Serum Hcy Levels Research Articles

Association of Serum Homocysteine With Peripheral Arterial Disease in Patients Without Diabetes: A Study Based on National Health and Nutrition Examination Survey Database

This study aimed to investigate the association of serum homocysteine (Hcy) levels with peripheral arterial disease (PAD) in patients without diabetes on the basis of data from the National Health and Nutrition Examination Survey. The study used data from 3 survey cycles (1999 to 2004) in the National Health and Nutrition Examination Survey database as the research dataset. Serum Hcy levels were considered an independent variable, whereas PAD was a dependent variable. Weighted logistic regression and restricted cubic spline methods were used to explore the relation between Hcy level and PAD risk in patients without diabetes. A total of 4,819 samples were included. In the weighted logistics regression model, a significant positive association was observed between Hcy levels and the risk of PAD (odds ratio >1, p <0.05). Subgroup analysis results indicated a particularly significant association between Hcy levels and PAD risk in the older population (age ≥60 years), those with a history of smoking, and those without a history of myocardial infarction (all odds ratio >1, p <0.05) (p <0.05). Exploring the nonlinear association between Hcy levels and PAD risk through restricted cubic spline curves revealed an overall significant trend (p allover <0.05). In conclusion, elevated Hcy levels increased the risk of PAD, with a more pronounced effect observed in populations of patients without diabetes, especially in older patients (age ≥60 years), those with smoking history, and those without a history of myocardial infarction.

Effect of high-frequency (5Hz) rTMS stimulating left DLPFC combined with galantamine on cognitive impairment after ischemic stroke and serum homocysteine and neuron-specific enolase.

To investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with galantamine in patients with cognitive impairment after stroke and its effect on serum homocysteine (Hcy) and neuron-specific enolase (NSE) levels. A total of 90 patients with cognitive impairment after the first ischemic stroke were enrolled. They were randomly divided into rTMS+ cognitive rehabilitation group, Galantamine + cognitive rehabilitation group, and rTMS+ Galantamine + cognitive rehabilitation group. All groups received routine medical treatment and limb rehabilitation treatment. The rTMS stimulation site was the left dorsolateral prefrontal cortex (left DLPFC), the magnetic stimulation frequency was 5 Hz, the magnetic stimulation intensity was 80% of the motor threshold level, and 3,000 pulses were given every day. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fugl-Meyer scale, and modified Barthel index, as well as rehabilitation scale and serum NSE and Hcy were evaluated before and after treatment (after 4 weeks). After 4 weeks of treatment, the scores of MMSE, MoCa scale, Fugl-Meyer scale, and modified Barthel index in the three groups were significantly higher than those before treatment (all p < 0.05), while the serum NSE and Hcy levels of the three groups were decreased. rTMS+ Galantamine + cognitive rehabilitation group had higher scale scores, and the difference between the three groups was statistically significant compared with the other two groups (all p < 0.05). Cognitive rehabilitation combined with HF-rTMS and galantamine could improve the cognitive function of patients to the greatest extent, promote the recovery of physical activity, improve the self-care ability of daily life, and effectively reduce the serum HCY and NSE levels in patients with cognitive impairment after stroke. No randomized controlled trials of similar combination treatments have been reported. The better therapeutic effect may be related to the fact that galantamine combined with repetitive transcranial magnetism can activate the brain cholinergic system more extensively, promote brain neural remodeling through long-term potentiation and inhibit local neuroinflammatory responses in brain injury.

Exercise attenuates the perioperative neurocognitive disorder induced by hyperhomocysteinemia in mice

