Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors

運動刺激に応答して生じる骨格筋間葉系前駆細胞（Fibro-adipogenic Progenitors: FAPs）の細胞老化が，骨格筋の再生に重要であることを明らかにした．一方で，慢性炎症性筋疾患モデルマウスではFAP の細胞老化が不十分で，運動がむしろ筋の線維化を悪化させることがわかった．さらに，慢性炎症性筋疾患モデルマウスに対して，運動刺激と薬物治療の併用でAMP-activated protein kinase（AMPK）の活性化とともにFAPs の細胞老化を誘導することで，高い治療効果を発揮できることを明らかにした．これらの成果は，運動刺激がなぜ，筋再生を促す場合と線維化や炎症を悪化させる場合があるかという，臨床上の問題点を解決する，新しいメカニズムのひとつを解明したものであり，慢性炎症性筋疾患に対する安全で効果的な治療につながることが期待できる

Stretching positions for the coracohumeral ligament: Strain measurement during passive motion using fresh/frozen cadaver shoulders

<p>Abstract</p> <p>Background</p> <p>Contracture of the coracohumeral ligament is reported to restrict external rotation of the shoulder with arm at the side and restrict posterior-inferior shift of the humeral head. The contracture is supposed to restrict range of motion of the glenohumeral joint.</p> <p>Methods</p> <p>To obtain stretching position of the coracohumeral ligament, strain on the ligament was measured at the superficial fibers of the ligament using 9 fresh/frozen cadaver shoulders. By sequential measurement using a strain gauge, the ligament strain was measured from reference length (L0). Shoulder positions were determined using a 3 Space Tracker System. Through a combination of previously reported coracohumeral stretching positions and those observed in preliminary measurement, ligament strain were measured by passive external rotation from 10° internal rotation, by adding each 10° external rotation, to maximal external rotation.</p> <p>Results</p> <p>Stretching positions in which significantly larger strain were obtained compared to the L0 values were 0° elevation in scapula plane with 40°, 50° and maximum external rotation (5.68%, 7.2%, 7.87%), 30° extension with 50°, maximum external rotation (4.20%, 4.79%), and 30° extension + adduction with 30°, 40°, 50° and maximum external rotation (4.09%, 4.67%, 4.78%, 5.05%)(P < 0.05). No positive strain on the coracohumeral ligament was observed for the previously reported stretching positions; ie, 90° abduction with external rotation or flexion with external rotation.</p> <p>Conclusions</p> <p>Significant strain of the coracohumeral ligament will be achieved by passive external rotation at lower shoulder elevations, extension, and extension with adduction.</p

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine

Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.</p> <p>Methods</p> <p>We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.</p> <p>Results</p> <p>We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.</p> <p>Conclusion</p> <p>Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.</p

Serotonin and GI Disorders: An Update on Clinical and Experimental Studies

The gastrointestinal (GI) tract is the largest producer of serotonin (5-hydroxytryptamine (5-HT)) in the body, and as such it is intimately connected with GI function and physiology. 5-HT produced by enterochromaffin (EC) cells is an important enteric mucosal signaling molecule and has been implicated in a number of GI diseases, including inflammatory bowel disease and functional disorders such as irritable bowel syndrome. This review will focus on what is known of basic 5-HT physiology and also on the emerging evidence for its novel role in activation of immune response and inflammation in the gut. Utilizing pubmed.gov, search terms such as “5-HT,” “EC cell,” and “colitis,” as well as pertinent reviews, were used to develop a brief overview of EC cell biology and the association between 5-HT and various GI disorders. It is the aim of this review to provide the readers with an update on EC cell biology and current understanding on the role of 5-HT in GI disorders specifically in inflammatory conditions