RESUMEN
Thiols function as antioxidants in food, prolonging shelf life and enhancing flavor. Moreover, thiols are vital biomolecules involved in enzyme activity, cellular signal transduction, and protein folding among critical biological processes. In this paper, the fluorescent probe PYL-NBD was designed and synthesized, which utilized the fluorescent molecule pyrazoline, the lysosome-targeted morpholine moiety, and the sensing moiety NBD. Probe PYL-NBD was tailored for the recognition of biothiols through single-wavelength excitation, yielding distinct fluorescence emission signals: blue for Cys, Hcy, and GSH; green for Cys, Hcy. Probe PYL-NBD exhibited rapid reaction kinetics (<10 min), distinct fluorescence response signals, and low detection limits (15.7 nM for Cys, 14.4 nM for Hcy, and 12.6 nM for GSH). Probe PYL-NBD enabled quantitative determination of Cys content in food samples and L-cysteine capsules. Furthermore, probe PYL-NBD had been successfully applied for confocal imaging with dual-channel detection of biothiols in various biological specimens, including HeLa cells, zebrafish, tumor sections, and Arabidopsis thaliana.
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Cisteína , Colorantes Fluorescentes , Análisis de los Alimentos , Glutatión , Lisosomas , Espectrometría de Fluorescencia , Pez Cebra , Humanos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Lisosomas/química , Lisosomas/metabolismo , Células HeLa , Cisteína/análisis , Animales , Análisis de los Alimentos/métodos , Glutatión/análisis , Espectrometría de Fluorescencia/métodos , Homocisteína/análisis , Arabidopsis/química , Límite de Detección , Microscopía ConfocalRESUMEN
Background: DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980âs, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369âpg/mL and homocysteine (tHcy) of 9.5µmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15µmol/L) predicted greater declines in cognitive function. Objective: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. Methods: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. Results: Baseline geometric mean B12 levels for these studies ranged from 484- 618âpg/ml and for tHcy ranged from 7.4- 10µmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcyâ>â15µmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. Conclusions: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.
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Homocisteína , Enfermedad de Parkinson , Vitamina B 12 , Humanos , Vitamina B 12/sangre , Homocisteína/sangre , Masculino , Femenino , Anciano , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/tratamiento farmacológico , Persona de Mediana Edad , Progresión de la Enfermedad , Antiparkinsonianos/uso terapéutico , Levodopa/administración & dosificación , Levodopa/farmacología , Suplementos Dietéticos , Disfunción Cognitiva/sangre , Disfunción Cognitiva/etiología , Disfunción Cognitiva/tratamiento farmacológicoRESUMEN
BACKGROUND: Biothiols are important for numerous cellular processes, such as resisting oxidative stress and protecting cell health. Their abnormal levels and molecular configurations have been associated with various diseases. So, establishing an effective and reliable method for the specific detection and enantiomeric discrimination of diverse biothiols is highly meaningful. RESULTS: We have developed a new NMR and CD probe using 1,4-dinitroimidazole, specifically targeting the thiol group. This probe allows for the specific detection and enantiomeric recognition of biothiols in complex mixtures. We achieved this by identifying the distinguishable 1H NMR signals of 2nd in imidazole-ring of the resulting 4NI-biothiols in the downfield region at 7-8 ppm and newly discovered induced CD signals within 290-430 nm. Using this probe, the limits of detection of Cys, GSH, and Hcy, the recovery rates, and the concentration of GSH extracted from HEK293T cells were determined by measuring the unique downfield 1H NMR signals. Moreover, Cys, GSH, and Hcy can be discriminated simultaneously in complicated samples at a pH range of 2-3.5. Furthermore, this probe can also be utilized to sense chiral thiol-drugs. SIGNIFICANCE: This method offers a cost-effective and accurate sensing solution for the specific detection of biothiols in complex mixtures, with stereochemical recognition.