The perioperative neurocognitive disorder (PND) is a severe complication that affects millions of surgical patients each year. Homocysteine (Hcy) is known to increase the risk of developing PND in both young and elderly mice. However, whether Hcy alone can induce cognitive deficits in middle-aged mice (12-month-old), whether exercise can attenuate Hcy-induced hippocampus-related cognitive deficits after surgery through suppressing neuroinflammation, synaptic elimination, and the level of Hcy remains unknown. The present study aimed to answer these questions through testing the possibility of establishing a PND model using 12-month-old mice which received homocysteine injections before exploratory laparotomy and the therapeutic mechanism of exercise. In the present study, it was found that levels of serum homocysteine were age-dependently increased in mice with a significant difference between that of 18-month-old mice and 6-week, 6-month, and 12-month-old mice. PND occurred in 18-month but not in 12-month-old mice after exploratory laparotomy under isoflurane anesthesia. Intraperitoneal injection of Hcy for 3 consecutive days before surgery rendered 12-month-old mice to develop PND after abdominal laparotomy under isoflurane anesthesia at a minimal dosage of 20mg/kg. Neuroinflammation and synaptic elimination was present in 12-month-old preoperative Hcy-injected mice. Preoperative voluntary wheel exercise could prevent PND in 12-month-old mice that have received Hcy injection before surgery, which might be related to the decreased level of serum Hcy. Activation of glial cells, proinflammatory phenotype markers and synaptic elimination were attenuated in the hippocampus of 12-month-old preoperative Hcy-injected mice by this exercise. These results provide direct evidence that hyperhomocysteinemia can induce postoperative cognitive deficits in middle-aged mice. Pre-surgery exercise can effectively prevent Hcy-precipitated postoperative cognitive dysfunction.

Associations between one-carbon metabolism and valproic acid-induced liver dysfunction in epileptic patients.

Valproic acid (VPA) has been widely used as an antiepileptic drug for decades. Although VPA is effective and well-tolerated, long-term VPA treatment is usually associated with hepatotoxicity. However, the underlying mechanisms of VPA-caused hepatotoxicity remain unclear. In this study, a total of 157 pediatric patients with epilepsy were recruited and divided into normal liver function (NLF, 112 subjects) group and abnormal liver function (ABLF, 45 subjects) group. We observed that MTHFR A1298C and MTHFR C677T variants may be linked to VPA-induced liver dysfunction (p = 0.001; p = 0.023, respectively). We also found that the MTHFR A1298C polymorphism was associated with a higher serum Hcy level (p = 0.001) and a lower FA level (p = 0.001). Moreover, the serum Hcy levels was strongly correlated with the GSH and TBARS concentrations (r = -0.6065, P < 0.001; r = 0.6564, P < 0.001, respectively). Furthermore, logistic analysis indicated that MTHFR A1298C/C677T polymorphisms and increased Hcy concentrations may be risk factors for VPA-induced liver dysfunction. These results suggested that individual susceptibility to VPA-induced liver dysfunction may result from MTHFR A1298C/C677T polymorphisms and increased Hcy levels. This study may be helpful for the prevention and guidance of VPA-induced liver dysfunction.

Effects of glycated serum protein, homocysteine, and cystatin-C levels on pregnancy outcomes in patients with gestational diabetes mellitus.

To explore the effects of serum glycated serum protein (GSP), homocysteine (Hcy) and cystatin-C (Cys-C) levels on pregnancy outcomes in patients with gestational diabetes mellitus (GDM). Retrospective selection of 247 pregnant women who underwent normal prenatal examinations in The Yan'an People's Hospital from January 2020 to May 2022 were included in this retrospective study. Among them, 119 were pregnant women with diabetes (GDM-group) and 128 were pregnant women with normal blood glucose (Normal-group). The levels of serum GSP, HCY, CYS-C, and incidence of adverse pregnancy outcomes were compared between the two groups. The clinical value of levels of serum GSP, Hcy, and Cys-C in predicting adverse pregnancy outcomes were analyzed. Compared with the Normal-group, the overall incidence of adverse pregnancy outcomes, serum GSP, Hcy, and Cys-C levels in the GDM-group were significantly higher (p<0.05). Logistic regression analysis showed that the levels of GSP, Hcy, and Cys-C were independent risk factors for adverse pregnancy outcomes in the GDM-group (p<0.05). Receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) for diagnosing adverse pregnancy outcomes in pregnant women with GDM using serum GSP, Hcy, and CysC levels alone were 0.817, 0.843, and 0.775, respectively. The AUC of the three indicators combined was 0.921, indicating that this combination has a good predictive value for diagnosing adverse outcomes in GDM-complicated pregnancies. GDM is associated with a high risk of adverse pregnancy outcomes. Levels of serum GSP, Hcy, and Cys-C are higher in patients with GDM. The higher the levels of GSP, Hcy, and Cys-C, the greater the risk of adverse pregnancy outcomes. Combining these three indicators can effectively predict maternal pregnancy outcomes.

