Search

BACKGROUND: Hyperhomocysteinemia is closely related to the function of islet β cells, but its specific molecular mechanism is not fully understood. OBJECTIVE: To investigate the role of N6 methyltransferase-like 3 (METTL3) in homocysteine (Hcy)-induced autophagy of mouse islet β cells. METHODS: The 3rd and 4th generation mouse islet β cells were taken for the experiment. (1) Cell modeling and grouping: cells in control group were not treated with Hcy, while those in homocysteine group were treated with 100 µmol/L Hcy for 48 hours. (2) The mouse islet β-cells were transfected with the plasmids overexpressing Ad-METTL3 and si-METTL3 according to the instructions of LipofectamineTM 2000. Three different interfering fragments were designed, and the one with the best interfering efficiency was verified and screened by PCR. (3) After transfection, the cells were divided into control group, Hcy group, Ad-NC (negative control)+Hcy group, Ad-METTL3+Hcy group, si-NC (negative control)+Hcy group and si-METTL3+Hcy group. (4) qRT-PCR and western blot were used to detect the expression levels of METTL3 and autophagy-related proteins LC3II/I and p62 in cells. Insulin level was determined by ELISA to evaluate insulin secretion capacity of islet cells. Autophagy-related proteins and insulin level were detected after overexpression and interference with METTL3. RESULTS AND CONCLUSION: Compared with the control group, the expression level of LC3II/I was increased (P < 0.05), the expression of p62 was significantly reduced (P < 0.05), and the insulin secretion capacity was significantly decreased (P < 0.05) in the Hcy group. Compared with the control group, the protein and mRNA levels of METTL3 were reduced in the Hcy group (P < 0.05). After METTL3 silencing in islet β cells, Hcy further upregulated the expression of LC3II/I (P < 0.05), significantly dowregulated the expression of p62 (P < 0.05), and increased the insulin level (P < 0.05). After overexpression of METTL3, Hcy significantly decreased the LC3II/I expression and increased the p62 expression in islet β cells (P < 0.05). To conclude, METTL3 is involved in the Hcy-induced autophagy regulation of islet β cells and plays a role in the regulation of insulin secretion. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased homocysteine level induces apoptosis of human umbilical vein endothelial cells, but the mechanism remains unclear. OBJECTIVE: To investigate the role of hsa-circ-0001360 in human umbilical vein endothelial cell apoptosis induced by homocysteine. METHODS: In vitro cultured human umbilical vein endothelial cells were divided into control group, homocysteine group, interference control group, interference control + homocysteine group, hsa-circ-0001360 interference group, hsa-circ-0001360 + homocysteine interference group, overexpression control group, overexpression control + homocysteine group, hsa-circ-0001360 overexpression group and hsa-circ-0001360 + homocysteine overexpression group. All groups were treated with 100 μmol/L homocysteine. After 72 hours of intervention, the expressions of apoptosis-related proteins Bax, Bcl-2, and Caspase-3 were detected by western blot assay. The apoptotic rate was detected by flow cytometry. Quantitative real-time PCR was used to detect the expression of hsacirc-0001360. RESULTS AND CONCLUSION: (1) Compared with the control group, the expression of Caspase-3 and Bax was significantly increased (P < 0.01), and the expression of Bcl-2 was significantly decreased (P < 0.01), and the apoptotic rate was significantly increased (P < 0.01) in the homocysteine group. (2) Compared with control group, the expression of hsa-circ-0001360 was significantly increased in the homocysteine group (P < 0.01). (3) The expression of hsa-circ-0001360 was significantly higher in the cytoplasm than that in the nucleus (P < 0.01). (4) Compared with the interference control C group and interference control + homocysteine group, the expressions of Caspase-3 and Bax were significantly decreased (P < 0.01), while the expression of Bcl-2 was significantly increased (P < 0.01); the apoptotic rate was significantly decreased (P < 0.01) in sh-hsa-circ-0001360 interference group and sh-hsa-circ-0001360 + homocysteine interference group. (5) Compared with overexpression control group and overexpression control + homocysteine group, the expressions of Caspase-3 and Bax were significantly increased (P < 0.01), while the expression of Bcl-2 was significantly decreased (P < 0.01); the apoptotic rate was significantly increased (P < 0.01) in the hsa-circ-0001360 overexpression group and the hsa-circ-0001360 + homocysteine overexpression group. (6) In conclusion, hsa-circ-0001360 can promote the apoptosis of human umbilical vein endothelial cells induced by homocysteine. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is an internal relationship between hyperhomocysteinemia and vascular calcification. However, the pathogenesis of hyperhomocysteinemia promoting vascular calcification is still unclear. OBJECTIVE: To investigate the role of bone morphogenetic protein-2 in hyperhomocysteinemia-induced vascular calcification. METHODS: Human carotid wax samples were divided into a calcified group (n=29) and a non-calcified group (n=13) according to the presence or absence of calcified plaque. Sixteen ApoE-/- mice were randomly divided into a control group and a hyperhomocysteinemia group, with 8 mice in each group. Bone morphogenetic protein-2 vector was used to transfect rat thoracic artery smooth muscle A7r5 cells, and gradient concentration of homocysteine (50, 100, 200, and 400 μmol/L) was utilized to treat A7r5 cells. Calcification was detected by alizarin red staining and hematoxylin-eosin staining. The interaction of bone morphogenetic protein 2 with Runt-related transcription factor 2 was detected by immunofluorescence, and the expressions of bone morphogenetic protein 2, Runt-related transcription factor 2, and α-smooth muscle actin were detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION: (1) Human carotid artery tissue staining revealed that compared with the non-calcification group, inflammatory cells increased and calcification positive rate increased in the calcification group (P < 0.05). Compared with the non-calcification group, the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated, and the expression of α-smooth muscle actin was decreased in the calcification group (all P < 0.05). (2) The staining of mouse arterial specimens exhibited that, the positive rate of calcified area in the hyperhomocysteinemia group was significantly higher than that in the control group (P < 0.05); serum homocysteine level in the hyperhomocysteinemia group was significantly higher than that in the control group (P < 0.05). Compared with the control group, the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated, and the expression of α-smooth muscle actin was decreased in the hyperhomocysteinemia group (all P < 0.05). (3) A7r5 cell culture analysis demonstrated that with the increase of homocysteine concentration gradient, the degree of calcification, the content of bone morphogenetic protein-2 and Runt-related transcription factor 2 protein in A7r5 cells increased (P < 0.05), and the content of α-smooth muscle actin protein decreased (P < 0.05). (4) The A7r5 cell culture analysis of overexpressed bone morphogenetic protein 2 showed that the calcification degree of the overexpressed bone morphogenetic protein 2 group was increased compared with the corresponding control group, the β-sodium glycerophosphate group, and the homocysteine group. RUNtrelated transcription factor 2 expression up-regulated (P < 0.05) and α-smooth muscle actin expression down-regulated (P < 0.05). (5) The expression of bone morphogenetic protein 2 increased in A7r5 cells cultured with homocysteine in calcified medium, and the expression of Runt-related transcription factor 2 increased with the increase of bone morphogenetic protein 2 expression. (6) The results confirm that bone morphogenetic protein-2 is a key target gene in the regulation of smooth muscle cell phenotypic transformation resulting in vascular calcification by hyperhomocysteinemia. Targeted regulation of bone morphogenetic protein-2 reduces hyperhomocysteinemia-induced vascular calcification. [ABSTRACT FROM AUTHOR]

Background: Lacunes, a characteristic feature of cerebral small vessel disease (CSVD), are critical public health concerns, especially in the aging population. Traditional neuroimaging techniques often fall short in early lacune detection, prompting the need for more precise predictive models. Methods: In this retrospective study, 587 patients from the Neurology Department of the Affiliated Hospital of Hebei University who underwent cranial MRI were assessed. A nomogram for predicting lacune incidence was developed using LASSO regression and binary logistic regression analysis for variable selection. The nomogram's performance was quantitatively assessed using AUC-ROC, calibration plots, and decision curve analysis (DCA) in both training (n = 412) and testing (n = 175) cohorts. Results: Independent predictors identified included age, gender, history of stroke, carotid atherosclerosis, hypertension, creatinine, and homocysteine levels. The nomogram showed an AUC-ROC of 0.814 (95% CI: 0.791-0.870) for the training set and 0.805 (95% CI: 0.782-0.843) for the testing set. Calibration and DCA corroborated the model's clinical value. Conclusion: This study introduces a clinically useful nomogram, derived from binary logistic regression, that significantly enhances the prediction of lacunes in patients undergoing brain MRI for various indications, potentially advancing early diagnosis and intervention. While promising, its retrospective design and single-center context are limitations that warrant further research, including multi-center validation. [ABSTRACT FROM AUTHOR]

