Bioactivity, hemocompatibility, and inflammatory response of calcium incorporated sulfonated polyether ether ketone on mouse-derived bone marrow cells.

Natural and synthetic polymeric materials, particularly soft and hard tissue replacements, are paramount in medicine. We prepared calcium-incorporated sulfonated polyether-ether ketone (SPEEK) polymer membranes for bone applications. The bioactivity was higher after 21 days of immersion in simulated body fluid (SBF) due to calcium concentration in the membrane.

All-trans retinoic acid and dexamethasone regulate phagocytosis-related gene expression and enhance dead cell uptake in C2C12 myoblast cells.

Extensive mechanical stress frequently causes micro-traumas in skeletal muscle, followed by a regeneration period. The effective removal of dead myofibers is a prerequisite for proper regeneration, and several cell types, including professional phagocytes, were reported to be active in this process. Myoblasts express several molecules of the phagocytic machinery, such as BAI1, stabilin-2, and TAM (Tyro3, Axl, Mertk) tyrosine kinase receptors, but these molecules were reported to serve primarily cell fusion and survival, and their role in the phagocytosis was not investigated.

Loss of adenosine A3 receptors accelerates skeletal muscle regeneration in mice following cardiotoxin-induced injury.

Skeletal muscle regeneration is a complex process orchestrated by multiple interacting steps. An increasing number of reports indicate that inflammatory responses play a central role in linking initial muscle injury responses to timely muscle regeneration following injury. The nucleoside adenosine has been known for a long time as an endogenously produced anti-inflammatory molecule that is generated in high amounts during tissue injury.

Transglutaminase 2 associated with PI3K and PTEN in a membrane-bound signalosome platform blunts cell death.

Atypically expressed transglutaminase 2 (TG2) has been identified as a poor prognostic factor in a variety of cancers. In this study, we evaluated the contribution of TG2 to the prolonged cell survival of differentiated acute promyelocytic leukaemia (APL) cells in response to the standard treatment with combined retinoic acid (ATRA) and arsenic trioxide (ATO). We report that one advantage of ATRA + ATO treatment compared to ATRA alone diminishes the amount of activated and non-activated CD11b/CD18 and CD11c/CD18 cell surface integrin receptors.

Nur77 and PPARγ regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation.

Macrophage polarization is a process whereby macrophages develop a specific phenotype and functional response to different pathophysiological stimuli and tissue environments. In general, two main macrophage phenotypes have been identified: inflammatory (M1) and alternatively activated (M2) macrophages characterized specifically by IL-1β and IL-10 production, respectively. In the cardiotoxin-induced skeletal muscle injury model bone marrow-derived macrophages (BMDMs) play the central role in regulating tissue repair.

Retinoids Promote Mouse Bone Marrow-Derived Macrophage Differentiation and Efferocytosis via Upregulating Bone Morphogenetic Protein-2 and Smad3.

Clearance of apoptotic cells by bone marrow-derived macrophages differentiated from monocytes plays a central role in the resolution of inflammation, as the conversion of pro-inflammatory M1 macrophages to M2 macrophages that mediate the resolution process occurs during efferocytosis. Thus, proper efferocytosis is a prerequisite for proper resolution of inflammation, and failure in efferocytosis is associated with the development of chronic inflammatory diseases. Previous studies from our laboratory have shown that (13)-all--13,14-dihydroretinol (DHR), the product of retinol saturase, acting from day 4 of monocyte differentiation enhances the efferocytosis capacity of the resulted macrophages.

Involvement of phosphatidylserine receptors in the skeletal muscle regeneration: therapeutic implications.

Sarcopenia is a progressive loss of muscle mass and strength with a risk of adverse outcomes such as disability, poor quality of life, and death. Increasing evidence indicates that diminished ability of the muscle to activate satellite cell-dependent regeneration is one of the factors that might contribute to its development. Skeletal muscle regeneration following myogenic cell death results from the proliferation and differentiation of myogenic stem cells, called satellite cells, located beneath the basal lamina of the muscle fibres.

Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice.

Skeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering the timed polarization of the inflammatory phenotype of macrophages into the healing one. While pro-inflammatory cytokines produced by the inflammatory macrophages induce satellite cell proliferation and differentiation into myoblasts, healing macrophages initiate the resolution of inflammation, angiogenesis, and extracellular matrix formation and drive myoblast fusion and myotube growth.

Impaired Skeletal Muscle Development and Regeneration in Transglutaminase 2 Knockout Mice.

Skeletal muscle regeneration is triggered by local inflammation and is accompanied by phagocytosis of dead cells at the injury site. Efferocytosis regulates the inflammatory program in macrophages by initiating the conversion of their inflammatory phenotype into the healing one. While pro-inflammatory cytokines induce satellite cell proliferation and differentiation into myoblasts, growth factors, such as GDF3, released by healing macrophages drive myoblast fusion and myotube growth.

TAM kinase signaling is indispensable for proper skeletal muscle regeneration in mice.

Skeletal muscle regeneration following injury results from the proliferation and differentiation of myogenic stem cells, called satellite cells, located beneath the basal lamina of the muscle fibers. Infiltrating macrophages play an essential role in the process partly by clearing the necrotic cell debris, partly by producing cytokines that guide myogenesis. Infiltrating macrophages are at the beginning pro-inflammatory, but phagocytosis of dead cells induces a phenotypic change to become healing macrophages that regulate inflammation, myoblast fusion and growth, fibrosis, vascularization and return to homeostasis.

Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity.

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway.

Macrophages engulf apoptotic and primary necrotic thymocytes through similar phosphatidylserine-dependent mechanisms.

One of the major roles of professional phagocytes is the removal of dead cells in the body. We know less about the clearance of necrotic cells than apoptotic cell phagocytosis, despite the fact that both types of dead cells need to be cleared together and necrotic cells appear often in pathological settings. In the present study, we examined phagocytosis of heat- or HO-killed necrotic and apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs) and found that the two cell types are engulfed at equal efficiency and compete with each other when added together to BMDMs.

Short-term high-fat meal intake alters the expression of circadian clock-, inflammation-, and oxidative stress-related genes in human skeletal muscle.

Dietary food, depending on timing, amount and composition can influence gene expression in various tissues. Here, we investigated the effect of high-fat meal diets of different compositions on the gene expression pattern of human skeletal muscle. Gene expression data of skeletal muscle samples from human volunteers prior and 4 h after the consumption of high lipid-containing meal consisting of either saturated-, monounsaturated- or polyunsaturated fatty acids were downloaded from the public repository.

Altered Gene Expression of Muscle Satellite Cells Contributes to Agerelated Sarcopenia in Mice.

Background: During aging, muscle tissue undergoes profound changes which lead to a decline in its functional and regenerative capacity. We utilized global gene expression analysis and gene set enrichment analysis to characterize gene expression changes in aging muscle satellite cells.

Method: Gene expression data; obtained from Affymetrix Mouse Genome 430 2.

Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men.

Background: Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men.

Transglutaminase 2 in human diseases.

Transglutaminase 2 (TG2) is an inducible transamidating acyltransferase that catalyzes Ca(2+)-dependent protein modifications. In addition to being an enzyme, TG2 also serves as a G protein for several seven transmembrane receptors and acts as a co-receptor for integrin β1 and β3 integrins distinguishing it from other members of the transglutaminase family. TG2 is ubiquitously expressed in almost all cell types and all cell compartments, and is also present on the cell surface and gets secreted to the extracellular matrix via non-classical mechanisms.

Anti-inflammatory Mechanisms Triggered by Apoptotic Cells during Their Clearance.

In the human body, billions of cells die by apoptosis every day. The subsequent clearance of apoptotic cells by phagocytosis is normally efficient enough to prevent secondary necrosis and the consequent release of cell contents that would induce inflammation and trigger autoimmunity. In addition, apoptotic cells generally induce an anti-inflammatory response, thus removal of apoptotic cells is usually immunologically silent.