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

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

Inferring the genetic effects of serum homocysteine and vitamin B levels on autism spectral disorder through Mendelian randomization.

The previous studies have suggested that serum homocysteine (Hcy) and vitamin B levels are potentially related to autism spectrum disorder (ASD). However, the causality between their concentrations and ASD risk remains unclear. To elucidate this genetic association, we used a Mendelian randomization (MR) design. For this MR analysis, 47 single-nucleotide polymorphisms (SNPs)-13 related to Hcy, 13 to folate, 14 to vitamin B6, and 7 to vitamin B12-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). Our study used three approaches to calculate the MR estimates, including inverse-variance weighted (IVW) method, MR-Egger method, and weighted median (WM) method. Among these, the IVW method served as our primary MR method. False discovery rate (FDR) was implemented to correct for multiple comparisons. We also performed a series of sensitivity analyses, including Cochran's Q test, MR-Egger's intercept, MR-PRESSO, leave-one-out analysis, and the funnel plot. Univariable Mendelian randomization (UVMR) analysis revealed a statistical association between serum vitamin B12 levels and ASD risk (OR = 1.68, 95% CI 1.12-2.52, P = 0.01) using the IVW method. However, neither the WM method (OR = 1.57, 95% CI 0.93-2.66, P = 0.09) nor the MR-Egger method (OR = 2.33, 95% CI 0.48-11.19, P = 0.34) was significantly association with higher levels of serum vitamin B12 and ASD risk. Additionally, we found no evidence of causal relationships between serum levels of vitamin B6, folate, Hcy, and ASD risk. After correcting for the FDR, the causality between serum vitamin B12 levels and ASD risk remained significant (q value = 0.0270). Multivariate Mendelian randomization (MVMR) analysis indicated an independent association between elevated serum vitamin B12 levels and the risk of ASD (OR = 1.74, 95% CI 1.03-2.95, P = 0.03) using the IVW method, but this finding was inconsistent when using the WM method (OR = 1.73, 95% CI 0.89-3.36, P = 0.11) and MR-Egger method (OR = 1.60, 95% CI 0.95-2.71, P = 0.08). Furthermore, no causal associations were observed for serum levels of vitamin B6 and folate in MVMR analysis. Sensitivity analyses confirmed that these results were reliable. Our study indicated that elevated serum vitamin B12 levels might increase the risk of ASD. The potential implications of our results for ASD risk warrant validation in randomized clinical trials.

A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients.

Bortezomib results in peripheral neuropathy (PN) in approximately 50% of patients, during multiple myeloma (MM) treatment, a complication known as Bortezomib-induced peripheral neuropathy (BIPN). The drug response varies among individuals. Genetic factor may play an important role in BIPN. A next-generation sequencing (NGS) panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy. mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR (RT-qPCR). Serum homocysteine (Hcy) levels were detected in 40 samples by chemiluminescent microparticle immunoassay (CMIA). Compared with the non-BIPN group (n = 89), a total of 8 significantly associated single nucleotide polymorphisms (SNPs) were identified in the BIPN group (n = 115): MTHFR (rs1801131, rs1801133, rs17421511), EPHX1 (rs1051740), MME (rs2016848), ALDH1A1 (rs6151031), HTR7 (rs1935349) and CYP2A6 (rs8192720). The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment (NP group) was lower than that of newly diagnosed patients without peripheral neuritis after treatment (NnP group) (1.70 ± 0.77 vs. 2.81 ± 0.97, p= 0.009). Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group (11.66 ± 1.79 μmol/L vs. 8.52 ± 3.29 μmol/L, p= 0.016) and healthy controls (11.66 ± 1.79 μmol/L vs. 8.55 ± 2.13 μmol/L, p≤ 0.001). CYP2A6, EPHX1, MTHFR, ALDH1A1, HTR7, MME and BIPN are linked in Chinese MM patients. BIPN is more likely to occur in patients with lower MTHFR mRNA expression, which might result in higher serum Hcy levels.

