Homocysteine Levels Research Articles

Review on Alzheimers Disease

Abstract: Loss of Abstract Thinking Someone with Alzheimer’s disease may lose the ability to draw conclusions and solve problems. It may become difficult to balance a checkbook, for example, because the patient has forgotten what to do with the numbers. About 29.8 million people worldwide had been diagnosed with Alzheimer’s disease (AD) in 2015, And the number is projected to triple by 2050. In 2018, AD was the fifth leading cause of death in Americans with 65 years of age or older, but the progress of AD drug research is very limited. It is Helpful to identify the key factors and research trends of AD for guiding further more effective Studies. Alzheimer’s disease is a degenerative disease of the brain, the most common cause of dementia in the geriatric population, and a major cause of death. Alzheimer’s disease is one of the fastest growing risk factors in middle age, which Increases the risk of Alzheimer’s disease in coronary weddings and higher levels of Homocysteine, which can lead to withdrawal due to lifestyle changes. Cigarettes prevent Alzheimer’s disease by recalling memories. Also, despite the fact that there is no Definitive cure for Alzheimer’s, the ability to increase acetylcholine levels and reduce Ameloid beta deposition and your medications such as Donepezil has proven to be very Effective when treating Alzheimer’s disease (AD) is a progressive neurodegenerative disease. It Is characterized by progressive cognitive deterioration together with Declining activities of daily living and behavioral changes. It is the Most common type of pre-senile and senile dementia. Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence Extracellular b-amyloid deposition as neuritic plaques and intracellular accumulation of hyperphos . Phorylated tau as neurofibrillary tangles remains the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles For other critical cellular and molecular processes. Despite this, no disease-modifying treatment Currently exists, and numerous phase 3 clinical trials have failed to demonstrate benefits. Here ,We review recent advances in our understanding of AD pathobiology and discuss current treatment Strategies, highlighting recent clinical trials and opportunities for developing future disease modifying therapies.

Serum homocysteine levels and mortality: a cohort study

Abstract Background Homocysteine, an intermediate metabolite derived from dietary methionine, plays a pivotal role in deoxyribonucleic acid expression and contribute to its antioxidant capabilities. Elevated homocysteine levels can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorder; however, low levels of homocysteine are generally not considered harmful. This study evaluates the association between all levels of homocysteine-both low and high-and the risk of all-cause and cause-specific mortality in Korean adult men. Methods A study involving 221,356 Korean adult men categorized them into quintiles based on their homocysteine levels. The main outcomes examined were mortality from all causes, cardiovascular disease (CVD), cancer, and dementia. Hazard ratios (HRs) were determined using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further analyzed using a restricted cubic splines model. Results Compared to 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 homocysteine levels after adjusting for multiple variables (Pinteraction=0.002). Furthermore, spline regression revealed a U-shaped relationship between homocysteine levels and both all-cause and CVD mortality, with an inflection point at 9.1 µmol/L. This U-shaped association was not observed in the subgroup that received vitamin supplements. Conclusions Among young and middle-aged Korean adult men, both low and high homocysteine levels were found to increase the risk of all-cause and CVD mortality, demonstrating a U-shaped relationship. However, this association lost statistical significance with vitamin supplementation. These findings underscore the importance of monitoring both low and high homocysteine levels as potential mortality risk factors in men and suggest a possible protective role of vitamins. Key messages • Both low and high levels of homocysteine in young and middle-aged Korean men are associated with increased risks of all-cause and cardiovascular mortality, demonstrating a U-shaped relationship. • Vitamin supplementation appears to nullify this association, suggesting a potential protective effect against mortality.

Hypertension and global DNA methylation: a population-based study in rural, Punjab, India

