Homocysteine Levels Research Articles

MTHFRC 677T Gene Polymorphism and Homocysteine in North China Patients with Varicocele

To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, homocysteine, and male infertility with varicocele in North China. One Hundred infertile males with varicocele (VC; grade II-III, VC group) and 100 healthy males with normal semen parameters and no varicocele (NC group) were recruited for PCR microarray, blood and semen testing. Compared with the CC genotype in the NC group, the TT genotype in the NC group and the CC genotype in the VC group showed no significant changes in sperm motility (P=0.191; P=0.130), sperm density (P=0.591, P=0.643), plasma homocysteine level (P=0.511; P=0.677), and seminal plasma MDA (P=0.752; P=0.451). In contrast, VC patients with the TT genotype had higher plasma homocysteine level and seminal plasma MDA levels (P <0.001), lower partial pressure of oxygen in seminal pulse (PO2; P <0.001) and poorer sperm quality (P <0.001), as compared with the CC genotype. This suggests that MTHFR C677C>T may not be a risk factor for male Varicocele in North China. However, this may affect the oxidative stress associated with homocysteine expression, which in turn affects semen parameters in VC patients. Larger studies are needed to validate our findings.

Study on the Correlation between Hcy and Hs-CRP Levels and Cognitive Function in Patients with Bipolar Disorder and Borderline Personality Disorder.

This study aims to explore the correlation and clinical significance of homocysteine and high-sensitivity C-reactive protein levels with cognitive function in patients with bipolar disorder (BD) and borderline personality disorder (BPD). Patients with BD admitted to our hospital from January 2022 to December 2022 were chosen retrospectively. BPD patients were categorized into comorbidity groups, while those without BPD were assigned to non-comorbidity groups, each consisting of 60 cases. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess serum levels of homocysteine (Hcy) and high-sensitivity C-reactive protein (hs-CRP) in both patient groups. Clinical symptoms were evaluated by the Hamilton Depression Rating Scale (HAMD) and the Young Mania Rating Scale (YMRS). Cognitive function was evaluated and compared using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pearson correlation analysis was performed on the correlation between patients' serum Hcy and hs-CRP levels and HAMD, YMRS, and RBANS scores. In the comorbidity group, patients exhibited significantly elevated serum Hcy and hs-CRP levels compared to the non-comorbidity group (p < 0.05). Patients in the comorbidity group displayed higher HAMD and YMRS scores than those in the non-comorbidity group (p < 0.05). Additionally, attention, speech, visual span, immediate memory, and delayed memory in the comorbidity group were notably lower than in the non-comorbidity group (p < 0.05). The speech, visual span, and immediate memory of RBANS in bipolar depressive patients with comorbid BPD were lower than those in bipolar depressive patients without comorbid BPD (p < 0.05), the speech of RBANS in bipolar manic patients with comorbid BPD was lower than those in bipolar manic patients without comorbid BPD (p < 0.05). Pearson correlation analysis showed that the expression of Hcy and hs-CRP in the comorbid group was positively correlated with HAMD and YMRS scores, and negatively correlated with attention, speech, visual span, immediate memory, and delayed memory, and these differences were statistically significant (p < 0.05). High serum Hcy and hs-CRP expression levels may regulate inflammatory responses, aggravating cognitive impairment in patients with BD and BPD. Serum Hcy and hs-CRP expression levels are significantly related to cognitive dysfunction. They are expected to guide the prevention and treatment of BD comorbid BPD patients.

Ursodeoxycholic and chenodeoxycholic bile acids attenuate systemic and liver inflammation induced by lipopolysaccharide in rats.

Bacterial lipopolysaccharide (LPS) induces general inflammation, by activating pathways involving cytokine production, blood coagulation, complement system activation, and acute phase protein release. The key cellular players are leukocytes and endothelial cells, that lead to tissue injury and organ failure. The aim of this study was to explore the anti-inflammatory, antioxidant, and cytoprotective properties of two bile acids, ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in LPS-induced endotoxemia in rats. The experiment involved six distinct groups of Wistar rats, each subjected to different pretreatment conditions: control and LPS groups were pretreated with propylene glycol, as a bile acid solvent, while the other groups were pretreated with UDCA or CDCA for 10 days followed by an LPS injection on day 10. The results showed that both UDCA and CDCA reduced the production of pro-inflammatory cytokines: TNF-α, GM-CSF, IL-2, IFNγ, IL-6, and IL-1β and expression of nuclear factor-κB (NF-κB) induced by LPS. In addition, pretreatment with these bile acids showed a positive impact on lipid profiles, a decrease in ICAM levels, an increase in antioxidant activity (SOD, |CAT, GSH), and a decrease in prooxidant markers (H2O2 and O2-). Furthermore, both bile acids alleviated LPS-induced liver injury. While UDCA and CDCA pretreatment attenuated homocysteine levels in LPS-treated rats, only UDCA pretreatment showed reductions in other serum biochemical markers, including creatine kinase, lactate dehydrogenase, and high-sensitivity troponin I. It can be concluded that both, UDCA and CDCA, although exerted slightly different effects, can prevent the inflammatory responses induced by LPS, improve oxidative stress status, and attenuate LPS-induced liver injury.

