Hcy Levels Research Articles

Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke.

Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method. A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated. No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion. In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.

Dapagliflozin's effect on serum homocysteine in patients with hypertension complicated with insulin resistance.

Most patients with hypertension are complicated with insulin resistance (IR), which is one of the risk factors of hypertension and can increase the level of serum homocysteine (Hcy) by affecting Hcy's metabolic enzyme and insulin level. Investigations in recent years have shown that Hcy is an independent risk factor for cardiovascular diseases. At present, folic acid is the prominent medicine used to reduce Hcy, but its effection for Hcy has an obvious individual difference, which is closely related to individual genes. Moreover, folic acid is chiefly used in patients with Hcy ≥15μmol/L, but Hcy ≥10μmol/L has had an adverse effect on the cardiovascular system. Randomized clinical trials have shown that dapagliflozin can improve IR. Therefore, whether it can reduce Hcy has become a new direction. This study was a retrospective case-control study. Patients with high serum Hcy and hypertension complicated with IR were divided into two groups: the dapagliflozin group (n=166) and the control group (n=198). Before and after 12weeks of treatment, the changes in serum Hcy and IR index were measured and compared. We found that dapagliflozin could reduce the serum Hcy level of patients with hypertension and IR to a certain extent. Dapagliflozin could be a viable option for hypertension complicated with IR and hyperhomocysteinemia. However, these findings need to be further confirmed in future randomized clinical trials with a large number of samples.

Effects of New Antiepileptic Drugs on Homocysteine in Epileptic Patients: A Systematic Review and Meta-Analysis

Background. Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and new antiepileptic drugs (AEDs). In this meta-analysis, we aimed to assess the effects of new AEDs on Hcy. Methods. PubMed, Embase, Cochrane, and Web of Science databases were searched from inception to June 2022 for articles that focused on the effects of new AEDs on Hcy. A meta-analysis was performed using Stata 16.0 software. The results were presented as the mean difference (MD) and corresponding to 95% confidence intervals (CIs) comparing epileptic patients with new AEDs to the control subjects. Results. A total of 11 studies were included in the meta-analysis. Hcy was markedly increased in the new AEDs group compared with the control group (MD = 2.220, 95% CI: 0.596–3.844, P = 0.007 ), with a high degree of heterogeneity (I2 = 99.5%). In the drugs subgroup, the oxcarbazepine (OXC) (MD = 2.30, 95% CI: −1.11–5.72, P = 0.187 ) and lamotrigine (LTG) (MD = 1.14, 95% CI: −0.209–2.482, P < 0.001 ) groups had no significant differences when compared with the control group. The levetiracetam (LEV) (MD = 1.81, 95% CI: 1.03–2.18, P < 0.001 ) and topiramate (TPM) (MD = 6.922, 95% CI: 0.788–13.055, P = 0.027 ) groups were significantly higher than the control group. Conclusions. The new AEDs, especially TPM and LEV, may increase the plasma of Hcy. The role of Hcy in patients with epilepsy who are given TPM and LEV should not be ignored in clinical situations. Patients with epilepsy who also have a high-risk vascular profile are recommended to use OXC and LTG.

Could homocysteine represent a negative acute phase reactant in canine infections-a pilot study?

Homocysteine (Hcy) was investigated as the biomarker of cardiac, renal, and gastrointestinal disorders in dogs. Data about low Hcy concentrations in the systemic inflammatory response syndrome raised a hypothesis that Hcy in dogs is a negative acute-phase reactant. This survey compared Hcy concentrations, serum amyloid A (SAA), and the routine laboratory parameters between healthy (HD, N=6) and dogs with inflammation of different extent: mild ( dirofilariosis (DIR), N=31), moderate (babesiosis (BAB), N=12), and severe (pyometra (PYO), N=8). The BAB and PYO groups had lower Hcy er than HD. Also, the levels in the PYO group were below those in the DIRO group. SAA had the inverse pattern. Across the groups, Hcy and SAA levels correlated negatively (ρ = -0.502, P<0.001). Hcy and SAA correlated with the erythrocyte count, hematocrit, hemoglobin and mean cellular hemoglobin concentrations, and neutrophil count, with correlations being positive for Hcy and negative for SAA. Among all dogs, hemoglobin was the only independent predictor of Hcy concentration. Hcy levels in canine infections, decreased as acute-phase reaction (APR) intensified. Also, they were related with the hematology changes accompanying the APR. Further studies will establish the clinical potential of these alterations.

