The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension.

H-type hypertension, which is a specific form of hypertension characterized by elevated plasma homocysteine (Hcy) levels, has become a major public health challenge worldwide. This study investigated the hypotensive effects and underlying mechanisms of Huotan Jiedu Tongluo decoction (HTJDTLD), a highly effective traditional Chinese medicine formula commonly used to treat vascular stenosis. Methionine was used to induce H-type hypertension in rats, and HTJDTLD was administered intragastrically. Then, the systolic and diastolic blood pressures of the caudal artery of rats were measured by noninvasive rat caudal manometry. Histological assessment of the aorta was performed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure Hcy levels, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were used to determine the mRNA and protein levels of Glucose regulatory protein 78 (GRP78), Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinases (JNK), and caspase-3. The results showed that HTJDTLD significantly lowered blood pressure, alleviated histopathological lesions, and decreased Hcy levels after methionine treatment. Moreover, HTJDTLD significantly inhibited the gene and protein expression of GRP78, JNK, TRAF2, and caspase 3, which are involved mainly in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. Overall, the results indicated that HTJDTLD had effective antihypertensive effects in rats with H-type hypertension and revealed the antihypertensive mechanisms associated with inhibition of ER stress-induced apoptosis pathway activation.

Relationships between minerals' intake and blood homocysteine levels based on three machine learning methods: a large cross-sectional study.

BACKGROUND: Blood homocysteine (Hcy) level has become a sensitive indicator in predicting the development of cardiovascular disease. Studies have shown an association between individual mineral intake and blood Hcy levels. The effect of mixed minerals' intake on blood Hcy levels is unknown. METHODS: Data were obtained from the baseline survey data of the Shanghai Suburban Adult Cohort and Biobank(SSACB) in 2016. A total of 38273 participants aged 20-74 years met our inclusion and exclusion criteria. Food frequency questionnaire (FFQ) was used to calculate the intake of 10 minerals (calcium, potassium, magnesium, sodium, iron, zinc, selenium, phosphorus, copper and manganese). Measuring the concentration of Hcy in the morning fasting blood sample. Traditional regression models were used to assess the relationship between individual minerals' intake and blood Hcy levels. Three machine learning models (WQS, Qg-comp, and BKMR) were used to the relationship between mixed minerals' intake and blood Hcy levels, distinguishing the individual effects of each mineral and determining their respective weights in the joint effect. RESULTS: Traditional regression model showed that higher intake of calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese was associated with lower blood Hcy levels. Both Qg-comp and BKMR results consistently indicate that higher intake of mixed minerals is associated with lower blood Hcy levels. Calcium exhibits the highest weight in the joint effect in the WQS model. In Qg-comp, iron has the highest positive weight, while manganese has the highest negative weight. The BKMR results of the subsample after 10,000 iterations showed that except for sodium, all nine minerals had the high weights in the joint effect on the effect of blood Hcy levels. CONCLUSION: Overall, higher mixed mineral's intake was associated with lower blood Hcy levels, and each mineral contributed differently to the joint effect. Future studies are available to further explore the mechanisms underlying this association, and the potential impact of mixed minerals' intake on other health indicators needs to be further investigated. These efforts will help provide additional insights to deepen our understanding of mixed minerals and their potential role in health maintenance.

Non-causal relationship of polycystic ovarian syndrome with homocysteine and B vitamins: evidence from a two-sample Mendelian randomization.

Objective: Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level. Methods: A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (P<5×10-8) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results. Results: The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), P = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), P = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), P = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), P = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes. Conclusion: Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer.

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 µmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 µmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia.

OBJECTIVE: This trial analyzed high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), and macrophage migration inhibitory factor (MIF) level in serum and their correlation with symptom severity and cognitive function in patients with schizophrenia (SP). METHODS: Sixty-eight SP patients were enrolled in the SP group, and 68 healthy volunteers were in the control (CN) group. Serum hs-CRP, Hcy, and MIF were measured, and symptom severity was assessed with the Positive and Negative Symptom Scale (PANSS). Cognitive function was determined with the MATRICS Consensus Cognitive Battery (MCCB). The SP group was divided into high PANSS score (PANSS ≥70 points) and low PANSS score (PANSS <70 points), or the mild cognitive dysfunction group and severe cognitive dysfunction group according to the median MCCB score. The correlation between serum hs-CRP, Hcy, and MIF levels and PANSS and MCCB scores in SP patients was examined by Pearson correlation analysis. RESULTS: SP patients had higher serum hs-CRP, Hcy, and MIF levels and showed higher PANSS scores and lower MCCB total score. Serum hs-CRP, Hcy, and MIF levels in the high PANSS group were higher than those in the low PANSS group and in the severe cognitive dysfunction group than in the mild cognitive dysfunction group. Serum hs-CRP, Hcy, and MIF levels in SP patients were positively correlated with PANSS total score and negatively correlated with MCCB total score. CONCLUSION: High serum hs-CRP, Hcy, and MIF levels in SP patients are correlated with symptom severity and cognitive dysfunction.

