RESUMEN

BACKGROUND: Aging is a complex biological process that may be accelerated in certain pathological conditions. DNA methylation age (DNAmAge) has emerged as a biomarker for biological age, which can differ from chronological age. This research peels back the layers of the relationship between fast-forward aging and ischemic stroke, poking and prodding the potential two-way causal influences between stroke and biological aging indicators. METHODS: We analyzed a cohort of ischemic stroke patients, comparing DNAmAge with chronological age to measure age acceleration. We assessed variations in age acceleration among stroke subtypes and between sexes. Using Mendelian randomization, we examined the causal links between stroke, aging biomarkers like telomere length, and age acceleration's effect on stroke risk. RESULTS: Our investigation reveals a pronounced association between ischemic stroke and age acceleration, most notably in patients with cardioembolic strokes, who exhibited a striking median difference of 9 years between DNAmAge and chronological age. Furthermore, age acceleration differed significantly across stroke subtypes and was higher in women than in men. In terms of causality, MR analysis indicated a modest negative effect of stroke on telomere length, but no causal effect of age phenotypes on stroke or its subtypes. However, some indication of a potential causal effect of ischemic stroke on PhenoAge acceleration was observed. CONCLUSION: The study provides insight into the relationship between DNAmAge and ischemic stroke, particularly cardioembolic stroke, and suggests possible gender differences. These insights carry profound clinical significance and set stage for future investigations into the entwined pathways of stroke and accelerated aging.

Asunto(s)

RESUMEN

Under unfavorable agricultural conditions, ammonia toxicity has become a major problem, resulting in a large number of deaths. Ammonia has been shown to be hepatotoxic. Research has also shown that ammonia can damage the livers of carp, but the mechanism is unclear. In this study, normal grass carp hepatocytes (L8824) were exposed to ammonia water to investigate the effect of ammonia on hepatocyte injury and apoptosis and its mechanism. The results showed that ammonia (50 mM) reduced the viability of L8824 cells and increased glutamic pyruvic transaminase (ALT, up 144.95%, P < 0.01) and glutamic oxalacetic transaminase (AST, up 65.27%, P < 0.01). Furthermore, exposure to ammonia induced oxidative stress and endoplasmic reticulum (ER) stress in L8824 cells. Elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased mitochondrial membrane potential indicated that L8824 cells suffered oxidative damage. Endoplasmic reticulum stress manifests as increased expression degrees of PERK, ATF4, and IRE-1α. These results confirmed the toxicity of ammonia to hepatocytes. In addition, the rate of apoptosis in L8824 cells was increased 69.66% after exposure to ammonia (50 mM, P < 0.01). However, pretreatment of L8824 cells with ER stress inhibitor 2-APB reduced ammonia-induced calcium release (26.50%, P < 0.01) in endoplasmic reticulum. These results indicate that ammonia can exert toxic effects on L8824 cells through inducing endoplasmic reticulum stress and oxidative stress, resulting in apoptosis in L8824 cells.

Asunto(s)

RESUMEN

BACKGROUND: The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China. METHODS: We enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test. RESULTS: We found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found. CONCLUSIONS: In northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.

Asunto(s)

