Functional differences in visceral and subcutaneous fat pads originate from differences in the adipose stem cell.

Metabolic pathologies mainly originate from adipose tissue (AT) dysfunctions. AT differences are associated with fat-depot anatomic distribution in subcutaneous (SAT) and visceral omental (VAT) pads. We address the question whether the functional differences between the two compartments may be present early in the adipose stem cell (ASC) instead of being restricted to the mature adipocytes.

Inflammatory response in human skeletal muscle cells: CXCL10 as a potential therapeutic target.

Inflammatory myopathies (IMs) are systemic diseases characterized by a T helper (Th) 1 type inflammatory response and cell infiltrates within skeletal muscles. The mainstay of treatment is drugs aimed at suppressing the immune system - corticosteroids and immunosuppressants. About 25% of patients are non-responders.

Gonadotropin-releasing hormone modulates cholesterol synthesis and steroidogenesis in SH-SY5Y cells.

Neurosteroids are involved in Central Nervous System development, brain functionality and neuroprotection but little is known about regulators of their biosynthesis. Recently gonadotropins, Gonadotropin-releasing Hormone (GnRH) and their receptors have been localized in different brain regions, such as hippocampus and cortex. Using human neuronal-like cells we found that GnRH up-regulates the expression of key genes of cholesterol and steroid synthesis when used in a narrow range around 1.

Peroxisome-proliferator-activated receptor gamma (PPARgamma) is required for modulating endothelial inflammatory response through a nongenomic mechanism.

Besides their well-known anti-diabetic effects, the peroxisome-proliferator-activated receptor gamma (PPARgamma) thiazolidinedione ligands (TZD) have been suggested to also display anti-inflammatory properties. The receptor role in mediating such effects is far from being elucidated. Here, we demonstrated that PPARgamma is necessary for TZD to interfere with TNFalpha and IFNgamma inflammatory activity in human endothelial cells.

Comparison between VDR analogs and current immunosuppressive drugs in relation to CXCL10 secretion by human renal tubular cells.

During kidney allograft rejection, CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) trafficking between peripheral blood and tissues initiates alloresponse and perpetuates a self-inflammatory loop; thus, CXCL10-CXCR3 axis could represent a pharmacologic target. In this perspective, immunosuppressors targeting graft-resident cells, beside immune cells, could be very advantageous. Vitamin D receptor (VDR) agonists exhibit considerable immunomodulatory properties.

Interferon-alpha, -beta and -gamma induce CXCL9 and CXCL10 secretion by human thyrocytes: modulation by peroxisome proliferator-activated receptor-gamma agonists.

It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in "primary cultures of human thyroid follicular cells" (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant.

Rosiglitazone impairs proliferation of human adrenocortical cancer: preclinical study in a xenograft mouse model.

Adrenocortical carcinoma (ACC) is a rare aggressive tumor with a poor prognosis. The lack of a specific and effective medical treatment is due to the poor knowledge of the mechanisms underlying tumor growth. Research on potential drugs able to specifically interfere with tumor proliferation is essential to develop more efficacious therapies.

Peroxisome proliferator-activated receptor gamma (PPARgamma): Is the genomic activity the only answer?

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily of transcription factors, widely expressed in the organism, including adipose, vascular and immune cells. Besides the well-known role in lipid/glycidic homeostasis, PPARgamma has also recently emerged as a key regulator of inflammatory and immune responses. Besides the natural ligands, more potent synthetic agonists of PPARgamma have been developed, including thiazolidinediones (TZDs), currently used in type 2 diabetes treatment, which also exert anti-inflammatory and anti-neoplastic effects.

Seladin-1 and testicular germ cell tumours: new insights into cisplatin responsiveness.

The molecular basis for the exquisite sensitivity of testicular germ cell tumours of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell tumours, to chemo/radiotherapy has not been fully clarified so far. It has been suggested that it may be dependent on factors involved in the regulation of apoptosis. Seladin-1 is a multi-functional protein involved in various biological processes, including apoptosis.

Molecular mechanisms underlying the pro-inflammatory synergistic effect of tumor necrosis factor alpha and interferon gamma in human microvascular endothelium.

Tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) are among the most potent cytokines involved in orchestrating the inflammation response. The molecular mechanisms implicated in the synergism between cytokines are still poorly characterized. We demonstrate that both cytokines dose-dependently stimulate IFNgamma-inducible-protein-of-10-kDa (IP-10) secretion in human microvascular endothelial cells (HMEC-1), showing a potent synergism which is not restricted to IP-10, but is also evident for monokine-induced-by-IFNgamma (MIG) and IL-6 secretion.