Introduction: The term "acute myocardial infarction" (AMI) describes the destruction of heart muscle tissue brought on by ischemia, or the lack of oxygen to the heart's tissue. Aim: To investigate the correlation between serum levels of homocysteine, uric acid, and C-reactive protein in patients diagnosed with acute myocardial infarction (AMI). Methods: A total of 60 patients with AMI were enrolled in this study. After recruitment, detailed history was recorded and physical examination of subjects was carried out. A serum sample, used to determine the homocysteine, uric acid concentrations and other general biochemical assays, was obtained with one anticoagulant-free 7.5 mL test tube. Other biochemical assays were performed and CRP (mg/L) was measured. Subjects were grouped according to Killip classification. Results: In present study, mean Homocysteine (umol/l) in Killip class I was 4.86±2.01, in class II was 5.97±2.30, in class III was 8.44±4.73 and in class IV was 13.47±6.12 (p <0.01). Mean uric acid (mg/dl) in Killip class I was 2.13±1.81, in class II was 2.54±1.74, in class III was 3.65±1.11 and in class IV was 4.51±1.07 (p <0.01). Mean C-Reactive Protein (mg/l) in Killip class I was 0.72±0.57, in class II was 1.61±0.88, in class III was 5.96±3.03 and in class IV was 8.75±4.84, (p value <0.01). A statistically significant correlation was found between Homocysteine & Uric acid level with Coefficient of correlation being 0.58 ( p value <0.01) ; between Homocysteine & C-Reactive Protein level with Coefficient of correlation being 0.43 (p=0.002) ; between Uric acid & C-Reactive Protein level with Coefficient of correlation being 0.41 (p value=0.005). Conclusion: The study found a significant correlation between blood levels of C-Reactive Protein (CRP), Uric acid, and Homocysteine with Killip classification in patients with Acute Myocardial Infarction. As the Killip classification stages progressed, the levels of these biomarkers also increased. There was a positive and statistically significant correlation between Homocysteine and Uric acid levels, Homocysteine and CRP levels, as well as Uric acid and CRP levels. These findings suggest that since these biomarkers are involved in Myocardial Infarction, monitoring their serum levels together could be beneficial for evaluating and managing these patients. [ABSTRACT FROM AUTHOR]

Object: Vertebrobasilar dissecting aneurysms (VBDAs) are known to have a poor natural history with high rates of re-bleeding and mortality. There is a strong relation between hyperhomocysteinemia (HHcy) and cerebrovascular disease; we perform a retrospective study within the male of Chinese Han population to explore the association between HHcy and VBDAs. Methods: Eighty-eight male patients with VBDA and Eighty-one male control subjects were evaluated for their serum total homocysteine levels. With multiple logistic regression analysis, the association between HHcy and the risk of VBDAs was estimated. Interaction and stratified analyses were conducted according to age, BMI, smoking status, drinking status, and chronic disease histories. The two-piecewise linear regression model examined the threshold effect. Results: The multivariate logistic regression analyses revealed a significant association between HHcy and VBDAs (odds ratio (OR) = 2.62; 95% confidence interval (CI), 1.02–6.71) after adjusting for classical vascular risk factors. The relationship was stable in all subgroup analysis. The interactive role was not found in the association between HHcy and VBDAs for the potential risk factor. Conclusions: In summary, our study provides evidence that HHcy can increases the risk of VBDAs in the male Han Chinese population. Further researches with appropriate study designs including sex differences and aneurysm types are needed to verify this association. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 deficiency is widely prevalent in all age groups which is of major concern. However, there is no valid Food Frequency Questionnaire (FFQ) for dietary vitamin B12 estimation. Hence, we aimed to develop and validate an FFQ for the estimation of dietary intake of Vitamin B12. Materials and Methods: Commonly consumed B12-rich food items were selected from literature and filtered using a market survey. For concordant and discriminant validation, B12 and homocysteine levels were estimated. To establish convergent validity, the Cobalamin Intake in North Indians by Food Frequency Questionnaire (COIN-FFQ) and 72-hour dietary recall (72HrDR) were both administered to the same subjects. The COIN-FFQ was readministered after initial administration for test-retest reliability. Internal consistency of the FFQ was then tested using Cronbach's alpha. Results: We enrolled 115 adults with a mean age and weight of 31.9 ± 8.7 years and 66.0 ± 11.8 kg, respectively. In total, 19.1% were vegetarian. The dietary B12 using COIN-FFQ (n = 60; mean = 4.3 ± 1.8 µg/d) was significantly correlated (r = 0.255; P = 0.049) with serum levels (mean = 120.1 ± 62.6 pmol/L) establishing concordant validity. A significant difference was noted between the dietary, serum B12, and homocysteine levels of vegetarians versus nonvegetarians establishing discriminant validity (mean diff 1.4 (0.5-2.4), P = 0.004; Z-statistic -2.182, P value 0.029, and Z-statistic -2.438; P value 0.015), respectively. FFQ was strongly correlated with 72HrDR and test--retest FFQ (n = 27; r = 0.814, P < 0.001 and r = 0.869, P < 0.001, respectively) establishing convergent validity and test--retest reliability. The internal consistency with Cronbach's alpha was in the acceptable range, 0.631 (n = 115). Conclusion: The newly developed COIN-FFQ is valid and reliable in estimating dietary B12 intake. [ABSTRACT FROM AUTHOR]

Methionine is an essential amino acid for mammals and it is limiting for monogastric animals. It can be oxidized easily by UV light. This could influence the bioaccessibility and bioavailability of methionine. In this work, the photosensitized degradation of peptide-bound methionine in the presence of riboflavin was investigated in a model system. Capillary electrophoresis was employed to analyze the time course of the degradation. The products were identified by liquid chromatography coupled to mass spectrometry (LC–MS/MS). Benzoyl methionine was degraded by 50% during UV irradiation in the presence of riboflavin after 5.0 min with 10 mol% riboflavin and 6.4 min with 3 mol% riboflavin. Homocysteine (16–20 mol%) and β-aspartic semialdehyde (ca. 30 mol%) were found as major degradation products next to methionine sulfoxide (ca. 25 mol%). A smaller molar ratio of riboflavin led to a higher formation of aspartic semialdehyde. The formation of homocysteine was paralleled by the formation of formaldehyde. Furthermore, the experiment was transferred to small peptides, which showed the analogous degradation products of peptide-bound methionine. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is an independent and serious risk factor for dementia, including Alzheimer's disease (AD), but the precise mechanisms are still poorly understood. In the current study, we observed that the permissive histone mark trimethyl histone H3 lysine 4 (H3K4me3) and its methyltransferase KMT2B were significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of synaptic plasticity and cognitive function. Further research found that histone methylation inhibited synapse-associated protein expression, by suppressing histone acetylation. Inhibiting H3K4me3 by downregulating KMT2B could effectively restore Hcy-inhibited H3K14ace in N2a cells. Moreover, chromatin immunoprecipitation revealed that Hcy-induced H3K4me3 resulted in ANP32A mRNA and protein overexpression in the hippocampus, which was regulated by increased transcription Factor c-fos and inhibited histone acetylation and synapse-associated protein expression, and downregulating ANP32A could reverse these changes in Hcy-treated N2a cells. Additionally, the knockdown of KMT2B restored histone acetylation and synapse-associated proteins in Hcy-treated primary hippocampal neurons. These data have revealed a novel crosstalk mechanism between KMT2B-H3K4me3-ANP32A-H3K14ace, shedding light on its role in Hcy-related neurogenerative disorders. We observed that the permissive histone mark H3K4me3 and its methyltransferase KMT2B were significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of cognitive function. Further research found that H3K4me3 inhibited synapse associated protein expression, by suppressing ANP32A/H3K14ace. Moreover, siKMT2B restored ANP32A/H3K14ace and synapse-associated proteins in Hcy-treated N2a cells and primary hippocampal neurons. We found a novel crosstalk between KMT2B-H3K4me3-ANP32A-H3K14ace, shedding light on its role in Hcy-related neurogenerative disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of vitamin A (VA), vitamin D (VD), and homocysteine (Hcy) on cardiometabolic multimorbidity (CMM). Methods: This study is a cross-sectional study conducted in Ningxia Province, China. A total of 5000 participants aged 25–74 were recruited and divided into two groups based on the definition of cardiometabolic multimorbidity: the CMM group and the Non CMM group. Demographic, lifestyle, and laboratory data were collected to investigate the correlation between vitamin A, D, Hcy levels and CMM risk. The association was analyzed using multiple logistic regression and restricted cubic spline method. Results: CMM incidence increased with age, being higher in females (20.05%) compared to males, Hypertension was present in 96.20% of CMM cases. Reduced VD levels correlated with an elevated CMM risk (OR = 1.799, 95% CI: 1.466–2.238), showing an inverse dose-response relationship, even after adjusting for confounders (OR = 1.553, 95% CI: 1.233–1.956). However, VA and Hcy levels were not significantly associated with CMM risk. The inverse correlation between VD status and CMM risk was more pronounced in males, obese individuals, and those with normal blood lipid profiles (P < 0.05). Conclusions: The risk of CMM increases with age, especially in women. Inadequate VD status increases vulnerability to CMM, suggesting that optimising VD reduces the risk of CMM. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke's Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [β (95% CI) − 1.354 (− 2.655, − 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [β (95% CI) − 5617.182 (− 11062.762, − 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function. [ABSTRACT FROM AUTHOR]