Evaluation of Serum Homocysteine and Nitric Oxide Levels in Women with Polycystic Ovarian Syndrome and Periodontal Diseases

Polycystic ovary syndrome (PCOS) and periodontal diseases are common chronic inflammatory disorders. PCOS is a complicated condition affects overall health and causes broad spectrum changes that affect periodontal health status. Available evidence suggests that oxidative stress might comprise a link for the association between periodontal diseases and components of the metabolic syndrome. Both homocysteine (Hcy) and nitric oxide (NO) are considered to reflect the strength of oxidative stress. The aims of the study were to compare the periodontal health condition among the study groups (gingivitis, gingivitis +PCOS, chronic periodontitis (CP) and CP + PCOS group) by measuring the clinical periodontal parameters (Plaque Index (PLI), Gingival Index (GI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL), and measure serum (Hcy) and (NO) and compare their levels between study groups , then correlate between these parameters with each other and with clinical periodontal parameters in order to determine the effect of PCOS on periodontal health status and levels of serum Hcy and NO.

Homocysteine and Lp-PLA2 levels: Diagnostic value in coronary heart disease.

Coronary heart disease (CHD) is the leading cause of mortality worldwide. Identifying effective diagnostic markers and understanding risk factors is crucial for prevention and management. This study aimed to investigate the levels of homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in human plasma and their roles in the diagnosis and prognosis of CHD. A retrospective study was conducted on 232 patients with CHD, divided into Acute Myocardial Infarction, unstable angina pectoris, and stable angina pectoris groups, and a control group of 75 healthy adults. Blood samples were analyzed for serum Hcy and Lp-PLA2 levels using the cycling enzyme method and ELISA method, respectively. Statistical analyses were performed to evaluate the risk factors, and diagnostic efficacy was assessed using receiver operating characteristic (ROC) curves. No significant differences in age and sex were observed between the study and control groups, whereas marked disparities in risk factors such as obesity, hypertension, diabetes, and hyperlipidemia were noted. Significant differences in serum Hcy and Lp-PLA2 levels were identified among the CHD subgroups. Univariate and multivariate logistic regression analyses revealed that Hcy, Lp-PLA2, hypertension, and hyperlipidemia were significant risk factors for CHD. The combined diagnostic Area Under the Curve (AUC) for Hcy and Lp-PLA2 was found to be higher than that when using them individually. This study identified the elevation of Hcy and Lp-PLA2 levels as independent risk factors for CHD, and their conjoint analysis significantly enhanced clinical diagnostic efficacy. These findings provide valuable insights for CHD diagnosis, treatment, and prevention, highlighting the importance of these markers in CHD management.

Hypermethylation of the CTRP9 promoter region promotes Hcy induced VSMC lipid deposition and foam cell formation via negatively regulating ER stress