Hypertension is a significant public health concern and a modifiable risk factor for increased mortality worldwide. It is reported to be influenced by gene-environment interactions and micronutrient intake. This study aims to understand the relationship between global DNA methylation levels and hypertension, independently and in the context of micronutrient status, among rural population in Punjab, India. A total of 2300 individuals, aged 30–75 years, (54.9% females) were screened for blood pressure. Of 2300 screened individuals, 900 (age sex matched 450 cases and 450 controls of hypertension) individuals were selected to examine the relationship between hypertension, global DNA methylation (5mC), and biochemicals (Folate, Vitamin B12, and Homocysteine). Folate, vitamin B12, and homocysteine levels were estimated using chemiluminescence technique. The ELISA-based colorimetric technique was used for performing peripheral blood leucocyte (PBL) global DNA methylation (5mC). Statistical analyses were performed using SPSS version 22.0. Hypertensives were found to have significantly lower levels of global DNA methylation than normotensives (0.65 vs. 0.72 respectively; p-value = 0.01*). Individuals in the 1st quartile of 5mC were at significantly (OR: 1.671; 95% CI: 1.206–2.315; p-value = 0.01*) increased risk for hypertension in comparison to those in the 4th quartile (reference). Further hypertensives on medication with controlled blood pressure (BP) were significantly hypermethylated as compared to hypertensives on medication with uncontrolled BP (0.70 vs. 0.62 respectively; p-value = 0.04*). Folate appeared to mediate global DNA methylation among hypertensives on medication-controlled BP. Further hypertension driven hypomethylation hints towards accelerated biological aging among younger hypertensives. Hypertension may be associated with Global DNA hypomethylation in the studied rural population of Punjab, India. Folate sufficiency may prove to be an aid in improving the methylation levels among the cases of hypertension who were on medication and had controlled BP.

. Predictive Value of Pre-delivery Serum β-human Chorionic Gonadotropin, Fibrinogen, and Homocysteine for Hypertensive Disorders of Pregnancy

Introduction: it was to investigate the relationship between pre-delivery serumβ-human chorionic gonadotropin (β-HCG), fibrinogen (FIB), and homocysteine (HCY) with hypertensive disorder complicating pregnancy (HDCP). Materials and Methods: 200 HDCP patients and 150 normal pregnant women were selected as study subjects. Fasting cubital venous blood samples were collected to measure serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), as well as β-HCG, FIB, and HCY levels. Pearson correlation analysis examined relationship between β-HCG, FIB, HCY, and HDCP. Receiver operating characteristic (ROC) curve analysis evaluated the predictive value of these indicators for HDCP. Multiple logistic regression analysis identified risk factors (RFs) for HDCP.Results: serum TG, TC, HDL, LDL, FIB,β-HCG, and HCY were greatly elevated in the HDCP group versus control group (CG) (P<0.05). Serumβ-HCG, FIB, and HCY showed notable positive correlations with HDCP (r = 0.935, 0.547, 0.811; P<0.05), and the areas under the ROC curve (AUC) for predicting HDCP based on serum β-HCG, FIB, HCY, and their combination were 0.743, 0.659, 0.801, and 0.886, respectively (P<0.05). Lipid indicators and serum levels of FIB, β-HCG, and HCY were RFs for HDCP.Conclusion:pregnant women with HDCP exhibited markedly elevated serum lipid levels and FIB, β-HCG, and HCY levels before delivery, which can serve as predictive indicators for HDCP.

Contribution of haptoglobin phenotypic variation to the presence of hyperhomocysteinemia in type 2 diabetics with and without angiopathy.

The genetic polymorphism of haptoglobin (Hp) has been associated with several cardiovascular risk factors, but a possible relationship between Hp phenotypic variation and increased levels of homocysteine (Hcy) and cysteine (Cy) is still unknown. The objective of this study is to evaluate the relationship between the Hp polymorphism and hyperhomocysteinemia (HHcy) and hypercysteinemia (HCy) in type 2 diabetics (T2D) with and without angiopathy (AGP). A case-control study was carried out on 293 adults: Group I (GI) - 75 subjects with T2D and AGP; Group II (GII) - 75 subjects with T2D without AGP; Group III (GIII) - 143 controls. Plasma levels of Hcy, Cy and vitamin B6 were measured by high performance liquid chromatography (HPLC) and vitamins B9 and B12 determined by electrochemiluminescence (ECL). The Hp polymorphism was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and peroxidase staining. The results were analyzed in SPSS®, version 26.0 with a significance of 95%. Mean Hcy concentrations were significantly lower in carriers of the Hp2-2 phenotype (6.14 µM; p = 0.046) compared to the other genotypes. The presence of Hp2-1 is associated with an approximately 3.3 times greater probability of occurrence of HHcy (p = 0.015) and 3.7 times greater probability occurrence of HCy (p = 0.021) in T2D with AGP. The presence of the Hp2-1 phenotype is associated with the predisposition of HHcy and HCy in individuals with T2D and AGP, possibly through a positive heterosis mechanism. Carriers of the Hp2-2 phenotype appear to have a greater activation of the transsulfuration pathway in the Hcy cycle and consequent protection for its accumulation.