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Imidazoles , Compuestos de Sulfhidrilo , Humanos , Estereoisomerismo , Imidazoles/química , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/análisis , Células HEK293 , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Cisteína/análisis , Glutatión/análisis , Glutatión/química , Homocisteína/análisis , Límite de Detección , Estructura MolecularRESUMEN
l-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of l-homocysteinesulfinic acid (l-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities. Herein, the chemical synthesis of l-HCSA, from l-homocystine, was the starting point for establishing the bio-based synthesis of HHT using recombinant Escherichia coli glutamate decarboxylase (EcGadB), an enzyme already successfully employed for the bio-based synthesis of GABA and its phosphinic analog. Prior to HHT synthesis, kcat (33.92 ± 1.07) and KM (38.24 ± 3.45 mM) kinetic constants were determined for l-HCSA on EcGadB. The results of our study show that the EcGadB-mediated synthesis of HHT can be achieved with good yields (i.e., 40% following enzymatic synthesis and column chromatography). Purified HHT was tested in vitro on primary human umbilical vein endothelial cells and rat cardiomyoblasts and compared to the fully oxidized analog, homotaurine (OT, also known as tramiprosate), in widespread pharmaceutical use. The results show that both cell lines display statistically significant recovery from the cytotoxic effects induced by H2O2 in the presence of HHT.
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Escherichia coli , Glutamato Descarboxilasa , Homocisteína , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Humanos , Homocisteína/análogos & derivados , Homocisteína/metabolismo , Glutamato Descarboxilasa/metabolismo , Glutamato Descarboxilasa/genética , Proteínas Recombinantes/metabolismo , CinéticaRESUMEN
The bioavailability of natural folates is 50% lower than that of synthetic folic acid (FA); however, it remains unclear whether this value is universally applicable to all foods. Therefore, the present study investigated the bioavailability of folate from spinach using multiple biomarkers in a folate depletion-repletion mouse model. Mice were fed a folate-deficient diet for 4 wk and subsequently divided into three groups: folate-deficient, FA, and spinach folate. The folate repletion group received either FA or spinach folate at 2 mg/kg diet for 9 d. On the 7th day of repletion, half of each group underwent low-dose total body X-ray irradiation to induce chromosomal damage in bone marrow. Folate bioavailability biomarkers included measurements of folate levels in plasma, liver, and bone marrow along with an analysis of plasma homocysteine levels and chromosome damage, both of which are functional biomarkers of body folate. The consumption of a folate-deficient diet led to decreased tissue folate levels, increased plasma homocysteine levels, and chromosomal damage. Repletion with spinach folate restored folate levels in plasma, liver, and bone marrow to 69, 13, and 68%, respectively, of FA levels. Additionally, spinach folate repletion reduced plasma homocysteine levels and chromosome damage to 83% and 93-117%, respectively, of FA levels. Collectively, the present results demonstrated that the bioavailability of spinach folate exceeded 83% of FA, particularly when assessed using functional biomarkers.
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Disponibilidad Biológica , Biomarcadores , Deficiencia de Ácido Fólico , Ácido Fólico , Homocisteína , Hígado , Spinacia oleracea , Animales , Spinacia oleracea/química , Ácido Fólico/sangre , Biomarcadores/sangre , Deficiencia de Ácido Fólico/metabolismo , Hígado/metabolismo , Ratones , Masculino , Homocisteína/sangre , Homocisteína/metabolismo , Médula Ósea/metabolismo , Dieta , Modelos Animales de EnfermedadRESUMEN
AIM: Hyperhomocysteine has been recognized as an independent risk factor of multiple diseases, including several eye diseases. In this study, we aim to investigate whether increased homocysteine (Hcy) is related to cataracts, and to explore whether dysregulation of mTOR-mediated autophagy and connexin expression are underlying mechanisms. METHOD: We first developed a method of liquid chromatography tandem mass spectrometry to accurately measure serum concentrations of Hcy in 287 cataract patients and 334 healthy controls. Next, we treated human lens epithelial (HLC-B3) cells with Hcy at different concentrations and durations, and then analyzed expression of autophagy-related markers and connexins, as well as phosphorylated mTOR (p-mTOR) in these cells by Western blotting. Formation of autophagic vacuoles and intracellular Ca2+ in the Hcy-treated cells were observed by fluorescence microscopy. Further, we performed a rescue experiment in the Hcy-treated HLC-B3 cells by pre-incubation with rapamycin, an mTOR inhibitor. RESULTS: The serum levels of Hcy in patients with cataracts were significantly increased compared to those in healthy controls. In cultured HLC-B3 cells, expression of autophagy related markers (LC3B and Beclin1) and connexins (Cx43 and Cx50) was inhibited by Hcy treatment in a dose- and duration-dependent manner. Accumulation of Ca2+ in the Hcy-treated lens epithelial cells was observed as a consequence of reduced connexin expression. Meanwhile, expression of p-mTOR increased, representing up-regulation of the mTOR pathway. Importantly, inhibition of autophagy and connexin expression due to hyperhomocysteine was rescued via mTOR suppression by pretreatment with rapamycin in HLC-B3 cells. CONCLUSION: Our results demonstrate that hyperhomocysteine might promote cataract development through two mTOR-mediated pathways in the lens epithelial cells: 1) dysregulation of autophagy and 2) accumulation of intracellular calcium via decreased connexin expression.