An imbalance in cysteine (Cys) levels in the cells and plasma has been identified as the risk indicator for various human diseases. The structural similarity of cysteine with its congener homocysteine and glutathione offers challenges in its measurement. Herein, we report a hydrogen‐bonded organic‐inorganic framework of Cu(II) (HOIF) for the selective detection of cysteine over other biothiols. The non‐fluorescent HOIF showed 12‐fold green emission in the presence of cysteine. The monomeric unit of HOIF is stabilized via intermolecular hydrogen bonds, resulting in a non‐porous network structure. Non‐interference from homocysteine, glutathione, and other competitive bio‐analytes revealed explicit affinity of HOIF for cysteine. Fluorimetric titration showed a wide working concentration window (650 nM–800 μM) for measuring cysteine in an aqueous medium. The mechanistic investigation involving HRMS, EPR, and UV‐vis spectroscopic studies revealed the decomplexation of HOIF with Cys, resulting in a fluorescence turn‐on response from the luminescent ligand. Validation using a commercial dye, “Cysteine Green”, confirmed the prospect of HOIF for early diagnostic purposes. Utilizing the fluorescence turn‐on property of HOIF in the presence of cysteine, we measured cysteine quantitatively in the blood plasma samples. Bio‐imaging of endogenous cysteine in cancer cells indicated the ability of HOIF to monitor the intracellular cysteine. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between H - type hypertension and chronic kidney disease (CKD) and provide scientific basis for the prevention and treatment of chronic kidney disease. Methods From December 2021 to December 2022, 257 patients with CKD were randomly collected from the Department of Nephrology of Hunan Provincial People' s Hospital, and 257 patients were collected in the physical examination department as the control group. Data on general demographic characteristics, lifestyle habits, disease history, and clinical indicators were collected for all study subjects. The epidemic status and influencing factors of CKD, and the relationship between H - type hypertension and CKD were analyzed by univariate and multivariate analysis methods. An interaction model was constructed to analyze the interaction effect of homocysteine (Hey) and hypertension on the onset of CKD. The effect of H - type hypertension and related influencing factors on CKD were explored by subgroup analysis. Results The results of univariate analysis of general demographic characteristics and clinical indicators between CKD and control groups showed: age, ethnicity, educational level, per capita income, exercise status, sleep duration, BMI, history of H - type hypertension, triglycerides (TG), High - density lipoprotein cholesterol (HDL), albumin (ALB), glomerular filtration rate (GFR), blood urea nitrogen (BUN), uric acid (UA), Hcy, total bilirubin (TBIL), direct bilirubin (DBIL), C reactive protein (CRP) levels (P < 0. 05). Dichotomized Logistic regression analysis showed that the risk of CKD, adjusted for age, nationality, educational level, family income, exercise, sleep duration, BMI, TG, HDL, ALB, GFR, BUN, UA, TBIL, CRP was 2. 333 times higher than in those without H - type hypertension (OR - 2.333, 95% CI: 1.365 - 3.989, P = 0.002). The interaction results between hyperhomocysteinemia (HHcy) and hypertension suggested that there was a positive additive interaction between HHcy and hypertension, with no multiplicative interaction. There was an interaction between H - type hypertension and age, educational level, average annual family income, and sleep duration on the onset of CKD (P < 0. 05). Conclusion H - type hypertension is a risk factor for CKD, and there is an additive interaction between the effects of HHcy and hypertension on CKD. [ABSTRACT FROM AUTHOR]

Background: Hyperhomocysteinemia can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorders; however, hypohomocysteinemia is generally not considered harmful. This study aimed to evaluate the relationship between all levels of homocysteine, both low and high homocysteine levels, and the risk of all-cause and cause-specific mortality in adult Korean men. Methods: Adult Korean men (n = 221,356) were categorized into quintiles based on their homocysteine levels. The primary endpoints were all-cause, CVD, cancer, and dementia mortality. Hazard ratios were calculated using Cox proportional hazards models, and the dose–response relationship between homocysteine levels and mortality risk was further explored using restricted cubic spline models. Results: Compared with the reference category (Q2, 8.8–9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L). This association was not observed in the vitamin supplementation subgroup. Conclusion: Among Korean adult men, both low and high homocysteine levels increased the risk of all-cause and CVD mortality, indicating a U-shaped relationship. However, this relationship was not statistically significant with vitamin supplementation, suggesting a potential protective role for vitamins. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. Method: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. Results: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). Conclusion: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia. [ABSTRACT FROM AUTHOR]

Purpose: To assess age at 1st central retinal vein occlusion (CRVO) in carriers ≤ 45 years old of the methylenetetrahydrofolate reductase (MTHFR) C667T genotype compared to heterozygous and wild type, and to identify predictors of age at CRVO. Methods: Retrospective cohort study consisting of 18 MTHFR TT, 23 MTHFR TC and 28 MTHFR CC participants; information regarding age, sex, age at CRVO, history of dyslipidaemia, hypertension, smoking and plasma HC measured by immunoassay were collected. Results: Age at CRVO was lower in MTHFR TT than MTHFR TC and CC (32 ± 6 vs 38 ± 5 vs 37 ± 6 years, respectively, p = 0.005); plasma HC was higher in MTHFR TT than in the other genotypes [14.4 (10.8, 19.6) vs 10.4 ((8.6,12.5) vs 8.5 ((7.5,9.8) μmol/l, p = 0.0002). Smoking (cigarettes/day) independently predicted age at CRVO (p = 0.039) and plasma HC (p = 0.005); smoking status (yes/no) predicted ischemic CRVO (p = 0.01) that was more common in the MTHFR TT group (p = 0.006). Conclusions: Carriers of the MTHFR TT genotype ≤ 45 years old develop their 1st CRVO on average 5 years earlier than the MTHFR CC genotype; smoking contributes to the prematurity and severity of CRVO in MTHFR TT carriers. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate the association of homocysteine level and lipid profiles with ischemic heart disease. Methods: This 12-month prospective case control study was undertaken at a tertiary care hospital. The Department of Medicine accepted IHD patients. The research gathered data from hospital inpatients and outpatients who met inclusion and exclusion criteria. Healthy persons were picked among hospital workers and regular checkup patients. Results: The homocysteine levels of the patients and controls differed significantly. As a result, we discovered that in our investigation, increased homocysteine levels were substantially linked to IHD. The chi-square test revealed no significant difference in cholesterol levels between the patients and controls (p-value >0.05). As a result, there was no evidence of a substantial link between hypercholesterolemia and IHD. Triglyceride levels did not significantly vary between the patients and controls. HDL levels did not significantly vary between the patients and controls. Conclusion: According to this research, hyperhomocysteinemia is independently linked to hypertriglyceridemia, high total cholesterol, high LDL, and low HDL values. [ABSTRACT FROM AUTHOR]