Homocysteine thiolactone and other sulfur-containing amino acid metabolites are associated with fibrin clot properties and the risk of ischemic stroke.

Homocysteine (Hcy) and Hcy-thiolactone (HTL) affect fibrin clot properties and are linked to cardiovascular disease. Factors that influence fibrin clot properties and stroke are not fully understood. To study sulfur-containing amino acid metabolites, fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to stroke, we analyzed plasma and urine from 191 stroke patients (45.0% women, age 68 ± 12 years) and 291 healthy individuals (59.7% women, age 50 ± 17 years). Plasma and urinary levels of sulfur-containing amino acid metabolites and fibrin clot properties were significantly different in stroke patients compared to healthy individuals. Fibrin CLT correlated with fibrin Absmax in healthy males (R2 = 0.439, P = 0.000), females (R2 = 0.245, P = 0.000), female stroke patients (R2 = 0.187, P = 0.000), but not in male stroke patients (R2 = 0.008, P = ns). Fibrin CLT correlated with age in healthy females but not males while fibrin Absmax correlated with age in both sexes; these correlations were absent in stroke patients. In multiple regression analysis in stroke patients, plasma (p)CysGly, pMet, and MTHFR A1298C polymorphism were associated with fibrin Absmax, while urinary (u)HTL, uCysGly, and pCysGly were significantly associated with fibrin CLT. In healthy individuals, uHTL and uGSH were significantly associated with fibrin Absmax, while pGSH, and CBS T833C 844ins68 polymorphism were associated with fibrin CLT. In logistic regression, uHTL, uHcy, pCysGly, pGSH, MTHFR C677T polymorphism, and Absmax were independently associated with stroke. Our findings suggest that HTL and other sulfur-containing amino acid metabolites influence fibrin clot properties and the risk of stroke.

Associations of serum vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults.

Introduction: The effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults. Methods: The data from the National Health and Nutrition Examination Survey 2001-2002 were used to investigate the effects of serum vitamin B12 and its biomarkers (homocysteine and methylmalonic acid) on skeletal muscle health. Bone mineral density (BMD), lean mass, gait speed and knee extensor strength were used as indicators for musculoskeletal health. Results: Serum vitamin B12 level was positively correlated with the total and appendicular lean mass (ß = 584.83, P = 0.044; ß = 291.65, P = 0.043) in older adults over 65 years of age. In the full population, plasma homocysteine was associated with total lean mass, appendicular lean mass, gait speed, and knee extensor strength (all P < 0.05). Among older adults over 65 years of age, homocysteine level was significantly negatively correlated with gait speed and knee extensor strength (ß = -12.75, P = 0.019; ß = -0.06, P <0.001). Plasma methylmalonic acid was negatively associated with total BMD and femur BMD in the full population (ß = -0.01, P = 0.018; ß = -0.01, P = 0.004). In older adults, methylmalonic acid significantly affected total BMD, femur BMD and knee extensor strength (ß = -0.01, P = 0.048; ß = -0.01, P = 0.025; ß = -7.53, P = 0.015). Conclusions: Vitamin B12 and its biomarkers are closely related to BMD, body composition, muscle strength and physical function in middle-aged and older adults. Vitamin B12 may be an important indicator of musculoskeletal health in the elderly.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.

The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.

High plasma homocysteine levels predict the progression from mild cognitive impairment to dementia.

