Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying me...Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying mechanisms.Methods:The chemical composition and quality of STDP were characterized using ultra-high performance liquid chromatography,and its absorbed components were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.CMD was induced in C57BL/6J mice by feeding a 3%methionine diet for four weeks.STDP efficacy was evaluated using laser speckle perfusion imaging,tomato lectin staining,and quantification of plasma nitric oxide(NO),reactive oxygen species(ROS),and endothelial adhesion molecules(intercellular cell adhesion molecule-1[ICAM-1],vascular cell adhesion molecule-1[VCAM-1]).Network pharmacology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify potential targets and regulatory pathways.An in vitro Hcy-induced endothelial injury model was used to validate the effects of STDP on cell viability,NO production,and activation of phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)pathway.Results:STDP was stable,with 180 constituents identified in the preparation and 30 absorbed components in plasma.STDP treatment restored perfusion,increased plasma NO,decreased ROS,and downregulated ICAM-1 and VCAM-1.Network analysis identified 152 putative targets,highlighting the PI3K/Akt pathway as the central,with PIK3CA,AKT1,and NOS3 as key nodes.In vitro,STDP enhanced cell viability,NO production,and PI3K/Akt/eNOS phosphorylation,these effects were abolished by pharmacological inhibition of PI3K and eNOS.Conclusion:A 3%methionine diet for four weeks effectively induces CMD in C57BL/6J mice.STDP,rich in bioactive components,alleviates Hcy-induced CMD by activating the PI3K/Akt/eNOS pathway,thereby improving endothelial function and microvascular perfusion.These findings support STDP as a promising therapeutic candidate for CMD management.展开更多
Objective Data on homocysteine(Hcy) status and its determinants are limited among women during pregnancy and postpartum. This cross-sectional study aimed to investigate Hcy levels during pregnancy and postpartum, and ...Objective Data on homocysteine(Hcy) status and its determinants are limited among women during pregnancy and postpartum. This cross-sectional study aimed to investigate Hcy levels during pregnancy and postpartum, and to explore the determinants like geographic factor.Methods This study was conducted in women at mid-pregnancy, late-pregnancy and postpartum from southern, central and northern China. Approximately 132 women were included in each stratum by the three phases and regions. Plasma Hcy concentrations were assessed using high-performance liquid chromatography(HPLC), with hyperhomocysteinemia defined as > 10.0 μmol/L. Quantile regression was to estimate medians and interquartile ranges(IQRs), and logistic regression to examine the determinants of hyperhomocysteinemia.Results For 1,190 women included, the median(IQR) Hcy concentration was 5.66(4.62, 7.37) μmol/L.The adjusted median in mid-pregnancy, late-pregnancy and postpartum women was 4.75(4.13, 5.54),5.72(4.81, 6.85) and 7.09(5.65, 8.75) μmol/L, respectively, showing an increasing trend(P < 0.001). This increasing trend persisted across the three regions. Higher Hcy concentrations were observed in women residing in northern region and those with younger age or lower economic status. A total of 106(8.9%)women had hyperhomocysteinemia, with a higher prevalence in those residing in northern region(16.0%), or in postpartum women(16.5%).Conclusion Hcy levels, varying with geographic region, maternal age and economic status, are increased from mid-pregnancy to late-pregnancy and postpartum, indicating a need to monitor Hcy levels in pregnant and postpartum women to control potential risks related to elevated Hcy levels.展开更多
Elevated homocysteine is a clinically relevantmetabolic signal in chronic obstructive pulmonary disease(COPD).Higher circulating levels track with oxidative stress,endothelial dysfunction,mitochondrial impairment,and ...Elevated homocysteine is a clinically relevantmetabolic signal in chronic obstructive pulmonary disease(COPD).Higher circulating levels track with oxidative stress,endothelial dysfunction,mitochondrial impairment,and pulmonary vascular remodeling,rise with disease severity,and may contribute to the excess cardiovascular risk—although effect sizes and causality remain uncertain.This review centers on the homocysteine–carnitine relationship in COPD pathophysiology.Carnitine deficiency,prevalent in COPD,can worsen mitochondrial bioenergetics,promote accumulation of acyl intermediates,and reduce nitric oxide bioavailability via endothelial nitric oxide synthase uncoupling(eNOS).Conversely,restoring carnitine status in experimental and early clinical settings has been associated with lower homocysteine,improved nitric oxide signaling,and attenuation of vascular remodeling,suggesting a reciprocal link rather than a one-way pathway.We review existing evidence on various COPD phenotypes and severities,delineate mechanisms that connect homocysteine,carnitine metabolism,mitochondria,redox balance and eNOS uncoupling,and evaluate therapeutic strategies—ranging from lowering homocysteine with B-group vitamins to integrated approaches that also supportmitochondrial function and redox homeostasis,including targeted carnitine supplementation.The role of L-carnitine as a potential therapeutic agent for lowering homocysteine and improving mitochondrial and vascular function warrants further investigation,as it may help slow the progression of COPD and its related comorbidities.展开更多
BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression,causing negative distress to patients.Elevated homocysteine(Hcy)concentrations and gut microbiome dysfunction may be observed ...BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression,causing negative distress to patients.Elevated homocysteine(Hcy)concentrations and gut microbiome dysfunction may be observed in patients with depression.AIM To investigate the relationship between Hcy,microbiome,and cognition in depressive patients.METHODS We recruited 67 patients with major depressive disorder(MDD)(MDD group)and 94 healthy controls(HCs)individuals(HCs group).Serum Hcy levels were determined using the enzyme circulation method.16s rRNA sequencing was used to classify and identify the fecal bacteria.17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora,Hcy, and depressive cognitive function.RESULTSElevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients withMDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, workingmemory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed anegative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was alsosignificantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).CONCLUSIONOur results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may berelated to the physiological and pathological mechanisms underlying cognitive deficits in depression.展开更多
This study aims to explore the correlation between plasma homocysteine (Hcy) levels and the clinical grading of varicocele (VC) when analyzing the potential pathogenesis of endothelial cells injury by Hcy. A total of ...This study aims to explore the correlation between plasma homocysteine (Hcy) levels and the clinical grading of varicocele (VC) when analyzing the potential pathogenesis of endothelial cells injury by Hcy. A total of 184 VC patients, aged 18–46 years, were included in this study. These patients visited The Second Hospital of Dalian Medical University (Dalian, China), between January 2022 and September 2024. Patients were divided into three groups based on clinical grading: Group A (59 cases, Grade I), Group B (28 cases, Grade II), and Group C (97 cases, Grade III). Additionally, 120 individuals with normal fertility test results during the same period were selected as the control group. Routine blood and biochemical indices were collected from the patients. Differences in clinical indices between groups were compared, and univariate and multivariate linear regression analyses were performed to identify factors associated with clinical grading. The results showed that the median Hcy levels in the control group and in patients with Grade I, II, and III VC were 9.56 (interquartile range [IQR]: 8.66, 14.02) µmol l−1, 11.28 (IQR: 9.71, 14.55) µmol l−1, 11.84 (IQR: 10.14, 15.60) µmol l−1, and 12.27 (IQR: 9.52, 15.40) µmol l−1, respectively. The differences between the four groups were statistically significant (χ2 = 12.41, P = 0.006). Multivariate regression analysis indicated that Hcy is a factor associated with the clinical grading of VC (t = 2.53, P = 0.013). Hcy is associated with the clinical grading and may have clinical value in assessing severity of VC.展开更多
BACKGROUND Elevated plasma homocysteine(Hcy)levels are associated with increased risk of colorectal cancer(CRC),particularly in patients with systemic inflammation or AIM To evaluate serum Hcy levels as a predictive m...BACKGROUND Elevated plasma homocysteine(Hcy)levels are associated with increased risk of colorectal cancer(CRC),particularly in patients with systemic inflammation or AIM To evaluate serum Hcy levels as a predictive marker of lesion risk and CRC to prioritize patients undergoing diagnostic colonoscopy.METHODS We conducted a prospective cohort study of 301 fecal occult blood test-positive patients at San Agustín University Hospital in Asturias,Spain.Plasma Hcy levels were measured prior to the colonoscopy and classified into three thresholds:≤12,12-15,and>15μmol/L.Colonoscopy and histopathology determined the presence of low-risk,high-risk polyps or adenocarcinoma.Predictive performance of serum Hcy to detect lesions was assessed using logistic regression and diagnostic accuracy measures,including models adjusted for age and sex.RESULTS Median Hcy levels rose progressively with lesion severity,reaching 15.3μmol/L in adenocarcinoma(P<0.001).Higher levels were also observed in men and individuals aged 65 or older.A threshold above 15μmol/L showed good sensitivity(76.6%)and positive predictive value(87.2%)for detecting adenocarcinoma.When combined with age and sex,predictive accuracy improved(area under the receiver operating characteristic curve=0.706).Based on these findings,we propose a three-tier triage system:Green(≤12μmol/L in both sexes,colonoscopy within three months),Yellow(>12-15μmol/L in men,intervention within one month and red(≥15 in either sex or>12μmol/L in women,immediate colonoscopy).CONCLUSION Serum Hcy is a clinically useful biomarker for identifying high-risk colorectal lesions and cancer,particularly when interpreted in combination with age and sex.This composite model improves predictive accuracy and enables a structured three-tiered triage system that supports faster colonoscopy scheduling for at-risk groups.The traffic light approach offers a low cost,scalable strategy to reduce delays and optimize resource use in CRC screening,especially in public health systems with limited endoscopic capacity.展开更多
