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Frontiers in Endocrinology 2024The effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of...
INTRODUCTION
The effects of vitamin B12 metabolism on musculoskeletal health and the exact mechanism have not been fully determined. Our study aimed to assess the association of vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults.
METHODS
The data from the National Health and Nutrition Examination Survey 2001-2002 were used to investigate the effects of serum vitamin B12 and its biomarkers (homocysteine and methylmalonic acid) on skeletal muscle health. Bone mineral density (BMD), lean mass, gait speed and knee extensor strength were used as indicators for musculoskeletal health.
RESULTS
Serum vitamin B12 level was positively correlated with the total and appendicular lean mass (β = 584.83, = 0.044; β = 291.65, = 0.043) in older adults over 65 years of age. In the full population, plasma homocysteine was associated with total lean mass, appendicular lean mass, gait speed, and knee extensor strength (all < 0.05). Among older adults over 65 years of age, homocysteine level was significantly negatively correlated with gait speed and knee extensor strength (β = -12.75, = 0.019; β = -0.06, 0.001). Plasma methylmalonic acid was negatively associated with total BMD and femur BMD in the full population (β = -0.01, = 0.018; β = -0.01, = 0.004). In older adults, methylmalonic acid significantly affected total BMD, femur BMD and knee extensor strength (β = -0.01, = 0.048; β = -0.01, = 0.025; β = -7.53, = 0.015).
CONCLUSIONS
Vitamin B12 and its biomarkers are closely related to BMD, body composition, muscle strength and physical function in middle-aged and older adults. Vitamin B12 may be an important indicator of musculoskeletal health in the elderly.
Topics: Humans; Vitamin B 12; Aged; Female; Male; Biomarkers; Middle Aged; Bone Density; Homocysteine; Methylmalonic Acid; Muscle Strength; Muscle, Skeletal; Nutrition Surveys; Body Composition; Cross-Sectional Studies; Aged, 80 and over
PubMed: 38808112
DOI: 10.3389/fendo.2024.1387035 -
International Journal of Molecular... May 2024Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at... (Review)
Review
Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.
Topics: Humans; Coronary Artery Disease; Thrombophilia; Thrombosis; Factor V; Prothrombin; Plasminogen Activator Inhibitor 1; Risk Factors; Genetic Predisposition to Disease; Mutation
PubMed: 38791267
DOI: 10.3390/ijms25105228 -
Biomedicines May 2024In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in... (Review)
Review
In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.
PubMed: 38791047
DOI: 10.3390/biomedicines12051085 -
Heliyon May 2024This study aimed to investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and early neurological deterioration (END) in...
OBJECTIVE
This study aimed to investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) and any possible interactions between specific MTHFR alleles and traditional risk factors among a Han Chinese cohort.
METHODS
434 AIS patients were consecutively recruited between January 2017 and June 2019, including 129 END and 305 non-END cases. A candidate gene association study design was used to analyze the association between MTHFR gene polymorphism and END risk. The polymerase chain reaction-restriction fragment length polymorphism (RFLP) method was employed to genotype the MTHFR C677T polymorphism. The interactional analyses were performed using the multifactor dimensionality reduction test.
RESULTS
Hyperglycemia (odds ratio [OR]: 2.410, 95 % confidence interval [CI]: 1.436-4.046, p = 0.001), neurological function impairment (NIHSS score >5) (OR: 2.158, 95%CI: 1.337-3.484, = 0.002) on admission, and hyperhomocysteinemia (HHcy) (OR: 2.570, 95%CI: 1.229-5.376, = 0.012) were independently associated with END. The TT genotype (OR: 1.710, 95%CI: 1.021-2.863, p = 0.043) and T allele (OR: 1.710, 95%CI: 1.021-2.863, p = 0.043) of this C677T polymorphism were associated with susceptibility to END, and the TT genotype was more common in the subjects with HHcy (OR: 2.525, 95%CI: 1.111-5.739, P = 0.023). In addition, we also found interactions for END risk between the C677T polymorphism and traditional risk factors for END, including: hyperglycemia on admission, drinking, and moderate to severe neurological deficits (OR 1.237, 95 % CI 0.227-6.734), although the results were not statistically significant (p = 0.806).
CONCLUSIONS
Our results show a possible association between MTHFR C677T polymorphism and gene-environment interactions with END susceptibility in a Han Chinese cohort.
PubMed: 38784530
DOI: 10.1016/j.heliyon.2024.e31003 -
Annals of Indian Academy of Neurology 2024Cerebral venous sinus thrombosis (CVST) is a rare, treatable cause of stroke. Even though CVST has an established medical treatment, 15% of patients remain refractory to...