High levels of blood homocysteine (HCy), a well-known cardiovascular risk factor and promoter of oxidative stress, have been associated with the incidence of cognitive impairment and dementia. Nonetheless, contrasting data are still present on its involvement in the progression from Mild Cognitive Impairment (MCI) to overt dementia. In this study we aimed to observe whether blood HCy level are associated with the evolution from MCI, divided into amnestic MCI (aMCI) and non-amnestic MCI (naMCI), to dementia. Blood HCy was measured in 311 MCI subjects (aMCI: 64%, naMCI: 36%) followed-up for a median of 33 months (range 10-155 months). At follow-up, 137 individuals converted to dementia (naMCI, n = 34; aMCI, n = 103). Based on HCy distribution, subjects in the highest tertile had a greater risk to convert to dementia compared to tertile I (Hazard Ratio (95% confidence interval): 2.25 (1.05-4.86); p = 0.04). aMCI subjects did not show increased risk to convert to dementia with increasing HCy concentration, but was significant in naMCI (p = 0.04). We observed a non-significant increase in the risk of progression to dementia from naMCI/low HCy (reference group, HCy cutoff value = 16 µmol/L) to naMCI/high HCy, but it was significant from aMCI/low HCy (HR: 2.73; 95%CI: 1.06-7.0; p:0.03), to aMCI/high HCy (HR: 3.24; 95%CI: 1.17-8.47; p:0.02). Our results suggest that HCy levels are associated with the progression from MCI to dementia. This association seems significant only for the naMCI group, indirectly supporting the notion that hyperhomocysteinemia damages the nervous system through its role as a vascular risk factor.

Impact of homocysteine on acute ischemic stroke severity: possible role of aminothiols redox status.

BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Serum Uric Acid Combined with Homocysteine as a Predictive Biomarker of Lupus Nephritis.

Serum uric acid (UA) and homocysteine (Hcy) are potential biomarkers of systemic lupus erythematosus (SLE). In this study, the expressions of UA and Hcy in SLE patients and the predictive value of these two parameters for lupus nephritis (LN) were studied. A total of 476 SLE patients were recruited to this case-control study, of which 176 SLE patients diagnosed with LN and 300 without LN. Serum UA and Hcy levels were analyzed. Multivariate logistic regression analysis was used to evaluate the relationship between serum UA and Hcy and LN. The receiver operating characteristic (ROC) curves were used to predict the role of combination of serum UA and Hcy in LN. We found that serum UA and Hcy levels in SLE patients with LN were significantly higher than those in controls (p<0.05). Multivariate logistic regressions showed that serum UA (OR+=+1.003, 95+% CI: 1.001-1.006, p+=+0.003), apolipoprotein B (Apo B) (OR+=+21.361, 95+% CI: 2.312-195.373, p+=+0.007) and Hcy (OR+=+1.042, 95+% CI: 1.011-1.080, p+=+0.014) were independent markers of LN. Combined serum UA and Hcy revealed a better result (AUC+=+0.718, 95+% CI: 0.670-0.676, p<0.001) in prediction of LN compared to that of the serum UA (AUC+=+0.710) and Hcy (AUC+=+0.657) independently. In conclusion, serum UA and Hcy could be predictive biomarkers of LN, and joint detection of serum UA and Hcy might be useful in the clinical setting.

Role of vitamin B12 and folic acid in treatment of Alzheimer's disease: a meta-analysis of randomized control trials.

Vitamin B12 and folic acid could reduce blood homocysteine levels, which was thought to slow down the progression of Alzheimer's disease (AD), but previous studies regarding the effect of vitamin B12 and folic acid in treatment of AD have not reached conclusive results. We searched PubMed and Embase until January 12, 2023. Only randomized control trials involving participants clearly diagnosed with AD and who received vitamin B12 and folic acid were enrolled. Five studies that met the criteria were selected for inclusion in the meta-analysis. Changes in cognitive function were measured based on either the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Changes in daily life function and the level of blood homocysteine were also investigated. After a 6-month treatment, administration of vitamin B12 and folic acid improved the MMSE scores more than placebo did (SMD = 0.21, 95% CI = 0.01 to 0.32, p = 0.04) but did not significantly affect ADAS-Cog scores (SMD = 0.06, 95% CI = -0.22 to 0.33, p = 0.68) or measures of daily life function. Blood homocysteine levels were significantly decreased after vitamin B12 and folic acid treatment. Participants with AD who received 6 months of vitamin B12 and folic acid supplementation had better MMSE scores but had no difference in ADAS-Cog scores. Daily life function did not improve after treatment.

Effects of Blood Flow Restriction Resistance Training on Autonomic and Endothelial Function in Persons with Parkinson's Disease.

Background: Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD). Objective: To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol. Methods: Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines. Results: LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar. Conclusions: LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable.

Homocystein, Vitamin B12 and Folic Acid as Screening Biomarkers in Early Diagnosis and Gastric Cancer Monitoring.

Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and increased accessibility to educational initiatives for the general population. Nevertheless, it persists as the third leading cause of mortality globally among both men and women. These fatalities are typically associated with delayed disease detection. The current study assessed the levels of homocysteine, vitamin B12, and folic acid as a means of establishing a screening biomarker profile that could be integrated into routine testing protocols to facilitate swift diagnosis of the illness. A total of 207 control subjects and 207 individuals with gastric cancer were scrutinized, with biochemical measurements conducted using chemiluminescence for homocysteine, folic acid, and vitamin B12. The two groups were matched based on age, tumor location, subtype, tumor classification, presence of Epstein-Barr Virus infection (EBV), and Helicobacter pylori (H. pylori). Significant statistical variances were identified in the mean levels of the triad of substances among cancer patients when compared to the control group for all corresponding variables. In conclusion, our study indicated that analyzing the triad of homocysteine, vitamin B12, and folic acid holds diagnostic value for gastric cancer and could potentially serve as an effective screening marker for this type of cancer in the future.

Gestational diabetes mellitus is associated with distinct folate-related metabolites in early and mid-pregnancy: A prospective cohort study.

AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

A lateral flow strip for on-site detection of homocysteine based on a truncated aptamer.

An elevated level of homocysteine (Hcy) in serum is closely related to the development of various diseases. Therefore, homocysteine has been widely employed as a biomarker in medical diagnosis and the on-site detection of homocysteine is highly desired. In this study, a truncated highly specific aptamer for homocysteine was screened and used to design a lateral flow strip (LFS) for the detection of homocysteine. The aptamer was derived from a previously reported sequence. Based on the result of molecular docking, the original sequence was subjected to truncation, resulting in a reduction of the length from 66 nt to 55 nt. Based on the truncated aptamer, the LFS was designed for the detection of homocysteine. In the presence of homocysteine, the aptamer selectively binds to it, releasing cDNA from the aptamer/cDNA duplex. This allows cDNA to bind to the capture probe immobilized on the T zone of the strip, resulting in a red signal on the T zone from gold nanoparticles (AuNPs). The strip enables the visual detection of homocysteine in 5 min. Quantitative detection can be facilitated with the aid of ImageJ software. In this mode, the linear detection range for homocysteine is within 5-50 µM, with a detection limit of 4.18 µM. The strip has been effectively utilized for the detection of homocysteine in human serum. Consequently, the combination of the truncated aptamer and the strip offers a method that is sensitive, quick, and economical for the on-site detection of homocysteine.

Association between Homocysteine and Vitamin D Levels in Asymptomatic Korean Adults.

An increased homocysteine level is a risk factor for cardiovascular disease, venous thromboembolism, cerebrovascular disease, and chronic kidney disease. In addition, vitamin D deficiency is associated with coronary artery disease and metabolic disorders. The present study included data from 1375 adults (895 men and 480 women) with a mean age of 52.62 ± 9.94 years who visited the Health Promotion Center of the University Hospital in Gyeonggi-do, Republic of Korea from January 2018 to December 2022 for routine checkups that included assessments of their homocysteine and vitamin D levels. Homocysteine levels were positively associated with age, a history of hypertension, a history of diabetes, current smoking habits, and levels of low-density lipoprotein cholesterol, creatinine, uric acid, and high-sensitivity C-reactive protein. By contrast, vitamin D levels were negatively associated with serum levels of homocysteine after adjusting for covariates (ß = -0.033, p < 0.001). Additional long-term prospective studies are needed to elucidate the presence of a causal relationship between vitamin D status and serum levels of homocysteine in asymptomatic Korean adults. An intervention trial is warranted to determine whether the administration of vitamin D is helpful for the primary prevention of cardiovascular disease by lowering the homocysteine level in this population.

Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis.

The contents of homocysteine (HCy), cyanocobalamin (vitamin B12), folic acid (vitamin B9), and pyridoxine (vitamin B6) were analyzed and the genotypes of the main gene polymorphisms associated with folate metabolism (C677T and A1298C of the MTHFR gene, A2756G of the MTR gene and A66G of the MTRR gene) were determined in children at the onset of multiple sclerosis (MS) (with disease duration of no more than six months), healthy children under 18 years (control group), healthy adults without neurological pathology, adult patients with MS at the onset of disease, and adult patients with long-term MS. A significant increase in the HCy levels was found in children at the MS onset compared to healthy children of the corresponding age. It was established that the content of HCy in children has a high predictive value. At the same time, an increase in the HCy levels was not accompanied by the deficiency of vitamins B6, B9, and B12 in the blood. The lack of correlation between the laboratory signs of vitamin deficiency and HCy levels may be due to the polymorphic variants of folate cycle genes. An increased HCy level should be considered as a marker of functional disorders of folate metabolism accompanying the development of pathological process in pediatric MS. Our finding can be used to develop new approaches to the prevention of demyelination in children and treatment of pediatric MS.

Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis.

OBJECTIVE: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD. METHODS: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367. RESULTS: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC. CONCLUSION: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.