Establishment of a prediction model for venous thromboembolism in patients with acute exacerbation of chronic obstructive pulmonary disease based on serum homocysteine levels and Wells scores: a retrospective cohort study

BackgroundWe evaluated the diagnostic value of homocysteine (Hcy) levels combined with the Wells score and established a prediction model for venous thromboembolism (VTE) occurrence in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on the Hcy level and the Wells score.Patients and methodsClinical information from 914 patients with AECOPD was retrospectively collected in our hospital from June 2020 to October 2023. Receiver operating characteristic curves were plotted to evaluate the diagnostic ability of Hcy concentrations combined with Wells scores and the prediction ability of the model. Univariate and multivariate logistic regressions were used to explore the effects of Hcy levels and the Wells score on VTE occurrence. A nomogram was established for individual risk evaluation.ResultsHcy levels and Wells scores were significantly greater in the VTE group than in the non-VTE group (P < 0.001). The diagnostic ability of Hcy levels combined with the Wells score was greater than that Hcy levels or the Wells score alone. The AUC of the combined parameters was 0.935, with a sensitivity of 0.864 and a specificity of 0.855. Multivariate logistic regression indicated that elevated Hcy levels (OR:5.17, 95%CI: 3.76–7.09, P < 0.001) and Wells score (OR: 5.26, 95%CI: 3.22–8.59, P < 0.001) were independently associated with the risk of developing VTE in AECOPD patients. Decision curve analysis indicated that the net benefit of the nonadherence prediction nomogram was greater than that of the models adjusted for no or all variables, with a threshold of approximately 0.1-1.0.ConclusionsThe established prediction model can be used to evaluate an individual’s risk of developing VTE on the basis of the Hcy level, Wells score, and clinical parameters. AECOPD patients may benefit from the early intervention based on estimated risk probability.

Folic acid supplementation during fattening period affects growth and nutritional metabolism in Japanese Black beef cattle

The folate requirements for beef cattle have not been established. Therefore, we investigated whether rumen-unprotected folic acid supplementation during the fattening period affects carcass traits and nutritional metabolism in Japanese Black beef cattle. Eighteen Beef cattle aged 16 months were divided into three groups: control, low folic acid supplementation (0.43 g DM/day), and high folic acid supplementation (0.86 g DM/day). Treatment was administered for 12 months. Folic acid supplementation dose-dependently increased serum folate levels, suggesting that supplemental folic acid can be absorbed into the body. Folic acid supplementation dose-dependently decreased serum vitamin B12 levels, while plasma total homocysteine and methylmalonic acid levels—markers for deficiency of folate and/or vitamin B12—were unaffected. Thus, the treatment did not clearly affect the nutritional status of these vitamins. Supplementation increased body weight, with no negative effects on other carcass traits. The levels of insulin-like growth factor 1, retinol, albumin, and some amino acids in serum or plasma were affected by supplementation. These results suggest that rumen-unprotected folic acid supplementation during the fattening period could increase the body weight of Japanese Black beef cattle and the mechanism of action may be related to growth-related hormones and/or the metabolism of some nutrients, including folate.

Synergies between diabetes and hyperhomocysteinaemia: New insights to predict and prevent adverse cardiovascular effects.

To explore the association of hyperhomocysteinaemia (HHcy) and diabetes synergies with cardiovascular events in the adult population of northern China. Data were collected from the Asymptomatic Polyvascular Abnomalities Community study for 2010 to 2019. Serum homocysteine (Hcy) levels were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their Hcy levels and diabetes status: non-diabetes/non-HHcy, non-diabetes/HHcy, diabetes/non-HHcy and diabetes/HHcy. The composite endpoint consisted of the occurrence of first-ever stroke, myocardial infraction (MI) or all-cause mortality. Cox regression analyses were performed to evaluate the associations of diabetes and HHcy with cardiovascular disease (CVD) events. In total, 5278 participants were eligible (average age 55.1 years, 60% male). Over a follow-up of 9.1 years, 618 events were identified, 202 stroke, 52 MI and 406 all-cause deaths. Compared with the non-diabetes/non-HHcy group, hazard ratios with 95% confidence intervals in the diabetes/HHcy group for stroke, MI, major adverse cardiovascular event (MACE), all-cause death and composite endpoint were 1.85 (1.12-3.04), 1.33 (0.42-4.23), 1.78 (1.13-2.80), 2.24 (1.56-3.23) and 1.97 (1.47-2.65), respectively. Significant interactions between HHcy and diabetes status were found for stroke, MI and MACE (P for interaction = .002, .027 and .044, respectively). In addition, the association of diabetes/HHcy with stroke was modified by age (< 60 and ≥ 60 years; P for interaction = .016). The findings highlight the synergistic impact of diabetes and HHcy on CVD. Joint assessments of diabetes and Hcy levels should be emphasized for risk stratification and primary prevention of CVD.