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia.

The aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ). Patients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons. Sixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group (p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores (r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume (r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)]. Oxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.

Association between Micronutrients and Hyperhomocysteinemia: A Case-Control Study in Northeast China.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular and cerebrovascular diseases where the plasma homocysteine (Hcy) concentration exceeds 15 µmol/L. HHcy is affected by vitamins B12, B6, and folic acid (fol); however, its relationship with other nutrients is not fully understood. We investigated the nutritional and genetic factors associated with HHcy and the possible dose-response relationships or threshold effects in patients in Northeast China. Genetic polymorphisms and micronutrients were tested with polymerase chain reaction and mass spectrometry, respectively. This trial was registered under trial number ChiCTR1900025136. The HHcy group had significantly more males and higher body mass index (BMI), methylenetetrahydrofolate reductase (MTHFR 677TT) polymorphism proportion, and uric acid, Zn, Fe, P, and vitamin A levels than the control group. After adjusting for age, sex, BMI, vitamin B12, fol, and MTHFR C677T, the lowest Zn quartile reduced the odds ratio of HHcy compared with the highest Zn quartile. The dose-response curves for the association between plasma Zn and HHcy were S-shaped. High plasma Zn concentrations were significantly correlated with high HHcy odds ratios, and the curve leveled off or slightly decreased. Most importantly, HHcy risk decreased with decreasing plasma Zn concentration; the threshold was 83.89 µmol/L. Conclusively, individuals residing in Northeast China, especially those with the MTHFR 677TT polymorphism, must pay attention to their plasma Zn and Hcy levels.

Hyperhomocysteinemia acts via DNA-hypomethylation to induce atherosclerosis

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis responsible for chronic and acute cardiovascular events, such as myocardial infarction, stroke, and peripheral vascular disease. The aim of this review is to evaluate the mechanisms through which increased homocysteine (Hcy) ​​levels cause atherosclerotic events. It is knonw that the amino-acid Hcy, through the trans-methylation pathway, results in S-adenosyl-methionine (SAM). In turn, SAM transfers a methyl group (-CH3) to some substrates, such as DNA, turning in S-Adenosyl-Homocysteine (SAH). But, this compound is able to inhibit DNA methyltransferase (DNT), that is the enzyme responsible for DNA methylation. The consequent DNA hypomethylation favors the Cyclin A inhibition, responsible for the atherosclerotic findings. Thus, DNA hypomethylation is a risk factor for atherosclerosis rather than HHcy, that is a simple indicator of this complication. Concordantly, several reports and large trials indicate that folate (vit. B-9) and B-6-12 vitamins supplementation, even lowers HHcy levels, did not reduce the incidence of atherosclerosis. But, that can be antagonized by the product of Hcy-transsulfuration, as H2S. Conclusively, the contemporary administration of H2S + folic acid (that antagonizes HHcy) should reduce both high Hcy serum levels and cardiovascular acute events.

Association of low-level blood lead with plasma homocysteine in US children and adolescents.

Although research in adults has revealed a positive relationship between blood lead levels (BLLs) and homocysteine (Hcy) levels in adults, few studies have investigated this relationship in children and adolescents. We evaluated the relationship between lowlevel blood lead and Hcy levels in US children and adolescents. A total of 8,313 children and adolescents aged 8-19 participated in this study via the National Health and Nutrition Examination Survey 1999-2006. Multivariable linear regression analyses were performed to examine the association between continuous BLLs and Hcy levels. The dose-dependent relationship between continuous BLLs and Hcy levels was analyzed using smooth curve fitting. The average age of participants was 14.1 ± 3.3 years (50.3% male). The mean values of BLLs and Hcy levels were 1.45 μg/dL and 5.77 μmol/L, respectively. In a multivariable adjusted model, an increase in 1.0 μg/dL of BLLs was associated with an elevation of 0.06 μmol/L in Hcy levels (β = 0.06, 95%CI:0.02-0.10, P = 0.001). A linear relationship between BLLs and Hcy levels was discovered using smooth curve fitting (P non-linearity = 0.464). The relationship between low-level blood lead and Hcy levels was stronger on participants with lower serum folate levels (P for interaction = 0.002). Low BLLs were positively associated with plasma Hcy levels in children and adolescents, which varies depending on the levels of folate, vitamin B, and dietary supplements involved in Hcy metabolism.