Objective To investigate the factors involved in the development of thyroid nodules and the correlation between homocysteine (Hey) and albumin-globulin ratio (AGR) and thyroid autoantibodies in adults. Methods As a retrospective study, a total of 1 427 people who received physical examination at the Second Hospital Affiliated to Hebei North College from October 2019 to August 2020 and the clinical data of the subjects who fulfilled the criteria of NAR were selected for analysis by simple random sampling. All of subjects underwent thyroid color ultrasound scanning and were divided into a control group (without thyroid nodules, n = 52 and an observation group (with thyroid nodules, n = 48 . The general clinical data of the two study groups were compared, and the correlation between Hcy and AGR and thyroid autoantibodies was analyzed. Confunding factors affecting the incidence of thyroid nodules were screened using multifactorial unconditional logistic regression analysis. Results The observation group showed statistically significant differences in gender, age, diastolic blood pressure, systolic blood pressure, Hey, AGR, TGAb, and TPOAb as compared to the control group (P < 0.05) ; Using adult Hey as the dependent variable and Spearman's correlation analysis of AGR, TGAb and TPOAb, adult Hey was negatively correlated with AGR ( r = 0.384 P < 0.05 ) and TGAb and TPOAb were positively correlated ( r = 0.218, 0. 224, P < 0.05 ) ; Using age, sex, diastolic blood pressure, systolic blood pressure, Hey, AGR TGAb and TPOAb as independent variables and thyroid nodules as dependent variables, a multifactor logistic regression analysis was performed in 100 subjects who experienced physical check. The analysis showed that age ≥40 years and female were relevant factors for the development of thyroid nodules factors (P < 0.05), Hey, AGR, TGAL and TPOAb were correlated with thyroid nodules (P < 0.05) . Conclusions Thyroid nodules are more common in middle-aged women, and there is a correlation between Hey, AGR, TGAb, and TPOAb levels and thyroid nodules. Regular thyroid screening examination should be carried out based on the above indicators. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency with which suspected pathogenic factors, including metals and metabolites that might contribute to Alzheimer's disease (AD), may be found in patients with cognitive impairment through commonly available blood tests. Methods: A variety of serum studies, including metals, ammonia, homocysteine, vitamin B12, folate, thyroid tests, metabolic products, and inflammatory markers, were measured in two cohorts: one meeting mild cognitive impairment (MCI) criteria and the other meeting mild-to-moderate dementia (DE) criteria. Medications these patients received were reviewed. Results: Metal abnormalities were detected in over half the subjects, including evidence of mercury, lead, and arsenic elevation as well as instances of excessive essential metals, iron (Fe), and copper. Some metal aberration was detected in 64% of the DE group and 66% of the MCI group. Females were more likely to have elevated copper, consistent with hormonal effects on copper excretion. Homocysteinemia was the most common abnormality, detected in 71% with DE and 67% with MCI, while methylmalonic acid was not elevated. Slight hyperammonemia was moderately common (38%) suggesting a hepatic factor in this subset. Findings of moderate insulin resistance were present in nearly half (44% DE, 52% MCI). Sixty of 65 (92%) had at least one abnormal biomarker and 60% had two or more. The most common drug taken by the total cohort was proton pump inhibitors at 22% DE and 38% MCI. Conclusions: This study suggests that both toxic metals and excessive vital metals such as copper and iron, as well as common metabolic and hepatic factors are detectable at both stages of MCI and DE. There appears to be a multiplicity of provocative factors leading to DE. Individualized interventions based on these parameters may be a means to reduce cognitive decline leading to DE. A more comprehensive prospective study of these environmental and metabolic factors with corrective early interventions appears warranted. [ABSTRACT FROM AUTHOR]

Background: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. Methods: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. Results: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. Conclusions: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. ClinicalTrials.gov Identifier: NCT03472508 (Registration Date: March 21, 2018). [ABSTRACT FROM AUTHOR]

The association between 25-hydroxyvitamin D and cognitive impairment and emotional disorder in patients with cerebral small vessel disease is unknown. This retrospective study included, 504 Chinese patients with cerebral small vessel disease admitted to the Department of Neurology of the First Hospital of Hebei Medical University between June 2019 and October 2021. The Montreal Cognitive Assessment and Hamilton Anxiety Scale (14 items) scores were utilized to divide the patients into four groups. The multivariate Cox regression analysis revealed that low 25-hydroxyvitamin D, high homocysteine, hyperuricemia, severity of white matter lesions, and a history of hypertension were independent risk factors for cognitive impairment among patients with cerebral small vessel disease. However, a high level of education is a protective factor. Furthermore, the level of 25-hydroxyvitamin D was significantly associated with the changes in brain functional regions. Serum 25-hydroxyvitamin D is a promising biomarker for predicting cognitive and emotional disorders in patients with cerebral small vessel disease and is highly associated with alterations in brain functional regions. [ABSTRACT FROM AUTHOR]

Arsenic contamination in environmental waters poses global health and environmental risks. This study addresses the urgent need for rapid, selective, and sensitive detection of inorganic arsenic (iAsIII) in environmental samples. Leveraging the unique properties of gold nanoparticles (AuNPs) and the selective binding affinity of homocysteine (Hcy), we developed a novel colorimetric sensor for iAsIII detection. Our investigation elucidates the mechanism by which Hcy modifies AuNPs, enabling the selective detection of iAsIII ions through chelation between amine and carboxyl groups, primarily with the predominant species H2AsO3− at pH 12.0. Our sensor achieves high selectivity (>10‐fold) for iAsIII amid various interfering ions commonly found in environmental samples. Furthermore, we demonstrate exceptional sensitivity in detecting iAsIII, with a low limit of detection (LOD) of 67 nM, aligning with regulatory standards for arsenic concentration in drinking water. The selectivity and sensitivity of our sensor were validated through experiments with various metal ions and real water samples. In conclusion, our study presents a comprehensive understanding of the mechanism, selectivity, and sensitivity of Hcy‐modified AuNPs in detecting iAsIII, offering a versatile nanosensor platform with significant implications for environmental monitoring and public health. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) patients present a high prevalence of cardiometabolic risk, associated with worse clinical manifestations and mortality. Folate, an essential micronutrient that participates in vital immune cellular functions, could positively affect the cardiometabolic and disease risk in SLE, through the methylenetetrahydrofolate reductase (MTHFR) enzyme, which participates in the folate metabolism, where single nucleotide variants (SNVs) have been described as a potential genetic risk factor for SLE. The aim of this study was to determine the association of the c.+677 C>T (rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic risk and clinical disease variables in SLE patients. A case-control study was conducted on 394 unrelated Mexican-mestizo women: 199 with SLE according to the 1997 SLE-ACR criteria and 196 control subjects (CS). Folic acid and homocysteine levels were evaluated by immunoassays. Genotyping of MTHFR genetic variants was carried out by allelic discrimination. No significant differences were found for folic acid (p =.15) and homocysteine serum levels (p =.59) between groups. According to the CC c.+677 MTHFR genotype, this was associated with low cardiovascular disease (CVD) risk by the Castelli index (OR = 0.42; p =.03) in SLE patients. The TC (OR = 1.3; p =.03) and the TA (OR = 1.6; p <.01) haplotypes from c.+677 C>T plus c.+1298 MTHFR were associated with SLE risk, while the CC MTHFR haplotype (OR = 0.5; p =.01) was found as a non-risk factor for the disease. In conclusion, the TC and the TA MTHFR haplotypes are associated with disease risk; meanwhile, the CC c.+677 MTHFR genotype confers lower cardiometabolic risk in Mexican-mestizo SLE patients. [ABSTRACT FROM AUTHOR]