To provide a theoretical basis for the prevention and treatment of atherosclerosis (As), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on inducing the lipid deposition and foam cell formation of the vascular smooth muscle cell (VSMC) via C1q/Tumor necrosis factor-related protein9 (CTRP9) promoter region Hypermethylation negative regulating endoplasmic reticulum stress (ERs). Therefore, apolipoprotein E deficient (ApoE−/−) mice were randomly divided into the control [ApoE−/− + normal diet (NC)] and high methionine [ApoE−/− + (normal diet supplemented with 1.7% methionine (HMD)] groups (n = 6 mice/group). Following feeding for 15 weeks, the serum levels of Homocysteine (Hcy), total cholesterol (TC), and triglyceride (TG) were measured using an automatic biochemical analyzer. HE and oil red O staining were performed on the aorta roots to observe the pathological changes. Additionally, immunofluorescence staining was performed to detect the protein expression levels of CTRP9, glucose-regulated protein 78 kD (GRP78), phosphorylated protein kinase RNA-like ER kinase (p-PERK), activating transcription factor 6a (ATF6a), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), sterol regulatory element binding proteins-1c (SREBP1c) and sterol regulatory element binding proteins-2 (SREBP2) in VSMC derived from murine aortic roots. In vitro, VSMC was stimulated with 100 μmol/l Hcy. After transfection of plasmids with overexpression and interference of CTRP9, ERs agonist (TM) and inhibitor (4-PBA) were given to stimulate VSMC cells. HE staining and oil red O staining were used to observe the effect of Hcy stimulation on lipid deposition in VSMC. Additionally, The mRNA and protein expression levels of CTRP9, GRP78, PERK, ATF6a, IRE1α, SREBP1c, and SREBP2 in VSMC were detected by RT-qPCR and western blot analysis, respectively. Finally, The methylation modification of the CTRP9 promoter region has been studied. The NCBI database was used to search the promoter region of the CTRP9 gene, and CpG Island was used to predict the methylation site. After Hcy stimulation of VSMC, overexpression of DNMT1, and intervention with 5-Azc, assess the methylation level of the CTRP9 promoter through bisulfite sequencing PCR (BSP). The results showed that the serum levels of Hcy, TC, and TG in the ApoE−/− + HMD group were significantly increased compared with the ApoE−/− + NC group. In addition, HE staining and oil red O staining showed obvious AS plaque formation in the vessel wall, and a large amount of fat deposition in VSMC, thus indicating that the hyperhomocysteinemia As an animal model was successfully established. Furthermore, CTRP9 were downregulated, while GRP78, p-PERK, ATF6a, p-IRE1α, SREBP1c, SREBP2 was upregulated in aortic VSMC in the ApoE−/− + HMD group. Consistent with the in vivo results, Hcy can inhibit the expression of CTRP9 in VSMC and induce ERs and lipid deposition in VSMC. Meanwhile, the increased expression of CTRP9 can reduce ERs and protect the lipid deposition in Hcy induced VSMC. Furthermore, ERs can promote Hcy induced VSMC lipid deposition, inhibition of ERs can reduce Hcy induced VSMC lipid deposition, and CTRP9 may play a protective role in Hcy induced VSMC lipid deposition and foam cell transformation through negative regulation of ERs. In addition, The CTRP9 promoter in the Hcy group showed hypermethylation. At the same time as Hcy intervention, overexpression of DNMT1 increases the methylation level of the CTRP9 promoter, while 5-Azc can reduce the methylation level of the CTRP9 promoter. Finally, Hcy can up-regulate the expression of DNMT1 and down-regulate the expression of CTRP9. After overexpression of DNMT1, the expression of CTRP9 is further decreased. After 5-Azc inhibition of DNMT1, the expression of DNMT1 decreases, while the expression of CTRP9 increases. It is suggested that the molecular mechanism of Hcy inhibiting the expression of CTRP9 is related to the hypermethylation of the CTRP9 promoter induced by Hcy and regulated by DNMT1. 5-Azc can inhibit the expression of DNMT1 and reverse the regulatory effect of DNMT1 on CTRP9. Overall, the results of the present study suggested that Hcy induces DNA hypermethylation in the CTRP9 promoter region by up-regulating DNMT1 expression, and negatively regulates ERs mediated VSMC lipid deposition and foam cell formation. CTRP9 may potentially be a therapeutic target in the treatment of hyperhomocysteinemia and As.

The effect of homocysteine-lowering therapy on the formation of carotid atherosclerosis: A follow-up study in the rural areas of northwest China

ObjectiveTo explore the risk factors for carotid atherosclerosis in the rural areas of Northwest China, and to assess whether reducing serum homocysteine can prevent carotid atherosclerosis in subjects with hyperhomocysteinemia. MethodThis observational study with 767 participants aged 40 years or older was conducted over 3 years. Color Doppler ultrasonography was performed to measure carotid atherosclerosis. We recorded biochemical indexes and carotid ultrasound results in the first and fourth years. ResultA total of 767 individuals (48.5 % men) were analyzed. Older age, hypertension, and higher levels of baseline low-density lipoprotein cholesterol (LDL-C) were risk factors for increased carotid intima-media thickness (CIMT), carotid plaque, and carotid stenosis (All P < 0.05). No association was found between decreased serum homocysteine (Hcy) levels and CIMT, carotid plaque, or carotid stenosis in individuals with hyperhomocysteinemia. ConclusionOlder age, hypertension, and higher baseline levels of LDL-C were independent risk factors for carotid atherosclerosis. Reducing serum Hcy levels may not prevent carotid atherosclerosis in the general population with hyperhomocysteinemia.

