysteine aggravates neurological dysfunction and brain edema in rats with cerebral hemorrhage. The mechanisms of action are likely associated with production of oxygen-free radical and cellular apoptosis following cerebral hemorrhage.