Blood Homocysteine Research Articles

Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy.

Classical homocystinuria is a hereditary defect of the enzyme cystathionine beta synthase, which is produced in the liver. If this enzyme fails, the synthesis pathway of cysteine from methionine is interrupted, leading to the accumulation of homocysteine in the blood plasma and homocysteine in the urine. After birth, the children are unremarkable except for the characteristic laboratory findings. Symptoms rarely appear before the second year of life. The most common symptom is a prolapse of the crystalline lens. This finding is seen in 70% of untreated 10-year-old affected individuals. As the earliest symptom, psychomotor retardation occurs in the majority of patients already during the first two years of life. Limiting factors in terms of life expectancy are thromboembolism, peripheral arterial disease, myocardial infarction, and stroke. These symptoms are due to the damage to the vessels caused by the elevated amino acid levels. About 30% suffer a thromboembolic event by the age of 20, about half by the age of 30. This review focus on present and new therapeutical approaches like the role of enzyme replacement with presentation of different novel targets in research like pegtibatinase, pegtarviliase, CDX-6512, erymethionase, chaperones, proteasome inhibitors and probiotic treatment with SYNB 1353. Furthermore, we analyze the role of liver-directed therapy with three dimensional (3D) bioprinting, liver bioengineering of liver organoids in vitro and liver transplantation. The role of different gene therapy options to treat and cure this extremely rare disease in childhood will be discussed.

P343 Eosinophilic inflammation as an indicator of the activity of the course of Inflammatory Bowel Diseases

Abstract Background Eosinophils have been identified as cells that promote immune cell infiltration in inflammatory bowel diseases (IBD). Activation of eosinophils causes degranulation, which can lead to tissue damage due to the release of toxic oxygen radicals, including eosinophilic cationic protein (ECP). The potential role of eosinophils in inflammation and fibrosis in patients with IBD remains relevant. Purpose of the study to study the effect of changes in the level of eosinophilic cationic protein on the activity of the course of inflammatory bowel diseases. Methods The study was conducted from January 2016 to April 2022, among 400 patients with IBD (MC 12 patients, women 8, men 4; UC 150 patients, women 71, men 79; CD 238 patients, women 120, men 118). Patients underwent endoscopy with biopsy sampling for pathomorphological examination, as well as laboratory blood tests (general blood count, h/s CRP, homocysteine, vitamin D, ANCA-parameters, α-THF and IL-1β, IL-4, IL -8, IL-10, IL-18, total protein, albumin, iron, ferritin, eosinophilic cationic protein (ECP), İgE; urinalysis and urinary albumin; fecal analysis and fecal calprotectin and lactoferrin. Results In 250 patients (62.5%) with a poor response to basic therapy, a study was conducted on ECP and in 69 cases (27.6%) the result was positive, the number of positive endoscopic manifestations was 190 (76%), the number of patients with a positive pathological conclusion for the presence of eosinophils in the biopsy material (more than 30-35 eosinophils per field of view) - 95 (38%), the number of patients with concomitant allergic diseases - 14 (5.6% / 20.2%). The level of EPC fluctuated within 29-228 ng/mL (N<24 ng/mL). Indicators for the studied parameters are presented in Table 1. Table 1. Changes in activity in some laboratory, endoscopic and pathological parameters During the follow-up in the group of patients with elevated levels of eosinophilic cationic protein for 6-24 months, some changes occurred: new cases of fibrosis appeared in patients with CD, as well as cases of non-response to basic therapy and, as an outcome, cases of surgical interventions in patients with ulcerative colitis (Diagram 1). Diagram 1. Outcome of patients with elevated EPC levels Conclusion The increase in the level of ECP in the study group of patients was 27.6% and correlated with higher rates both in laboratory and in endoscopic and morphological activity of IBD. The study of the increase in ECP is of interest in the context of the “non-response” marker to basic therapy in IBD and in the search for new targets for treatment.

Unexplored Roles of Erythrocytes in Atherothrombotic Stroke.

Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death.