The relationship between sleep quality, snoring symptoms, night shift and risk of stroke in Chinese over 40 years old.

To analyze the relationship between sleep quality, snoring symptoms, night shift and risk of stroke in Chinese population over 40 years old. Based on the national screening and intervention program for high-risk population of stroke in 2016, 15,016 people completed the study of "the association between sleep and stroke," 58,696 people completed the snoring questionnaire, and 58,637 people completed the night shift questionnaire. The proportion of coronary heart disease, hypertension, hyperlipidemia, diabetes, snoring, atrial fibrillation, stroke and high-risk group of stroke risk rating were higher in the group with poor sleep quality (p < 0.05). The proportion of high blood pressure, hyperlipidemia, diabetes, atrial fibrillation, transient ischemic attack (TIA), or high-risk group of stroke risk rating was higher in snoring group (p < 0.05). The body mass index (BMI), waist circumference, neck circumference, fasting blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and homocysteine (Hcy) levels in snoring group were higher than the non-snoring group, and high density lipoprotein (HDL) levels were lower (p < 0.05). People with TIA, high risk for stroke, and high blood pressure were higher in night shift workers than non-night shift workers (p < 0.05). The levels of BMI, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, TG, TC, LDL, HDL and Hcy in night shift group were lower than the non-night shift group (p < 0.05). Sleep quality, snoring and night shift might be related to the risk factors of stroke.

The diagnostic value of echocardiography combined with serum Hcy and PCSK9 in coronary heart disease

ABSTRACT Coronary heart disease (CHD) is one of the most common cardiovascular diseases. This study analyzed the diagnostic value of echocardiography combined with serum homocysteine (Hcy) and proprotein convertase subtilisin 9 (PCSK9) in CHD. Here, 108 CHD patients were selected as the study group. Additionally, 108 patients with suspected CHD excluded by coronary angiography were selected as the control group. Serum Hcy and PCSK9 levels were detected by circulating enzymatic and biochemical analysis assay. The contrast echocardiography showed that the contrast agent filling velocity (β) and the maximum number of microbubbles (A) in the study group were declined compared to the control group. Serum Hcy and PCSK9 levels in the study group were higher than those in the control group. In addition, β, A, Hcy and PCSK9 are important influencing factors of CHD. The coronary artery disease branch numbers and the degree of stenosis in CHD patients were negatively correlated with β and A values, and positively correlated with serum Hcy and PCSK9 levels. β, A combined with serum Hcy and PCSK9 levels have diagnostic value for CHD, and are significantly correlated with the severity of CHD.

Potential Biomarkers and Therapeutic Targets: Inflammation and Oxidative Stress in Left Carotid Artery Stenosis with Coronary Artery Disease.

Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether markers of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2-isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.

Associations of MTHFR gene polymorphism with lipid metabolism and risk of cerebral infarction in the Northwest Han Chinese population.

Genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to the development of cerebral infarction (CI); however, results have been inconsistent across studies with different populations, including studies of the Chinese population. The aim of this study was to analyze the effect of MTHFR gene polymorphism on serum lipid and homocysteine levels among patients with CI in the Northwest Chinese Han population. A total of 521 CI patients and 524 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to identify MTHFR gene polymorphisms. Multivariate logistic regression analysis was used to assess the associations of MTHFR gene polymorphism with risk of CI. Frequencies of the TT genotype and the T allele were markedly higher among CI patients than among controls. After stratifying our data by sex and age, we determined that these differences in frequency of the TT genotype and the T allele were statistically significant among participants of two different age brackets and among men, but not among women (i.e., there were no statistically significant differences between female patients and female controls). CI patients and control participants with the CT or TT genotype had significantly higher homocysteine (Hcy) levels than those with the CC genotype. Among CI patients, CT/TT carriers showed significantly lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) levels as compared with CC carriers, but there was no significant difference for control participants. Multivariable logistic regression analysis showed that drinking; smoking; diabetes mellitus; levels of Hcy, direct bilirubin (DB), indirect bilirubin (IB), ApoA-I, and total protein (TP); and TT genotype were significant independent risk factors for CI. The results suggested that the TT genotype of the MTHFR C677T gene polymorphism, which is associated with hyperhomocysteinemia (HHcy), might be of great clinical significance in the identification of new biomarkers for CI and in the development of individualized preventive and therapeutic strategies.