Features of coronary heart disease in a cohort of tajik patients and the condition of the vascular endothelium in its different clinical forms

Relevance. In the Republic of Tajikistan, in recent years there has been a steady increase in cardiovascular diseases. In this regard, special attention is paid to coronary heart disease with its various manifestations, which can often cause permanent disability, even death. In recent decades, there has been great interest among research scientists in studying the functioning of the endothelium in various forms of coronary heart disease, as well as in individuals with post-infarction cardiosclerosis as a complication of coronary heart disease. Despite the large number of studies in this area, the role and relationship of some sensitive markers of endothelial dysfunction with the clinical course of various forms of coronary heart disease have not yet been determined. That is why its detailed study is of unconditional clinical interest and provides the opportunity for a deep understanding of its theoretical aspects. Purpose of the study: to study risk factors for cardiovascular diseases and mark­ers of endothelial dysfunction in patients with stable angina pectoris in comparison with patients with post-infarction cardiosclerosis, i.e. previous myocardial infarction.Object and methods. Of 60 patients with various forms of coronary heart disease, whose average age was 62.6 ± 3.5 years, and 20 practically healthy individuals of the same age who made up the control group, three groups were formed: Group I (n = 20) included respondents without coronary heart disease; Group II (n = 30) included patients with stable angina pectoris of functional class II and III; Group III (n = 30) included patients who were diagnosed with post-infarction cardiosclerosis, i.e. previously suffered a myocardial infarction. Endothelial cell dysfunction was detected by determining desquamated endothelial cells, as well as by the activity of von Willebrand factor and the level of homocysteine in the blood plasma.Results. In the examined patients, risk factors for coronary heart disease in the form of arterial hypertension, physical inactivity and obesity were observed with greater frequency in persons with stable angina pectoris of functional class II, in contrast to those with functional class III. Patients with stable angina pectoris of functional class III all had chronic heart failure of varying severity (100%). Most patients had at least three risk factors for coronary heart disease. All persons with post-infarction cardiosclerosis had risk factors for coro­nary heart disease, while arterial hypertension was detected in 100%. Based on the indicators of endothelial dysfunction, it can be said that individuals in group III have a more severe functional and morphological condition (increased homocysteine levels, von Willebrand factor activity and the number of desquamated endothelial cells) compared to group II (p &lt; 0.001).Conclusion. In all forms of coronary heart disease (stable exertional angina of functional class II, III and post-infarction cardiosclerosis), the content of desquamated endothelial cells in the blood serum, the activity of von Willebrand factor and homocysteine are increased. A positive correlation was established between the level of desquamated endothelial cells and the level of homocysteine, von Willebrand factor, fibrinogen and platelets. After complex therapy of patients with various forms of coronary heart disease, the functional state of the endothelium improves (decrease in the level of desquamated endothelial cells, ho­mocysteine, von Willebrand factor).

Correlation between Trabecular Bone Score and Homocysteine Level in Rheumatoid Arthritis Patients on Anti-TNF Inhibitors.