Emerging studies indicate that oxidative stress may contribute to deficit syndrome (DS) in patients with schizophrenia. Homocysteine (Hcy) is a well-known marker and mediator of oxidative stress that exhibits tight associations with schizophrenia. However, no previous studies have assessed the relationship of DS with Hcy. This study evaluated the prevalence, clinical characteristics, and association of DS with Hcy in 491 patients with schizophrenia. Plasma levels of Hcy and other metabolic parameters were measured. Positive and Negative Syndrome Scale and the proxy scale for deficit syndrome were employed to assess psychiatric symptoms and DS. The logistic regression model was conducted to assess independent factors associated with DS, and the Area Under the Curve (AUC) was used to assess the performance of our model. There was a high incidence of hyperhomocysteinemia (58.8%) and DS (24.4%). Plasma Hcy levels were significantly higher in patients with DS. Age, Hcy levels, and psychiatric symptoms were independently associated with DS. The combination of these variables perfectly differentiated DS and non-DS patients with an AUC value of 0.89. Our study suggests that elevated Hcy levels may be related to DS. Routine monitoring of Hcy is essential and may facilitate early detection of DS in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

This study aimed to explore the associations between homocysteine, rumination, affective temperaments, clinical features, and hopelessness in bipolar disorder-1 (BD-1). In total, 57 euthymic patients with BD-1 and 57 healthy controls were included. The Beck Hopelessness Scale (BHS), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), and Ruminative Responses Scale Short Form (RRS-SF) were administered. Homocysteine, folate, and vitamin B12 levels were measured. The BHS total (p = 0.047), TEMPS-A irritable (p = 0.007), and TEMPS-A cyclothymic (p= 0.001) scores were significantly higher than the control group in the BD-1 group. Hyperhomocysteinemia (HHcy) was found in 33.3% of the patients (n = 19). In the HHcy group, age of onset of disease (p = 0.020) was significantly lower than the non-HHcy group in patients. Previous suicide attempt number was significantly correlated with scores of reflective pondering, brooding, and global rumination in BD-1 (p ˂ 0.05). Except for hyperthymic temperament, all types of affective temperaments were correlated with the scores of RRS-SF brooding (p ˂ 0.05) in the BD-1 group. The RRS-SF brooding scores significantly correlated with the BHS total scores (r = 0.263, p < 0.05); the TEMPS-A hyperthymic (β = −0.351, p = 0.001) and TEMPS-A irritable (β = 0.536, p < 0.001) scores significantly predicted the BHS total scores in the BD-1 group. The findings may lead clinical efforts and future clinical trials to explore and intervene in related sources and presentations of BD-1's adverse consequences. [ABSTRACT FROM AUTHOR]

Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer's disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to a protein's function and biological integrity, Hcy-thiolactone-detoxifying enzymes—PON1, BLMH, BPHL—have evolved. This narrative review provides an account of the biological function of these enzymes and of the consequences of their impairments, leading to the phenotype characteristic of AD. Overall, accumulating evidence discussed in this review supports a hypothesis that Hcy-thiolactone contributes to neurodegeneration associated with a dysregulated Hcy metabolism. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). Materials and Methods: An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. Results: Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). Conclusions: The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is associated with hypertension. However, the differential mechanisms underlying OSA-related hypertension between normal-weight vs. obese patients is limited. We studied 92 patients with OSA and 24 patients with continuous positive airway pressure (CPAP) treatment. Blood pressure (BP) was measured twice during awake and continuously monitored during sleep. Obesity was defined as body mass index ≥28 kg/m2. Serum metabolite levels were assessed by metabolomics. Among 59 normal-weight and 33 obese patients, 651 and 167 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling confounders. These metabolites involved 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients respectively, whereas 6 pathways overlapped. Among these 6 overlapping pathways, 4 were related to homocysteine metabolism and 2 were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.083) and 8 metabolites associated with DBP (all interaction-p≤0.033) were opposite between normal-weight and obese patients. Specifically, increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration in normal-weight patients, whereas associated with enhanced betaine-dependent remethylation and reduced transsulfuration in obese patients. Similar findings were observed in ambulatory BP during sleep. After CPAP treatment, baseline low homocysteine levels predicted greater decrease in DBP among normal-weight but not obese patients. Mechanisms in OSA-related hypertension differ between normal-weight and obese patients, which are explained by different changes in homocysteine metabolism. • Mechanisms of OSA-related hypertension differ between patients with different weight. • Homocysteine metabolism differently regulates hypertension in OSA patients with different weight. • Assessing homocysteine metabolism guides personalized treatments for hypertension in OSA. [ABSTRACT FROM AUTHOR]

Objective To understand the levels of serum homocysteine (Hcy), folic acid (FA) and vitamin B12 (VitB12) in pregnant women during different pregnancy periods in Guiyang area and their effects on adverse outcomes of offspring, so as to provide reference for individualized supplementation of FA and VitB12 in pregnant women, prevention of pregnancy complications and fetal birth defects. Methods From January to December 2022, a total of 400 pregnant women with singleton pregnancy were selected from the obstetrics clinic of Guizhou Provincial People's Hospital. Among them, 50 pregnant women with adverse fetal outcomes were selected as the observation group, and 350 pregnant women with normal fetal outcomes were selected as the control group. The observation group and the control group were divided into early pregnancy group, middle pregnancy group and late pregnancy group according to different gestational weeks. Another 100 healthy non-pregnant women of childbearing age who underwent physical examination in the hospital during the same period were selected as the healthy group. The levels of Hcy. FA and VitB12 were detected by enzyme circulation method and chemiluminescence microparticle immunoassay. The changes of serum Hey. FA and VitB12 levels in the three groups were compared. The regression analysis of serum Hcy, FA and VitB12 was carried out by Pearson linear correlation and the related risk factors of adverse fetal outcomes were analyzed by unconditional logistic multiple stepwise regression. Results The levels of serum Hcy, FA and VitB12 in the observation group and the control group were significantly higher than those in the healthy group, and the levels of FA and VitB12were significantly lower than those in the healthy group, the differences were statistically significant( P < 0.05 ) The levels of serum Hey, FA and VitB12 in the observation group were significantly higher than those in the control group, while the levels of FA and Vit B12 were lower than those in the control group, the differences were statistically significant P < 0.05 ) The levels of serum Hcy, FA and VitB12 in pregnant women decreased gradually with the increase of gestational age. Pearson correlation analysis showed that serum Hcy was negatively correlated with FA(r = 0.772, P < 0.05) . Serum Hcy was negatively correlated with VitB12 (r=-0.613,P<0.05). There was a positive correlation between FA and VitB12(r=0.568, P < 0.05 ) The results of unconditional logistic multiple stepwise regression showed that the increase of Hey level, the decrease of FA level and the decrease of VitB12 level were all risk factors for adverse fetal outcomes in pregnant women P < 0.05 ) . Conclusion The levels of serum Hcy, FA and VitB12 in pregnant women are closely related to the occurrence of adverse fetal outcomes. Therefore, the monitoring of these indicators should be strengthened during pregnancy, and intervention measures should be taken once abnormalities are found to reduce the risk of adverse fetal outcomes. [ABSTRACT FROM AUTHOR]

Objective Subjects and Methods Results Conclusion This case–control study investigated the associations between maternal plasma vitamin B12, homocysteine, and red blood cell (RBC) folate levels and the risk of cleft lip with or without cleft palate (CL/P) in offspring.The study compared 94 mothers and children with non‐syndromic CL/P from a teaching hospital in Thailand to 94 mother‐infant controls from local well‐baby clinics, frequency‐matched by birth date and mother's education. Data included anthropometric measurements, blood sample analyses, and a questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the associations through multiple logistic regression, adjusting for confounders.Mothers with higher plasma vitamin B12 levels had a lower risk of having a child with CL/P compared to those in the lowest quartile. This association was more pronounced among mothers without a family history of orofacial clefts and those who were not underweight. Conversely, elevated homocysteine levels, a marker of impaired B vitamin metabolism, increased the risk of CL/P. No association was found between RBC folate and CL/P.Higher maternal vitamin B12 levels are associated with a reduced risk of CL/P, while elevated homocysteine levels may increase the risk. [ABSTRACT FROM AUTHOR]