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 &lt; 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 &lt; 0.05). Conclusion: NT-proBNP, hs-CRP, and Hcy levels can be used to predict CV in CHF patients, thus having clinical application value.

The association of homocysteine level with the risk of diabetic nephropathy and diabetic retinopathy in NHANES.

To examine the association of homocysteine (Hcy) with diabetic nephropathy (DN) and diabetic retinopathy (DR) in a representative United States population. This was a cross-sectional study using data from participants in the National Health and Nutrition Examination Survey 2005-2006. Metrics including Hcy level, urinary albumin to creatinine ratio, estimated glomerular filtration rate, and retinopathy grading were collected. Multiple logistic regression models were employed to assess the association of Hcy with DN and DR. 630 participants were included in this study. The Hcy level was significantly higher in those with DN and DR than those without DN and DR. Hcy was associated with an increased risk of DN (OR = 1.31, 95% CI 1.18-1.46; P < 0.001). In the fully adjusted model of DN (model II), compared to participants in quartiles 1 of Hcy, the adjusted ORs for participants in quartiles 2-4 were 1.49 (95% CI 0.52-4.26; P = 0.426), 3.81 (95% CI 1.35-10.73; P = 0.015), and 14.08 (95% CI 3.84-51.66; P = 0.001), respectively. Hcy was also associated with an increased risk of DR (OR = 2.260, 95% CI 1.212-4.216; P = 0.014), but this association was non-significant in the fully adjusted model of DR (model II). In diabetic patients, Hcy was associated with increased risk of DN in a non-linear manner. In addition, Hcy was associated with the risk of DR, but the association was attenuated after adjusting for confounders. In the future, Hcy can potentially be used as an early screening indicator for diabetic microvascular complications.

Methylenetetrahydrofolate reductase polymorphisms and elevated plasma homocysteine levels in small vessel disease.

Despite its public health importance, the causes of small vessel disease (SVD) are not fully understood. The presence of SVD in monogenic twins indicates the involvement of genetic factors in the pathogenesis of this disease. The purpose of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with SVD risk. Patients with SVD and matched controls were recruited from Tianjin Union Medical Center and Tianjin Huanhu Hospital. Clinical and laboratory data were collected. Plasma total homocysteine (tHcy) and folate levels were measured, and MTHFR rs1801133 (C677T) and rs1801131 (A1298C) single-nucleotide polymorphisms were genotyped. We analyzed potential associations among SVD and MTHFR polymorphisms, tHcy, and folate levels. Patients with SVD displayed significantly decreased plasma folate levels (Z=-3.537, p<.001) and increased tHcy levels (Z=4.910, p<.001) compared with controls. Significantly different plasma tHcy levels were associated with rs1801133 (χ2 =6.664, p=.036), and post hoc analysis indicated higher plasma tHcy levels in individuals carrying the TT allele compared with levels in those carrying the TC allele (Z=2.478, p=.013). No significant differences in tHcy levels were observed for rs1801131 alleles. The genotype and allele frequencies of rs1801133 were different between SVD and control groups (χ2 =9.378, p=.009). There was no significant difference in distributions of rs1801131 genotypes between the two groups, and multivariable logistic regression analysis showed that rs1801131 and rs1801133 were not significantly associated with the risk of SVD. Our study indicates that an elevated plasma tHcy level is independently associated with the development of SVD. Although MTHFR rs1801133 is linked to increased plasma homocysteine (Hcy) levels, it is not a risk factor for SVD. rs1801131 is not related to Hcy levels or SVD risk.