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Autofagia , Catarata , Conexinas , Homocisteína , Cristalino , Serina-Treonina Quinasas TOR , Humanos , Catarata/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Autofagia/efectos de los fármacos , Homocisteína/sangre , Masculino , Persona de Mediana Edad , Femenino , Conexinas/metabolismo , Cristalino/metabolismo , Cristalino/efectos de los fármacos , Línea Celular , Calcio/metabolismo , Anciano , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Conexina 43/metabolismo , Adulto , Beclina-1/metabolismoRESUMEN
Hyperhomocysteinemia or high levels (> 15 µmol/L) of homocysteine (Hcy)in the blood has been suggested to affect the brain through vascular and neurodegenerative pathways and potentially impact cognition. The current study aims to explore the association of high homocysteine with cognition and brain volume changes in a cohort of middle and old agedr adults. The study recruited 1296 participants aged ≥ 45 years from Tata Longitudinal Study of Ageing (TLSA), an ongoing cohort study. The participants underwent detailed cognitive assessments using Addenbrooke's Cognitive Examination-III (ACE-III) and Computerized Assessment of Adult Information Processing (COGNITO) neuropsychological battery and MR imaging using a 3T scanner. The participants were classified based on the median homocysteine level (16.89 µmol/L) into low Hcy (≤ median) and high Hcy (> median) groups. When adjusted for age, gender, years of education, vitamin B12, folate and dyslipidaemia, Generalised Linear Model (GLM) found a significant association of high Hcy with vocabulary task [ß (95% CI) - 1.354 (- 2.655, - 0.052); p = 0.041]. Significant associations was also obtained between cerebral white matter volume and high Hcy [ß (95% CI) - 5617.182 (- 11062.762, - 173.602); p = 0.043]. The results suggest that people with high Hcy levels performed poorer in cognitive tasks related to language domain and had lesser cerebral white matter volume. This indicates that homocysteine might have a profound impact on brain structure as well as function.
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Envejecimiento , Cognición , Homocisteína , Hiperhomocisteinemia , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Envejecimiento/fisiología , Homocisteína/sangre , Cognición/fisiología , Imagen por Resonancia Magnética , Lenguaje , Estudios Longitudinales , Pruebas Neuropsicológicas , Sustancia Blanca/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismoRESUMEN
BACKGROUND: Hyperhomocysteinemia can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorders; however, hypohomocysteinemia is generally not considered harmful. This study aimed to evaluate the relationship between all levels of homocysteine, both low and high homocysteine levels, and the risk of all-cause and cause-specific mortality in adult Korean men. METHODS: Adult Korean men (n = 221,356) were categorized into quintiles based on their homocysteine levels. The primary endpoints were all-cause, CVD, cancer, and dementia mortality. Hazard ratios were calculated using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further explored using restricted cubic spline models. RESULTS: Compared with the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L). This association was not observed in the vitamin supplementation subgroup. CONCLUSION: Among Korean adult men, both low and high homocysteine levels increased the risk of all-cause and CVD mortality, indicating a U-shaped relationship. However, this relationship was not statistically significant with vitamin supplementation, suggesting a potential protective role for vitamins.