RESUMEN

BACKGROUND: The monotherapies of statin and ezetimibe had not successfully achieved their objectives in the management of lipid levels of dyslipidemia patients. We aimed to compare the effects of combined low-dose simvastatin and ezetimibe versus high-dose statin on the lipid-lowering treatment of dyslipidemia patients. METHODS: We searched five databases published before May 2018, namely PubMed, EMBASE, Cochrane, Web of Science, and Clinicaltrials.gov. Completely published randomized controlled trials (RCTs) comparing the effect of high-dose statin (S) with ezetimibe/simvastatin (10/10 mg; E/S) on the management of dyslipidemia patients were included. RESULTS: A total of ten RCTs met the inclusion criteria, including 1,624 patients (E/S:691, S:933). Six outcomes underwent pooled analysis, including weighted mean difference (WMD) from baseline in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high sensitivity C-reactive protein (hs-CRP), triglyceride (TG), and non-high-density lipoprotein cholesterol (non-HDL-C). No significant gap was found between high-dose statin and ezetimibe/simvastatin (10/10 mg) in LDL-C (-1.55; 95% confidence interval [CI]: -4.42∼1.31, P=0 .29), HDL-C (1.05; 95%CI: -0.21∼2.3, P=0 .1), TG (4.03; 95%CI: -4.53∼12.58, P=0.36), and hs-CRP (0.14; 95%CI: -0.50∼0.78, P=0.67). However, there was significant difference found between the two lipid-lowering treatments in TC (-0.45; 95%CI: -9.07∼-0.83, P=0.02) and non-HDL-C (-4.97; 95%CI -8.46∼-1.49, P=0.005). CONCLUSION: Ezetimibe co-administered with simvastatin (10 mg) and high-dose statin monotherapy may show similar effects in reducing LDL-C, TG, and hs-CRP levels and in increasing HDL-C levels. However, the results suggest that there was greater TC and non-HDL-C lowering through high-dose statin monotherapy as compared with ezetimibe/simvastatin co-administration.

RESUMEN

Polymorphisms in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are associated with severe hypercholesterolemia and stroke. Here, we investigated the relationship between single nucleotide polymorphisms in PCSK9 and stroke in 237 patients with lacunar infarction in the Uygur and Han populations in Xinjiang Uygur Autonomous Region of China. Using the SNaPshot single-base terminal extension method, four PCSK9 gene polymorphisms were analyzed. We found a significantly strong relationship between the PCSK9 rs17111503 (G > A) polymorphism and increased susceptibility to lacunar infarction by variant homozygote comparison, and using the dominant and recessive models in the Han population but not in the Uygur population. Low triglyceride levels were found in AA carriers (rs17111503, G > A) in the Han population but not in the Uygur population. Association analysis revealed that the rs17111503 (G > A) polymorphism was not significantly associated with smoking, alcohol drinking, history of hypertension or diabetes in the Han or Uygur lacunar infarction patients. rs11583680, rs483462 and rs505151 were not associated with risk of lacunar infarction in the Han or Uygur populations. Our findings suggest that the PCSK9 rs17111503 (G > A) polymorphism is associated with susceptibility to lacunar infarction in the Han population but not in the Uygur population.

RESUMEN

BACKGROUND: Cerebral ischemic stroke (CIS) is a major cause of morbidity and mortality. Its main pathological basis is atherosclerosis (AS); in turn, the main risk factor in AS is dyslipidemia. Human proprotein convertase subtilisin/kexin9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein (LDL) cholesterol levels. We sought to assess the association between PCSK9 and CIS in Chinese Han and Uygur populations. MATERIAL AND METHODS: We selected 408 CIS patients and 348 control subjects and used a single-base terminal extension (SNaPshot) method to detect the genotypes of the 20 single-nucleotide polymorphisms (SNPs) in PCSK9. RESULTS: Distribution of SNP8 (rs529787) genotypes showed a significant difference between CIS and control participants (P=0.049). However, when analyzing Han and Uygur populations separately, we found that only Han subjects showed distribution of SNP1 (rs1711503), SNP2 (rs2479408), and SNP8 (rs529787) alleles that was significantly different between CIS and control participants (P=0.028, P=0.013, P=0.006, respectively), and distribution of SNP2 (rs2479408) in the dominant model (CC vs. CG + GG) was significantly different between CIS and control participants (P=0.013), even after adjustment for covariates (OR: 75.262, 95% confidence interval [CI]: 7.232-783.278, P<0.001). Distribution of the 2 haplotypes (A-C and G-C) (rs1711503 and rs2479408) was significantly different between CIS and control participants (both, P=0.011). CONCLUSIONS: Both rs1711503 and rs2479408 of PCSK9 genes were associated with CIS in the Han population of China. A-C haplotype may be a genetic marker of CIS risk in this population.

Asunto(s)