Vitamin B12 is correlated with insulin resistance and metabolism disorder markers in women with recurrent pregnancy loss

ObjectivesRecurrent pregnancy loss (RPL) seriously affects women's reproductive and mental health, and the incidence has increased in recent years. Insulin resistance (IR) acts as a significant contributing factor to RPL. Studies suggest that vitamin B12, folate intake, and homocysteine are correlated with IR, but the exact nature remains controversial and requires further investigation. In this study, we aimed to assess the levels and correlations between vitamin B12-folate-homocysteine and insulin resistance in RPL patients. Study design73 control subjects and 256 RPL patients (144 RPL patients without IR and 112 RPL patients with IR) were included in this observational retrospective cross-sectional study. The differences in vitamin B12, folate, and homocysteine levels between RPL patients with and without IR were analyzed using a Student's t-test. Pearson correlations were utilized to examine the correlation between vitamin B12-folate-homocysteine and glucose and lipid metabolism parameters. Multivariable linear regressions were used to assess the independent correlation of each factor with HOMA-IR. ResultsCompared to the control subjects, RPL patients exhibited lower vitamin B12 (p < 0.001) and folate (p < 0.001), and higher homocysteine (p = 0.001). RPL patients with IR described decreases in vitamin B12 (p = 0.003) and folate (p = 0.028), and increases in homocysteine (p = 0.033) as RPL patients without IR. Vitamin B12 in RPL patients was significantly negatively correlated with homocysteine (r = −0.348, p < 0.001), HOMA-IR (r = −0.214, p < 0.001), BMI (r = −0.160, p = 0.017), TG (r = −0.148, p = 0.039) and CHO (r = −0.149, p = 0.038) and positively correlated with folate (r = 0.217, p < 0.001). In multivariable linear regressions, after adjusting for age, strong correlations were observed between vitamin B12 (β = −0.197, p = 0.010), BMI (β = 0.466, p < 0.001), and HOMA-IR in RPL patients. ConclusionVitamin B12 is significantly correlated with IR in RPL patients. Circulating vitamin B12-folate-homocysteine metabolism could be a window of the pathological process of IR, obesity, and lipid metabolism disorders in RPL patients.

Efficacy of Vitamin-D supplementation in improving the prognosis of H-type hypertension in elderly patients

Objective: To investigate the correlation between 25-hydroxyvitamin D and H-type hypertension in elderly patients, and to observe the clinical efficacy of vitamin D supplementation in those patients. Methods: This was a retrospective study. One hundred and twenty elderly hypertensive patients treated at The Affiliated Hospital of Hebei University from June 2022 to June 2023 were randomly divided into Group-A (n=60) with hypertension and elevated homocysteine (Hcy) levels (H-type hypertension), and Group-B(n=60) with hypertension and normal Hcy levels. Blood levels of 25-hydroxyvitamin D and 24 hours ambulatory blood pressure were assessed in both groups of patients upon admission, with the correlation analysis performed simultaneously. The therapeutic effects were compared between the two groups. Results: Through Pearson correlation analysis, there were negative correlations of serum 25-hydroxyvitamin D levels with 24 hours SSD, 24 hours DSD, dnSBP, and nDBP(all p&lt;0.05). After 12 weeks of treatment, the treatment group had higher 25-hydroxyvitamin D levels and lower 24 hours SBP, 24h DBP, dSBP, dDBP, nSBP, nDBP levels than those of the control group(p&lt;0.05). After treatment, the treatment group had lower blood Hcy, IMT, TC, TG, and LDL-C levels(p&lt;0.05), and higher HDL-C levels(p&lt;0.05) than those of the control group. Conclusion: Serum 25-hydroxyvitamin D levels in elderly patients with H-type hypertension have negative correlations with 24 hours SSD, 24 hours DSD, dnSBP, and nDBP. Oral vitamin D supplementation for H-type hypertensive patients exhibits significant therapeutic effects, with improvements in 24 hours ambulatory blood pressure monitoring results, blood lipid levels, IMT, and blood Hcy levels after treatment. doi: https://doi.org/10.12669/pjms.40.10.8464 How to cite this: Zang S, Zhao Q, Xiao N, Liu S. Efficacy of Vitamin-D supplementation in improving the prognosis of H-type hypertension in elderly patients. Pak J Med Sci. 2024;40(10):2379-2383. doi: https://doi.org/10.12669/pjms.40.10.8464 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia

Objective: To investigate the correlations of cognitive function with serum levels of homocysteine (Hcy), sex hormone binding globulin (SHBG), and leptin in patients with schizophrenia. Methods: This was retrospective study. This study included 58 patients with schizophrenia (SCZ) as observation group and 60 clinically healthy individuals as control group admitted to Xiangshan County Hospital of Traditional Chinese Medicine Medical and Health Group Third Hospital from March 2022 to June 2023. Serum levels of Hcy, SHBG, and leptin in the two groups were measured, and Pearson correlation analysis was conducted to investigate the correlations between the Hcy, SHBG, and leptin levels and the psychiatric symptoms and cognitive function in the observation group. Results: The Hcy and SHBG levels in the observation group were significantly higher than those in the control group (p&lt;0.05, respectively), and the leptin level was lower than that in the control group (p&lt;0.05). The observation group scored significantly lower than the control group for each dimension of the MCCB (p&lt;0.05, respectively). In the observation group, Hcy was positively correlated with negative symptoms and the PANSS total score (p&lt;0.05, respectively) and was negatively correlated with scores for the leptin was negatively correlated with negative symptoms and the PANSS total score (p&lt;0.05, respectively) and was positively correlated with scores for speed of processing (SOP), WMS-III, BVMT, and MSCEIT (p&lt;0.05, respectively). Conclusions: Increased levels of Hcy and SHBG and decreased leptin are strongly associated with the occurrence of cognitive impairment in SCZ cases. Therefore, clinical observation and monitoring of these markers can help identify changes in patient conditions. doi: https://doi.org/10.12669/pjms.40.10.8923 How to cite this: Xu Y, Qian X, Zhang M, Liang M. Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia. Pak J Med Sci. 2024;40(10):2319-2323. doi: https://doi.org/10.12669/pjms.40.10.8923 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Higher Serum Level of MMP-3 and Homocysteine in Patients Admitted With COVID-19

Background: SARS-CoV-2 predominantly affects the lungs, leading to severe acute respiratory syndrome (ARDS). The lack of specific biomarkers underscores the urgent need for novel indicators for early diagnosis and severity assessment of COVID-19. Specific Background: Matrix metalloproteinase-3 (MMP-3) is implicated in various inflammatory diseases, particularly viral infections, while homocysteine (Hcy) plays a crucial role in maintaining cell homeostasis and regulating inflammatory responses. Knowledge Gap: Despite their relevance in inflammation, the potential of MMP-3 and Hcy as biomarkers for COVID-19 remains underexplored. Aims: This study aimed to evaluate the serum levels of MMP-3 and Hcy in COVID-19 patients and assess their utility in diagnosis and severity prediction. Results: A study analyzing 90 serum samples from 60 ICU patients and 30 healthy controls found elevated CRP levels, higher Hcy and MMP-3 levels in the moderate group, but lower in the ICU group, with a significant correlation between MMP-3 activity and Hcy levels. Novelty: This research highlights the potential role of MMP-3 and Hcy as valuable biomarkers for COVID-19 diagnosis. Implications: While MMP-3 and homocysteine may aid in the diagnostic process, they could not be reliably used to predict severity outcomes in COVID-19 patients. Further studies are warranted to clarify the clinical implications of these biomarkers in the context of COVID-19. Highlights: MMP-3 and homocysteine identified as potential COVID-19 biomarkers. No correlation found between biomarkers and disease severity. Further research needed for clinical utility assessment. Keywords: COVID-19, MMP-3, homocysteine, biomarkers, diagnosis