Diabetic liver injury is a widespread complication of diabetes and carries a high risk to liver function.Therefore,early diagnosis of diabetic liver injury is of great significance for providing quality of life for di...Diabetic liver injury is a widespread complication of diabetes and carries a high risk to liver function.Therefore,early diagnosis of diabetic liver injury is of great significance for providing quality of life for diabetic patients.Most of the activated dual-modal probes are usually activated by single factor stimulation,which greatly reduces the diagnostic accuracy of liver injury.Here,a novel cysteine(Cys)/homocysteine(Hcy)and viscosity-enhanced dual-modal probe DAL was developed for the first time to monitor diabetic liver injury and its repair process.In the presence of Cys/Hcy,the near-infrared fluorescence(NIRF)and photoacoustic(PA)signals of the probe DAL were activated,with further signal enhancement in high viscosity environments.This Cys/Hcy and viscosity cascade probe exhibits heightened sensitivity and enhanced anti-interference capabilities,contributing to the advancement of liver injury diagnosis accuracy.In addition,the probe DAL shows exceptional mitochondrial targeting ability,enabling sensitive monitoring of Cys/Hcy and viscosity alterations within mitochondria.Based on NIRF/PA dual-modal imaging technology,the probe was successfully used for the first time in a mouse diabetic liver injury model to evaluate the extent of liver damage and the repair process by tracking the levels of Cys/Hcy and viscosity.Therefore,the two-factor activated dual-modal probe developed in this study provides a powerful instrument for accurate diagnosis and efficacy evaluation of complications related to diabetes.展开更多
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 depr...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.展开更多
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 examine...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.展开更多
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...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.展开更多
Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three t...Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-KB-positve cells in the frontal cortex. Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2 diminished in the frontal cortex. In situ hybridization and western blotting revealed that N-methyi-D- aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus. These results indicate that hyperhomocysteinemia can induce brain cell apoptosis, increase nerve excitability, and promote the occurrence of preeclampsia in pregnant rats.展开更多
AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC).METHODS: Fasting ho...AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC).METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 UC patients and 50 healthy controls. Clinical data regarding UC were gathered.RESULTS: Median serum Hcys levels in UC patients were similar to those in controls (12.26 μmol/L vs 12.32 μmol/L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028). UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125;95% CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2 = 0.4; P＜0.001).CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.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
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
Objective To observe the therapeutic efficacy of moxibustion combined with mecobalamin on diabetic perineuropathy and the effects on blood homocysteine in pa ents with diabe c perineuropathy. Methods One hundred and f...Objective To observe the therapeutic efficacy of moxibustion combined with mecobalamin on diabetic perineuropathy and the effects on blood homocysteine in pa ents with diabe c perineuropathy. Methods One hundred and fifty patients with diabetic perineuropathy meeting with the inclusive criteria were randomized into a moxibus on group,a mecobalamin group and a therapeutic alliance group by using random digits table. Moxibustion was carried out on Tàixī（太溪 KI 3）,Sānyīnjiāo（三阴交 SP 6）,Zúsānl？（足三里 ST 36）,Hég？