The inhibitory effect of vitamin D on myocardial homocysteine levels involves activation of Nrf2-mediated methionine synthase

BackgroundHomocysteine (Hcy) is a synthetic amino acid containing sulfhydryl group, which is an intermediate product of the deep metabolic pathway of methionine and cysteine. The abnormal increase in fasting plasma total Hcy concentration caused by various factors is called hyperhomocysteine (HHcy). HHcy is closely relevant to the occurrence and progression of diverse cardiovascular and cerebrovascular diseases, such as coronary heart disease, hypertension and diabetes, etc. Vitamin D/vitamin D receptor (VDR) pathway is pointed out that prevent cardiovascular disease by reducing serum homocysteine levels. Our research is designed to explore the potential mechanism of vitamin D in the prevention and treatment of HHcy. Methods and resultsThe Hcy and 25(OH)D3 levels in mouse myocardial tissue, serum or myocardial cells were detected using ELISA kits. The expression levels of VDR, Nrf2 and methionine synthase (MTR) were observed using Western blotting, immunohistochemistry and real time polymerase chain reaction (PCR). General information of the mice, including diet, water intake and body weight, was recorded. Vitamin D up-regulated the mRNA and protein expression of Nrf2 and MTR in mouse myocardial tissue and cells. CHIP assay determined that the combination of Nrf2 binding to the S1 site of the MTR promoter in cardiomyocytes using traditional PCR and real time PCR. Dual Luciferase Assay was applied to detect the transcriptional control of Nrf2 on MTR. The up-regulation effect of Nrf2 on MTR was verified by Nrf2 knockout and overexpression in cardiomyocytes. The role of Nrf2 in vitamin D inhibition of Hcy was revealed using Nrf2-knockdown HL-1 cells and Nrf2 heterozygous mice. Western blotting, real time PCR, IHC staining and ELISA showed that Nrf2 deficiency could restrain the increase in MTR expression and the decrease in Hcy level induced by vitamin D. The transcriptional activities of Nrf2/MTR were activated by vitamin D/VDR with a decrease in Hcy. ConclusionVitamin D/VDR upregulates MTR in an Nrf2-dependent manner, thereby reducing the risk of HHcy.

Study of Homocysteine, SDMA, ADMA, UMOD, AVP, and KIM-1 in serum of chronic renal disease patients suffering from Type-2 diabetes in Basra Province

Chronic kidney disease (CKD) is a reduction in renal function manifested by a GFR of less than 60 mL/min per 1.73 m2 or kidney damage marker, or maybe both, last about 3 months, regardless of actual cause. Diabetes mellitus (DM) seem to be the causative factors of CKD in all high- middle-income regions, as well as in numerous low country income. Mellitus accounts for 30–50% of all CKD and affects 285 million (6.4%) individuals globally. A case-control study included 30 CKD patients with T2DM and 30 healthy subjects as a control group who visited Al-Basrah Teaching Hospital in Al-Basrah province between October 2021 and February 2022. The Age average for study population was (25-60) years. Serum levels of human AVP, ADMA, KIM-1, HCY, UMOD, and SDMA were measured by a sandwich-ELISA technique. The results revealed a highly significant increase in the levels of homocysteine, SDMA, ADMA, AVP, and KIM-1 in CKD-diabetic patients (P &lt; 0.05) and a highly significant decrease in the level of UMOD (P&lt;0.05) compared to control. According to the results, we conclude: Hyperhomocysteinemia occurs in chronic and end-stage kidney diseases. A potential indicator of renal health, uromodulin allows for the early identification of CKD. This tubular secretion marker may possibly represent intrinsic "kidney function" and residual nephron mass in addition to glomerular filtration. The oxidative stress markers ADMA and SDMA are both known to contribute significantly to the emergence of endothelial dysfunction. Increased kidney damage molecule-1 and arginein vasopressin levels suggest that these molecules may be involved in the etiology of declining renal function.