Rheumatoid arthritis (RA) is an independent osteoporosis risk factor. Biologic and immunosuppressive treatment, and levels of homocysteine and 25-OH vitamin D may influence the trabecular bone score (TBS) in RA patients. We aimed to compare the effects of biological (b) and conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) on TBS in patients with RA and hyperhomocysteinemia (HHcy) or 25-OH vitamin D deficiency. Patients who had tests conducted for trabecular bone score, bone mineral density (BMD), homocysteine (Hcy) and 25-OH vitamin D at an interval of one year and met the inclusion criteria were enrolled in this retrospective study. Sixty-four patients with RA were enrolled and were divided into the following two groups: the first group (34 patients) had received treatment with bDMARDs and the second group (30 patients) had received csDMARDs. BDMARDs and csDMARDs had a positive influence on TBS and BMD. The best results were observed in the Adalimumab group (p = 0.033). Hyperhomocysteinemia and 25-OH vitamin D deficiency led to lower TBS values. Both bDMARDs and csDMARDs positively affected TBS and BMD in RA patients. High homocysteine serum levels or 25-OH vitamin D deficiency had a negative impact on TBS and BMD after 12 months. Our study aims to show the potential benefits of anti-TNF α drugs on TBS. This impact appears to be strongly associated with serum 25-OH vitamin D and homocysteine levels. Anti-TNF drugs may increase bone mineral density and microstructure. As a result, they may minimize the incidence of fractures in RA patients.

The factors influencing the occurrence of post-ischemic stroke depression and its relationship with the burden score of cerebral small vessel disease.

This study explored the determinants of post-stroke depression (PSD) in ischemic stroke (AIS) patients and its association with the burden score of cerebral small vessel disease (CSVD). We analyzed 374 AIS patients treated between January 2020 and January 2022. Patients were categorized into 90 with PSD and 284 without PSD, enabling an investigation into PSD risk factors and the CSVD-PSD relationship. There was no significant difference in health factors between PSD and non-PSD patients (p>0.05). However, significant disparities were noted in age, gender, initial Barthel Index (BI), Mini-Mental State Examination (MMSE) score, plasma fibrinogen, homocysteine, red cell distribution width, National Institutes of Health Stroke Scale (NIHSS) score, and CSVD burden score (p<0.05). Regression analysis indicated that these variables were pivotal PSD predictors (OR>1, p<0.05). Surprisingly, a positive correlation with PSD occurrence was found for age, NIHSS score, plasma fibrinogen, homocysteine levels, red cell distribution width, CSVD burden score (r=0.565, 0.615, 0.482, 0.514, 0.572, 0.608, respectively; p<0.05). Meanwhile, the MMSE score and BI index were inversely related to PSD onset (r=-0.604, -0.590; p<0.05). The ROC curve analysis of the combination model based on MMSE, NIHSS and CSVD score revealed an AUC of 0.926 and Youden's index of 0.744. Age, MMSE score, BI index, NIHSS score, plasma fibrinogen concentration, homocysteine level, red blood cell distribution width, and CSVD burden score are all major influencing factors in the occurrence of PSD. The combination model based on MMSE, NIHSS, and CSVD scores presented a valuable approach to predicting PSD.

Relationship between Folate, B12 and Homocysteine levels and Obstetrical Outcomes in Preterm Premature Rupture of Membrane

