Lower risk of low bone mineral density in high vitamin E level in older people: A cross-sectional study.

INTRODUCTION: Osteoporosis and osteopenia, together known as low bone mineral density (LBMD), are common problems in the elderly. LBMD may cause fragility fractures in the elderly. The relationship between Vitamin E and LBMD in old Americans is still unclear. In this study, we investigated the relationship between serum Vitamin E levels and LBMD in the elderly. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 and ultimately included 378 participants aged 50 to 79. Multivariable logistic or linear regression models were applied to examine the associations between serum Vitamin E levels and LBMD, total femur or lumbar spine BMD after adjusting for covariates. RESULTS: After adjusting for all covariates, higher serum Vitamin E levels reduced the risk of LBMD (OR 0.76; 95% CI 0.58-1.00) and were positively associated with total femur BMD (ß: 0.02; 95% CI: 0.01-0.03)， after adjusting for all covariates. In the subgroup analysis, for the BMI normal group (BMI<25), the serum Vitamin E levels were positively associated with the total femur (ß: 0.03; 95% CI: 0.01-0.05) and lumbar spine BMD (ß: 0.04; 95% CI: 0.01-0.07). In the BMI normal group, people with high serum Vitamin E levels have a lower incidence of LBMD (OR:0.43; 95% CI: 0.21-0.88). Though the P for interaction was larger than 0.05. CONCLUSION: This study found serum Vitamin E levels were negatively associated with LBMD in older Americans. Serum Vitamin E levels were positively associated with femur BMD in older Americans.

Adaptive evolution characteristics of mitochondrial genomes in genus Aparapotamon (Brachyura, Potamidae) of freshwater crabs.

BACKGROUND: Aparapotamon, a freshwater crab genus endemic to China, includes 13 species. The distribution of Aparapotamon spans the first and second tiers of China's terrain ladder, showing great altitudinal differences. To study the molecular mechanisms of adaptive evolution in Aparapotamon, we performed evolutionary analyses, including morphological, geographical, and phylogenetic analyses and divergence time estimation. We sequenced the mitogenomes of Aparapotamon binchuanense and Aparapotamon huizeense for the first time and resequenced three other mitogenomes of Aparapotamon grahami and Aparapotamon gracilipedum. These sequences were combined with NCBI sequences to perform comparative mitogenome analysis of all 13 Aparapotamon species, revealing mitogenome arrangement and the characteristics of protein-coding and tRNA genes. RESULTS: A new species classification scheme of the genus Aparapotamon has been detected and verified by different aspects, including geographical, morphological, phylogenetics and comparative mitogenome analyses. Imprints from adaptive evolution were discovered in the mitochondrial genomes of group A, including the same codon loss at position 416 of the ND6 gene and the unique arrangement pattern of the tRNA-Ile gene. Multiple tRNA genes conserved or involved in adaptive evolution were detected. Two genes associated with altitudinal adaptation, ATP8 and ND6, which experienced positive selection, were identified for the first time in freshwater crabs. CONCLUSIONS: Geological movements of the Qinghai-Tibet Plateau and Hengduan Mountains likely strongly impacted the speciation and differentiation of the four Aparapotamon groups. After some group A species dispersed from the Hengduan Mountain Range, new evolutionary characteristics emerged in their mitochondrial genomes, facilitating adaptation to the low-altitude environment of China's second terrain tier. Ultimately, group A species spread to high latitudes along the upper reaches of the Yangtze River, showing faster evolutionary rates, higher species diversity and the widest distribution.

TNNT2 Gene Polymorphisms are Associated with Susceptibility to Idiopathic Dilated Cardiomyopathy in Kazak and Han Chinese.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement, systolic dysfunction, and heart failure. Both genetic and non-genetic factors have been linked to DCM pathogenesis. Familial DCM (FDCM) accounts for 20%-50% of all DCM cases, highlighting the importance of genetics in pathogenesis. Indeed, more than 40 DCM-associated genes have been identified, including the gene encoding cardiac troponin T type-2 (TNNT2). We examined polymorphisms of the TNNT2 gene in idiopathic DCM (IDCM) patients of Kazak and Han ethnicity compared with healthy Kazak and Han controls. MATERIAL AND METHODS: Peripheral blood samples were collected from 180 patients with IDCM (90 Kazak and 90 Han), and 180 healthy controls (90 Kazak and 90 Han). PCR was used to amplify 15 exons and nearby introns of the TNNT2 gene. The amplified products were sequenced and compared to the standard sequence in PubMed by BLAST and CHROMAS software, to identify mutation sites. RESULTS: Results from Kazak and Han IDCM patients were complied for Hardy-Weinberg equilibrium analysis. There was a significant difference in the genotype distribution (χ2=6.67, P=0.015) and allele frequency (χ2=5.71, P=0.017) between Kazaks with IDCM and Kazak controls of SNP rs3729547. There was also a difference in the genotype distribution (χ2=6.62, P=0.036) and allele frequency (χ2=4.91, P=0.018) between Han with IDCM and Han controls. The TNNT2 gene polymorphism loci rs3729547 may be associated with the IDCM onset in Kazak and Han patients (OR=2.5, 95% CI: 1.233~5.068). CONCLUSIONS: The TNNT2 polymorphisms might play an important role in susceptibility to DCM in Xinjiang Kazak and Han patients.

Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age­dependent changes in HCN2, HCN4, miR­1 and miR­133 expression may contribute to age­associated atrial fibrillation, and therefore the correlation between expression levels, among adult (≤65 years) and aged patients (≥65 years), and sinus rhythm was determined. Right atrial appendage samples were collected from 60 patients undergoing coronary artery bypass grafting. Reverse transcription-quantitative polymerase chain reaction (PCR) and western blot analyses were performed in order to determine target RNA and protein expression levels. Compared with aged patients with sinus rhythm, aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel mRNA and protein expression levels (P<0.05), but significantly lower expression levels of miR­1 and miR­133 (P<0.05). In addition, aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR­1 and ­133 (P<0.05), compared with those of adult patients with sinus rhythm. Expression levels of HCN2 and HCN4 increased with age, and a greater increase was identified in patients with age­associated atrial fibrillation compared with that in those with aged sinus rhythm. These electrophysiological changes may contribute to the induction of ectopic premature beats that trigger atrial fibrillation.

Effects of ivabradine on cardiac electrophysiology in dogs with age-related atrial fibrillation.

BACKGROUND: Ivabradine is an inhibitor of mixed Na+-K+ current that could combine with HCN channels to reduce the transmembrane velocity of funny current (If), heart rate, and cardiac efficiency, and thus be used for the treatment of cardiovascular diseases such as chronic heart failure. As an ion channel blocker, Ivabradine is also a potential antiarrhythmic agent. MATERIAL/METHODS: Twelve aging dogs (8-10 years old) underwent rapid atrial pacing for 2 months to induce age-related AF in this study. The dogs were randomly divided into the Ivabradine group and aging-AF group. The effects of Ivabradine on the electrophysiological parameters, including the effective refractory period (ERP) of the pulmonary veins and atrium, duration of AF, and inducing rate of AF, were investigated. RESULTS: As compared to the aging-AF group, the ERPs of the left superior pulmonary vein (139.00±4.18 ms vs. 129.00±4.08 ms, P=0.005) and left auricle (135.00±3.53 ms vs. 122.00±4.47 ms, P=0.001) were significantly increased, while the duration of AF (46.60±5.07 s vs. 205.40±1.14 s, P=0.001) and inducing rate of AF (25% vs. 60%, P=0.001) were significantly decreased. CONCLUSIONS: Ivabradine could effectively reduce the inducing rate of AF, and thus be used as an upstream drug for the prevention of age-related AF.

Association between reversal in the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and age-related atrial fibrillation.

BACKGROUND: We compared cardiac electrophysiological indicators and regional expression levels of cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) channels between adult and aged dogs to identify possible mechanisms of age-related atrial fibrillation. MATERIAL/METHODS: Corrected sinus node recovery time (SNRTc) and effective refractory period (ERP) of the atrium and pulmonary veins were measured in 10 adult (3-6 years old) and 10 aged dogs (>9 years old). Expression levels of HCN2 and HCN4 channel mRNAs and proteins were measured in the sinoatrial node, atrium, and pulmonary veins by real-time PCR and Western blotting. RESULTS: Aged dogs exhibited a higher induction rate of atrial fibrillation (AF) in response to electrical stimulation, longer AF duration after induction, longer SNRTc, longer right atrial effective refractory period (AERP), shorter left AERP, and increased AERP dispersion compared to adults. Expression levels of HCN2 and HCN4 channel mRNAs and proteins were lower in the sinoatrial node but higher in the atrium and pulmonary veins of aged dogs. CONCLUSIONS: Changes in atrial electrophysiological indicators in aged dogs revealed sinoatrial node dysfunction. There was a reversal in the local tissue distribution of HCN2 and HCN4 channel mRNA and protein, a decrease in sinoatrial node expression, and increase in atrial and pulmonary vein expression with age. Changes in atrial electrophysiological characteristics and regional HCN channel expression patterns were associated with the onset and maintenance of age-related atrial fibrillation.