BACKGROUND
Cerebral venous sinus thrombosis (CVST) is a rare, treatable cause of stroke. Even though CVST has an established medical treatment, 15% of patients remain refractory to treatment. These patients may be candidates for endovascular treatment (EVT), yet the selection of patients remains a challenge. The study aims to understand the profile and outcome of patients treated with EVT and the type of procedure associated with good outcomes.
METHODS
This is a single-center, retrospective analysis of CVST patients who underwent EVT from 2009 till 2022. Patients who received only medical management were excluded. Modified Rankin Scale (mRS) ≤2 at 3 months was taken as the primary outcome. Secondary outcomes assessed were hospital stay, death, recurrence, mRS ≤ 2 at discharge, and angiographic recanalization.
RESULTS
Fifty-two patients were included. Twenty-eight (53.8%) were males; the mean age was 33.3 ± 12.3 years. Headache ( = 44, 84.6%) predominated among the symptoms. The common risk factors were anemia ( = 13, 25.5%) and hyperhomocysteinemia ( = 13, 25.5%). Worsening of sensorium ( = 21, 40.3%) and non-improvement of symptoms ( = 15, 28.8%) were the common indications for the procedure. Twenty-five (48.1%) people underwent thrombolysis (IST). Death occurred in eight (15.3%) patients. Thirty-six (73.5%; 36/49) patients had a good outcome at 3 months. IST had a significantly better outcome (mRS ≤ 2, = 20, 80%) compared to other procedures ( = 0.04). Hospital stay was lesser in the IST subgroup, but without statistical significance. Midline shift >5 mm (odds ratio [OR] 6.8 [1.5-30.9], = 0.01) and Glasgow Coma Scale <9 before the procedure (OR 27.2 [3.1-236.4], = 0.002) predicted bad outcomes at 3 months. Female gender (OR 4.5 [1.07-8.8], = 0.03), presence of altered sensorium (OR 10.2 [1.2-87.5], = 0.01), encephalopathic syndrome ( = 0.02), presence of parenchymal bleed (OR 3.7 [0.9-4.5], = 0.04), and midline shift (OR 4.8 [1.1-20.2], = 0.03) were associated with poor outcome at discharge.
CONCLUSION
EVT yielded good outcomes in carefully selected, medically refractory patients of CVST. IST performed well compared to other procedures.
PubMed: 38751919
DOI: 10.4103/aian.aian_965_23 -
Neurochemistry International May 2024High levels of blood homocysteine (HCy), a well-known cardiovascular risk factor and promoter of oxidative stress, have been associated with the incidence of cognitive...
High levels of blood homocysteine (HCy), a well-known cardiovascular risk factor and promoter of oxidative stress, have been associated with the incidence of cognitive impairment and dementia. Nonetheless, contrasting data are still present on its involvement in the progression from Mild Cognitive Impairment (MCI) to overt dementia. In this study we aimed to observe whether blood HCy level are associated with the evolution from MCI, divided into amnestic MCI (aMCI) and non-amnestic MCI (naMCI), to dementia. Blood HCy was measured in 311 MCI subjects (aMCI: 64%, naMCI: 36%) followed-up for a median of 33 months (range 10-155 months). At follow-up, 137 individuals converted to dementia (naMCI, n = 34; aMCI, n = 103). Based on HCy distribution, subjects in the highest tertile had a greater risk to convert to dementia compared to tertile I (Hazard Ratio (95% confidence interval): 2.25 (1.05-4.86); p = 0.04). aMCI subjects did not show increased risk to convert to dementia with increasing HCy concentration, but was significant in naMCI (p = 0.04). We observed a non-significant increase in the risk of progression to dementia from naMCI/low HCy (reference group, HCy cutoff value = 16 μmol/L) to naMCI/high HCy, but it was significant from aMCI/low HCy (HR: 2.73; 95%CI: 1.06-7.0; p:0.03), to aMCI/high HCy (HR: 3.24; 95%CI: 1.17-8.47; p:0.02). Our results suggest that HCy levels are associated with the progression from MCI to dementia. This association seems significant only for the naMCI group, indirectly supporting the notion that hyperhomocysteinemia damages the nervous system through its role as a vascular risk factor.
PubMed: 38723899
DOI: 10.1016/j.neuint.2024.105763 -
Neuropsychiatric Disease and Treatment 2024Cognitive impairment, a prevalent non-motor symptom in advanced Parkinson's disease (PD), has been associated with hyperhomocysteinemia, an important risk factor for PD...