التمزق التلقائي لأغشية الجنين قبل بدء الولادة الذي يحدث قبل اكتمال 37 أسبوعًا من الحمل ، يشار إليه على أنه تمزق الأغشية المبكر قبل الولادة . يحدث في 2٪ من حالات الحمل. يعتمد التنبؤ بـه على تحديد عوامل الخطر المرتبطة واستخدام مؤشرات حيوية محددة لمنع النتائج الضارة على الام والجنين. ان الهدف من الدراسة لمعرفة العلاقة وفهم الدور بين حامض الفوليت ، فيتامين بي 12 والهميوسستين في تمزق الغشاء الامينوسي المبكر قبل حدوث الولادة ولتحديد النتائج من تمزق الغشاء الامنيوسي على الام والطفل . تم تطبيق دراسة حالة وشواهد ، اشتملت الدراسة على 100 امرأة حامل بجنين واحد حي مع عمر حمل للمرضى يتراوح بين 24 الى 36 أسبوعًا وستة أيام من الحمل .أجريت الدراسة في قسم أمراض النساء والولادة بمستشفى الخنساء التعليمي للولادة خلال فترة خمسة أشهر وعشرة ايام من 20 / كانون الثاني إلى 1 / تموز / 2022. وشملت الدراسة 50 امرأة حامل يعانين من تمزق الغشاء الامنيوسي المبكر قبل حدوث الولادة كمجموعة حالات. 50 امرأة أخرى كانت من النساء الحوامل اللواتي لديهن عمر حمل متطابق مع غشاء سليم وليس لديها ولادة دون أي مضاعفات خلال الحمل كمجموعة ضابطه .وتم تقدير مستوى الفوليت ، بي 12 والهيموسستين من المصل .ثم تم جمع البيانات وتحليلها احصائيا. ان عوامل الخطورة ذو اهمية لتمزق الغشاء الامنيوسي المبكر قبل الولادة هي : النساء العاملات، والأميات، عدم وجود أو وجود اقل من ثلاثة زيارات لرعاية الحمل والولادة، الفاصل الزمني القصير بين الحمل ، وجود ولادة مبكرة سابقة أو تمزق الأغشية المبكر قبل الولادة ، المدخنات الثانويات ، نقص مستوى الفوليت ومستوى مرتفع من الهيموسيستين .فيما يتعلق بالبيانات الديموغرافية ومستوى فيتامين بي 12 لم يكن مختلفًا بين المجموعتين. من ناحية أخرى ، كان مستوى الفوليت أقل في مجموعة الحالات تمزق الأغشية المبكر قبل الولادة منه في المجموعه الضابطه. كان مستوى الهيموسيستين أعلى بشكل ملحوظ في مجموعة الحالات من المجموعة الضابطة . ارتبط مستوى الهيموسيستين ≥ 28.85 نانومول / مل بحساسية عالية وخصوصية ودقة (90 و 84 و 87٪ على التوالي) ، بالتالي يمكن استخدامه أيضًا كأداة جيدة لاستبعاد التنبؤ بالخطر لتمزق الأغشية المبكر قبل الولادة . بينما يرتبط مستوى الفوليت ≤3.22 نانوغرام / مل بحساسية معتدلة ونوعية منخفضة. نستنتج من ذلك ان مستوى الهيموسيستين ومستوى الفوليت هو علامة جيدة لتمزق الأغشية المبكر قبل الولادة، بالاضافة الى ارتقاع الهميوسيستين هو احد عوامل الخطورة لتمزق الاغشية المبكر قبل الولادة. مستوى فيتامين بي 12 لم يترافق مع زيادة خطر تمزق الأغشية المبكر قبل الولادة.

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

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

Vitamin D, vitamin B12, folate, homocysteine, and major haemato-chemical parameters in patients with mood disorders

IntroductionThe potential involvement of the immune and inflammatory systems has been extensively studied in mood disorders (MDs). Despite these findings and despite the fact that the pathogenetic role of altered immunologic and metabolic profiles in MDs is being confirmed in many current studies, there is still a lack of consensus about it, due to controversial results.ObjectivesThe present study aimed to appraise peripheral metabolic parameters (blood glucose, lipoproteins, triglycerides, uric acid, blood urea nitroge [BUN], transaminases and others9 and plasma/serum levels of essential nutrients (vitamin D, B12, folate and homocysteine) in a group of inpatients affected by MDs, as compared with healthy controls.MethodsMethods. Ten ml of venous blood was drawn from fasting subjects. The metabolic parameters and vitamins were measured according to common clinical-chemistry methods.Comparisons for continuous variables were performed by the Student’s t-test for variables that follow a normal distribution, and by the Wilcoxon-Mann-Whitney test for variables not normally distributed. The correlations between biological markers were explored by calculating the Pearson’s correlation coefficient or Spearman rank correlation.Results Most patients showed loer circulating vitamin D levels, in respect to both control subjects (P&lt; .0001) and the normative cut-off values. This finding was paralleled by increased serum homocysteine concentrations i (P&lt;.0001), indicating an imbalance in their methionine metabolism. Homocysteine levels were negatively correlated with vitamin D, vitamin B12 and folate in control subjects, but not in patients. In addition, patients displayed higher blood glucose and lower BUN than controls, indicating an impaired protein-to-carbohydrate metabolism and/or altered nutritional/dietary status.ConclusionsWe provide herein further support to the notion that MD patients are a population where vitamin deficits, dysmetabolism and/or dietary defects are common feature, and, s such, they might be more vulnerable to a variety of somatic illnesses than the general population. This cross-sectional investigation, albeit preliminary, might contribute to improve the characterization and the monitoring of the clinical status of mood disorder patients, as well as to identify new molecular targets for more tailored treatments ad of more pointed health-care intervention,Disclosure of InterestNone Declared

Association between polymorphism in the MTHFR gene and encephaloduroarteriosynangiosis-induced collateral circulation formation.

