Age-related hearing impairment (ARHI) is a complex neurodegenerative disorder caused by a combination of environmental and genetic factors. We have reported previously that obesity increases the risk for ARHI, and that plasma levels of adiponectin are associated with ARHI. In the present study, we further explored the role of adiponectin in the pathophysiology of ARHI by investigating the genotypes of ADIPOQ and ADIPOR1, the genes of adiponectin and its type 1 receptor, respectively. A total of 1682 volunteers were enrolled, and their audiological phenotypes were determined according to the z scores converted from their original frequency-specific hearing thresholds. A total of 9 tag-single nucleotide polymorphisms (tagSNPs) in ADIPOQ and 4 tagSNPs in ADIPOR1 were genotyped, and the genotypes were correlated to the audiological phenotypes under the assumption of various inheritance models. Significant associations were identified between certain ADIPOQ tagSNPs and z scores under dominant, codominant, or additive models, whereas no association was identified between ADIPOR1 tagSNPs and z scores. The associations between ADIPOQ tagSNPs and z scores appear to exist only in subjects with specific ADIPOR1 genotypes, indicating an interaction between adiponectin and AdipoR1. Measurement of plasma adiponectin in 736 subjects revealed that ADIPOQ genotypes might exert their effects on hearing levels via modulation of plasma adiponectin levels. Subsequently, we confirmed the expression of AdipoR1 in the inner ear of mice, and demonstrated antiapoptotic effects of adiponectin in cochlear explant cultures. These results provide insights into the physiological function and potential clinical implications of adiponectin against ARHI.

Myoblast proliferation and differentiation are essential for skeletal muscle regeneration. Myoblast proliferation is a critical step in the growth and maintenance of skeletal muscle. The precise action of inorganic arsenic on myoblast growth has not been investigated. Here, we investigated the in vitro effect of inorganic arsenic trioxide (As2O3) on the growth of C2C12 myoblasts. As2O3 decreased myoblast growth at submicromolar concentrations (0.25-1 μM) after 72 h of treatment. Submicromolar concentrations of As2O3 did not induce the myoblast apoptosis. Low-concentration As2O3 (0.5 and 1 μM) significantly suppressed the myoblast cell proliferative activity, which was accompanied by a small proportion of bromodeoxyuridine (BrdU) incorporation and decreased proliferating cell nuclear antigen (PCNA) protein expression. As2O3 (0.5 and 1 μM) increased the intracellular arsenic content but did not affect the reactive oxygen species (ROS) levels in the myoblasts. Cell cycle analysis indicated that low-concentrations of As2O3 inhibited cell proliferation via cell cycle arrest in the G1 and G2/M phases. As2O3 also decreased the protein expressions of cyclin D1, cyclin E, cyclin B1, cyclin-dependent kinase (CDK) 2, and CDK4, but did not affect the protein expressions of p21 and p27. Furthermore, As2O3 inhibited the phosphorylation of Akt. Insulin-like growth factor-1 significantly reversed the inhibitory effect of As2O3 on Akt phosphorylation and cell proliferation in the myoblasts. These results suggest that submicromolar concentrations of As2O3 alter cell cycle progression and reduce myoblast proliferation, at least in part, through a ROS-independent Akt inhibition pathway.

The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and is triggered via abnormal accumulation of amyloid-β peptide (Aβ). Aggregated Aβ is responsible for disrupting calcium homeostasis, inducing neuroinflammation, and promoting neurodegeneration. In this study, we generated curcuminoid submicron particle (CSP), which reduce the average size to ~60 nm in diameter. CSP had elevated the bioavailability in vivo and better neuroprotective effect against oligomeric Aβ than un-nanosized curcuminoids in vitro. Two months of CSP consumption reversed spatial memory deficits and the loss of a calcium binding protein calbindin-D28k in the hippocampus of AD mouse model. In addition, CSP consumption lowered amyloid plaques and astrogliosis in vivo and enhanced microglial Aβ phagocytosis in vitro, implying that the beneficial effects of CSP also mediated via modulating neuroinflammation and enhancing amyloid clearance. Taken together, our study demonstrated the protective effects of CSP toward ameliorating the memory impairment and pathological deficits in AD mouse model.

Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear.