BACKGROUND
Cognitive impairment, a prevalent non-motor symptom in advanced Parkinson's disease (PD), has been associated with hyperhomocysteinemia, an important risk factor for PD progression and cognitive decline in PD. However, evidence regarding the association between homocysteine (Hcy) and cognitive function during early PD remains insufficient. Therefore, this study aims to examine the correlation between Hcy levels and cognitive function in the early stage of PD.
METHODS
The study included 218 individuals in the early stages of PD who were consecutively admitted to the Suining Central Hospital Neurology Department. All the individuals completed the Parkinson's Disease Cognitive Rating Scale (PD-CDR). The Unified Parkinson's Disease Rating Scale part III (UPDRS-III) was employed for measuring the severity of motor symptoms, while the Hoehn-Yahr scale was used to measure the clinical symptom stage. Fasting venous blood samples were also drawn to measure the Hcy concentration, red blood cell folate, and vitamin B12.
RESULTS
In this cross-sectional study, 47 (21.5%) patients with PD showed cognitive dysfunction. The serum Hcy levels were significantly higher in the cognitive impairment PD (PDCI) group compared with the cognitive normal PD group (P<0.001). The Generalized Additive Model (GAM) analysis revealed a nonlinear relationship between Hcy and the risk of PDCI. Multiple logistic regression analyses demonstrated a positive relationship between elevated Hcy and the risk of PDCI in the fully adjusted model ([OR]:3.1, 95% CI, 1.1-8.5, P=0.028). Segmented linear regression analysis showed that when Hcy levels were above 17.7 umol/l, the risk of PDCI increased by 1.6 times for every 1 unit elevated in Hcy (95% CI:1.1-2.2, P=0.008).
CONCLUSION
This study revealed a nonlinear positive correlation between the risk of PDCI and elevated serum Hcy levels in early PD patients, suggesting hyperhomocysteinemia as one of the treatable factors for cognitive impairment in the early stages of PD.
PubMed: 38707522
DOI: 10.2147/NDT.S460938 -
Redox Biology Apr 2024In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and...
In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA β-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.
PubMed: 38696898
DOI: 10.1016/j.redox.2024.103139 -
Cureus Mar 2024Severe vitamin B12 deficiency presents a diagnostic challenge due to its diverse clinical manifestations, which can mimic serious hematologic disorders such as...
Severe vitamin B12 deficiency presents a diagnostic challenge due to its diverse clinical manifestations, which can mimic serious hematologic disorders such as thrombotic thrombocytopenic purpura (TTP) or leukemia. The case we present here illustrates the unique characteristics of severe B12 deficiency, highlighting key differentiators from other conditions, including decreased reticulocyte counts and markedly elevated lactate dehydrogenase levels indicative of suppressed erythropoiesis. Advanced cobalamin deficiency affects all cell lines, leading to peripheral pancytopenia. Proposed mechanisms include fragile red blood cells prone to shearing, resulting in schistocyte formation, and hyperhomocysteinemia-induced oxidative stress exacerbating hemolysis. Prompt recognition and treatment with B12 replacement are critical, as illustrated by this case of hemolytic anemia and pancytopenia secondary to pernicious anemia, to prevent severe hematologic complications.
PubMed: 38690452
DOI: 10.7759/cureus.57286 -
Frontiers in Pharmacology 2024NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a... (Review)
Review
NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 inflammasome leads to the production of pro-inflammatory cellular contents, such as interleukin (IL)-1β and IL-18, and induction of inflammatory cell death known as pyroptosis, thereby amplifying or sustaining inflammation. While a balanced inflammatory response is beneficial for resolving damage and promoting tissue healing, excessive activation of the NLRP3 inflammasome and pyroptosis can have harmful effects. The involvement of the NLRP3 inflammasome has been observed in various cardiovascular diseases (CVD). Indeed, the NLRP3 inflammasome and its associated pyroptosis are closely linked to key cardiovascular risk factors including hyperlipidemia, diabetes, hypertension, obesity, and hyperhomocysteinemia. Exercise compared with medicine is a highly effective measure for both preventing and treating CVD. Interestingly, emerging evidence suggests that exercise improves CVD and inhibits the activity of NLRP3 inflammasome and pyroptosis. In this review, the activation mechanisms of the NLRP3 inflammasome and its pathogenic role in CVD are critically discussed. Importantly, the purpose is to emphasize the crucial role of exercise in managing CVD by suppressing NLRP3 inflammasome activity and proposes it as the foundation for developing novel treatment strategies.
PubMed: 38681198
DOI: 10.3389/fphar.2024.1368835