The proteomic profile of a mouse model of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) develops as a complication of retinal detachment surgery and represents a devastating condition leading to serious vision loss. A good animal model that permits extensive functional studies and drug testing is crucial in finding better therapeutic modalities for PVR. A previously established mouse model, using dispase injection, was analyzed from the proteomic point of view, examining global protein profile changes by 2D electrophoresis, image analysis and HPLC-tandem mass spectrometry-based protein identification.

Novel circulating placental markers prokineticin-1, soluble fms-like tyrosine kinase-1, soluble endoglin and placental growth factor and association with late miscarriage.

Study Question: Are novel circulating placental markers prokineticin-1 (PK-1), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) associated with late miscarriage in asymptomatic first trimester pregnant women?

Summary Answer: Increased serum sFlt-1 or PlGF, but not sEng or PK-1, were significantly associated with reduced miscarriage risk after adjustment for age, BMI, gestational age, smoking and blood pressure.

What Is Known Already: Abnormal placental development is observed in two-thirds of miscarriages. Identifying women at high risk of late miscarriage could help diagnose potentially treatable causes of miscarriage such as infection, thrombosis or immunological disease.

Altered expression of autophagy-related genes might contribute to glucocorticoid resistance in precursor B-cell-type acute lymphoblastic leukemia.

Objectives: Autophagy is an evolutionarily conserved process playing an important role in tumor cell's resistance to chemotherapy. Response to glucocorticoid (GC) treatment is out of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL); however, only few data are available connecting GC response and role of autophagy. Our aim was to investigate whether altered expression of autophagy-related genes contributes to GC-resistant phenotype in GC-sensitive and GC-resistant precursor B-cell-type (PBC) ALL cells.

Extended Recipient Criteria in Lung Transplantation: Impact of Pleural Abnormalities on Primary Graft Dysfunction.

Background: Because of improved surgical expertise and intraoperative management, pleural disease (PD+) represents a relatively minor contraindication to lung transplantation (LTx). The presence of pleural abnormalities from previous procedures or pleural involvement from fungal or bacterial disease is not considered a limiting factor for LTx. However there are no studies available to assess the impact of pleural diseases on short- and midterm outcomes after LTx.

The metastatic tumor antigen 1-transglutaminase-2 pathway is involved in self-limitation of monosodium urate crystal-induced inflammation by upregulating TGF-β1.

Introduction: Transglutaminase 2 (TG2), a protein crosslinking enzyme with multiple biochemical functions, has been connected to various inflammatory processes. In this study, the involvement of TG2 in monosodium urate (MSU) crystal-induced inflammation was studied.

Methods: Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect TG2 expression in synovial fluid mononuclear cells (SFMCs) and synovial tissue from patients with gouty arthritis.

Neurokinin B administration induces hot flushes in women.

Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes.

Retinoids induce Nur77-dependent apoptosis in mouse thymocytes.

Nur77 is a transcription factor, which plays a determinant role in mediating T cell receptor-induced cell death of thymocytes. In addition to regulation of transcription, Nur77 contributes to apoptosis induction by targeting mitochondria, where it can convert Bcl-2, an anti-apoptotic protein into a proapoptotic molecule. Previous studies have demonstrated that retinoids are actively produced in the mouse thymus and can induce a transcription-dependent apoptosis in mouse thymocytes.

Glucocorticoids enhance prolonged clearance of apoptotic cells by upregulating liver X receptor, peroxisome proliferator-activated receptor-δ and UCP2.

Efficient phagocytic clearance of apoptotic cells (efferocytosis) is essential to prevent the development of chronic inflammation and autoimmunity. Glucocorticoids are widely used in the therapy of chronic inflammatory diseases, and increasing evidence suggests that they act partly via enhancing efferocytosis by macrophages. Glucocorticoids were previously shown to promote both protein S- and MFG-E8-dependent efferocytosis.