（合谷 LI 4） and Qūchí（曲池 LI 11） for the patients in the moxibustion group,the treatments were carried out once every other day,treatments for ten mes were considered as a treatment course,and totally three treatment courses were carried out. The pa ents in the mecobalamin group were orally administered with mecobalamin tablet 500 μg once,three times a day,20 days were considered as a treatment course,and totally three treatment courses were carried out. Moxibustion was carried out on the basis of oral administration with mecobalamin tablet in the therapeutic alliance group. The clinical symptoms,nerve conductive velocities and changes in blood homocysteine were observed before and after the treatments in the three groups. Results The total eff ec ve rate in the moxibus on group was 74.0%（37/50）,82.0%（41/50） in the mecobalamin group,94.0%（47/50） in the therapeutic alliance group,and the total effective rate in the therapeutic alliance group was significantly be er than the other two groups（P0.01）. The nerve conductive velocities in the mecobalamin group and the therapeutic alliance group after the treatments were significantly increased and the blood homocysteine level decreased in comparison to those before the treatments（P0.01）,while the nerve conductive velocity increased and the blood homocysteine level decreased in the therapeutic alliance group after the treatments in comparison to those in the other two groups（P0.01）. Conclusion Treatments on diabe c perineuropathy by therapeu c alliance of moxibustion and mecobalamin can not only improve symptoms of patients,increase nerve conduc ve velocity in aff ected limbs,but also decrease blood homocysteine level. The method is simple,economical and safe,and it deserves being generalized in clinical prac ces.展开更多
Objective： To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease （CHD） mortality, cardiovascular mortality or all-cause mortality in the general population by a m...Objective： To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease （CHD） mortality, cardiovascular mortality or all-cause mortality in the general population by a meta- analysis. Methods： In a systematic search conducted in the databases of PubMed and Embase prior to October 2013, we identified relevant prospective observational studies evaluating the association between baseline homocysteine levels and CHD mortality, cardiovascular or all-cause mortality in the general population. Pooled adjust risk ratio （RR） and corresponding 95% confidence interval （CI） were calculated separately for categorical risk estimates and con- tinuous risk estimates. Results： Twelve studies with 23 623 subjects were included in the meta-analysis. Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% （RR 1.66; 95% CI 1.12-2.47; P=-0.012）, cardiovascular mortality increased by 68% （RR 1.68; 95% CI 1.04-2.70; P=0.033）, and all-cause mortality increased by 93% （RR 1.93; 95% CI 1.54-2.43; P〈0.001）. Moreover, for each 5 pmol/L homocysteine increment, the pooled RR was 1.52 （95% CI 1.26-1.84; ,〈0.001） for CHD mortality, 1.32 （95% CI 1.08-1.61; P=0.006） for cardio- vascular mortality, and 1.27 （95% CI 1.03-1.55; P=-0.023） for all-cause mortality. Conclusions： Elevated homocysteine levels are an independent predictor for subsequent cardiovascular mortality or all-cause mortality, and the risks were more pronounced among elderly persons.展开更多
Objective:To investigate the effect of enalapril on plasma homocysteine(Hcy) levels and the association of methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism with the changes of Hcy levels in response to en...Objective:To investigate the effect of enalapril on plasma homocysteine(Hcy) levels and the association of methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism with the changes of Hcy levels in response to enalapril among patients with essential hypertension.Methods:A total of 130 patients with mild-to-moderate essential hypertension were enrolled and enalapril was orally administered at a dose of 10 mg/d for eight weeks.Plasma Hcy levels were measured by denaturing high-performance liquid chromatography(DHPLC) at baseline and after eight weeks of treatment.Genotyping of MTHFR C677T polymorphism was performed by TaqMan probe technique.Results:Compared with baseline,plasma Hcy levels did not change significantly after eight weeks(P=0.81).Stratified by baseline Hcy levels,a significant increase in plasma Hcy levels(P=0.02) among those with Hcy <10 μmol/L was observed,in contrast to no significant changes in plasma Hcy levels(P=0.54) among those with Hcy ≥10 μmol/L.No significant association was observed between MTHFR C677T polymorphism and changes in Hcy levels in response to enalapril.Conclusions:Enalapril may cause an increase in plasma Hcy levels among the hypertensives with low baseline Hcy levels.There was no significant association between MTHFR C677T genotypes and changes in Hcy levels in response to enalapril among subjects with essential hypertension.展开更多
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 t...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.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
基金supported by the National Key Research and Development Program of China(2022YFC3500100)the National Natural Science Foundation of China(82230126 and U24A20800)+2 种基金the National Science and Technology Major Project of the Ministry of Science and Technology of China(2023ZD0502600)National Science Fund for Excellent Young Scholars(82222075)the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory(Project HQL2024PZ045 and HQCML).