Nontargeted metabolomics reveals the potential mechanism underlying the association between birthweight and metabolic disturbances

AimsThe aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances.Research design and methodsWe recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed.ResultsWe found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a “U-shaped” trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as “line-shaped”, which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood.ConclusionsThese investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women.

Blood counts and homocysteine in acute stroke: What is the relation?

Objectives: Stroke is the second-leading cause of death and the third-leading cause of death and disability combined in the world. We need to find easy, available, and reliable parameters on which we can depend to prevent stroke, predict outcome, and determine prognosis. This will help in stroke management in the future. Materials and Methods: We noted blood counts and serum homocysteine levels in acute stroke patients after the exclusion of confounding factors. Our team recorded the detailed demographic and blood parameters (blood counts and homocysteine) of acute stroke patients who got admitted to different departments of our hospital in 5 months. We later correlated or tried to find the association between these parameters and stroke severity (NIHSS), other clinical parameters such as dysarthria and stroke outcome (Modified Rankin Score (mRS) at discharge and at 3 months). The team also tried to find relationships, if any, with different stroke subtypes as per the Trial of ORG 10172 in Acute Stroke Treatment classification. Results: Out of 100 patients (34 females and 66 males), we had 28 patients with hyperhomocysteinemia (HHcy). The high neutrophil count and total leukocyte count correlated with stroke severity, dysarthria, and outcome at 3 months (poor mRS). While, it was the opposite in the case of lymphocyte count. Homocysteine level did not correlate with stroke severity or outcome but with dyslipidemia. HHcy was more prevalent among patients with large artery atherosclerotic disease. Conclusion: Findings of our study were agreeable to earlier studies on the relationship between blood counts and stroke prognosis. Although high homocysteine level was associated with stroke, its level was not found to be related to stroke severity or outcome. However, further study with a larger sample size is required to draw a confident conclusion.

Retracted: Influence of Different Antiepileptic Drugs on Blood Ammonia and Homocysteine Levels in Children with Epilepsy.

[This retracts the article DOI: 10.1155/2021/5698765.].

Cerebral microangiopathy in men with obstructive sleep apnea syndrome

To determine factors associated with the development of small vessel disease (SVD) in patients with obstructive sleep apnea syndrome (OSA). One hundred and fifty-two patients with risk factors for the development of cerebrovascular diseases were examined. Based on the results of polysomnography, patients were divided into groups with- (n=84) and without (n=68) OSA. The groups were matched by age, prevalence of arterial hypertension and diabetes mellitus. SVD was diagnosed using brain MRI. Laboratory tests included an assessment of parameters of lipid metabolism, glucose metabolism, concentration of C-reactive protein (CRP), levels of homocysteine and creatinine with the calculation of glomerular filtration rate (GFR). Patients with OSA, compared with those without OSA, were characterized by a statistically significant number of gliosis foci, with their large sizes, more frequent changes on the Fazekas scales and the Hassan scale. The most severe degree of damage according to the Hassan scale in patients with OSA was detected more often (55 (66%) and 27 (39%) OR=2.89, 95% CI 1.47-5.67, p=0.002). More pronounced atrophic changes in the brain, an increase in the size of the III ventricle and the index of the anterior horns, significantly lower GFR and higher levels of CRP were noted in the OSA group. Patients with OSA and duration of nocturnal hypoxia for more than 2 minutes were more likely to have hyperintensity of subcortical regions. In patients with OSAS, pronounced manifestations of SMD were associated with a significantly higher level of morning systolic blood pressure (MAP): 140 [120; 150] vs. 127 [120; 130] p=0.029; increased levels of blood homocysteine: 14 [11; 17.8] vs. 13 [9.7; 12.5] p=0.049; a decrease in GFR: 79 [71; 87.3] vs. 89.8 [80.3; 94] p=0.002, respectively. OSA and intermittent nocturnal hypoxia are independent risk factors for SMD. A more severe micro-focal vascular lesion in OSA is associated with a decrease in renal filtration function, an increase in morning blood pressure and an elevation in homocysteine level.

