Phosphatidylinositol 3-Kinase Signaling Enhances Intestinal Crypt Epithelial Cell Recovery after Radiation.

Intestinal stem cell (ISC) signaling maintains the balance of self-renewal and differentiation. Herein, the role of phosphatidylinositol 3-kinase (PI3K) signaling in ISC responses to radiation was interrogated using Villin-Cre pik3r1 (p85) mice and p85α-deficient human enteroids (shp85α). Lethal whole-body irradiation in mice was performed to monitor PI3K-mediated survival responses.

Update on the Basic Science Concepts and Applications of Adipose-Derived Stem Cells in Hand and Craniofacial Surgery.

Adipose-derived stem cell therapy offers plastic surgeons a novel treatment alternative for conditions with few therapeutic options. Adipose-derived stem cells are a promising treatment because of their broad differentiation potential, capacity for self-renewal, and ease of isolation. Over the past decade, plastic surgeons have attempted to harness adipose-derived stem cells' unique cellular characteristics to improve the survival of traditional fat grafting procedures, a process known as cell-assisted lipotransfer.

Current risk of breast implant-associated anaplastic large cell lymphoma: a systematic review of epidemiological studies.

Recent epidemiological studies have attempted to accurately determine the risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). However, comparisons of previously published works are difficult due to widespread variations in reporting. We systematically review the epidemiology in order to better define the current risk of BIA-ALCL.

Cellular and Molecular Mechanisms of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and highly treatable cancer of the immune system that can form around textured-surface breast implants. Although the underlying cause has yet to be elucidated, an emerging theme-linking pathogenesis to a chronic inflammatory state-continues to dominate the current literature. Specifically, the combination of increasing mutation burden and chronic inflammation leads to aberrant T-cell clonal expansion.

Breast Implant-associated Anaplastic Large Cell Lymphoma: An Evidence-based Systematic Review.

Objective: This evidence-based systematic review synthesizes and critically appraises current clinical recommendations and advances in the diagnosis and treatment of BIA-ALCL. This review also aims to broaden physician awareness across diverse specialties, particularly among general practitioners, breast surgeons, surgical oncologists, and other clinicians who may encounter patients with breast implants in their practice.

Background: BIA-ALCL is an emerging and treatable immune cell cancer definitively linked to textured-surface breast implants.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Defining Future Research Priorities.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that is exclusively associated with textured-surface breast implants. This clinical review provides an update on the diagnosis and management of BIA-ALCL with an emphasis on major advances. The epidemiology and pathophysiology of the disease are also reviewed, focusing on current paradigm shifts and highlighting current controversies related to disease classification and risk mitigation.

Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease.

TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models.

Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats.

Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN(+/+) ) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTN(Δ/Δ) ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue.

Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

Background: The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries.

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

Background: A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles.

Elevation in circulating biomarkers of cartilage damage and inflammation in athletes with femoroacetabular impingement.

Background: Femoroacetabular impingement (FAI) is one of the most common causes of early cartilage and labral damage in the nondysplastic hip. Biomarkers of cartilage degradation and inflammation are associated with osteoarthritis. It was not known whether patients with FAI have elevated levels of biomarkers of cartilage degradation and inflammation.

Aging-associated exacerbation in fatty degeneration and infiltration after rotator cuff tear.

Background: Rotator cuff tears are one of the most common musculoskeletal complaints and a substantial source of morbidity in elderly patients. Chronic cuff tears are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of cuff tears in elderly patients, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential.

Changes in circulating biomarkers of muscle atrophy, inflammation, and cartilage turnover in patients undergoing anterior cruciate ligament reconstruction and rehabilitation.

Background: After anterior cruciate ligament (ACL) reconstruction, there is significant atrophy of the quadriceps muscles that can limit full recovery and place athletes at risk for recurrent injuries with return to play. The cause of this muscle atrophy is not fully understood.

Hypothesis: Circulating levels of proatrophy, proinflammatory, and cartilage turnover cytokines and biomarkers would increase after ACL reconstruction.

Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.

Full-thickness tears to the rotator cuff can cause severe pain and disability. Untreated tears progress in size and are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of rotator cuff tears, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential.

Mechanical loading and TGF-β change the expression of multiple miRNAs in tendon fibroblasts.

Tendons link skeletal muscles to bones and are important components of the musculoskeletal system. There has been much interest in the role of microRNA (miRNA) in the regulation of musculoskeletal tissues to mechanical loading, inactivity, and disease, but it was unknown whether miRNA is involved in the adaptation of tendons to mechanical loading. We hypothesized that mechanical loading and transforming growth factor-β (TGF-β) treatment would regulate the expression of several miRNA molecules with known roles in cell proliferation and extracellular matrix synthesis.

Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts.

Scleraxis is a basic helix-loop-helix transcription factor that plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. Mice with a targeted inactivation of scleraxis (Scx(-/-)) fail to properly form limb tendons, but the role that scleraxis has in regulating the growth and adaptation of tendons of adult organisms is unknown. To determine if scleraxis expression changes in response to a physiological growth stimulus to tendons, we subjected adult mice that express green fluorescent protein (GFP) under the control of the scleraxis promoter (ScxGFP) to a 6-week-treadmill training program designed to induce adaptive growth in Achilles tendons.