文摘Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying mechanisms.Methods:The chemical composition and quality of STDP were characterized using ultra-high performance liquid chromatography,and its absorbed components were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.CMD was induced in C57BL/6J mice by feeding a 3%methionine diet for four weeks.STDP efficacy was evaluated using laser speckle perfusion imaging,tomato lectin staining,and quantification of plasma nitric oxide(NO),reactive oxygen species(ROS),and endothelial adhesion molecules(intercellular cell adhesion molecule-1[ICAM-1],vascular cell adhesion molecule-1[VCAM-1]).Network pharmacology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify potential targets and regulatory pathways.An in vitro Hcy-induced endothelial injury model was used to validate the effects of STDP on cell viability,NO production,and activation of phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)pathway.Results:STDP was stable,with 180 constituents identified in the preparation and 30 absorbed components in plasma.STDP treatment restored perfusion,increased plasma NO,decreased ROS,and downregulated ICAM-1 and VCAM-1.Network analysis identified 152 putative targets,highlighting the PI3K/Akt pathway as the central,with PIK3CA,AKT1,and NOS3 as key nodes.In vitro,STDP enhanced cell viability,NO production,and PI3K/Akt/eNOS phosphorylation,these effects were abolished by pharmacological inhibition of PI3K and eNOS.Conclusion:A 3%methionine diet for four weeks effectively induces CMD in C57BL/6J mice.STDP,rich in bioactive components,alleviates Hcy-induced CMD by activating the PI3K/Akt/eNOS pathway,thereby improving endothelial function and microvascular perfusion.These findings support STDP as a promising therapeutic candidate for CMD management.
文摘Objective Data on homocysteine(Hcy) status and its determinants are limited among women during pregnancy and postpartum. This cross-sectional study aimed to investigate Hcy levels during pregnancy and postpartum, and to explore the determinants like geographic factor.Methods This study was conducted in women at mid-pregnancy, late-pregnancy and postpartum from southern, central and northern China. Approximately 132 women were included in each stratum by the three phases and regions. Plasma Hcy concentrations were assessed using high-performance liquid chromatography(HPLC), with hyperhomocysteinemia defined as > 10.0 μmol/L. Quantile regression was to estimate medians and interquartile ranges(IQRs), and logistic regression to examine the determinants of hyperhomocysteinemia.Results For 1,190 women included, the median(IQR) Hcy concentration was 5.66(4.62, 7.37) μmol/L.The adjusted median in mid-pregnancy, late-pregnancy and postpartum women was 4.75(4.13, 5.54),5.72(4.81, 6.85) and 7.09(5.65, 8.75) μmol/L, respectively, showing an increasing trend(P < 0.001). This increasing trend persisted across the three regions. Higher Hcy concentrations were observed in women residing in northern region and those with younger age or lower economic status. A total of 106(8.9%)women had hyperhomocysteinemia, with a higher prevalence in those residing in northern region(16.0%), or in postpartum women(16.5%).Conclusion Hcy levels, varying with geographic region, maternal age and economic status, are increased from mid-pregnancy to late-pregnancy and postpartum, indicating a need to monitor Hcy levels in pregnant and postpartum women to control potential risks related to elevated Hcy levels.
基金financed by the Ryazan StateMedical University intra-university grant:Agreement No.1A/25 for the implementation of research on the topic:“Metabolic Markers of Impaired Adaptation to Hypoxia in COPD:The Role of Hyperhomocysteinemia and Carnitine Deficiency”dated 09 April 2025.
文摘Elevated homocysteine is a clinically relevantmetabolic signal in chronic obstructive pulmonary disease(COPD).Higher circulating levels track with oxidative stress,endothelial dysfunction,mitochondrial impairment,and pulmonary vascular remodeling,rise with disease severity,and may contribute to the excess cardiovascular risk—although effect sizes and causality remain uncertain.This review centers on the homocysteine–carnitine relationship in COPD pathophysiology.Carnitine deficiency,prevalent in COPD,can worsen mitochondrial bioenergetics,promote accumulation of acyl intermediates,and reduce nitric oxide bioavailability via endothelial nitric oxide synthase uncoupling(eNOS).Conversely,restoring carnitine status in experimental and early clinical settings has been associated with lower homocysteine,improved nitric oxide signaling,and attenuation of vascular remodeling,suggesting a reciprocal link rather than a one-way pathway.We review existing evidence on various COPD phenotypes and severities,delineate mechanisms that connect homocysteine,carnitine metabolism,mitochondria,redox balance and eNOS uncoupling,and evaluate therapeutic strategies—ranging from lowering homocysteine with B-group vitamins to integrated approaches that also supportmitochondrial function and redox homeostasis,including targeted carnitine supplementation.The role of L-carnitine as a potential therapeutic agent for lowering homocysteine and improving mitochondrial and vascular function warrants further investigation,as it may help slow the progression of COPD and its related comorbidities.