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Enfermedades Cardiovasculares , Homocisteína , Humanos , Masculino , Homocisteína/sangre , República de Corea/epidemiología , Persona de Mediana Edad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Adulto , Estudios de Cohortes , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/mortalidad , Factores de Riesgo , Causas de Muerte , Modelos de Riesgos Proporcionales , Anciano , Neoplasias/mortalidad , Neoplasias/sangreRESUMEN
BACKGROUND: Cross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults. METHODS: Longitudinal data [Visit 1 (2004-2009) and Visit 2 (2009-2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits. Overall, sex- and race-stratified associations were evaluated using mixed-effects linear regression models, adjusting for key potential confounders. Interaction effects between Hcy and serum levels of folate and vitamin B-12 were also tested. RESULTS: We found that greater LnHcyv1 was significantly associated with poorer baseline attention based on higher Loge (TRAILS A, in seconds) [ß (SE): 0.101 (0.031), P = 0.001]. Heterogeneity was also found by sex and by race. Most notably, among men only, LnHcyv1 was associated with faster decline on the BVRT (# of errors), a measure of visuo-spatial memory (ß (SE): 0.297(0.115), P = 0.010, reduced model); while among African American adults only, an elevated and increasing LnHcy over time was associated with faster rate of decline on Loge (TRAILS B, in seconds) [ß (SE): +0.012 (0.005), p = 0.008], a measure of executive function. Interactions between Hcy, folate and vitamin B-12 blood exposures were also detected. CONCLUSIONS: In summary, sex- and race-specific adverse association between elevated Hcy and cognitive performance over time were detected among middle-aged urban adults, in domains of attention, visuo-spatial memory and executive functioning.
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Cognición , Ácido Fólico , Homocisteína , Población Urbana , Vitamina B 12 , Humanos , Masculino , Femenino , Homocisteína/sangre , Estudios Longitudinales , Persona de Mediana Edad , Cognición/fisiología , Población Urbana/estadística & datos numéricos , Anciano , Vitamina B 12/sangre , Ácido Fólico/sangre , Pruebas Neuropsicológicas/estadística & datos numéricos , Atención/fisiología , Función Ejecutiva/fisiología , Factores Sexuales , Estudios TransversalesRESUMEN
Homocysteine, methionine, methylmalonic acid and 2-methylcitric acid are clinically relevant markers in the methionine, propionate, and cobalamin metabolism. This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously determining total homocysteine, methionine, methylmalonic acid and 2-methylcitric acid in dried blood spots. Three 3.2 mm discs were punched from each calibrator, quality control, and sample dried blood spot into a 96-well U-plate. Each sample was spiked with internal standards and extracted. Then the supernatant was transferred to another 96-well U-plate. After nitrogen drying, the dried residues were reconstituted, centrifuged, and the resulting supernatant was transferred to another 96-well plate for analysis. The method was performed using UPLC-MS/MS within 3 min, validated according to guidance documents, and applied to 72 samples from confirmed patients with methionine, propionate, and cobalamin metabolism disorders. The UPLC-MS/MS method provided satisfactory separation of the four analytes. The R2 values were ≥ 0.9937 for all analytes. The recoveries ranged from 94.17 to 114.29 %, and the coefficients of variation for intraday and interday precision were 0.19 % to 5.23 % and 1.02 % to 6.89 %, respectively. No significant carry-over was detected for the four analytes, and most of confirmed samples exhibited biomarker patterns characteristic of the relevant disorders. A simple and fast UPLC-MS/MS method was successfully developed, validated, and applied to clinical samples for the simultaneous determination of total homocysteine, methionine, methylmalonic acid, and 2-methylcitric acid in dried blood spots.
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Citratos , Pruebas con Sangre Seca , Homocisteína , Límite de Detección , Metionina , Ácido Metilmalónico , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Homocisteína/sangre , Homocisteína/análogos & derivados , Ácido Metilmalónico/sangre , Ácido Metilmalónico/análogos & derivados , Pruebas con Sangre Seca/métodos , Reproducibilidad de los Resultados , Metionina/sangre , Metionina/análogos & derivados , Metionina/química , Modelos Lineales , Citratos/sangre , Citratos/química , Masculino , Femenino , PreescolarRESUMEN
Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer's disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to a protein's function and biological integrity, Hcy-thiolactone-detoxifying enzymes-PON1, BLMH, BPHL-have evolved. This narrative review provides an account of the biological function of these enzymes and of the consequences of their impairments, leading to the phenotype characteristic of AD. Overall, accumulating evidence discussed in this review supports a hypothesis that Hcy-thiolactone contributes to neurodegeneration associated with a dysregulated Hcy metabolism.