The objective was to explore the effectiveness of glenohumeral joint distension for the treatment of frozen shoulder. We searched electronic data sources including PubMed, Scopus, and Embase from the earliest records available to February 2017. Eleven randomized controlled trials including at least one pair of comparisons between capsular distension and a reference treatment were included, comprising 747 participants. Patients' characteristics, details of reference treatments, aspects of capsular distension therapy, and outcome measurement were evaluated at three points in time: baseline, early following intervention, and at the trial's end. The primary and secondary outcomes were the between-group standardized mean differences of changes in shoulder function and range of motion, respectively. Regarding the long-term primary outcome, the superiority of capsular distension to reference treatments was not identified. One secondary outcome (external rotation limitation) showed a probable early positive response to capsular distension when compared to intra-articular corticosteroid injection. Aspects of approaches, imaging guiding techniques and doses of distension were not found to modify treatment effectiveness. In conclusion, distension of the glenohumeral joint provides a similar long-term efficacy to all reference treatments. A single dose of a corticosteroid-contained regimen introduced through the ultrasound-guided posterior approach is a preferable practice of capsular distension for the management of frozen shoulder.

The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO) group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old). The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), caspase 3, poly(ADP-ribose) polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice.

No abstract available

Myostatin and insulin-like growth factor 1 (IGF-1) are serum markers for muscle growth and regeneration. However, their value in the clinical monitoring of Pompe disease - a muscle glycogen storage disease - is not known. In order to evaluate their possible utility for disease monitoring, we assessed the levels of these serum markers in Pompe disease patients receiving enzyme replacement therapy (ERT).

Adipokines, including adipocyte fatty acid-binding protein (A-FABP), have been demonstrated to be involved in the pathogenesis of atherosclerosis. In the present study, we investigated the association of circulating A-FABP level with severity of myocardial perfusion abnormalities analyzed by Tl-201 dipyridamole single-photon emission computed tomography.

Microglia mediate amyloid-beta peptide (Aβ)-induced neuroinflammation, which is one of the key events in the pathogenesis of Alzheimer's disease (AD). Decoy receptor 3 (DcR3)/TNFRSF6B is a pleiotropic immunomodulator that promotes macrophage differentiation toward the M2 anti-inflammatory phenotype. Based on its role as an immunosupressor, we examined whether DcR3 could alleviate neuroinflammation and AD-like deficits in the central nervous system.

Patients with coronary heart disease or acute myocardial infarction after cardiac catheterization with stenting referred for phase II cardiac rehabilitation (CR) were grouped according to their preference. Cardio-pulmonary exercise testing (CPET) was used to determine oxygen uptake ((Equation is included in full-text article.)) at peak exercise and anaerobic threshold (AT). The control patients received counseling only while the experiment group received 36 sessions of CR in 3 to 6 months. Exercise physiology parameters and serum myokines (myostatin, insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) were measured pre- and postrehabilitation.There were 29 patients in the experiment group and 10 in the control group, with no significant differences in baseline parameters. The experiment group had prominent progress in aerobic capacity and body composition after CR, but their serum myokine concentrations did not change significantly. Serum myostatin is positively correlated to peak (Equation is included in full-text article.)pre- and post-training, and pretraining AT (Equation is included in full-text article.), after adjusting for age, sex, and body composition. Serum IGF-1 is positively correlated with grip strength before training.Serum myostatin level is positively correlated to aerobic capacity, and IGF-1 level is positively correlated to grip strength in cardiac patients receiving CR.

Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance.