基金Supported by the Wuxi Municipal Health Commission Youth Fund Project,No.Q202268Wuxi Scientific and technological breakthrough of“Light of the Taihu Lake”(Basic Research),No.K20221039+4 种基金Jiangsu Shuangchuang Doctoral Program,No.JSSCBS20221991Beijing Municipal Administration of Hospital Incubating Program,No.PX2023070 and No.PX2024072Capital’s Funds for Health Improvement and Research,No.SF2024-4-2134Beijing Hospitals Authority Youth Program,No.QML20232003the Top Talent Support Program for young and middle-aged people of Wuxi Health Committee,No.HB2023089.
文摘BACKGROUND Cognitive impairment is one of the common clinical manifestations of depression,causing negative distress to patients.Elevated homocysteine(Hcy)concentrations and gut microbiome dysfunction may be observed in patients with depression.AIM To investigate the relationship between Hcy,microbiome,and cognition in depressive patients.METHODS We recruited 67 patients with major depressive disorder(MDD)(MDD group)and 94 healthy controls(HCs)individuals(HCs group).Serum Hcy levels were determined using the enzyme circulation method.16s rRNA sequencing was used to classify and identify the fecal bacteria.17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora,Hcy, and depressive cognitive function.RESULTSElevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients withMDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, workingmemory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed anegative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was alsosignificantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).CONCLUSIONOur results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may berelated to the physiological and pathological mechanisms underlying cognitive deficits in depression.
文摘This study aims to explore the correlation between plasma homocysteine (Hcy) levels and the clinical grading of varicocele (VC) when analyzing the potential pathogenesis of endothelial cells injury by Hcy. A total of 184 VC patients, aged 18–46 years, were included in this study. These patients visited The Second Hospital of Dalian Medical University (Dalian, China), between January 2022 and September 2024. Patients were divided into three groups based on clinical grading: Group A (59 cases, Grade I), Group B (28 cases, Grade II), and Group C (97 cases, Grade III). Additionally, 120 individuals with normal fertility test results during the same period were selected as the control group. Routine blood and biochemical indices were collected from the patients. Differences in clinical indices between groups were compared, and univariate and multivariate linear regression analyses were performed to identify factors associated with clinical grading. The results showed that the median Hcy levels in the control group and in patients with Grade I, II, and III VC were 9.56 (interquartile range [IQR]: 8.66, 14.02) µmol l−1, 11.28 (IQR: 9.71, 14.55) µmol l−1, 11.84 (IQR: 10.14, 15.60) µmol l−1, and 12.27 (IQR: 9.52, 15.40) µmol l−1, respectively. The differences between the four groups were statistically significant (χ2 = 12.41, P = 0.006). Multivariate regression analysis indicated that Hcy is a factor associated with the clinical grading of VC (t = 2.53, P = 0.013). Hcy is associated with the clinical grading and may have clinical value in assessing severity of VC.
文摘BACKGROUND Elevated plasma homocysteine(Hcy)levels are associated with increased risk of colorectal cancer(CRC),particularly in patients with systemic inflammation or AIM To evaluate serum Hcy levels as a predictive marker of lesion risk and CRC to prioritize patients undergoing diagnostic colonoscopy.METHODS We conducted a prospective cohort study of 301 fecal occult blood test-positive patients at San Agustín University Hospital in Asturias,Spain.Plasma Hcy levels were measured prior to the colonoscopy and classified into three thresholds:≤12,12-15,and>15μmol/L.Colonoscopy and histopathology determined the presence of low-risk,high-risk polyps or adenocarcinoma.Predictive performance of serum Hcy to detect lesions was assessed using logistic regression and diagnostic accuracy measures,including models adjusted for age and sex.RESULTS Median Hcy levels rose progressively with lesion severity,reaching 15.3μmol/L in adenocarcinoma(P<0.001).Higher levels were also observed in men and individuals aged 65 or older.A threshold above 15μmol/L showed good sensitivity(76.6%)and positive predictive value(87.2%)for detecting adenocarcinoma.When combined with age and sex,predictive accuracy improved(area under the receiver operating characteristic curve=0.706).Based on these findings,we propose a three-tier triage system:Green(≤12μmol/L in both sexes,colonoscopy within three months),Yellow(>12-15μmol/L in men,intervention within one month and red(≥15 in either sex or>12μmol/L in women,immediate colonoscopy).CONCLUSION Serum Hcy is a clinically useful biomarker for identifying high-risk colorectal lesions and cancer,particularly when interpreted in combination with age and sex.This composite model improves predictive accuracy and enables a structured three-tiered triage system that supports faster colonoscopy scheduling for at-risk groups.The traffic light approach offers a low cost,scalable strategy to reduce delays and optimize resource use in CRC screening,especially in public health systems with limited endoscopic capacity.