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Enfermedad de Alzheimer , Homocisteína , Humanos , Enfermedad de Alzheimer/metabolismo , Homocisteína/metabolismo , Homocisteína/análogos & derivados , Animales , Hiperhomocisteinemia/metabolismoRESUMEN
A disturbance in the metabolism of homocysteine in both the mother and the fetus has been implicated in several placental vasculopathy-related disorders, including pregnancy loss. This study aimed to provide insights into the potential role of homocysteine, Vitamin B12, and folic acid in early pregnancy losses, with a specific focus on the Turkish population. The results of 93 pregnant women who experienced miscarriage between 5 and 14 gestational weeks and 93 healthy pregnant women at the same gestational weeks were compared. The demographic and pregnancy characteristics of all pregnant women were recorded. Vitamin B12, folic acid, and homocysteine levels were measured in serum samples obtained from the groups at similar gestational weeks. In addition, any associations between these biomarkers and different types of pregnancy loss, such as spontaneous abortion and missed abortion, were evaluated. Vitamin B12 and folic acid serum levels were significantly lower in women with miscarriages (Pâ =â .019, Pâ <â .001, respectively). Homocysteine levels were higher in the patient group (Pâ <â .001). Logistic regression analysis showed that a higher homocysteine level was the only predictive factor of miscarriage (Pâ =â .001, odds ratioâ =â 0.596); however, folic acid and Vitamin B12 were not predictive factors. There was no significant difference in homocysteine and micronutrient levels between women with missed abortions and women with spontaneous abortions (Pâ >â .05). Our results support the continuing evidence of a link between maternal homocysteine levels and fetal loss. However, in exploring the shared pathways in the underlying mechanisms causing the 2 forms of pregnancy loss, maternal blood analysis showed no relationship.
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Aborto Espontáneo , Ácido Fólico , Homocisteína , Hiperhomocisteinemia , Vitamina B 12 , Humanos , Femenino , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/epidemiología , Embarazo , Adulto , Ácido Fólico/sangre , Vitamina B 12/sangre , Estudios Retrospectivos , Aborto Espontáneo/epidemiología , Aborto Espontáneo/sangre , Homocisteína/sangre , Estudios de Casos y Controles , Turquía/epidemiología , Biomarcadores/sangre , Centros de Atención TerciariaRESUMEN
BACKGROUND AND OBJECTIVE: Cerebral small vessel disease (CSVD) often coexists with cognitive dysfunction in patients, leading to significant challenges in treatment and management. This study aimed to examine the efficacy of combined application of donepezil and nimodipine on patients with comorbid CSVD and cognitive dysfunction and the effects on patients' albumin and prealbumin levels. METHODS: The records of 112 patients with comorbid CSVD and cognitive dysfunction treated at the People's Hospital of Suzhou New District from January 2019 to December 2022 were analysed retrospectively. A total of 50 patients receiving donepezil were allocated to the control group, and 62 patients receiving both nimodipine and donepezil to the study group. Outcomes compared between the two groups included serum homocysteine (Hcy), high sensitivity C-reactive protein (hs-CRP), albumin, and prealbumin before and after therapy, efficacy, and adverse reactions. Additionally, logistic regression was performed to analyze the risk factors impacting patient prognosis. RESULTS: Prior to therapy, the two groups did not differ significantly in Hcy and hs-CRP levels (p > 0.05), whereas after therapy, the levels in both groups dropped significantly (p < 0.01), with more obvious lower levels in the study group (p < 0.05). After treatment, the study group presented significantly higher albumin and prealbumin levels than the control group (p < 0.001). An obvious higher overall response rate was observed in the study group compared to the control group (p = 0.012). No significant inter-group discrepancy was found regarding the total incidence of adverse reactions (p = 0.752). Univariate analysis identified age, course of disease, heart rate (HR), Montreal Cognitive Assessment (MoCA) score, diastolic blood pressure (DBP), systolic blood pressure (SBP), drinking history, as well as medication regimen as risk factors impacting patient prognosis. Multivariate logistic regression analysis identified SBP, DBP, and medication regimen as the independent risk factors. CONCLUSION: Combined application of donepezil and nimodipine can effectively treat patients with comorbid CSVD and cognitive dysfunction. It can significantly lower the Hcy and hs-CRP levels and improve the nutritional status without increasing the frequency of adverse reactions. In addition, for CSVD patients with cognitive dysfunction, age, course of disease, MoCA score, HR, SBP, DBP, drinking history, and medication regimen are risk factors impacting patient prognosis, while SBP, DBP, and medication regimen are independent risk factors.