Retracted: Effect of Blood Homocysteine on the Outcome of Artificial Insemination in Women with Polycystic Ovary Syndrome.

[This retracts the article DOI: 10.1155/2022/6311419.].

Maternal Hyperhomocysteinemia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats

Maternal hyperhomocysteinemia (HCY) is a common pregnancy complication caused by high levels of the homocysteine in maternal and fetal blood, which leads to the alterations of the cognitive functions, including learning and memory. In the present study, we investigated the mechanisms of these alterations in a rat model of maternal HCY. The behavioral tests confirmed the memory impairments in young and adult rats following the prenatal HCY exposure. Field potential recordings in hippocampal slices demonstrated that the long-term potentiation (LTP) was significantly reduced in HCY rats. The whole-cell patch-clamp recordings in hippocampal slices demonstrated that the magnitude of NMDA receptor-mediated currents did not change while their desensitization decreased in HCY rats. No significant alterations of glutamate receptor subunit expression except GluN1 were detected in the hippocampus of HCY rats using the quantitative real-time PCR and Western blot methods. The immunofluorescence microscopy revealed that the number of synaptopodin-positive spines is reduced, while the analysis of the ultrastructure of hippocampus using the electron microscopy revealed the indications of delayed hippocampal maturation in young HCY rats. Thus, the obtained results suggest that maternal HCY disturbs the maturation of hippocampus during the first month of life, which disrupts LTP formation and causes memory impairments.

ВЗАИМОСВЯЗИ ГИПЕРГОМОЦИСТЕИНЕМИИ И ФУНКЦИОНАЛЬНОГО СОСТОЯНИЯ ПОЧЕК У ДЕТЕЙ С НАРУШЕНИЕМ ПУРИНОВОГО ОБМЕНА

Among the modified risk factors for chronic kidney disease hyperhomocysteinemia (HHC) and hyperuricemia (HU) play an important role in the development of the cardiorenal continuum. The purpose of the research was to study the relationship between HHC and the functional state of the kidneys in children with impaired purine metabolism. Materials and methods used: a single-center one-stage (cross-sectional) study was conducted in 54 pediatric patients aged 9 to 15 y/o with purine metabolism disorders (in the form of isolated HU or in combination with hyperuricosuria) in Feb. 2017 - March 2021. The level of homocysteine in the blood serum was determined by enzyme immunoassay. Evaluated clearance, excreted fraction, filtered volume and reabsorption of uric acid; the glomerular filtration rate (GFR) was calculated. The two groups were distinguished: the [main] Group 1 of 26 children with HHC; and the [comparison] Group 2 of 28 children with normal homocysteine levels. Results: the frequency of diagnosis of HHC among the examined was 47.8%, which is almost 5 times higher than in the population. In the main group, the analysis of Spearman's rank correlation revealed a positive statistically significant correlation between the level of homocysteine and uric acid: Rs=0.32, p=0.048. In this group, the clearance of uric acid, its excreted fraction and filtered volume were statistically significantly lower, while reabsorption and GFR were higher relative to the comparison group. The daily excretion of uric acid directly correlated statistically significantly with its clearance (Rs=0.71, p&lt;0.001) and excreted fraction (Rs=0.66, p=0.004) and inversely significantly correlated with the level of its reabsorption (Rs=- 0.66, p=0.004). Statistically significant direct correlation of blood homocysteine and creatinine levels (Rs=0.38, p=0.020) and inverse correlation with uric acid excretion (Rs=-0.38, p=0.020) were obtained. Conclusion: in children with impaired purine metabolism, HHC is associated with the early formation of tubular dysfunction, which is evidenced by a statistically significant decrease in the clearance of uric acid, its excreted fraction and filtered volume. The increase in GFR in this case probably reflects the formation of hyperfiltration as the initial stage of metabolic renal damage.