Impact of smokeless tobacco on psychological and oxidative stress in unemployed indian youth

In India, tobacco (nicotine) addiction among youth has increased, leading to substantial socioeconomic burdens, mortality, and morbidity. While minimal short-term nicotine consumption may have antioxidant effects, chronic exposure results in various adverse health outcomes. This study examines the impact of chronic nicotine consumption on cellular oxidative stress and psychological stress, and their correlation with Homocysteine (Hcy) levels in unemployed tobacco consumers. This case-control study included 156 healthy, educated, unemployed male volunteers aged 20–40 years, divided into nicotine-addicted (n = 80) and non-addicted (n = 76) groups. Psychological stress was assessed using perceived stress scales (PSS) and coping self-efficacy (CSE) scales. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase, were measured. Hcy levels were quantified using high-performance liquid chromatography (HPLC). Nicotine-addicted participants exhibited significantly higher perceived stress (p = 0.0001) and lower coping self-efficacy (p = 0.0001) compared to non-addicted individuals. MDA levels in erythrocytes were significantly increased (p = 0.0006), while SOD (p = 0.0001) and Catalase (p = 0.02) activities were significantly decreased in the addicted group. Nicotine intake influenced Hcy concentrations, with 55% of addicted individuals falling into moderate, 27.5% into intermediate, and 7.5% into severe Hcy categories. Chronic nicotine intake also reflected the hematological parameters (WBCs, RBCs, HGB, and Platelets). Chronic tobacco consumption induces oxidative stress and perceived psychological stress, leading to elevated Hcy levels in nicotine consumers. The study highlights the detrimental effects of nicotine addiction on cellular defensive mechanisms, emphasizing the need for targeted interventions to address this growing health issue among unemployed Indian youth.

Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.

One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon metabolism have been associated with changes in nuclear DNA methylation levels in individuals affected by age-related diseases. More and more studies are showing that even mitochondrial DNA (mtDNA) could be methylated. In particular, methylation of the mitochondrial displacement (D-loop) region modulates the gene expression and replication of mtDNA and, when altered, can contribute to the development of human illnesses. However, no study until now has demonstrated an association between circulating biomarkers of one-carbon metabolism and D-loop methylation levels. In the study presented herein, we searched for associations between circulating one-carbon metabolism biomarkers, including folate, homocysteine, and vitamin B12, and the methylation levels of the D-loop region in DNA obtained from the peripheral blood of 94 elderly voluntary subjects. We observed a positive correlation between D-loop methylation and vitamin B12 (r = 0.21; p = 0.03), while no significant correlation was observed with folate (r = 0.02; p = 0.80) or homocysteine levels (r = 0.02; p = 0.82). Moreover, D-loop methylation was increased in individuals with high vitamin B12 levels compared to those with normal vitamin B12 levels (p = 0.04). This is the first study suggesting an association between vitamin B12 circulating levels and mtDNA methylation in human subjects. Given the potential implications of altered one-carbon metabolism and mitochondrial epigenetics in human diseases, a deeper understanding of their interaction could inspire novel interventions with beneficial effects for human health.

Effect of sacubitril and valsartan combined with conventional therapy on patients with heart failure

Purpose: To investigate the clinical effectiveness of the combination of sacubitril and valsartan with conventional therapy in the treatment of patients with heart failure. Methods: This was a retrospective study comprising 100 heart failure patients randomized into study (n = 57) and control groups (n = 43). The study group received sacubitril/valsartan along with conventional drug therapy while control group received only conventional drugs, viz, irbesartan, metoprolol slow release, and furosemide tablets. Echocardiogram showing left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left anterior descending artery (LAD), Nterminal pro-b-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), glomerular filtration rate (eGFR), and homocysteine (HCY) of the two groups were compared before and after treatment. Multiple regression was used to analyze the correlation between re-hospitalization and sacubitril/valsartan intervention. Results: The study group showed significantly lower LVEF, LVESD, LVEDD, LAD, NT-proBNP, and homocysteine levels after treatment compared to control group (p &lt; 0.05). Re-hospitalization for abnormal cardiovascular events between the two groups was significantly different in the adjusted Cox proportional hazards regression model. Furthermore, multiple regression analysis showed that sacubitril/valsartan treatment was the independent variable (p &lt; 0.001). Conclusion: Sacubitril/valsartan improves heart function, with reduced incidence of adverse effects without affecting renal function. Further studies are required to validate these findings by expanding sample size, strictly controlling data quality and strengthening follow-up.