This study aimed to investigate whether high homocysteine (Hcy) levels associated with the MTHFR gene influence the formation of the collateral vascular network in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis (EDAS) by influencing the number of endothelial progenitor cells (EPCs) in peripheral blood. A total of 118 Chinese patients with bilateral primary MMD were prospectively included. Blood samples were collected from the anterior cubital vein before surgery, and MTHFR rs9651118 was genotyped using high-throughput mass spectrometry to determine the genotype of the test specimen. Serum Hcy and EPC levels were measured, the latter with flow cytometry. Digital subtraction angiography was performed 6 months after EDAS, and the formation of collateral circulation was evaluated using the Matsushima grade system. The correlations between MTHFR rs9651118 genotype, Hcy and EPC levels, and Matsushima grade were compared. Among the 118 patients, 53 had the TT genotype (wild type) of MTHFR rs9651118, 33 TC genotype (heterozygous mutation), and 32 CC genotype (homozygous mutation). The mean ± SD Hcy level was 13.4 ± 9.5 μmol/L in TT patients, 9.8 ± 3.2 μmol/L in TC patients, and 8.9 ± 2.9 μmol/L in CC patients (p < 0.001). The level of EPCs in the venous blood of TT patients was 0.039% ± 0.016%, that of TC patients 0.088% ± 0.061%, and that of CC patients 0.103% ± 0.062% (p < 0.001). When the rs9651118 gene locus was mutated, Matsushima grade was better (p < 0.001) but there was no difference between heterozygous and homozygous mutations. The results suggest that the MTHFR rs9651118 polymorphism is a good biomarker for collateral vascular network formation after EDAS in MMD patients.

Reduced ribonucleotide reductase RRM2 subunit expression increases DNA damage and mitochondria dysfunction in woody breast chickens.

The aim of this study was to investigate the roles of ribonucleotide reductase subunit M2 (RRM2; subunit of ribonucleotide reductase) in severe woody breast (WB) and normal breast muscles. 40 8-week-old male Ross-708 broiler chickens. Quantitative PCR was performed to determine gene expression, and commercial ELISA/assay kits were used to obtain several enzymatic activities. Results showed that RRM2 activity (P = .0002) and RRM2 (P = .05) and hydroxymethylbilane synthase expression (impaired oxygen transport and metabolism, P = .002) were reduced in WB, while caveolin-3 (defected membrane integrity, P = .09), endoglin (increased fibrosis, P = .06), and secreted protein acidic rich in cysteine (metabolic dysregulation, P = .09) expression tended to increase in WB. WB tended to have increased levels of homocysteine (P = .06), aspartate aminotransferase mitochondria (P = .02), pyruvate kinase (P = .04), DNA damage (P = .06), creatine kinase (P = .05), and triglyceride (P = .002) but decreased ATPase activity (P = .01), all indicating mitochondria dysfunction and tissue damage. In this study, differences in various enzyme activities and increased DNA damage suggest that RRM2-mediated mitochondrial abnormalities may play a role in WB myopathy.

Nitrous oxide induced spinal cord oedema with normal serum B12 level with high plasma homocysteine level

Nitrous oxide induced spinal cord oedema with normal serum B12 level with high plasma homocysteine level

Determination of Reference Interval for Serum Homocysteine, Magnesium, and Uric Acid from Tertiary Care Hospital Data By the Bhattacharya Method

Abstract Introduction: Direct ways of establishing reference intervals for analytes are time-consuming and costly. Bhattacharya analysis is an indirect way to mathematically derive reference intervals from the results of analytes in a hospital database and is practically a simple and inexpensive alternative to direct methods. Methods: Data of serum uric acid, magnesium, and plasma homocysteine levels measured in the department of clinical biochemistry over 3 years were extracted from the hospital database along with the age, gender, and location of the patients. Bhattacharya analysis was performed by identifying underlying Gaussian distribution within the non-Gaussian distribution of the patient data by log transformation of the distribution of the data. Reference intervals for each of the analytes were calculated from the identified Gaussian distribution. Results: The reference interval for serum uric acid was 1.49–8.97 mg/dL in men and 2.13–6.14 in women, serum magnesium in adults was 1.19–3.21 mg/dL, and plasma homocysteine in adults was 4.6–21 μg/dL. Conclusion: Using Bhattacharya analysis, we were able to derive reference intervals for analytes from our hospital data.