Short-Term Combined Intake of Vitamin B2 and Vitamin E Decreases Plasma Homocysteine Concentrations in Female Track Athletes

Female athletes who endure physical strain on the same bone area are prone to stress fractures. Preventing these improves their quality of life. Blood vitamin B2 (V.B2) and E (V.E) levels influence blood homocysteine (Hcy) levels, which, when elevated, increase the risk of stress fractures. We aimed to determine the effects of V.B2 and V.E supplementation on plasma Hcy concentrations in these athletes carrying the C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). This study is a before–after study in 16 female athletes. It was divided into three intervention periods of V.B2 (28 mg/day), V.E (60 mg/day), and V.B2 + V.E intake, and each period was 14 days. Blood samples were collected before and after each period, and plasma Hcy concentration and each blood vitamin concentration were measured. Plasma Hcy concentration significantly decreased in all periods, but the maximum lowering effect was obtained when V.B2 and V.E were used in combination. The administration of V.B2 might have lowered the plasma Hcy level by maximizing the catalytic activity of MTHFR; V.E might have suppressed cell oxidation, increasing the efficiency of folate in lowering the plasma Hcy level. We propose the combined intake of V.B2 and V.E as effective nutrients to reduce plasma Hcy concentrations in female athletes with MTHFR polymorphisms.

Influence of the Dietary Supplement of Protected Calcium Butyrate in Growing Japanese Quail Diets on Performance, Carcass Parameters, Blood Serum Biochemical Status, Meat Quality and Jejunum Histomorphology.

In this trial, it was planned to determine the effect of protected calcium butyrate (PCB) supplemented at different amounts on performance, carcass characteristics, blood biochemical values, jejunum histomorphology, and meat traits in Japanese quails. 196 one-day-old unsexed Japanese quails divided into 4 groups with 7 replicates. A conventional corn and soybean meal-based diet was formulated, and all groups’ diets were supplemented with 0, 0.5, 1.0 and 2.0 g/kg PCB respectively for 42 days. From the results, PCB supplementation significantly improved body weight (BW) on the 21st day, body weight gain (BWG) between 0 to 21 days, hot carcass yield (HCY), relative weights of the hearth. Similarly, blood urea nitrogen (BUN), total cholesterol (TC), low-density lipoprotein (LDL) and villus height (VH) levels were lower in PCB supplemented groups. Besides, PCB supplementation in Japanese quails decreased villus-crypt rate (VCR) except for the control and the group fed with 2.0 g/kg PCB. This study showed that dietary PCB supplementation in Japanese quails’ diet improved growth performance in young chicks and carcass yield, BUN, and lipid profile. On the other hand, the supplementation didn’t affect the antioxidant status, homocysteine, and folic acid values in blood and meat traits.

High frequencies of vitamin B12 and folic acid deficiencies and hyperhomocysteinemia in Taiwanese male patients with oral submucous fibrosis

Background/purpose: Oral submucous fibrosis (OSF) is a betel quid chewing-caused oral mucosal disease with progressive collagen deposition. This study evaluated whether Taiwanese male OSF patients had high frequencies of vitamin B12 and folic acid deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity. Materials and methodsThe blood hemoglobin (Hb), serum iron, vitamin B12, folic acid, homocysteine, and GPCA concentrations in 62 male OSF patients were measured and compared with the corresponding data in 124 age-matched male healthy control subjects. ResultsWe found that 5 (8.1%), 12 (19.4%), 32 (51.6%), 31 (50.0%), 22 (35.5%), and 6 (9.7%) of the 62 male OSF patients had Hb (<13 g/dL), iron (≤70 μg/dL), vitamin B12 (≤450 pg/mL), and folic acid (≤6 ng/mL) deficiencies, hyperhomocysteinemia (>12 μM), and serum GPCA positivity, respectively. Furthermore, OSF patients had significantly higher frequencies of Hb (P = 0.006), vitamin B12 (P < 0.001), and folic acid (P < 0.001) deficiencies, hyperhomocysteinemia (P < 0.001), and serum GPCA positivity (P = 0.030) than 124 healthy control subjects. Of the 22 OSF patients with hyperhomocysteinemia, 4 had vitamin B12 deficiency only, 7 had folic acid deficiency only, and 11 had both vitamin B12 and folic acid deficiencies. ConclusionWe conclude that Taiwanese male OSF patients have high frequencies of vitamin B12 and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity. The hyperhomocysteinemia in our OSF patients is predominantly due to deficiencies of either vitamin B12 or folic acid or both.