Sarcopenia is defined as aging-related loss of muscle mass and function. Telomere length in chromosomes shortens with age and is modulated by telomeric repeat-containing RNA (TERRA). This study aimed to explore the impact of aging and sarcopenia on telomere length and TERRA expression, and changes following strengthening exercise and nutrition intervention (supplement of branched-chain amino acids, calcium and vitamin D3) for 12 weeks in the sarcopenic population. Older adults (≥65 years old) were divided into non-sarcopenic controls (n = 36) and sarcopenic individuals (n = 36) after measurement of grip strength and body composition. The relative telomere length of leukocytes in all research participants was evaluated using the T/S ratio (telomere/single copy gene), and relative TERRA expression of leukocytes was determined by reverse-transcription qPCR (RT-qPCR). Generalized estimating equation (GEE) was used to analyze the influence of sarcopenia and intervention on the outcomes. There was no significant difference in telomere length between control subjects and participants with sarcopenia. TERRA expression was lower in sarcopenic participants compared to that in non-sarcopenic controls (5.18 ± 2.98 vs. 2.51 ± 1.89; p < 0.001). In the sarcopenic group, intervention significantly increased TERRA expression, but not telomere length. The GEE analysis demonstrated that TERRA expression was negatively associated with sarcopenia (β coefficient = -2.705, p < 0.001) but positively associated with intervention (β coefficient = 1.599, p = 0.023). Sarcopenia is associated with a decrease in TERRA expression in leukocytes. Rebound TERRA expression (returning to the level similar to the non-sarcopenic controls) was observed in the sarcopenic group after exercise and nutrition intervention. Future studies are warranted to examine the potential of TERRA as a biomarker for sarcopenia and its subsequent responses to intervention.

Despite the clinical utility of genetic diagnosis to address idiopathic sensorineural hearing impairment (SNHI), the current strategy for screening mutations via Sanger sequencing suffers from the limitation that only a limited number of DNA fragments associated with common deafness mutations can be genotyped. Consequently, a definitive genetic diagnosis cannot be achieved in many families with discernible family history. To investigate the diagnostic utility of massively parallel sequencing (MPS), we applied the MPS technique to 12 multiplex families with idiopathic SNHI in which common deafness mutations had previously been ruled out. NimbleGen sequence capture array was designed to target all protein coding sequences (CDSs) and 100 bp of the flanking sequence of 80 common deafness genes. We performed MPS on the Illumina HiSeq2000, and applied BWA, SAMtools, Picard, GATK, Variant Tools, ANNOVAR, and IGV for bioinformatics analyses. Initial data filtering with allele frequencies (<5% in the 1000 Genomes Project and 5400 NHLBI exomes) and PolyPhen2/SIFT scores (>0.95) prioritized 5 indels (insertions/deletions) and 36 missense variants in the 12 multiplex families. After further validation by Sanger sequencing, segregation pattern, and evolutionary conservation of amino acid residues, we identified 4 variants in 4 different genes, which might lead to SNHI in 4 families compatible with autosomal dominant inheritance. These included GJB2 p.R75Q, MYO7A p.T381M, KCNQ4 p.S680F, and MYH9 p.E1256K. Among them, KCNQ4 p.S680F and MYH9 p.E1256K were novel. In conclusion, MPS allows genetic diagnosis in multiplex families with idiopathic SNHI by detecting mutations in relatively uncommon deafness genes.

Genetic variation associated with human leukocyte antigen (HLA) genes has immunological functions and is associated with autoimmune diseases. To date, large-scale studies involving classical HLA genes have been limited by time-consuming and expensive HLA-typing technologies. To reduce these costs, single-nucleotide polymorphisms (SNPs) have been used to predict HLA-allele types. Although HLA allelic distributions differ among populations, most prediction model of HLA genes are based on Caucasian samples, with few reported studies involving non-Caucasians.

Adipocyte fatty acid-binding protein (AFABP) has been shown to be a biomarker of body weight change and atherosclerosis. Changes in thyroid function are associated with changes in body weight and risks of cardiovascular diseases. The association between AFABP and thyroid function status has been seldom evaluated.The aim of this study was to compare the serum AFABP concentrations in hyperthyroid patients and those in euthyroid individuals, and to evaluate the associations between serum AFABP and free thyroxine (fT4) levels.For this study, 30 hyperthyroid patients and 30 euthyroid individuals at a referral medical center were recruited. The patients with hyperthyroidism were treated with antithyroid regimens as clinically indicated. No medication was given to the euthyroid individuals. The body weight, body mass index, thyroid function, serum levels of AFABP, and biochemical data of both groups at baseline and at the 6th month were compared. Associations between AFABP and fT4 levels were also analyzed.At the baseline, the hyperthyroid patients had significantly higher serum AFABP levels than the euthyroid individuals (median [Q1, Q3]: 22.8 [19.4, 30.6] ng/mL vs 18.6 [15.3, 23.2] ng/mL; P = 0.038). With the antithyroid regimens, the AFABP serum levels of the hyperthyroid patients decreased to 16.6 (15.0, 23.9) ng/mL at the 6th month. No difference in the AFABP level was found between the hyperthyroid and the euthyroid groups at the 6th month. At baseline, sex (female vs male, ß = 7.65, P = 0.022) and fT4 level (ß = 2.51, P = 0.018) were significantly associated with AFABP levels in the univariate regression analysis. At the 6th month, sex and fT4 level (ß = 8.09, P < 0.001 and ß = 3.61, P = 0.005, respectively) were also significantly associated with AFABP levels. The associations between sex and fT4 level with AFABP levels remained significant in the stepwise multivariate regression analysis, both at baseline and at the 6th month.The patients with hyperthyroidism had higher serum AFABP levels than the individuals with euthyroidism. In the patients with hyperthyroidism, the serum AFABP concentrations decreased after the antithyroid treatment. In this study, the serum AFABP concentrations were positively associated with female sex and the serum fT4 level.