Investigation of Hemorheological Parameters in Ischemic Stroke Patients.

The aim of this study is to determine whether there are any changes in hemorheological parameters, including whole blood viscosity (WBV), plasma viscosity, erythrocyte aggregation, and erythrocyte deformability, in acute ischemic stroke patients, and to establish their relationship with stroke etiology. The study also aims to observe the changes in these parameters, if any, over time and after treatment, and to assess the correlation between risk factors for ischemic stroke and neuroimaging findings. This was a prospective observational study including 70 patients diagnosed with acute ischemic stroke within the first 3 days of the onset of symptoms and 96 healthy controls. Stroke patients were categorized based on TOAST criteria, and hemorheological parameters were measured at admission and on the fifth day post-treatment. Erythrocyte aggregation and deformability were measured using a laser ektacytometer, and viscosity assessment was conducted with a rotational viscometer. Stroke patients exhibited significant differences from the control group in aggregation amplitude, aggregation index, and aggregation half-time (p = 0.001, p = 0.013, p = 0.009, respectively) and showed elevated maximum value of elongation index (p = 0.000). No significant differences in WBV and plasma viscosity were observed between the groups. Post-treatment, the small vessel occlusion subgroup demonstrated a notable reduction in WBV. Additionally, homocysteine levels showed a positive correlation with scattered white matter lesions in basal ganglia and infratentorial regions (p = 0.002, p = 0.039, respectively). Increased predisposition to erythrocyte aggregation may contribute to the occurrence of acute ischemic stroke. Moreover, gaining the ability of erythrocytes to deform and increase blood flow may serve as a compensatory mechanism in the chronic vascular disease process. The risk factors for ischemic stroke may exhibit connections to specific areas within the brain.

Assessment of vitamin B12 and homocysteine levels in pregnant women admitted for delivery and cord blood samples of their newborn babies: a multicenter study.

Vitamin B12, an indispensable micronutrient, is pivotal in numerous physiological processes, with particular significance during pregnancy and fetal development. The increasing adoption of vegetarian diets and the economic challenges associated with accessing animal-based food sources contribute to the prevalence of vitamin B12 deficiency. This study aims to examine the levels of vitamin B12 and homocysteine in pregnant women upon admission for delivery and to analyze corresponding cord blood samples from their newborn infants in a substantial sample within the Istanbul metropolitan area. This cross-sectional multicenter study included women aged ≥16 years admitted for delivery and their newborns ≥34 weeks. The demographic data and the results of complete blood counts within the previous 24 hours before birth were recorded. Vitamin B12 and homocysteine levels were measured in maternal and cord blood samples. The study parameters were compared between the groups based on the mothers' and babies' homocysteine and vitamin B12 levels. The study included 832 pregnant women and 832 neonates. Anemia affected 36% of pregnant women, with a higher frequency in mothers with vitamin B12 deficiency. Seventy-eight mothers and 48.9% of neonates showed Vitamin B12 levels below 200 pg/mL, while elevated homocysteine levels were observed in 30% of mothers and 26% of neonates. Maternal vitamin B12 deficiency was significantly correlated with cord blood B12 deficiency and elevated homocysteine. The median cord blood vitamin B12 level was inversely correlated with the number of previous pregnancies. Vitamin B12 deficiency is extremely common in pregnant women before delivery, significantly correlating to cord blood homocysteine and vitamin B12 levels. However, homocysteine alone is not a reliable marker for maternal vitamin B12 status. Implementing strategies to detect vitamin B12 deficiency and supplying adequate vitamin B12 supplementation during pregnancy holds the potential to enhance maternal and neonatal health in Türkiye.

Comparative study of oxidative stress in cancer patients occupationally exposed to the mixture of pesticides.

Cancer isa leading cause of death worldwide, accounting for nearly 10 million deaths in 2020.Reviews indicated a positive relationship between exposure to pesticides and the development of cancers. In the present study, we have estimated the level of oxidative stress markers in serum samples of pesticide exposure and unexposed cancer patients as compared to normal control. We have found a significant decrease in peroxygenase (PON) and arylesterase (ARE) activity and substantial increases in homocysteine levels in both cancer groups. The level of heme biosynthesis rate-limiting enzymesdelta-aminolevulinic acid dehydratase(δ-ALA-D)also significantly decreased compared to control. The statistical comparison between the cancer groups does not show significant changes. We concluded the involvement of oxidative stress in carcinogenesis in both cancer group patients. However, more study is needed to put homocysteineas a novel marker for a variety of diseases on a single platform.