Characterization of human adult stem-cell populations isolated from visceral and subcutaneous adipose tissue.

Adipose tissue is a dynamic endocrine organ with a central role in metabolism regulation. Functional differences in adipose tissue seem associated with the regional distribution of fat depots, in particular in subcutaneous and visceral omental pads. Here, we report for the first time the isolation of human adipose-derived adult stem cells from visceral omental and subcutaneous fat (V-ASCs and S-ASCs, respectively) from the same subject.

Pretransplant positivity for circulating thyroid antibodies and graft survival in patients undergoing kidney transplant.

Background: Thyroid disturbances are common in kidney graft recipients and they may influence graft function. CXC chemokine ligand 10 plays a role in both autoimmune thyroiditis and graft rejection. Thyroid antibody (Ab) positivity has been regarded as a marker of imbalance of the immune system.

New insights on the neuroprotective role of sterols and sex steroids: the seladin-1/DHCR24 paradigm.

In 2000 a new gene, i.e. seladin-1 (for selective Alzheimer's disease indicator-1) was identified and found to be down regulated in vulnerable brain regions in Alzheimer's disease.

Globular adiponectin induces differentiation and fusion of skeletal muscle cells.

The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrophies, muscular atrophy, and cachexia. Studies focused on the ability of extracellular factors to promote myogenesis are therefore highly promising. We now report that an adipocyte-derived factor, globular adiponectin (gAd), is able to induce muscle gene expression and cell differentiation.

The CXCR4/CXCL12 axis in endometrial cancer.

Chemokines and their receptors seem to act as important regulators of the metastatic cascade. CXCL12 and its receptor CXCR4 were shown to be involved in human cancer progression. There is increasing evidences suggesting that the expression of CXCR4 in human cancers is correlated with poor patient prognosis and that CXCR4 neutralization can prevent metastases in vivo.

Predictive role of pretransplant serum CXCL10 for cardiac acute rejection.

Background: The detection of acute rejection in heart transplantation remains an important feature of transplant management, especially in the early phase. Frequent surveillance with endomyocardial biopsy is necessary, even though it is an invasive procedure and carries a certain risk. Hence, noninvasive biomarkers able to predict acute rejection could be a further helpful tool in patient management.

Regeneration of glomerular podocytes by human renal progenitors.

Depletion of podocytes, common to glomerular diseases in general, plays a role in the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can be repaired has not been established. Here, we demonstrate that in the adult human kidney, CD133+CD24+ cells consist of a hierarchical population of progenitors that are arranged in a precise sequence within Bowman's capsule and exhibit heterogeneous potential for differentiation and regeneration.

Estrogen receptor-mediated neuroprotection: The role of the Alzheimer's disease-related gene seladin-1.

Experimental evidence supports a protective role of estrogen in the brain. According to the fact that Alzheimer's disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. However, there is no general consensus on the beneficial effect of estrogen or selective estrogen receptor modulators in preventing or treating AD.

Neuroprotective effects of the Alzheimer's disease-related gene seladin-1.

The endocrine and the nervous system are closely correlated throughout life, starting from the embryo and until the late stages of life. Alzheimer's disease (AD) is the most common neurodegenerative disease associated with ageing. Unfortunately, an effective way to prevent or to cure this disease does not exist, so far.

Androgen receptor regulation of the seladin-1/DHCR24 gene: altered expression in prostate cancer.

Prostate cancer (CaP) represents a major leading cause of morbidity and mortality in the Western world. Elevated cholesterol levels, resulting from altered cholesterol metabolism, have been found in CaP cells. Seladin-1 (SELective Alzheimer Disease INdicator-1)/DHCR24 is a recently described gene involved in cholesterol biosynthesis.

Rosiglitazone inhibits adrenocortical cancer cell proliferation by interfering with the IGF-IR intracellular signaling.

Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-gamma, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R) of human adrenocortical carcinoma (ACC) and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR). We demonstrate a high expression of IGF-IR in the two cell lines and in ACC.

PPARgamma in Neuroblastoma.

Neuroblastoma (NB) is the most common extracranial tumor in children and accounts for around 15% of all paediatric oncology deaths. The treatment of NB includes surgery, chemotherapy, and radiotherapy. Unfortunately, most children with NB present with advanced disease, and more than 60% of patients with high-risk features will have a poor prognosis despite intensive therapy.

Seladin-1 is a fundamental mediator of the neuroprotective effects of estrogen in human neuroblast long-term cell cultures.

Estrogen exerts neuroprotective effects and reduces beta-amyloid accumulation in models of Alzheimer's disease (AD). A few years ago, a new neuroprotective gene, i.e.