Background: Data show that due to endothelial damage and thrombogenic effects, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may accelerate the development of atherosclerosis and increase the risk of cardiovascular diseases (CVDs). The impaired metabolism of aminothiols increases oxidative stress, as these molecules are involved in antioxidant defense as well as in thiol redox control. In this study, total levels of selected aminothiols (i.e., cysteine (Cys), homocysteine (HCy), and glutathione) in convalescents after coronavirus disease of 2019 (COVID-19) were evaluated. The analyses were made according to the sex of the patients, time from COVID-19 onset, and COVID-19 severity. Methods: The study group consisted of 212 patients after COVID-19. Levels of total aminothiols were assessed in the blood plasma using high-performance liquid chromatography (HPLC). Results: The mean Cys concentrations were higher in men than in women (229.92 µmol/L ± 51.54 vs. 210.35 µmol/L ± 41.90, respectively; p = 0.003). Differences in Cys levels were also noticed in the total study group between patients distinguished due to time from disease onset (226.82 µmol/L ± 40.57 in <12 weeks, 232.23 µmol/L ± 47.99 in patients 12–24 weeks, and 208.08 µmol/L ± 48.43 in patients >24 weeks; p = 0.005). In addition, over 11% of total patients 12–24 weeks from disease onset had Cys levels above 300 µmol/L compared to almost 4% of patients <12 weeks and 2% of patients >24 weeks (p = 0.046). In sex-adjusted subgroups, significant differences due to time from COVID-19 were found in Cys levels in women (p = 0.004) and in glutathione levels in men (p = 0.024). None of the aminothiol levels differed between the subgroups based on the severity of COVID-19. Conclusions: Men had overall higher Cys levels than women. Cys levels were lower >24 weeks after COVID-19 onset than in the earlier period after disease onset. A partial elevation in Cys levels 12–24 weeks after the disease onset may contribute to the increase in CVD risk in the post-COVID-19 period. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. Materials and methods: This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. Results: Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098–4.770), SVD (aOR = 4.471, 95% CI = 1.110–4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733–5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954–6.449), CEI (aOR = 2.809, 95% CI = 1.073–4.991), SVD (aOR = 5.376, 95% CI = 1.708–6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535–7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008–5.148), CEI (aOR = 2.212, 95% CI = 1.247–5.946), SVD (aOR = 2.957, 95% CI = 1.324–6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586–4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. Conclusions: Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD. [ABSTRACT FROM AUTHOR]

Cystathionine beta‐synthase‐deficient homocystinuria (HCU) is a life‐threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10‐fold increase in hepatic levels of 5‐methyl ‐THF and a 30‐fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF‐generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU‐mediated induction of the 20‐hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one‐carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease. [ABSTRACT FROM AUTHOR]

Scientific evidence regarding the effectiveness of vitamin and mineral supplements in healthy individuals remains scarce. In a randomized, double-blind study, 30 healthy individuals were assigned to receive a single daily dose of multivitamin and multimineral supplementation or a double daily dose for 30 days. Before and after the intake, an untargeted metabolomics assay for serum metabolites was conducted by hydrophilic interaction liquid chromatography–mass spectrometry, and clinical assessments of peripheral blood samples were performed. A paired t-test for metabolic analysis, adjusted using the false discovery rate (FDR) and p-value correction method (rate of change > 2 and FDR < 0.05), the Shapiro–Wilk test, Student's t-test, and the Mann–Whitney U test were applied depending on the variable, with a 5% significance level. An impact on oxidative stress was observed, with a significant reduction in homocysteine levels and an increment of pyridoxic acid (vitamin B6). The effect on energy metabolism was shown by a significant increase in diverse metabolites, such as linoleoylcarnitine. Serum iron and calcium levels were also impacted. Overall, we observed a nutritional balance compatible with a good state of health. In conclusion, beneficial effects on adult health were demonstrated in relation to oxidative stress, energy metabolism, and nutritional balance. [ABSTRACT FROM AUTHOR]

Gulf War Illness (GWI) is a chronic multi-symptom neurological disorder affecting veterans of the Gulf War that is commonly comorbid with depression. A secondary data analysis was conducted to examine serum homocysteine and inflammatory cytokines (IFN-γ, IL-6, IL-1β, TNF-α) as potential biomarkers of depression improvement among veterans with GWI after a one-month dietary intervention aimed at reducing excitotoxicity and increasing micronutrients. Analyses, including multiple linear and logistic regression, were conducted in R studio. Dietary adherence was estimated using a specialized excitotoxin food frequency questionnaire (FFQ), and depression was measured using the Center for Epidemiologic Studies Depression (CES-D) scale. After one month on the diet, 52% of participants reported a significant decrease in depression (p < 0.01). Greater dietary adherence (FFQ) was associated with increased likelihood of depression improvement; OR (95% CI) = 1.06 (1.01, 1.11), (p = 0.02). Reduced homocysteine was associated with depression improvement after adjusting for FFQ change (β = 2.58, p = 0.04), and serum folate and vitamin B12 were not mediators of this association. Reduction in IFN-γ was marginally associated with likelihood of depression improvement (OR (95% CI) = 1.11 (0.00, 1.42), (p = 0.06)), after adjustment for potential confounders. Findings suggest that homocysteine, and possibly IFN-γ, may serve as biomarkers for depression improvement in GWI. Larger trials are needed to replicate this work. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is a well-established psychiatric complication following stroke. Nevertheless, the relationship between earlyonset PSD and homocysteine (Hcy) or fibrinogen remains uncertain. Methods: Acute ischemic stroke (AIS) patients who met the established criteria were enrolled in this study. Early-onset PSD was diagnosed two weeks after the stroke. The severity of depressive symptoms was assessed by the Hamilton Depression Scale-17 items (HAMD-17), with patients scored =7 assigned to the early-onset PSD group. Spearman rank correlation analysis was employed to evaluate the associations between Hcy, fibrinogen, and HAMD scores across all patients. Logistic regression analysis was conducted to investigate the relationship between Hcy, fibrinogen, and early-onset PSD. Receiver operating characteristic curve (ROC) analysis was ASSDalso performed to detect the predictive ability of Hcy and fibrinogen for early-onset PSD. Results: Among the 380 recruited patients, a total of 106 (27.89%) patients were diagnosed with early-onset PSD. The univariate analysis suggested that patients in the PSD group had a higher admission National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score (mRS), Hcy, and fibrinogen levels than patients in the non-PSD group (P<0.05). The logistic regression model indicated that Hcy (odds ratio [OR], 1.344; 95% confidence interval [CI] 1.209-1.494, P<0.001) and fibrinogen (OR, 1.57 6; 95% CI 1.302-1.985, P<0.001) were independently related to early-onset PSD. Area under curve (AUC) of Hcy, fibrinogen, and Hcy combined fibrinogen to predict early-onset PSD was 0.754, 0.698, and 0.803, respectively. Conclusion: This study indicates that Hcy and fibrinogen may be independent risk factors for early-onset PSD and can be used as predictive indicators for earlyonset PSD. [ABSTRACT FROM AUTHOR]

Suicide is a global public health concern, and understanding its multifaceted determinants is crucial for effective prevention. This study was designed to find an answer to the question of whether serum homocysteine level can be a biomarker of suicide attempts. This preliminary study involving 90 participants (45 suicide attempt cases and 45 controls) was conducted at Elazig Fethi Sekin City Hospital. Biochemical analyses were performed to assess serum homocysteine, vitamin B12, and folic acid levels. Statistical analyses, including t-tests, Mann-Whitney U tests, and ROC analysis, were employed to explore differences between groups and assess the diagnostic potential of homocysteine. Elevated homocysteine levels were found in individuals who attempted suicide compared to the control group (p= <0.001). Additionally, lower levels of vitamin B12 (p=<0.001) and folic acid (p=<0.001) were observed in the suicide attempt group. ROC analysis indicated a significant diagnostic potential for homocysteine in predicting suicide attempts (AUC = 0.845, sensitivity = 91%, specificity = 71%). This study establishes a significant association between high homocysteine levels and suicide attempts, accompanied by lower vitamin B12 and folic acid levels. The findings suggest a potential link between disturbances in homocysteine metabolism and suicidal tendencies, urging further research to establish causation and explore therapeutic implications. Consideration of the study's limitations and directions for future research are warranted. [ABSTRACT FROM AUTHOR]