Homocysteine-induced sustained GluN2A NMDA receptor stimulation leads to mitochondrial ROS generation and neurotoxicity

Homocysteine, a sulfur-containing amino acid derived from methionine metabolism, is a known agonist of N-methyl-D-aspartate receptor (NMDAR) and is involved in neurotoxicity. Our previous findings showed that neuronal exposure to elevated homocysteine levels leads to sustained low-level increase in intracellular Ca2+, which is dependent on GluN2A subunit-containing NMDAR (GluN2A-NMDAR) stimulation. These studies further showed a role of ERK MAPK in homocysteine-GluN2A-NMDAR-mediated neuronal death. However, the intracellular mechanisms associated with such sustained GluN2A-NMDAR stimulation and subsequent Ca2+ influx have remained unexplored. Using live-cell imaging with Fluo3-AM and biochemical approaches, we show that homocysteine-GluN2A NMDAR-induced initial Ca2+ influx triggers sequential phosphorylation and subsequent activation of the proline rich tyrosine kinase 2 (Pyk2) and Src family kinases, which inturn phosphorylates GluN2A-Tyr1325 residue of GluN2A-NMDARs to maintain channel activity. The continuity of this cycle of events leads to sustained Ca2+ influx through GluN2A-NMDAR. Our findings also show that lack of activation of the regulatory tyrosine phosphatase STEP, which can limit Pyk2 and Src family kinase activity further contributes to the maintenance of this cycle. Additional studies using live-cell imaging of neurons expressing a redox-sensitive GFP targeted to the mitochondrial matrix show that treatment with homocysteine leads to a progressive increase in mitochondrial reactive oxygen species generation, which is dependent on GluN2A-NMDAR-mediated sustained ERK MAPK activation. This later findingdemonstrates a novel role of GluN2A-NMDAR in homocysteine-induced mitochondrial ROS generation and highlights the role of ERK MAPK as the intermediary signaling pathway between GluN2A-NMDAR stimulation and mitochondrial reactive oxygen species generation.

A Nomogram Including Total Cerebral Small Vessel Disease Burden Score for Predicting Mild Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI. To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM. A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness. The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit. The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.

Pre-pregnancy preparation of women with hypoandrogenism and female sexual dysfunction

The onset of pregnancy in the natural cycle is a task that requires the coordinated work of both central and peripheral levels of regulation of hypothalamic‑pituitary hormones. An analysis of the reproductive health of women with a menstrual cycle disorder against the background of hypoandrogenism indicates an unsatisfactory course of the early stages of the pregnancy process with the subsequent formation of infertility against the background of a reduced ovarian reserve. Hypolubrication is considered a clinical marker of hypoandrogenism in women of reproductive age.&#x0D; Objective — Optimization of pre‑pregnancy training in women with hypoandrogenism, menstrual cycle disorders and early pregnancy losses in the anamnesis.&#x0D; Materials and methods. A comprehensive clinical, laboratory and instrumental examination involved 90 women with menstrual cycle disorders and hypoandrogenism, from them 45 women received the proposed therapy (group Ia), and 45 patients traditional therapy (group IIa). The control group consisted of 30 healthy women at the stage of pre‑gravid examination. The age of women was 18 to 35 years. Hormonal reproductive background was determined on the 5 ‑ 7th day of the menstrual cycle in all examined women, as well as levels of thyroid‑stimulating hormone (TSH), thyroid peroxidase antibody, vitamin D, homocysteine. The proposed algorithm of pre‑gravid measures included: 1) optimization of thyroid gland function (after consultation with an endocrinologist); 2) restoration of pituitary‑ovarian relationships in case of functional central hypogonadism; 3) therapy aimed at optimizing the prolactin level (target value 12.5ng/ml); 4) reduction of homocysteine level (target level 5.6 mmol/l); 5) normalization of vitamin D level (norm is 75—125 nM/l, insufficiency defined as 50—75 nM/l, and deficiency &lt;50 nM/l). The target control parameters included restoration of lubrication, ovulatory menstrual cycle, onset and progression of pregnancy. IBM SPSS Statistics version 25.0 software was used for statistical processing of the obtained data. The control periods of therapy were 3, 6 and 9 months.&#x0D; Results. In women with proposed treatment algorithm, therapy resulted in the recovery of vitamin D levels, starting from the 6th month of therapy, and complete normalization was recorded at the 9th month of treatment. This indicates the need for long‑term supplementation of vitamin D in women with hypoandrogenism. A decrease in the homocysteine levels was also noted on the 6th month of treatment, and its normalization after 9 months of treatment. Elevated homocysteine levels and vitamin D insufficiency/deficiency were observed throughout the follow‑up period in the conventional therapy group. In women with the proposed therapy, the levels of follicle‑stimulating hormone (FSH), TSH, luteinizing hormone (LH) and prolactin tend to normalize already from the 3rd month of therapy, while the highest positive increase was noted in the LH indicator on the 3rd‑6th month of treatment. Ovarian steroidogenesis approached the indicators of the control group after 6—9 months of therapy. Proandrogenic steroidogenesis began to increase on the 3rd month of therapy, reaching maximum on the 9th month. Unsatisfactory indicators of changes in free testosterone and dehydroepiandrosterone sulfate (DHEA‑C) were noted in women from the group of the traditional pre‑pregnancy preparation even after 9 months.&#x0D; The specified features of steroid support of the hormonal background of women’s reproductive health demonstrated the following: signs of female sexual dysfunction in the group with the proposed therapy completely disappeared after the 9th month of treatment, and in the group of traditional therapy they continued to bother 91.1% of women. At the end of the observation period, the regular menstrual cycle was gained in 40.0% of women with the proposed therapy and in 6.7% with the traditional one. Progressive pregnancies in the group with the proposed algorithm were achieved in 37.5% of women (successfully overcame the luteoplacental barrier), and in 8.8% in the group of the traditional approach (ended by early termination of pregnancy).&#x0D; Conclusions. The period of formation of the luteal phase insufficiency is the specific feature of the restoration of menstrual cycle fullness in women with hypoandrogenism, which requires additional therapy to ensure the conditions for a full‑fledged secretory endometrium transformation. The pregnancy process takes place in unfavorable conditions, which can lead to early pregnancy losses. The period of pre‑pregnancy measures in this group of patients should last at least 6—9 months. Traditional pre‑pregnancy preparation does not contribute to the restoration of the central mechanisms of menstrual cycle regulation in women with hypoandrogenism, nor does it contribute to the restoration of full‑fledged ovarian steroidogenesis, it is accompanied by anovulation and insufficiency of the luteal phase, early pregnancy losses. Symptoms of female sexual dysfunction do not disappear under the influence of traditional treatment.