基金financially supported by the National Natural Science Foundation of China(Nos.21877048,22077048,and 22277014)Guangxi Natural Science Foundation(Nos.2021GXNSFDA075003,AD21220061)the Startup Fund of Guangxi University(No.A3040051003).
文摘Diabetic liver injury is a widespread complication of diabetes and carries a high risk to liver function.Therefore,early diagnosis of diabetic liver injury is of great significance for providing quality of life for diabetic patients.Most of the activated dual-modal probes are usually activated by single factor stimulation,which greatly reduces the diagnostic accuracy of liver injury.Here,a novel cysteine(Cys)/homocysteine(Hcy)and viscosity-enhanced dual-modal probe DAL was developed for the first time to monitor diabetic liver injury and its repair process.In the presence of Cys/Hcy,the near-infrared fluorescence(NIRF)and photoacoustic(PA)signals of the probe DAL were activated,with further signal enhancement in high viscosity environments.This Cys/Hcy and viscosity cascade probe exhibits heightened sensitivity and enhanced anti-interference capabilities,contributing to the advancement of liver injury diagnosis accuracy.In addition,the probe DAL shows exceptional mitochondrial targeting ability,enabling sensitive monitoring of Cys/Hcy and viscosity alterations within mitochondria.Based on NIRF/PA dual-modal imaging technology,the probe was successfully used for the first time in a mouse diabetic liver injury model to evaluate the extent of liver damage and the repair process by tracking the levels of Cys/Hcy and viscosity.Therefore,the two-factor activated dual-modal probe developed in this study provides a powerful instrument for accurate diagnosis and efficacy evaluation of complications related to diabetes.
文摘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.
文摘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.
文摘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.
基金funded by the General Project of Medical Technology of Military during the "12~(th) Five-Year Plan"Period, No. CWS11J00
文摘Hyperhomocysteinemia is an important risk factor for preeclampsia-eclampsia. This study established a pregnant rat model of hyperhomocysteinemia, in which blood plasma homocysteine concentrations were twice or three times greater than that of normal pregnant rats. TUNEL revealed an increase in the number of apoptotic cells in the frontal cortex of pregnant rats with hyperhomocysteinemia. In addition, immunohistochemical staining detected activated nuclear factor-KB-positve cells in the frontal cortex. Reverse transcription-PCR detected that mRNA expression of the anti-apoptotic gene bcl-2 diminished in the frontal cortex. In situ hybridization and western blotting revealed that N-methyi-D- aspartate receptor 1 mRNA and protein expression was upregulated in the frontal cortex and hippocampus. These results indicate that hyperhomocysteinemia can induce brain cell apoptosis, increase nerve excitability, and promote the occurrence of preeclampsia in pregnant rats.
文摘AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC).METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 UC patients and 50 healthy controls. Clinical data regarding UC were gathered.RESULTS: Median serum Hcys levels in UC patients were similar to those in controls (12.26 μmol/L vs 12.32 μmol/L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028). UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125;95% CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2 = 0.4; P＜0.001).CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.
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.
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.