In the analysis of complex traits such as fasting plasma glucose levels, researchers often adjust the trait for some important covariates before assessing gene susceptibility, and may at times encounter confounding among the covariates and the susceptible genes. Previously, the tree-based method has been employed to accommodate the heterogeneity in complex traits. In this study, we performed a genome-wide screen on fasting glucose levels in the offspring generation of the Framingham Heart Study provided by the Genetic Analysis Workshop 13. We defined one quantitative trait and converted it to a dichotomous trait based on a predetermined cut-off value, and performed association analyses using regression and classification trees for the two traits, respectively. A marker was interpreted as positive if at least one of its alleles exhibited association in both analyses. Our purpose was to identify candidate genes susceptible to fasting glucose levels in the presence of other covariates. The covariates entered in the analysis including sex, body mass index, and lipids (total plasma cholesterol, high density lipoprotein cholesterol, and triglycerides) of the subjects, and those of their parents.

Fetuin-A is a protein with various biological functions. It plays a role in insulin resistance and arterial calcium deposition. Thyroid dysfunction may affect energy expenditure, glucose metabolism, and the risk of cardiovascular diseases. In the present study, we compared the serum fetuin-A concentrations in hyperthyroid patients with those in euthyroid patients.We recruited 30 newly-diagnosed hyperthyroid patients (the HY group) and treated them with anti-thyroid regimens as clinically indicated. We recruited 30 euthyroid individuals (the EU group) as controls. We compared laboratory parameters at the baseline and at 6 months. We then determined the associations between the levels of fetuin-A and free thyroxine (fT4), thyroid-stimulating hormone (TSH), or log transformation of TSH (logTSH).At the baseline, the HY patients had significantly higher serum fetuin-A levels than the EU patients (median [Q1, Q3]: 735.4 [537.9, 843.4] ng/mL vs 561.1[449.2, 670.5] ng/mL, P = .010). At 6 months, the serum fetuin-A levels of the HY patients decreased but were still higher than those of the EU patients (698.4 [627.6, 924.3] ng/mL vs 616.5 [498.2, 727.7] ng/mL, P = .002). At baseline, the serum levels of fetuin-A were negatively associated with logTSH (β = -53.79, P = .010). At 6 months, the levels of fetuin-A were positively associated with fT4 (β = 86.91, P = .039), and negatively associated with logTSH (β = -104.28, P < .001). Changes to the levels of fetuin-A within 6 months were negatively associated with changes to logTSH (β = -57.80, P = .019). The negative associations between fetuin-A levels and logTSH at baseline and at 6 months, and the changes during the 6 months remained significant after adjustment for sex and age (β = -51.72, P = .016; β = -103.11, P < .001; and β = -59.36, P = .020, respectively).The patients with hyperthyroidism had higher serum fetuin-A levels than the patients with euthyroidism. In patients with hyperthyroidism, the serum fetuin-A concentrations decreased after the anti-thyroid treatment. In the present study, serum fetuin-A concentrations were negatively associated with logTSH.

Limited imaging studies have investigated whether limb muscle quantity and quality change after metabolic syndrome (MetS) development. This pilot study examined MetS influence on limb muscle characteristics in older adults.