Association Of the Methylene Tetrahydrofolate Reductase (MTHFR) Gene Polymorphism with Susceptibility to Recurrence of Cardiovascular Outcomes Among Ischemic Stroke- A Randomized Controlled Trial

Background: Hyperhomocystenemia and genetic variants are factors for causing young age stroke globally. This study aims to identify homocysteine related-MTHFR gene polymorphism that associated with recur-rent cardiovascular outcomes. Methodology: A randomized controlled trial conducted upon 90 hyperhomocysteinemic ischemic stroke patients were taken from the neurology wards of a tertiary care hospital were randomly selected into vita-min B therapy group and control groups (n=45 in each group). Baseline subject details were collected ve-nous blood sample for MTHFR genetic testing via PCR-RFLP technique along with blood homocysteine lev-els, vitamin B12, folic acid levels. Results: The results showed that the frequency of CT genotype polymorphism was 15.5% vs 13.3% for the MTHFR C677T gene without any significant difference between vitamin group and control group respective-ly (p-value &gt;0.05). The reduction in mean homocysteine up to -6.77±4.50 versus -2.08±0.71 µmol/L in the vitamin group as compared to control group respectively, p value 0.001. Conclusion: Considerable amount of MTHFR gene polymorphism found among hyperhomocysteinemic is-chemic stroke of sub-Himalayan region. Nutritional deficiencies including vitamin B 12 &amp; folic acid, and some hidden reasons found, which could lead to the primary cause of hyperhomocysteinemia. Vitamin B therapy is an effective for reducing homocysteine.

Effect of MTHFRC677 T Gene Polymorphism on Early Morning Blood Pressure in Elderly Female Patients with H-Type Hypertension.

The distribution characteristics of Methylenetetrahydrofolate Reductase (MTHFR) gene C677 T polymorphism and its influence on early morning blood pressure in elderly female patients with H-type hypertension are investigated. A total of 220 elderly female patients with hypertension who received diagnosis and treatment in our hospital from March to September 2021 are selected. All patients received serum index detection in our hospital and are grouped according to blood homocysteine (Hcy) level. Patients with Hcy>10 μmol/L are classified as H-type hypertension and included in H-type hypertension group (n = 166). Patients with Hcy≤10 μmol/L are included in the non-H-type hypertension group (n = 54). Both groups underwent 24-hour ambulatory blood pressure monitoring. Base frequency and allele distribution of MTHFR gene C677 T locus are compared between the two groups, and the relationship between different bases of MTHFR gene C677 T locus and morning blood pressure and Hcy level is analyzed. The risk factors of morning hypertension in patients with H-type hypertension are analyzed by binary logistic regression. Binary logistic regression analysis shows that smoking history, drinking history, high-salt diet, MTHFR gene C677 T genotype, and abnormal 24 h systolic blood pressure are the risk factors for the occurrence of morning hypertension in H-type hypertension patients. The frequency of TT homozygous mutation at the C677 T site of the MTHFR gene is high in patients with H-type hypertension, and the mutation of the C677 T site of the MTHFR gene had an effect on systolic blood pressure and Hcy level.