Differences in Ca 15-3 and Homocysteine Levels in Patients with Benign Tumor and Breast Cancer

More than 25% of women have complaints related to breast lumps during their lifetime and approximately 12% have breast cancer. Cancer antigen 15-3 and homocysteine can be used as biomarkers in breast cancer. Breast cancer produces pro-inflammatory cytokines that can lead to increased CA 15-3 levels and serum homocysteine levels. Objective: To investigate the differences in CA 15-3 and homocysteine levels between patients with benign tumors and breast cancer. Methods: Observational analytic study with a cross-sectional approach in 30 benign breast tumor patients and 31 breast cancer patients. Measurement of CA 15-3 levels using enzyme linked immunofluorescent assay (ELFA) and homocysteine using competitive enzyme linked immunosorbant assay (ELISA). Comparative tests used independent T test and Mann-Whitney test. The study was conducted in 2023 at Kariadi Hospital Semarang and Ken Saras Hospital Ungaran. Results: CA 15-3 levels in the benign breast tumor group had a median of 11.74 (2.00-40.00) U/mL, while the breast cancer group was 18.66 (7.22-168.97) U/mL (p = 0.001). Homocysteine levels in benign breast tumors had a median of 3.05 (0.10-11.50) µmol/L and in the breast cancer group was 9.90 (3.70-17.20) µmol/L (p = 0.0001). Conclusion: CA 15-3 and homocysteine levels were lower in benign breast tumor patients compared with breast cancer patients.

The relationship between homocysteine and no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention

Aims: The current study aimed to investigate the relationship between homocysteine and no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention (pPCI).&#x0D; Methods: Patients with ST-elevation myocardial infarctions (STEMI) who underwent pPCI in our center between May 01, 2022, and 20 August 2023 were included in this cross-sectional observational study. Patients were classified into two groups according to the occurrence of no-reflow during pPCI. Findings were compared between the two groups.&#x0D; Results: A total of 332 patients [male, 75 (%82.8)] with STEMI undergoing pPCI, were included. Among them, 35 (10.5%) patients developed no-reflow. Homocysteine level was significantly higher in the no-reflow(+) group than the no-reflow(-) group [median (IQR), 19.02 (16.11-22.23 vs. 12.45 (10.99-14.93), p=0.019]. According to the multivariate analysis, homocysteine level, TIMI risk score, and postdilatation were independent predictors of no-reflow occurrence [Odds Ratio (95% CI), 1.127 (1.042-1.218), p=0.003, 1.385 (1.157-1.659), p