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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Donepezilo , Quimioterapia Combinada , Nimodipina , Estado Nutricional , Humanos , Femenino , Masculino , Donepezilo/administración & dosificación , Donepezilo/uso terapéutico , Enfermedades de los Pequeños Vasos Cerebrales/tratamiento farmacológico , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Disfunción Cognitiva/tratamiento farmacológico , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Nimodipina/administración & dosificación , Nimodipina/uso terapéutico , Resultado del Tratamiento , Nootrópicos/administración & dosificación , Nootrópicos/uso terapéutico , Nootrópicos/efectos adversos , Homocisteína/sangreRESUMEN
Atherosclerosis, the leading cause of cardiovascular disease, cannot be sufficiently explained by established risk factors, including cholesterol. Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis and is closely linked to cardiovascular mortality. However, its role in atherosclerosis has not been fully clarified yet. We have previously shown that rabbits fed a diet deficient in B vitamins and choline (VCDD), which are required for Hcy degradation, exhibit an accumulation of macrophages and lipids in the aorta, aortic stiffening and disorganization of aortic collagen in the absence of hypercholesterolemia, and an aggravation of atherosclerosis in its presence. In the current study, plasma Hcy levels were increased by intravenous injections of Hcy into balloon-injured rabbits fed VCDD (VCDD+Hcy) in the absence of hypercholesterolemia. While this treatment did not lead to thickening of aortic wall, intravenous injections of Hcy into rabbits fed VCDD led to massive accumulation of VLDL-triglycerides as well as significant impairment of vascular reactivity of the aorta compared to VCDD alone. In the aorta intravenous Hcy injections into VCDD-fed rabbits led to fragmentation of aortic elastin, accumulation of elastin-specific electron-dense inclusions, collagen disorganization, lipid degradation, and autophagolysosome formation. Furthermore, rabbits from the VCDD+Hcy group exhibited a massive decrease of total protein methylated arginine in blood cells and decreased creatine in blood cells, serum and liver compared to rabbits from the VCDD group. Altogether, we conclude that Hcy contributes to atherogenic transformation of the aorta not only in the presence but also in the absence of hypercholesterolemia.
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Aorta , Aterosclerosis , Homocisteína , Hipercolesterolemia , Animales , Conejos , Aterosclerosis/patología , Aterosclerosis/metabolismo , Homocisteína/sangre , Aorta/patología , Aorta/metabolismo , Hipercolesterolemia/sangre , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Masculino , Colina/administración & dosificación , Modelos Animales de Enfermedad , Elastina/metabolismo , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/farmacologíaRESUMEN
Abnormal homocysteine (Hcy) levels in human serum have been associated with serious or vital diseases, making the reliable and easy detection of Hcy important to clinical analysis and biological study. In this work, five phosphorescent Ir(C^N)2(N^N) complexes (Irn) having aldehyde group were synthesized as probes (C^N and N^N denoted ligands). A discussion was conducted on their molecular structure, electronic structure, photophysical parameters, and Hcy sensing ability, revealing the correlations between their molecular structures and performances. Irn emission was enhanced (by â¼ two folds) and blue-shifted (by 100 nm) after meeting Hcy (free state), via a cyclization reaction between the -CHO group (from Irn) and Hcy. In addition, using RE(BTC) as a supporting material (RE = Tb and Eu), the Ir(III) probe was loaded onto a supporting material of RE(BTC) (H3BTC = 1, 3, 5-benzenetricarboxylic acid). The emission color was changed by increasing Hcy concentration. Straight working curves were obtained with LOD (limit of detection) of 1.9 µM and a response time of â¼200 s. The novelty of this work was the combination of Irn with RE(BTC), which offered enhanced and blue-shifted emission upon Hcy via a cyclization reaction. This demonstrated a high level of sensitivity towards homocysteine detection.