Homocysteine Levels and Clinical Outcomes in Schizophrenia—A Pilot Randomized Controlled Trial

Objectives: To find out the relation between homocysteine levels in peripheral blood and the effectiveness as well as the safety of haloperidol and olanzapine in schizophrenia treatment. Materials and Methods: A prospective randomized parallel-group open-label interventional clinical trial was conducted on 40 mild to moderate schizophrenia patients. To compare the efficacy of olanzapine and haloperidol Brief Psychiatric Rating Scale (BPRS) score was used. Homocysteine levels of peripheral blood and Abnormal Involuntary Movement Scale scores were evaluated. Results: BPRS score improved in both groups on day 14 and day 28. But significantly more with olanzapine ( P value =.001). The olanzapine group showed a higher reduction (13.91±0.47 to 9.74±0.5) in homocysteine levels than the haloperidol group. Also, the BPRS scores negatively correlated ( r = –0.66) to homocysteine levels. Conclusion: Therefore, our study shows that peripheral blood homocysteine levels can be used to predict and assess the treatment outcome in schizophrenia patients. Biomarker driven approach in schizophrenia will allow the patients to be treated promptly with the right drug. In this light, personalized treatment holds great potential in the future.

Effect of Blood Homocysteine on the Outcome of Artificial Insemination in Women with Polycystic Ovary Syndrome.

Background Polycystic ovary syndrome (PCOS) is the major reason for women's low fertility and the most frequent endocrine disorder in women of childbearing age. Homocysteine is an amino acid that contains sulfur that has been negatively correlated with the reproductive outcome of polycystic women treated with IVF/ICSI. However, the impact of blood homocysteine levels on the outcome of artificial insemination in polycystic ovary syndrome women is unknown. The goal of this study is to examine the impact of serum homocysteine on the result of intrauterine insemination in females who have polycystic ovary syndrome (PCOS). Methods 96 infertile women (129 cycles) treated with artificial insemination were collected, including 66 cases (87 cycles) in the case group (PCOS group) and 30 cases (42 cycles) in the control group (male factor infertility). The differences in general data amongst two groups, such as BMI, Hcy, and age, were compared. The case group has been classified into two groups based on serum Hcy level: LHcy group (Hcy < 15) and HHcy group (Hcy ≥ 15). The relationship among pregnancy and serum Hcy level outcome in PCOS women was compared. Results The PCOS group had substantially increased serum homocysteine levels in comparison to the control group (P = 0.019). Among PCOS women, the clinical pregnancy rates of artificial insemination in the HHcy group and LHcy group were 14.29% and 37.88%. The difference among the two groups was substantial (P = 0.044). Artificial insemination frequency, ovulation induction, BMI, infertility years, AMH, serum testosterone, HOME IR, TSH, TPOAb, hCG, daily follicle size, intimal thickness, and other factors did not differ greatly between the two groups. Conclusion Serum homocysteine levels are increased in women having PCOS. Their levels above the threshold will lower the clinical pregnancy rate of intrauterine insemination in PCOS women.

Effects of guanidinoacetic acid and betaine on growth performance, energy and nitrogen metabolism, and rumen microbial protein synthesis in lambs

In this study, we investigated the effects of guanidinoacetic acid (GAA) and betaine (BT) on growth performance, nutrient digestion, energy-nitrogen metabolism, and microbial protein synthesis in lambs. Forty-eight 3-month-old Dorper × Thin-tailed Han first crossbred generation ram lambs with similar body weight (22.03 ± 1.3 kg; mean ± SD) were randomly divided into 4 groups. According to the 2 × 2 factorial arrangement, lambs in each of the 4 groups were fed basal diets, or basal diets supplemented with 0.9 g GAA/kg dietary dry matter (DM), 5 g BT/day, or 5 g BT/day + 0.9 g GAA/kg dietary DM. Before the formal trial, all lambs were allowed to adapt to the facilities as well as the basal diet for 15 days. This study lasted for 71 days including a 60-day period for feeding trial and an 11-day period for digestion and metabolism trials. The results showed that supplementation with GAA or BT increased the average daily gain (ADG) and feed efficiency (FE). However, no further increase in ADG or FE was observed with the combination of GAA and BT compared to that induced by addition of GAA or BT alone. Moreover, the addition of GAA or BT improved the apparent digestibility of dry matter (DM) and neutral detergent fiber (NDF), while GAA increased acid detergent fiber (ADF). GAA or BT supplementation decreased ruminal pH but increased the concentration of total volatile fatty acids (T-VFA), propionate, and valerate. Ruminal ammonia N content was not influenced by GAA or BT supplementation. Addition of GAA or BT resulted in an increase in microbial protein (MCP) synthesis. Additionally, supplementation with GAA or BT promoted digestible nitrogen (N), retained N, digestible energy and apparent digestibility of gross energy, and reduced fecal N. Supplementation with GAA decreased urinary N and increased metabolizable energy. The addition of GAA or BT increased total protein and creatine levels in serum, but the addition of BT alone decreased blood homocysteine (Hcy) levels. GAA elevated blood insulin-like growth factors-1 (IGF-1). These results demonstrate that supplementation with GAA or BT improves growth performance, nutrient digestibility, and energy-nitrogen metabolism, but the addition of BT and GAA in combination does not further improve the growth of lambs.

