Resistance Exercise Training-Induced Muscle Hypertrophy Was Associated with Reduction of Inflammatory Markers in Elderly Women

Aging is associated with low-grade inflammation. The benefits of regular exercise for the elderly are well established, whereas less is known about the impact of low-intensity resistance exercise on low-grade inflammation in the elderly. Twenty-one elderly women (mean age ± SD, 85.0 ± 4.5 years) participated in 12 weeks of resistance exercise training. Muscle thickness and circulating levels of C-reactive protein (CRP), serum amyloid A (SAA), heat shock protein (HSP)70, tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP-1), insulin, insulin-like growth factor (IGF)-I, and vascular endothelial growth factor (VEGF) were measured before and after the exercise training. Training reduced the circulating levels of CRP, SAA (P < .05), HSP70, IGF-I, and insulin (P < .01). The training-induced reductions in CRP and TNF-α were significantly (P < .01, P < .05) associated with increased muscle thickness (r = −0.61, r = −0.54), respectively. None of the results were significant after applying a Bonferroni correction. Resistance training may assist in maintaining or improving muscle volume and reducing low-grade inflammation

Clock mutation affects circadian regulation of circulating blood cells

BACKGROUND: Although the number of circulating immune cells is subject to high-amplitude circadian rhythms, the underlying mechanisms are not fully understood. METHODS: To determine whether intact CLOCK protein is required for the circadian changes in peripheral blood cells, we examined circulating white (WBC) and red (RBC) blood cells in homozygous Clock mutant mice. RESULTS: Daytime increases in total WBC and lymphocytes were suppressed and slightly phase-delayed along with plasma corticosterone levels in Clock mutant mice. The peak RBC rhythm was significantly reduced and phase-advanced in the Clock mutants. Anatomical examination revealed hemoglobin-rich, swollen red spleens in Clock mutant mice, suggesting RBC accumulation. CONCLUSION: Our results suggest that endogenous clock-regulated circadian corticosterone secretion from the adrenal gland is involved in the effect of a Clock mutation on daily profiles of circulating WBC. However, intact CLOCK seems unnecessary for generating the rhythm of corticosterone secretion in mice. Our results also suggest that CLOCK is involved in discharge of RBC from the spleen

Identification of Autoantibodies against TRPM1 in Patients with Paraneoplastic Retinopathy Associated with ON Bipolar Cell Dysfunction

Background: Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. Methodology/Principal Findings: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response wit

SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle

Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P < 0.001). SIRT1-regulated Akt, endothelial nitric oxide synthase and GLUT4 levels were also induced in hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased forkhead box O 1 (FOXO1) and increased K48 polyubiquitination also suggest that SIRT1 could be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1 and Nampt levels. Our results reveal a strong correlation between SIRT1 levels and activity, SIRT1-regulated pathways and overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing.National Strength and Conditioning Association OTKA. Grant Number: 112810 Hungarian Academy of Science National Institute of Environmental Health Sciences. Grant Number: ES00359

Nutrition Support for Head and Neck Squamous Cell Carcinoma Patients Treated with Chemoradiotherapy: How Often and How Long?

Background. Oral intake of many patients with locally advanced head and neck cancer (LAHNC) decrease during chemoradiotherapy (CRT). Although prophylactic percutaneous endoscopic gastrostomy (PEG) is recommended, not a few patients complete CRT without using PEG tube. Patients and Methods. The subjects were patients with LAHNC who received CRT. We retrospectively investigated the incidence and duration of nutritional support during and after CRT, and predicting factors of nutritional support. For patients who required nutritional support, we also checked the day of initiation and the duration of nutritional support. Results. Of 53 patients, 29 patients (55%) required nutritional support during and/or after CRT. While no clear relation between requirement of nutritional support and variables including age, T stage, N stage, clinical stage and chemotherapy regimen, there could be some relationships between tumor primary sites and the requirement and duration of nutritional support. 17 (77%) of 22 patients with oropharynx cancer(OP) required nutritional support and prolonged for 4.4 months, and 11 (46%) of 24 patients with hypopharynx cancer(HP) required nutritional support and prolonged for 21.9 months. Conclusion. Nutritional support is indicated many HNC patients treated with CRT and primary sites may have some relation to its indication and duration

Detection of the Onset of Ischemia and Carcinogenesis by Hypoxia-Inducible Transcription Factor-Based In Vivo Bioluminescence Imaging

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential

MafB silencing in macrophages does not influence the initiation and growth of lung cancer induced by urethane

An increased number of tumor-associated macrophages (TAMs) that exhibit the M2 macrophage phenotype is related to poorer prognosis in cancer patients. MafB is a transcription factor regulating the differentiation of macrophages. However, involvement of MafB for the development of TAMs is unknown. This study was designed to investigate the role of MafB in a murine urethane-induced lung cancer model. Urethane was injected intraperitoneally into wild-type and dominant-negative MafB transgenic mice. Twenty-four weeks later, mice were sacrificed and their lungs removed for pathological analysis. The numbers and mean areas of lung cancer were evaluated. In addition, the numbers of Mac-3-positive macrophages were evaluated in each tumor. The numbers and mean areas of lung cancer induced by urethane administration were not significantly different between wild-type and dominant-negative MafB transgenic mice. The numbers of TAMs in lung cancer tissue were not significantly different between the two groups. MafB silencing using dominant-negative MafB did not influence the initiation and growth of lung cancer in mice exposed to urethane. These data suggest that MafB may not be related to the development of TAMs

男子大学生アスリートの栄養摂取状況と食品群別摂取頻度による評価点との関連性

　運動部に所属する男子大学生アスリートの食事調査結果を用いて、栄養摂取状況の特徴を評価した。さらに、食品群別摂取頻度による評価点を算出して、エネルギー、栄養素摂取量や各栄養素摂取量による評価点との関連性を検討し、アスリートの食生活バランスの評価に用いることができる簡易な方法について考察することを目的とした。食事調査の結果、対象集団にはエネルギー、栄養素摂取量が身体活動量に見合わないものが複数いた。一方で、サプリメントやプロテインを利用している者が多数おり、食事に関して無関心ではないことが窺われた。食品群別摂取頻度による評価点を用いた簡易な食生活評価法については、たんぱく質、鉄、カルシウム、ビタミンB1など、アスリートにとって重要な栄養素摂取量との有意な関連性を認めた。さらに、食品群別摂取頻度の得点と8項目のエネルギーと栄養素摂取量を、食事摂取基準の推奨量ならびにアスリートの推奨量と比較して得点化した栄養素摂取量評価得点を算出し関連について分析を行ったところ、有意な関連性が認められた。10種の食品群別摂取頻度を把握することは、アスリートの食生活とそれに付随する栄養摂取状況の概要について評価することができると考えられ、栄養アセスメントの一次的なスクリーニング評価に活用できる可能性が示唆された