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Oxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice. Immobilization for 2 weeks increased the expression of cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle weight loss and a reduction in treadmill running times induced by immobilization were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization-associated increases in ubiquitinated protein levels were lower in the TLR2 KO mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and increased the levels of ubiquitinated proteins, although these levels were increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a potential target for preventing skeletal muscle atrophy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: The present study examined the effect of the heme oxygenase (HO)-1 inducer hemin on skeletal muscle atrophy induced by single limb immobilization in mice., Main Methods: Immobilization was conducted in the left hindlimb of C57BL/6 mice for 1 week and the right hindlimb was used as a control. Hemin (30 mg/kg) was administered intraperitoneally once a day during the immobilization period. Gastrocnemius muscles were used for analysis. Muscle weight was measured to quantify degree of atrophy, and exhaustion treadmill test was performed to assess muscle function., Key Findings: Immobilization increased HO-1 protein levels in skeletal muscle, which was further increased by hemin treatment. Immobilization induced weight loss and a functional reduction in skeletal muscle, which were attenuated by hemin treatment. Gene expression and protein levels of MuRF1 and atrogin-1 were increased by immobilization and hemin treatment attenuated the increment. The phosphorylation of mTOR and p70S6k was decreased by immobilization in skeletal muscle and hemin had no effect on mTOR and p70S6k phosphorylation. Gene expression of the antioxidants superoxide dismutase and glutathione peroxidase 1 in skeletal muscle was reduced by immobilization and hemin treatment recovered the reduction. Immobilization increased levels of carbonylated protein and nitrotyrosine in skeletal muscle, which was reversed by hemin treatment. Gene expression of inflammatory cytokines was increased by immobilization and was normalized as a result of hemin treatment., Significance: These results suggest that hemin attenuates immobilization-induced skeletal muscle atrophy through the suppression of protein degradation via its anti-oxidant and anti-inflammatory properties., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The occurrence of adult intussusception from colorectal cancer in a 27-year-old man is quite uncommon., Objectives: To raise awareness of the incidence of intussusception in adults, to educate others about the protean manifestations and high association with malignancy of the disease, and to provide treatment recommendations., Case Report: We present a case of a 27-year-old man with a non-contributory family history who presented to the Emergency Department multiple times over a 10-month period with vague abdominal complaints. Clinical symptoms ultimately included a 75-lb weight loss, fatigue, mild right-sided abdominal pain, and anemia. Computed tomography scan of the abdomen revealed right-sided colocolic intussusception with a lead point. The patient underwent a right hemicolectomy with ileocolic anastomosis. Pathologic evaluation and staging revealed a stage IIIB poorly differentiated adenocarcinoma. Molecular analysis was negative for genetic causes., Conclusion: This case demonstrates how intussusception and possible colorectal cancer must be included in the differential diagnosis even in young adults who have persistent abdominal complaints., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We investigated the effects of aging on the IL-7-mediated CD8+ T-cell survival pathway and of IL-7 therapy on T-cell immunity. Cells expressing IL-7 receptor (IL-7R) alphahigh and alphalow were identified in a CD45RA+ effector memory (EM(CD45RA+), CD45RA+CCR7-) CD8+ T-cell subset. Elderly subjects (65 years and older) had an increased frequency of EM(CD45RA+) IL-7Ralphalow) CD8+ T cells, leading to decreased STAT5 phosphorylation and survival responses to IL-7 compared with young subjects (40 years and younger). These EM(CD45RA+) IL-7Ralphalow cells were largely antigen experienced (CD27-CD28-), replicatively senescent (CD57+), and perforinhigh CD8+ T cells that had decreased IL-7Ralpha mRNA, independent of guanine and adenine binding protein alpha (GABPalpha) and growth factor independence-1 (GFI1) expression. In measuring T-cell receptor (TCR) repertoires of EM(CD45RA+) CD8+ T cells, the elderly had a limited repertoire in IL-7Ralphahigh and IL-7Ralphalow cells, whereas the young had a diverse repertoire in IL-7Ralphahigh but not in IL-7Ralphalow cells. These findings suggest that aging affects IL-7Ralpha expression by EM(CD45RA+) CD8+ T cells, leading to impaired signaling and survival responses to IL-7, and that IL-7 therapy may improve the survival of EM(CD45RA+) CD8+ T cells with a diverse TCR repertoire in the young but not in the elderly.