Objectives: Many single nucleotide polymorphisms affect the incidence of Alzheimer's disease (AD). This investigation aimed to consider the frequency of the C677T single nucleotide polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in Alzheimer's patients. Materials and Methods: This study was conducted in two groups of control (n = 80) and patient (n = 80) with a ratio of 1: 1 male to female. Amplification-refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) method was used to study mutations and ELISA was used to measure homocysteine and the chemiluminescence method was used to measure cholesterol, vitamin B12 and folate. Results: Based on the results of the PCR test of the MTHFR gene, the incidence rate of mutation in the healthy allele was 44.6% and in the mutant allele was 27.9% of the total study population. Conclusion: In this study, it was discovered that an increase in cholesterol levels is related with an increased risk of developing the disease, but more studies are needed to confirm this. It should also be noted that this increase is not related to the MTHFR gene polymorphism at the C677T position. [ABSTRACT FROM AUTHOR]

Background: The precision of test measurements is critical in clinical diagnostics, especially for biomarkers like total PSA and homocysteine, which are essential to disease assessment. Using the CMIA approach, this study investigates the repeatability and reproducibility of these biomarkers on the Abbott Alinity system. Methods: The present study was conducted in the clinical chemistry laboratory at Mohammed VI University Hospital of Oujda. The evaluation of the Alinity i-system’s analytical performance for total PSA and homocysteine focused on assessing repeatability and intermediate precision. The assessment followed the protocols and guidelines established by the French Accreditation Committee (COFRAC). Results: Our analysis yielded favorable findings regarding the performance of the Alinity assays. The coefficients of variation for both the within-run and between-run precision were less than 5.89% and 4.29%, respectively. These findings produce acceptable outcomes compared to the manufacturer’s claims and the SFBC database. Our study underscores the tests’ precision, affirming the CMIA method’s reliability in measuring total PSA and homocysteine levels. Conclusions: The assessment of the Alinity i-system for total PSA and homocysteine showed significant analytical performance. Our findings have implications for laboratory personnel, researchers, and physicians supporting a continuous diagnostic accuracy improvement culture. [ABSTRACT FROM AUTHOR]

• The novelty is that MTHFR genotype may modulate the response to betaine intake. • Betaine concentrations increase more in TT/CT compared to CC. • Betaine supplementation decreases serum homocysteine concentration. • Betaine does not affect amino acid profile in healthy, athletic males. • The effect of betaine was not dose dependent. Betaine supplementation is used by athletes, but its mechanism of action is still not fully understood. We hypothesized that betaine supplementation would increase betaine concentration and alter amino acid profiles in relation to MTHFR genotype and dose in physically active males. The study followed a randomized placebo-controlled cross-over design. Blood samples were collected before and after each supplementation period. Serum was analyzed for amino acid profile, homocysteine, betaine, choline, and trimethylamine N-oxide (TMAO) concentrations. For the washout analysis, only participants starting with betaine were included (n = 20). Statistical analysis revealed no differences in the amino acid profile after betaine supplementation. However, betaine concentration significantly increased after betaine supplementation (from 4.89 ± 1.59 µg/mL to 17.31 ± 9.21 µg/mL, P <.001), with a greater increase observed in MTHFR (C677T, rs180113) T-allele carriers compared to CC (P =.027). Betaine supplementation caused a decrease in homocysteine concentration (from 17.04 ± 4.13 µmol/L to 15.44 ± 3.48 µmol/L, P =.00005) and a non-significant increase in TMAO concentrations (from 0.27 ± 0.20 µg/ml to 0.44 ± 0.70 µg/ml, P =.053), but had no effect on choline concentrations. Serum betaine concentrations were not significantly different after the 21-day washout from the baseline values (baseline: 4.93 ± 1.87 µg/mL and after washout: 4.70 ± 1.70 µg/mL, P = 1.000). In conclusion, betaine supplementation increased betaine and decreased homocysteine concentrations, but did not affect the amino acid profile or choline concentrations in healthy active males. Betaine concentrations may be dependent on MTHFR genotype. This was a randomized cross-over study of betaine supplementation in healthy athletic males. We showed that the increase in serum betaine concentrations was dependent on MTHFR genotype. Specifically, T-allele carriers experienced greater increase in betaine concentrations than CC homozygotes. Homocysteine concentration decreased with betaine supplementation. Abbreviations: BET, betaine; Hcy, homocysteine; MTHFR, methylenetatrahydrofolate; PL, placebo; WO, washout. [Display omitted] [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of 12 weeks of aerobic exercise (AT) and saffron supplementation on hemostasis, inflammatory markers, and insulin resistance in obese women diagnosed with type 2 diabetes (T2D). A total of 44 women with T2D (mean age: 54.12 ± 5.63 years, mean BMI: 31.15 ± 1.50 kg/m2, HbA1c: 85 ± 4.2 mmol/mol) were included in a randomized, double‐blind, placebo‐controlled study. We were randomly assigned to one of four groups (n = 11 per group): saffron + training (ST), placebo + training (PT), saffron supplement (SS), and placebo (P). The ST and PT groups completed 12 weeks of AT (three sessions per week of mild to moderate intensity). The ST and SS groups were administered a daily dose of 200 mg of saffron powder for 12 weeks. Fasting blood samples were collected 48 h before the first AT session and/or nutritional supplementation and 48 h after the last AT session and/or nutritional supplementation. Post‐evaluation, homeostatic model assessment of insulin resistance value (HOMA‐IR, p < 0.001) and serum levels of glucose (p < 0.001), fibrinogen (FIB, p < 0.001), homocysteine (HCY, p < 0.001), interleukin‐6 (IL‐6, p < 0.001), and tumor necrosis factor α (TNFα, p < 0.001) showed significant reduction in the ST, PT, and SS groups compared to the P group (p < 0.05). In particular, the ST group showed a more significant reduction in all variables compared to the PT and SS groups (p < 0.05). Our results suggest that a 12‐week intervention with AT and saffron supplementation can independently improve markers related to hemostasis, inflammation, and insulin resistance. However, their combination showed the greatest effectiveness on the above markers. Highlights: Type 2 diabetes can disturb hemostasis and induce inflammation.12 weeks of aerobic training (AT) and saffron supplementation can independently improve hemostasis, inflammation, and insulin resistance.The combination of 12 weeks of AT and saffron supplementation showed the greatest effectiveness on hemostasis, inflammation, and insulin resistance. [ABSTRACT FROM AUTHOR]

Chinese hamster ovary (CHO) cells require cysteine for growth and productivity in fed-batch cultures. In intensified processes, supplementation of cysteine at high concentrations is a challenge due to its limited solubility and instability in solution. Methionine can be converted to cysteine (CYS) but key enzymes, cystathionine beta-synthase (Cbs) and cystathionine gamma-lyase (Cth), are not active in CHO cells resulting in accumulation of an intermediate, homocysteine (HCY), in cell culture milieu. In this study, Cbs and Cth were overexpressed in CHO cells to confer cysteine prototrophy, i.e., the ability to grow in a cysteine free environment. These pools (CbCt) needed homocysteine and beta-mercaptoethanol (βME) to grow in CYS-free medium. To increase intracellular homocysteine levels, Gnmt was overexpressed in CbCt pools. The resultant cell pools (GnCbCt), post adaptation in CYS-free medium with decreasing residual HCY and βME levels, were able to proliferate in the HCY-free, βME-free and CYS-free environment. Interestingly, CbCt pools were also able to be adapted to grow in HCY-free and CYS-free conditions, albeit at significantly higher doubling times than GnCbCt cells, but couldn't completely adapt to βME-free conditions. Further, single cell clones derived from the GnCbCt cell pool had a wide range in expression levels of Cbs, Cth and Gnmt and, when cultivated in CYS-free fed-batch conditions, performed similarly to the wild type (WT) cell line cultivated in CYS supplemented fed-batch culture. Intracellular metabolomic analysis showed that HCY and glutathione (GSH) levels were lower in the CbCt pool in CYS-free conditions but were restored closer to WT levels in the GnCbCt cells cultivated in CYS-free conditions. Transcriptomic analysis showed that GnCbCt cells upregulated several genes encoding transporters as well as methionine catabolism and transsulfuration pathway enzymes that support these cells to biosynthesize cysteine effectively. Further, 'omics analysis suggested CbCt pool was under ferroptotic stress in CYS-free conditions, which, when inhibited, enhanced the growth and viability of these cells in CYS-free conditions. • Cysteine is difficult to supplement & control in CHO cell processes. • Cth, Cbs, & Gnmt (GnCbCt) or Cth & Cbs (CbCt) overexpression confers CYS prototrophy. • In -CYS, GnCbCt grows better than CbCt & produce titers comparable to WT in +CYS. • GnCbCt express other genes that further enable growth in CYS-free conditions. • CbCt cells appear to be under ferroptotic stress but not GnCbCt cells. [ABSTRACT FROM AUTHOR]