Acupuncture of revised acupoint combination around the skull base for post-stroke mild cognitive impairment: a randomized controlled trial

To observe the clinical efficacy of acupuncture of revised acupoint combination around the skull base in treating post-stroke mild cognitive impairment (PSMCI), and preliminary explore its action mechanism. A total of 76 PSMCI patients were randomly divided into an observation group (38 cases, 4 cases dropped off) and a control group (38 cases, 3 cases dropped off, 1 case was removed). In the observation group, acupuncture of revised acupoint combination around the skull base (bilateral Fengchi [GB 20], Wangu [GB 12], Tianzhu [BL 10] and Yamen [GV 15], Baihui [GV 20]) was used for treatment. In the control group, 8 non-meridian and non-acupoint points at the distal end were selected for shallow puncture treatment. Retaining the needles of 30 min, once every other day,3 times a week for 4 weeks in both groups. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Barthel index (BI) and serum levels of cystatin C (Cys-C) and homocysteine (Hcy) were compared in the two groups before and after treatment, and the clinical efficacy was evaluated. After treatment, the scores of MoCA were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The scores of MMSE and BI were increased compared with those before treatment in the observation group (P<0.05), and the score of MMSE in the observation group was higher than that in the control group (P<0.05). After treatment, the serum levels of Cys-C and Hcy were decreased compared with those before treatment in the observation group (P<0.05), and lower than those in the control group (P<0.05). After treatment, the serum level of Cys-C was increased compared with that before treatment in the control group (P<0.05). The total effective rate of the observation group was 88.2% (30/34), which was higher than 32.4% (11/34) of the control group (P<0.05). Acupuncture of revised acupoint combination around the skull base can improve cognitive function and daily living ability of PSMCI patients, which may be related to the down regulation of serum levels of Cys-C and Hcy.

Cognitive Dysfunction and Affective Mood Disorder Screening in Patients With Chronic Inflammatory Bowel Disease: Protocol for a Prospective Case-Control Study.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut-brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication. The aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD. A case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months. Data collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI. GBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development. ClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729. DERR1-10.2196/50546.

Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson’s disease

BackgroundDuring the course of their illness, people with Parkinson’s disease may see changes in their insulin-like growth factor (IGF-1) and serum homocysteine (Hcy) indices. In this study, patients with intermediate to severe Parkinson’s disease were examined for how Resagiline and levodopa and benserazide hydrochloride affected their motor performance, serum levels of homocysteine (Hcy), and insulin-like growth factor (IGF-1).MethodsFrom June 2020 to December 2021, a total of 100+ cases of Parkinson’s patients over 60 years old in the middle and late stages of Parkinson’s were seen in the outpatient and inpatient departments of the Third People’s Hospital of Chengdu City and had a detailed observation record, and according to the inclusion criteria, the patients who met the criteria were randomly grouped into a clinical observation group and a control group. The subjects in the control group received only levodopa and benserazide hydrochloride treatment, while the observation group was treated with Resagiline in combination with the clinical control group. The total treatment observation period was 1 year for both groups, and the motor function and serum Hcy and IGF-1 indexes of both groups were compared after the end of treatment.ResultsWe randomly and evenly grouped 64 patients who met the requirements of the inclusion criteria into a clinical observation group and a control group, each with 32 patients, from among 168 patients over 60 years of age with detailed observation records in the middle and late stages of Parkinson’s. After the 1-year observation period, we found that the total effective rate after treatment in the clinical observation group (93.75%) and significantly higher than that in the control group (68.75%) (P < 0.05); after 1 year of treatment, the UPDRS score decreased in both groups, and the observation group was significantly lower than the control group (P < 0.05); after treatment, serum Hcy decreased and IGF-1 increased in both groups, and the observation group was higher than the control group mean values (P < 0.05).ConclusionsIn patients with Parkinson’s disease who are in the middle and late stages of the disease, the administration of Resagiline combined with levodopa and benserazide hydrochloride can significantly lower the body’s serum Hcy level, significantly raise IGF-1 levels, and significantly improve motor function in patients with Parkinson’s disease. It can also have significant therapeutic effects.