8079 PPI Breaks a Leg! An Unusual Case of Atypical Femur Fracture

Abstract Disclosure: M. Sedghian: None. M. Flanagan: None. D. Pinkhasova: None. K. Selk: None. G. Moloney: None. Background: Atypical femur fractures (AFF) occur along the shaft of the femur extending from the subtrochanteric region proximally to the distal femoral metaphysis. These fractures have an increased incidence in patients taking bisphosphonates and denosumab for osteoporosis and develop as stress reactions in the lateral cortex of the femoral shaft (beaking). However, few cases that meet the characteristics of these fractures have occurred in patients who have never used antiresorptive drugs. We present a case with a history of long-term proton pump inhibitor (PPI) use and possible association with AFF. Clinical Case: The patient is a 68-year-old female with a past medical history of hypothyroidism who presented to the emergency department (ED) after an atraumatic femur fracture and consequently ground level fall. The patient reported experiencing a distinctive cracking sound in her femur while leaning over to wash her feet, resulting in a fall that prompted her to seek immediate care in the ED. Upon initial evaluation, radiographic imaging was significant for displaced left mid-femoral diaphyseal fracture and right femur lateral cortex thickening consistent with AFF. Labs were consistent with elevated PTH to 100.7 [18.4-80.1], Vit D2 1,25 (OH)2 &amp;lt;8 pg/mL, Vit D 25OH 34 ng/ml [30-100], and Calcium level of 9.5. Upon further history taking, the patient stated that she has been taking PPIs intermittently for more than 10 years. She denied a history of bisphosphonate and denosumab exposure, non-Hodgkin's lymphoma, rheumatoid arthritis, and COL1A2 variant mutations as main predisposing factors for atypical femur fractures. She had potential steroid exposure for less than a year before hospitalization as she was on "adrenal complex" from her functional medicine provider. The patient underwent open reduction and internal fixation of the left femur with placement of intramedullary nail and prophylactic fixation with placement of intramedullary nail of the right femur as there was radiographic evidence of beaking. Discussion/Conclusion: Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. Overall, PPIs are positively associated with elevated fracture risk in multiple studies. Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, decreasing bone turnover, impairing calcium absorption, and altering homocysteine levels through impairment of folate and vitamin B12 absorption.This case supports a potential association between long-term PPI use and atypical femur fractures. There have been other case reports that also highlight this potential risk of PPI use. This shows the importance of more comprehensive research on this topic as the number of patients on long-term PPIs is growing in outpatient settings. Presentation: 6/2/2024

Mechanism of action and impact of thiol homeostasis on efficacy of an enzyme replacement therapy for classical homocystinuria

Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency is characterized by elevated plasma and tissue homocysteine levels. There is no cure, but HCU is typically managed by methionine/protein restriction and vitamin B6 supplementation. Enzyme replacement therapy (ERT) based on human CBS has been developed and has shown significant efficacy correcting HCU phenotype in several mouse models by bringing plasma total homocysteine below the clinically relevant 100 μM threshold. As the reactive nature of homocysteine promotes disulfide formation and protein binding, and ERT is unable to normalize plasma total homocysteine levels, the mechanism of action of ERT in HCU remains to be further characterized. Here we showed that only a reduced homocysteine serves as a substrate for CBS and its availability restricts the homocysteine-degrading capacity of CBS. We also demonstrated that cells export homocysteine in its reduced form, which is efficiently metabolized by CBS in the culture medium. Availability of serine, a CBS co-substrate, was not a limiting factor in our cell-based model. Biological reductants, such as N-acetylcysteine, MESNA or cysteamine, increased the availability of the reduced homocysteine and thus promoted its subsequent CBS-based elimination. In a transgenic I278T mouse model of HCU, administration of biological reductants significantly increased the proportion of protein-unbound homocysteine in plasma, which improved the efficacy of the co-administered CBS-based ERT, as evidenced by significantly lower plasma total homocysteine levels. These results clarify the mechanism of action of CBS-based ERT and unveil novel pharmacological approaches to further increase its efficacy.