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Europio , Colorantes Fluorescentes , Homocisteína , Espectrometría de Fluorescencia , Terbio , Homocisteína/sangre , Homocisteína/análisis , Humanos , Europio/química , Terbio/química , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Límite de DetecciónRESUMEN
Objective:To analyze the related influencing factors of epistaxis in extremely high altitude area, and to provide evidence for the prevention and treatment of epistaxis in extremely high altitude area. Methods:From January 2021 to December 2022, 206 outpatients with epistaxis, 54 inpatients with epistaxis and 69 inpatients withoutepistaxis in theDepartment of Otorhinolarygology, Naqu People's Hospital were collected. The previous history, drinking history, smoking history, serum homocysteineï¼Hcyï¼, white blood cell countï¼WBCï¼, red blood cell countï¼RBCï¼, hematocritï¼HCTï¼, hemoglobinï¼HGBï¼ and mean hemoglobin concentrationï¼MCHCï¼ were compared between inpatients with or without epistaxis. The factors with significant differences were analyzed by binary Logistic regression. The monthly average temperature,air pressure, humidity and 2-minute wind speed were collected from January 2021 to December 2022 in Naqu City to analyze the correlation between epistaxis and climate factors. Results:The number of patients with hypertension in the case group was more than that in the control group, and the difference was significantï¼P=0.013ï¼. Serum Hcy level in the case group was higher than that in the control groupï¼P<0.001ï¼. RBC, HCT, HGB and MCHC were lower than that in the control groupï¼P=0.001, 0.001, 0.001, 0.039ï¼, and the difference was significant. History of hypertension and Hcy were risk factors for epistaxis. Patients with a history of hypertension were 3.713 times more likely to suffer from epistaxis than those without a history of hypertensionï¼P=0.022ï¼. Each 1 increase in Hcy concentration increased the risk of epistaxis by 13.1%ï¼P=0.001ï¼. Conclusion:Patients with epistaxis in Naqu area had higher serum Hcy level and lower RBC, HCT, HGB and MCHC. History of hypertension and Hcy were risk factors for epistaxis. Patients with a history of hypertension were 3.713 times more likely to suffer from epistaxis than those without a history of hypertension. Every 1 increase in Hcy concentration increased the risk of epistaxis by 13.1%. Active intervention of hypertension and serum Hcy can effectively prevent the incidence of epistaxis.
Asunto(s)
Altitud , Epistaxis , Homocisteína , Humanos , Epistaxis/sangre , Epistaxis/etiología , Homocisteína/sangre , Masculino , Femenino , Persona de Mediana Edad , Hipertensión/sangre , Hipertensión/epidemiología , Clima , Factores de Riesgo , AdultoRESUMEN
BACKGROUND: Cyanocobalamin or B12 deficiency is common in the Indian population, and responsible for anemia. Various clinical manifestations include central nervous system and cardiovascular manifestations, secondary to a rise in serum homocysteine levels. METHOD AND PATIENTS: In a routine outpatient department at Bawaskar Hospital and Clinical Research Centre, Mahad, patients with suspected clinical signs and symptoms suggestive of cyanocobalamin deficiency were studied in detail regarding their dietary habits, serum hemoglobin, B12, and homocysteine levels. FINDINGS: A total of 1,992 (female 1,009, 50.75%) were clinically examined in detail. Of these, 945 (49.94%), 999 (50.17%), and 48 (2.40%) were strict vegetarians, both vegetarian and nonvegetarian, and strict nonvegetarians, respectively. Common occupations associated with B12 deficiency include 666 (33.4%) housewives, 396 (19.9%) service workers, 316 (15.9%) businesspeople, 180 (9%), and 198 (9.9%) retired and industrial populations, respectively. Clinical manifestations include recurrent scalp hair loss in 268 (13.5%), poor memory in 240 (12%), tingling and numbness in 200 (10%), and generalized weakness in 387 (19.4%) patients. Additionally, 541 (27.15%) patients had pigmentation of the nail bed, knuckles, oral mucosa, and tongue, while 237 (10.81%) suffered from hypertension and ischemic heart disease. During the process of preparation of vegetarian and nonvegetarian food, there is a 30-48% reduction in vitamin content. Supplementation of vitamin by adding table salt to food on a plate at the time of eating improves the vitamin level in the blood. CONCLUSION: In the absence of laboratory investigations in rural settings, clinical signs and symptoms are helpful in detecting B12 deficiency. Directly adding vitamin powder, similar to table salt, to cooked food on the plate improved blood vitamin levels.