Relationship between the methylenetetrahydrofolate reductase (MTHFR) rs1801133 SNP and serum homocysteine levels of Zhuang hypertensive patients in the central region of Guangxi

BackgroundThe relationship between the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) and serum homocysteine (Hcy) levels or H-type hypertension in different populations is inconsistent. This study aimed to explore the association between the MTHFR rs1801133 SNP and serum Hcy levels of Zhuang hypertensive patients in the central region of Guangxi.MethodsA total of 606 Zhuang inpatients with essential hypertension were recruited in our hospital from August 2016 to December 2018. The patients were divided into H-type hypertension (Hcy > 10 µmol/L, n = 528) and non–H-type hypertension (Hcy ≤ 10 µmol/L, n = 78) groups. At the same time, an age- and sex-matched group of 379 subjects with normal physical examination in our hospital were selected as the control group. Blood biochemical measurements and genotyping of the MTHFR rs1801133 SNP were performed.ResultsThe prevalence of H-type hypertension was 87.13%. The levels of serum Hcy in patients with hypertension were higher than those in control group (14.20 ± 5.78 μmol/L vs. 11.97 ± 5.39 μmol/L, P < 0.001), especially in patients with H-type hypertension (15.08 ± 5.65 μmol/L, P < 0.001). The frequencies of TT genotype (22.73%) and T allele (46.21%) in patients with H-type hypertension were significantly higher than those in control group (11.35% and 30.47%, respectively) and non–H-type hypertension group (10.26% and 28.85%, respectively; P < 0.001 for all). Multivariate linear regression analysis showed that serum Hcy levels were significantly correlated with creatinine, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, and the MTHFR rs1801133 genotypes in control group, while serum Hcy levels were significantly correlated with creatinine, triglyceride, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, glycosylated hemoglobin, and the MTHFR rs1801133 genotypes in H-type hypertension group (P < 0.05–0.001). Serum Hcy levels in the T allele carriers were higher than those in the T allele noncarriers in both H-type hypertension and control groups.ConclusionsThere was closely related between the MTHFR rs1801133 SNP and serum Hcy levels in Zhuang patients with H-type hypertension in the central region of Guangxi. The MTHFR SNP may be an important reason for the increase of serum Hcy levels in Zhuang patients with H-type hypertension in this region.

Serum Levels of Hcy, sST2 and CA-125 in CHF Patients and Their Correlation with Cardiac Function Classification.

The relationships between serum levels of homocysteine (Hcy), soluble stromelysin 2 (sST2), and tumor-associated cancer antigen 125 (CA-125) and heart failure requires further investigation. The aim of the present study was to evaluate the levels of Hcy, sST2 and CA-125 in patients with congestive heart failure and to correlate these with cardiac function, thereby providing a reference for the clinical diagnosis and treatment of heart failure. Seventy patients with chronic heart failure (CHF) diagnosed between August 2020 and July 2022 were classified into heart failure groups II (n = 25), III (n = 23) and IV (n = 22). Seventy individuals with normal physical examination results were selected as the healthy group. Serum Hcy, sST2 and CA-125 levels for all participants were evaluated and correlated with each other and with cardiac function classification. The diagnostic value of individual Hcy, sST2, CA-125 levels for CHF was evaluated, as well as a combination of these factors. Hcy, sST2, and CA-125 levels were lower in the healthy group than in the heart failure group. Moreover, a progressive increase in Hcy, sST2, and CA-125 levels were observed in heart failure groups II, III, and IV. Individual Hcy, sST2 and CA-125 levels, as well as a combination of these factors, were significantly correlated with cardiac function classification (p < 0.05). Hcy, sST2 and CA-125 levels each showed diagnostic value for CHF, with the three combined having the best diagnostic value. Abnormally high levels of Hcy, sST2 and CA-125 occur in CHF patients and are positively correlated with cardiac function classification. Individual levels of these factors, and particularly a combination of the three, show good sensitivity and specificity for CHF diagnosis that could be widely used in clinical practice.

An observational association study between maternal homocysteine and pregnancy complications or perinatal outcomes with established trimester-specific reference intervals in pregnant women.