Diagnostic Value of the Combined Measurement of Serum HCY and NRG4 in Type 2 Diabetes Mellitus with Early Complicating Diabetic Nephropathy

This study aimed to investigate the value of combined detection of HCY and NRG4 in the diagnosis of early diabetic kidney disease (DKD) and to explore the association between the ratio of HCY/NRG4 and DKD. A total of 140 diabetic patients and 43 healthy people were prospectively enrolled. The plasma HCY level, NRG4 level and HCY/NRG4 of them were measured to compare their differences and analyze the correlation with DKD. The independent influencing factors of patients with DKD were screened, and the nomograph of DKD occurrence was constructed. The levels of HCY and HCY/NRG4 in diabetic patients were significantly increased, while the level of NRG4 was significantly decreased (p < 0.01). The AUCs of HCY/NRG4 predicted for DKD were 0.961. HCY/NRG4 and the course of DM were independent risk factors for DKD. A predictive nomograph of DKD was constructed, and decision curve analysis (DCA) showed good clinical application value. HCY/NRG4 was positively correlated with Scr, UACR, TG, UA, BUN, TCHOL and LDL and negatively correlated with eGFR and HDL (p < 0.05). The level of HCY and NRG4 is closely related to the severity of DM, and combined detection of HCY/NRG4 can identify patients with DKD at an early stage.

Investigation of Homocysteine, Vitamin B6 and Vitamin D among Patients with Colorectal Cancer

Background and objectives: Colorectal cancer (CRC) is a disease that begins exclusively in the colon or rectum and is caused by the abnormal growth of glandular epithelial cells within the colon. Homocysteine, vitamin B6, and vitamin D are recognized to play a significant role in colorectal tumor pathogenesis. The aim of this study to investigate serum levels of Hcy, vitamin D and vitamin B6 in colorectal cancer. Methods: The current study investigated the vital roles of homocysteine, vitamin B6 and vitamin D in cancer development by comparing serum levels of colorectal cancer patients with those of the healthy control group at Nanakaly hospital. The levels of serum homocysteine (Hcy), vitamin B6 and vitamin D in 50 colorectal cancer patients and 50 from the healthy control group have been examined. Results: The result shows significantly high values of serum homocysteine (p&lt;0.0001) and significant decreases in values of vitamin B6 and vitamin D (p&lt;0.0001and 0.0010) respectively, in patients with CRC when compared with the healthy group. Conclusions: Our findings demonstrate that increased levels of homocysteine and decreased levels of vitamin B6 and vitamin D could be associated with the pathogenesis and progression of colorectal cancer.

Morphological and Functional Remodeling of the Ischemic Heart Correlates with Homocysteine Levels.

Homocysteine (Hcy) is involved in various methylation processes, and its plasma level is increased in cardiac ischemia. Thus, we hypothesized that levels of homocysteine correlate with the morphological and functional remodeling of ischemic hearts. Thus, we aimed to measure the Hcy levels in the plasma and pericardial fluid (PF) and correlate them with morphological and functional changes in the ischemic hearts of humans. Concentration of total homocysteine (tHcy) and cardiac troponin-I (cTn-I) of plasma and PF were measured in patients undergoing coronary artery bypass graft (CABG) surgery (n = 14). Left-ventricular (LV) end-diastolic diameter (LVED), LV end-systolic diameter (LVES), right atrial, left atrial (LA) area, thickness of interventricular septum (IVS) and posterior wall, LV ejection fraction (LVEF), and right ventricular outflow tract end-diastolic area (RVOT EDA) of CABG and non-cardiac patients (NCP; n = 10) were determined by echocardiography, and LV mass was calculated (cLVM). Positive correlations were found between Hcy levels of plasma and PF, tHcy levels and LVED, LVES and LA, and an inverse correlation was found between tHcy levels and LVEF. cLVM, IVS, and RVOT EDA were higher in CABG with elevated tHcy (>12 µM/L) compared to NCP. In addition, we found a higher cTn-I level in the PF compared to the plasma of CABG patients (0.08 ± 0.02 vs. 0.01 ± 0.003 ng/mL, p < 0.001), which was ~10 fold higher than the normal level. We propose that homocysteine is an important cardiac biomarker and may have an important role in the development of cardiac remodeling and dysfunction in chronic myocardial ischemia in humans.