Asunto(s)
Suplementos Dietéticos , Deficiencia de Vitamina B 12 , Vitamina B 12 , Humanos , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/epidemiología , India/epidemiología , Femenino , Masculino , Vitamina B 12/sangre , Vitamina B 12/administración & dosificación , Adulto , Población Rural , Persona de Mediana Edad , Homocisteína/sangre , Hemoglobinas/análisis , Adulto Joven , Dieta Vegetariana/efectos adversosRESUMEN
BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke. Acquired and inherited prothrombotic conditions are the most common risk factors for CVST. Sometimes, an etiology is not found. Wide utilization of next generation sequencing technologies in clinical practice may lead to identification of risk factors other than those classically associated with CVST. METHOD AND RESULTS: This retrospective clinical-laboratory observational study has a reference patient who presented with CVST as an adolescent. Work up for prothrombotic conditions showed high homocysteine level secondary to homozygosity for a common polymorphism, c.677 C > T in the methylenetetrahydrofolate reductase (MTHFR) gene. His older unaffected brother has a similar MTHFR genotype and high homocysteine. The whole exome sequencing revealed a likely pathogenic variant in the sodium voltage gated channel, alpha subunit 1(SCN1A) gene. CONCLUSION: CVST is a multifactorial disease. Prothrombotic conditions are the most common risk factors for CVST. High homocysteine due to the common MTHFR polymorphisms was previously attributed to various thrombotic conditions including CVST. Although high homocysteine due to MTHFR polymorphism may be a contributing factor, additional risk factors such as blood flow abnormalities during SCN1A related seizures may be needed for thrombosis.
Asunto(s)
Metilenotetrahidrofolato Reductasa (NADPH2) , Canal de Sodio Activado por Voltaje NAV1.1 , Trombosis de los Senos Intracraneales , Humanos , Trombosis de los Senos Intracraneales/genética , Masculino , Canal de Sodio Activado por Voltaje NAV1.1/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Adolescente , Estudios Retrospectivos , Predisposición Genética a la Enfermedad , Factores de Riesgo , Homocisteína/sangre , Secuenciación del Exoma/métodos , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Hyperhomocysteinaemia (elevated blood levels of the amino acid homocysteine) attracted the interest of researchers in the middle of the 20th century. At first. Butz and du Vigneaud in 1932 described a disorder of methionine metabolism in children, which was manifested by homocysteinuria (homocysteine is not normally detected in the urine). In 1962 Cavon and Neil found that homocysteinuria in children is associated with a defect in cystathione-B-synthase and manifests early development of atherosclerosis. It is quite possible that these facts would have remained unnoticed by the medical community had it not been for further research by Kilmer McQuilley, a professor in the Department of Pathology at Harvard Medical School. The scientist suggested that while high concentrations of homocysteine could damage blood vessels in young people, it was likely that lower concentrations of homocysteine, acting over a longer period of time, could cause cardiovascular disease in adults. Subsequent studies enabled him to formulate the "homocysteine" theory of atherosclerosis and to publish its main points in 1969. Hyperhomocysteinaemia in young men has been shown to cause damage to the endothelium of blood vessels, and consequently males face the consequent equally global problem of developing erectile dysfunction. Erection is a state regulated by a neurovascular process, characterized by blood filling of the cavernous bodies, provided by neural and humoral mechanisms occurring at different levels of the nervous system. Erectile dysfunction (ED) refers to the inability to achieve and maintain an erection at a level necessary to ensure satisfactory sexual intercourse, Although ED is not life-threatening. it is a serious psychological and physiological problem, and it has now been shown to correlate the quality of intimate life with general health and even with life expectancy, In the USA alone, ED is reported in 20-30 million men, and the prevalence of these disorders increases with age. A study of the homocysteine level of multidisciplinary hospital patients was used as the main marker. The work used laboratory and statistical research methods, as well as analysis and synthesis methods. Using patient analyses, laboratory and statistical data, it has been shown that hyperhomosysteinaemia is one of the molecular mechanisms in the development of erectile dysfunction.
Asunto(s)
Disfunción Eréctil , Homocisteína , Hiperhomocisteinemia , Humanos , Hiperhomocisteinemia/complicaciones , Masculino , Disfunción Eréctil/etiología , Homocisteína/sangreRESUMEN
Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P < 0.05). Multivariable logistic regression analysis indicated that hypertension (odds ratio [OR] 0.504; 95% confidence interval [CI] 0.279-0.911; P = 0.023), hyperlipidemia (OR 1.924; 95% CI 1.079-3.429; P = 0.027), and plasma Hcy levels (OR 1.420; 95% CI 1.277-1.578; P < 0.001) were independently associated with the rupture of small to medium-sized IAs, all with statistical significance (P < 0.05). Our study suggests that critical plasma Hcy levels are an independent risk factor for increased rupture risk in small to medium-sized intracranial aneurysms. Therefore, reducing plasma Hcy levels may be considered a valuable strategy to mitigate the risk of intracranial vascular abnormalities rupture and improve patient prognosis.