Objectives: To measure the efficiency of combining clinical, biochemical markers, and doppler studies (uterine and umbilical arteries) as values to predict fetal growth restriction. Methods: This randomized clinical cross-sectional research has been carried out at the ultrasound unit in the Department of Obstetrics and Gynecology and the laboratory unit, Faculty of Medicine, Zagazig University between 2017 and 2021. Results: One hundred twenty-four pregnant women who visited the antenatal clinic at the Department of Obstetrics and Gynecology with suspected clinical criteria for FGR were included. In our study, the incidence of positive FGR in high-risk patients was 24.5%. Abnormal biochemical markers (PAPPA=0.42 + Homocysteine =6.3) were 42.3% sensitive, 88.0% specific, and 70.8% accurate in the prediction of FGR. Also, a statistically significant relationship between FGR and uterine artery doppler is noted. However, a combination of uterine artery doppler (PI>1.57 + diastolic notching) and biochemical markers was 46.2% sensitive, 58.8% specific, and 55.7% accurate in the prediction of FGR. Finally, there is a highly statistically significant relationship between both FGR and umbilical artery Doppler at 29th-31st weeks. Conclusions: The incorporated model of screening in this study can be a beneficial method to identify patients at increased risk of FGR. The best finding in this study is that a combination of uterine artery and umbilical artery doppler was 88.5% sensitive, 96.3% specific and 94.3% accurate in the prediction of FGR. [ABSTRACT FROM AUTHOR]

Background: the aim of this randomized placebo-controlled study was to investigate the effect of probiotics mainly on plasma lipids, homocysteine levels, glycemic biomarkers and inflammatory marker in people with hyperlipidemia, compared to a placebo. Methods: a randomized, double-blind placebo-controlled study was completed with a total of 51 men and women who have diagnosed with hyperlipidemia. The three study interventions were: 1) probiotic group I asked to take once a day 1 x 106 colony forming unit (CFU) Lactobacillus rhamnosus GG microorganism (n = 18) capsule; 2) probiotic group II asked to take once a day of a combined Lactobacillus acidophilus 1 x 109 CFU and Bifidobacterium animalis subsp. lactis 1 x 109 CFU probiotic capsule (n = 17); and 3) placebo group: emptied capsule (n = 16), plasma lipids, homocysteine, and glycemic biomarkers were were performed at baseline and week 8. Also, hs-CRP levels was assessed as inflammatory parameter. Results: compared to baseline there was a significant decrease in triglyceride and total cholesterol levels of the both intervention groups compared to the placebo group. Regarding the glycemic biomarkers. both intervention groups significantly alter the HOMA-IR values compared to the placebo group (p < 0.05). When homocysteine values were evaluated. a statistically significant decrease was observed only in the group using the combined strain (p < 0.05). Results demonstrated that regular and strain-specific use of probiotics have effective and favorable consequences on plasma lipids and glycemic biomarkers. Conclusion: probiotics containing Lactobacillus or Bifidobacterium could be effective in hypercholesterolemic patients, reducing serum lipids as well as homocysteine and glycaemia. [ABSTRACT FROM AUTHOR]

Background Motoric Cognitive Risk (MCR) syndrome, a predementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. Methods We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1826 community-dwelling older adults (55% women) from 2 cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Results Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (>14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI: 1.01–1.97, p  = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Conclusions Higher blood homocysteine levels are associated with an increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of an altered ratio of maternal RBC folate (MRF) to serum vitamin B12 (MB12) on pregnancy and newborn outcomes. Blood samples were collected from pregnant women and the umbilical cord at the time of delivery. Estimations of RBC folate and serum vitamin B12 from maternal and cord blood samples and total homocysteine (HCY) were performed. Maternal and newborn anthropometric parameters like placental weight (PW), head circumference (HC), chest circumference (CC), and body weight (BW) were measured in offsprings after birth. We stratified the pregnant women into six groups (a) vitamin B12 normal and folic acid normal (BNFN)-control group, (b) vitamin B12 normal and folic acid elevated (BNFE), (c) vitamin B12 normal and folic acid deficient (BNFD), (d) vitamin B12 deficient and folic acid normal (BDFN), (e) vitamin B12 deficient and folic acid elevated (BDFE) and (f) vitamin B12 deficient and folic acid deficient (BDFD) based on their levels of RBC folate (MRF) and vitamin B12 (MB12). The expression of the one-carbon metabolism genes (methionine synthase (MS), glycine N-methyltransferase (GNMT), and cystathionine β-synthase (CBS) was also studied in placental tissue by using real-time PCR. Cord blood RBC folate was significantly reduced in groups BDFE and BDFD as compared to the control group (BNFN). The cord blood vitamin B12 levels were also reduced in the BDFE group as compared to the BDFD. All the newborn parameters viz. PW, HC, CC, and BW, were reduced in the altered MRF/MB12 ratio (low & high vs. normal ratio). Total HCY was significantly elevated in the groups with (BDFE & BDFN) an imbalance of maternal RBC folate and serum vitamin B12 as compared to the control group. Downregulation of one-carbon metabolism genes like MS (p < 0.001), GNMT (p < 0.05), and CBS (p < 0.01) in placental tissue was observed in the high MRF/MB12 ratio group as compared to the normal ratio group. A strong positive correlation was also observed between MRF, MB12, and newborn parameters. The altered ratio of folate to vitamin B12 in the maternal blood is associated with adverse growth and development of the newborn. [ABSTRACT FROM AUTHOR]

BACKGROUND: The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. METHODS: Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed‐effects models. RESULTS: The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. DISCUSSION: Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. Highlights: Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p.pTau could be a pharmacological target to treat agitation and psychosis symptoms.MBI domains were linked to metabolic dysregulation involving insulin and homocysteine. [ABSTRACT FROM AUTHOR]

Objective To investigate the factors involved in the development of thyroid nodules and the correlation between homocysteine (Hcy) and albumin-globulin ratio (AGR) and thyroid autoantibodies in adults. Methods As a retrospective study, a total of 1 427 people who received physical examination at the Second Hospital Affiliated to Hebei North College from October 2019 to August 2020 and the clinical data of the subjects who fulfilled the criteria of NAR were selected for analysis by simple random sampling. All of subjects underwent thyroid color ultrasound scanning and were divided into a control group (without thyroid nodules, n=52) and an observation group (with thyroid nodules, n=48). The general clinical data of the two study groups were compared, and the correlation between Hcy and AGR and thyroid autoantibodies was analyzed.Confunding factors affecting the incidence of thyroid nodules were screened using multifactorial unconditional logistic regression analysis. Results The observation group showed statistically significant differences in gender, age, diastolic blood pressure, systolic blood pressure, Hcy, AGR, TGAb, and TPOAb as compared to the control group (P＜0.05); Using adult Hcy as the dependent variable and Spearman′s correlation analysis of AGR, TGAb and TPOAb, adult Hcy was negatively correlated with AGR (r=-0.384, P＜0.05) and TGAb and TPOAb were positively correlated (r=0.218, 0.224, P＜0.05); Using age, sex, diastolic blood pressure, systolic blood pressure, Hcy, AGR TGAb and TPOAb as independent variables and thyroid nodules as dependent variables, a multifactor logistic regression analysis was performed in 100 subjects who experienced physical check. The analysis showed that age ≥40 years and female were relevant factors for the development of thyroid nodules factors (P＜0.05), Hcy, AGR, TGAb and TPOAb were correlated with thyroid nodules (P＜0.05). Conclusions Thyroid nodules are more common in middle-aged women, and there is a correlation between Hcy, AGR, TGAb, and TPOAb levels and thyroid nodules. Regular thyroid screening examination should be carried out based on the above indicators.