Comparison of the Effect of 6 Weeks of Creatine and Ginseng Supplementation on Blood Ammonia, Lipoprotein and Homocysteine of Male Players of Iran's EPE Fencing Team in 2021

Background and Aim Food and sports supplements are used by athletes all over the world, and correct and optimal consumption improves performance and prevents sports injuries. In this regard, creatine and ginseng supplements can be effective on physiological indicators and sports performance. Therefore, considering that no research has been done on the use of these supplements on blood indicators on fencers. The present study compares the effect of creatine and ginseng supplements on blood ammonia, HDL, LDL and homocysteine indices of the male players of the Iranian Epe fencing team. Methods &amp; Materials In the present study, 14 male players of the Epe national fencing team were divided into two creatine supplement groups (7 people) and ginseng supplement group (7 people). Subjects in two groups performed their normal exercises with the team during the research, and on the day before the measurement, after a specific activity in a sitting position, blood was taken from the arm vein of the subjects by a specialist. The statistical significance difference was determined at the level of P ≥ 0.05 and ANCOVA test was used to determine the differences between groups and the data was analyzed by SPSS software, version 25. Ethical Considerations This article was approved by the Ethics Committee of Islamic Azad University, Shahrood Branch (Code: IR.IAU.SHAHROOD.REC.1400.073). Results The results showed that after six weeks, there is a significant difference between the creatine and ginseng groups in the blood indices of ammonia, LDL, HDL and homocysteine (P≥0.05). so that the average of creatine supplement group in ammonia, LDL, HDL and homocysteine index in terms of mg/dL respectively (2.56±0.83, 1.16±0.33, 7.45±0.48, 8.89±0.18) and Gensing group (2.05±0.29, 1.46±0.78, 8.11±0.27, 7.63±0.45). Conclusion The results showed that there is a significant difference in the average of blood ammonia, HDL, LDL and hemocytin between the creatine supplement group and the ginseng supplement group. Therefore, the role of ginseng supplement in reducing blood ammonia and homocysteine and in increasing HDL was more than that of creatine supplement, and the role of creatine supplement in reducing LDL was more than that of ginseng supplement. So it can be concluded that the role of ginseng supplement in the changes of blood ammonia, homocysteine and HDL is more than the role of creatine supplement.

Modifiable risk factors for incident dementia and cognitive impairment: An umbrella review of evidence

BackgroundDementia and cognitive impairment can be attributed to genetic and modifiable factors. Considerable evidence emerged in modifiable factors and urgently requires standardized evaluation. We conducted an umbrella review to evaluate the strength and validity of the existing evidence. MethodsWe searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors. For each association, we analyzed the summary effect size, 95 % confidence interval, 95 % prediction interval, heterogeneity, small study effect and excess significance bias. Mendelian randomization studies were descriptively reviewed further exploring the causality of the associations. ResultsIn total, 12,015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, BMI, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for that of midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified causal relationships of education and plasma glucose with Alzheimer's disease. LimitationsLow quality of the studies included. ConclusionsModifiable risk factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Our results support a valuable rationale for future experimental designs to establish further evidence for the associations in larger populations.