文摘Objective To observe the therapeutic efficacy of moxibustion combined with mecobalamin on diabetic perineuropathy and the effects on blood homocysteine in pa ents with diabe c perineuropathy. Methods One hundred and fifty patients with diabetic perineuropathy meeting with the inclusive criteria were randomized into a moxibus on group,a mecobalamin group and a therapeutic alliance group by using random digits table. Moxibustion was carried out on Tàixī（太溪 KI 3）,Sānyīnjiāo（三阴交 SP 6）,Zúsānl？（足三里 ST 36）,Hég？（合谷 LI 4） and Qūchí（曲池 LI 11） for the patients in the moxibustion group,the treatments were carried out once every other day,treatments for ten mes were considered as a treatment course,and totally three treatment courses were carried out. The pa ents in the mecobalamin group were orally administered with mecobalamin tablet 500 μg once,three times a day,20 days were considered as a treatment course,and totally three treatment courses were carried out. Moxibustion was carried out on the basis of oral administration with mecobalamin tablet in the therapeutic alliance group. The clinical symptoms,nerve conductive velocities and changes in blood homocysteine were observed before and after the treatments in the three groups. Results The total eff ec ve rate in the moxibus on group was 74.0%（37/50）,82.0%（41/50） in the mecobalamin group,94.0%（47/50） in the therapeutic alliance group,and the total effective rate in the therapeutic alliance group was significantly be er than the other two groups（P0.01）. The nerve conductive velocities in the mecobalamin group and the therapeutic alliance group after the treatments were significantly increased and the blood homocysteine level decreased in comparison to those before the treatments（P0.01）,while the nerve conductive velocity increased and the blood homocysteine level decreased in the therapeutic alliance group after the treatments in comparison to those in the other two groups（P0.01）. Conclusion Treatments on diabe c perineuropathy by therapeu c alliance of moxibustion and mecobalamin can not only improve symptoms of patients,increase nerve conduc ve velocity in aff ected limbs,but also decrease blood homocysteine level. The method is simple,economical and safe,and it deserves being generalized in clinical prac ces.
文摘Objective： To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease （CHD） mortality, cardiovascular mortality or all-cause mortality in the general population by a meta- analysis. Methods： In a systematic search conducted in the databases of PubMed and Embase prior to October 2013, we identified relevant prospective observational studies evaluating the association between baseline homocysteine levels and CHD mortality, cardiovascular or all-cause mortality in the general population. Pooled adjust risk ratio （RR） and corresponding 95% confidence interval （CI） were calculated separately for categorical risk estimates and con- tinuous risk estimates. Results： Twelve studies with 23 623 subjects were included in the meta-analysis. Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% （RR 1.66; 95% CI 1.12-2.47; P=-0.012）, cardiovascular mortality increased by 68% （RR 1.68; 95% CI 1.04-2.70; P=0.033）, and all-cause mortality increased by 93% （RR 1.93; 95% CI 1.54-2.43; P〈0.001）. Moreover, for each 5 pmol/L homocysteine increment, the pooled RR was 1.52 （95% CI 1.26-1.84; ,〈0.001） for CHD mortality, 1.32 （95% CI 1.08-1.61; P=0.006） for cardio- vascular mortality, and 1.27 （95% CI 1.03-1.55; P=-0.023） for all-cause mortality. Conclusions： Elevated homocysteine levels are an independent predictor for subsequent cardiovascular mortality or all-cause mortality, and the risks were more pronounced among elderly persons.
文摘Objective:To investigate the effect of enalapril on plasma homocysteine(Hcy) levels and the association of methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism with the changes of Hcy levels in response to enalapril among patients with essential hypertension.Methods:A total of 130 patients with mild-to-moderate essential hypertension were enrolled and enalapril was orally administered at a dose of 10 mg/d for eight weeks.Plasma Hcy levels were measured by denaturing high-performance liquid chromatography(DHPLC) at baseline and after eight weeks of treatment.Genotyping of MTHFR C677T polymorphism was performed by TaqMan probe technique.Results:Compared with baseline,plasma Hcy levels did not change significantly after eight weeks(P=0.81).Stratified by baseline Hcy levels,a significant increase in plasma Hcy levels(P=0.02) among those with Hcy <10 μmol/L was observed,in contrast to no significant changes in plasma Hcy levels(P=0.54) among those with Hcy ≥10 μmol/L.No significant association was observed between MTHFR C677T polymorphism and changes in Hcy levels in response to enalapril.Conclusions:Enalapril may cause an increase in plasma Hcy levels among the hypertensives with low baseline Hcy levels.There was no significant association between MTHFR C677T genotypes and changes in Hcy levels in response to enalapril among subjects with essential hypertension.
基金supported by Beijing Natural Science Foundation, China (No. 7072044).
文摘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.
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.