Elevated homocysteine (Hcy) level during pregnancy is positively associated with various gestational-specific diseases. However, there is no uniform standard for the reference interval (RI) of Hcy in pregnancy. From January 2017 to January 2019, 14,530 singleton pregnant women registered at our institute were included for the establishment of trimester-specific RIs of Hcy with both the nonparametric approach and the indirect Hoffmann method, followed by pregnancy outcome association analysis conducted with logistic regression. The serum Hcy level in the nonpregnant group was significantly higher than that of pregnant women. A relatively decreased Hcy concentration was observed in the second trimester when compared with that of the first or third trimester. The direct RIs of Hcy in the first or third, and second trimesters were 4.6 to 8.0 mmol/L (merged) and 4.0 to 6.4 mmol/L, respectively, which showed no significant difference compared with the RI derived from the indirect Hoffmann method. In the subsequent risk analysis, the first trimester Hcy was found to be negatively associated with GDM development; whereas the third trimester Hcy conferred increased risk of postpartum hemorrhage after delivery. Having established trimester-specific RIs, our study sheds light on the complicated roles of Hcy in pregnancy-related complications.

Clinical and laboratory findings and etiologies of genetic homocystinemia: a single-center experience.

Homocysteine (Hcy) is an endogenous nonprotein sulfur-containing amino acid biosynthesized from methionine by the removal of its terminal methyl group. Hyperhomocysteinemia (HHcy) has been linked to many systemic disorders, including stroke, proteinuria, epilepsy, psychosis, diabetes, lung disease, and liver disease. The clinical effects of high serum Hcy level, also known as hyperhomocysteinemia, have been explained by different mechanisms. However, little has been reported on the clinical and laboratory findings and etiologies of genetic HHcy in children. This study aimed to examine the relationships between clinical features, laboratory findings, and genetic defects of HHcy. We retrospectively evaluated 20 consecutive children and adolescents with inherited HHcy at the pediatric neurology division of Baskent University, Adana Hospital (Adana, Turkey) between December 2011 and December 2022. Our main finding is that the most common cause of genetic HHcy is MTHFR mutation. The other main finding is that the Hcy level was higher in patients with CBS deficiency and intracellular cbl defects than in MTHFR mutations. We also found that clinical presentations of genetic HHcy vary widely, and the most common clinical finding is seizures. Here, we report the first and only case of a cbl defect with nonepileptic myoclonus. We also observed that mild and intermediate HHcy associated with the MTHFR mutation may be related to migraine, vertigo, tension-type headache, and idiopathic intracranial hypertension. Although some of the patients were followed up in tertiary care centers for a long time, they were not diagnosed with HHcy. Therefore, we suggest evaluating Hcy levels in children with unexplained neurological symptoms. Our findings suggest that genetic HHcy might be associated with different clinical manifestations and etiologies. Therefore, we suggest evaluating Hcy levels in children with unexplained neurologic symptoms.

Effect of ginkgo leaf tablets combined with compound carbidopa on patients with Parkinson’s disease

Purpose: To determine the effect of a combination of ginkgo leaf tablets with compound carbidopa tablets on cognitive function, serum homocysteine (Hcy), malondialdehyde (MDA) and neuron-specific enolase (NSE) levels in patients with Parkinson's disease (PD).Methods: A total of eighty (80) PD patients admitted to The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China between December 2020 and December 2022 were randomly divided into two groups: Western medicine group (n = 40, using compound carbidopa tablets alone) and combination group (n = 40, using ginkgo leaf tablets combined with compound carbidopa tablets), and orally treated for 3 months. Mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess cognitive function before and after treatment. High-performance liquid chromatography was used to determine serum Hcy levels, while enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum MDA and NSE levels. Adverse reactions were also recorded during treatment.Results: Total response rate following treatment in combination group was significantly higher than in Western medicine group (95.00 vs 80.00 %, p &lt; 0.05). After treatment, MMSE and MoCA scores in combination group were significantly higher (p &lt; 0.05) than those in Western medicine group, while serum Hcy, MDA and NSE levels in combination group were significantly lower than those in Western medicine group (p &lt; 0.05). During treatment, there was no significant difference in incidence of adverse reactions between the two groups (p &gt; 0.05).Conclusion: Ginkgo leaf tablets in combination with carbidopa significantly improve cognitive functions associated with PD with high safety, when compared to carbidopa tablets alone. However, further clinical trials are commended to validate these findings.