Association of Serum Homocysteine with Gestational Diabetes Mellitus (GDM): A Case-Control Study

Gestational diabetes mellitus (GDM) is associated with an increased risk of maternal and fetal mortality and morbidity. There is an increasing trend in the prevalence of GDM in Bangladesh. The role of homocysteine (Hcy) as an independent risk factor of GDM has not been extensively studied. The aim of this study was to evaluate the association of serum homocysteine levels in gestationaldiabetes mellitus. It was a case-control study among pregnant women attending the inpatient and outpatient departments of Obstetrics and Gynecology,BSMMU, Shahbag Dhaka, from April 2020 to March 2021. A total of 80 singleton pregnant women between 18-35 years of age were included in this study in their 24-40 weeks of gestation. Among them, 40 diagnosed women with GDM were considered as the cases and the rest of the 40 matched healthy pregnant women were selected as controls matching for age and gestational age.The overall average Hcy levels in the cases and controls were 5.48±1.3 μmol/L and 4.06±0.98 μmol/L, respectively. Both in the late second trimester and the third-trimester serum Hcy levels were significantly higher in the GDM cases than non-GDM healthy pregnant women (p&lt;0.05). Considering Hcy level of 6.38 μmol/L as the cut-off value, GDM was 4.75 times more likely in pregnant women with elevated serum Hcy level (≥6.38) than those with &lt; 6.38 μmol/L (OR=4.75; 95% CI = 0.941-23.985). There was a significant positive correlation of serum Hcy level with both fasting blood sugar level (r = +0.600, p&lt;0.001) and 2 hrs after 75g glucose level (r = +0.438, p&lt;0.001). Elevated level of serum homocysteine was found associated with GDM. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):32-37

Association between early spontaneous abortion and homocysteine metabolism.

The purpose of this study is to explore the effects of homocysteine (HCY) metabolism and related factors on early spontaneous abortion. We conducted a hospital-based case-control study and included a total of 500 cases and 1,000 controls in Shaanxi China. Pregnant women waiting for delivery in the hospital were interviewed to report their characteristics and other relevant information during pregnancy. The unconditional Logisitic regression model was applied to assess the association between early spontaneous abortion and HCY metabolism and related factors. The multiplicative model was applied to assess the effects of interaction of HCY metabolism and related factors on early spontaneous abortion. The logit test method of generalized structural equation model (GSEM) was used to construct the pathway diagram of HCY metabolism and related factors affecting early spontaneous abortion. Folic acid supplementation and adequate folic acid supplementation during periconception were the protective factors of early spontaneous abortion (OR = 0.50, 95% CI: 0.38-0.65; OR = 0.44, 95% CI: 0.35-0.54). The serum folate deficiency, higher plasma HCY in early pregnancy, the women who carried the MTHFR 677TT genotype were the risk factors of early spontaneous abortion (OR = 5.87, 95% CI: 1.53-22.50; OR = 2.94, 95% CI: 1.14-7.57; OR = 2.32, 95% CI: 1.20-4.50). The women's educational level and maternal and child health care utilization affected the occurrence of early spontaneous abortion by influencing the folic acid supplementation during periconception. The folic acid supplementation during periconception affected the occurrence of early spontaneous abortion by influencing the level of serum folate or plasma HCY in early pregnancy. The maternal MTHFR 677 gene polymorphism affected the occurrence of early spontaneous abortion by influencing the level of serum folate in early pregnancy. In terms of the risks for early spontaneous abortion, there was multiplicative interaction between higher plasma HCY in early pregnancy, serum folate deficiency in early pregnancy and maternal MTHFR 677TT genotype (OR = 1.76, 95% CI: 1.17-4.03), and there was multiplicative interaction between higher plasma HCY and serum folate deficiency in early pregnancy (OR = 3.46, 95% CI: 2.49-4.81), and there was multiplicative interaction between serum folate deficiency in early pregnancy and maternal MTHFR 677TT genotype (OR = 3.50, 95% CI: 2.78-5.18). The above interactions are all synergistic. The occurrence risk of early spontaneous abortion was significantly increased if multiple factors existed at the same time. Our study is the first time to construct the pathway of HCY metabolism and related factors affecting early spontaneous abortion, and provides a comprehensively new idea to prevent and reduce the occurrence of spontaneous abortion.