Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes.

Osteoarthritis (OA) is a whole joint disease characterized by an important remodeling of the osteochondral junction. It includes cartilage mineralization due to chondrocyte hypertrophic differentiation and bone sclerosis. Here, we investigated whether gremlin-1 (Grem-1) and its BMP partners could be involved in the remodeling events of the osteochondral junction in OA.

Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis.

Osteoarthritis (OA) is a complex degenerative disease in which joint homeostasis is disrupted, leading to synovial inflammation, cartilage degradation, subchondral bone remodeling, and resulting in pain and joint disability. Yet, the development of new treatment strategies to restore the equilibrium of the osteoarthritic joint remains a challenge. Numerous studies have revealed that dietary components and/or natural products have anti-inflammatory, antioxidant, anti-bone-resorption, and anabolic potential and have received much attention toward the development of new therapeutic strategies for OA treatment.

The differentiation of prehypertrophic into hypertrophic chondrocytes drives an OA-remodeling program and IL-34 expression.

Objectives: We hypothesize that chondrocytes from the deepest articular cartilage layer are pivotal in maintaining cartilage integrity and that the modification of their prehypertrophic phenotype to a hypertrophic phenotype will drive cartilage degradation in osteoarthritis.

Design: Murine immature articular chondrocytes (iMACs) were successively cultured into three different culture media to induce a progressive hypertrophic differentiation. Chondrocyte were phenotypically characterized by whole-genome microarray analysis.

Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

Objectives: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed.

Adaptation of antibiotic treatment to clinical practice guidelines in patients aged ⩾65 years hospitalised due to community-acquired pneumonia.

Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013-14 and 2014-15 influenza seasons.

Factors associated with 30-day readmission after hospitalisation for community-acquired pneumonia in older patients: a cross-sectional study in seven Spanish regions.

Objective: Hospital readmission in patients admitted for community-acquired pneumonia (CAP) is frequent in the elderly and patients with multiple comorbidities, resulting in a clinical and economic burden. The aim of this study was to determine factors associated with 30-day readmission in patients with CAP.

Design: A cross-sectional study.

A Composite of Functional Status and Pneumonia Severity Index Improves the Prediction of Pneumonia Mortality in Older Patients.

Background: The baseline health status may be a determinant of interest in the evolution of pneumonia.

Objective: Our objective was to assess the predictive ability of community-acquired pneumonia (CAP) mortality by combining the Barthel Index (BI) and Pneumonia Severity Index (PSI) in patients aged ≥ 65 years.

Design, Patients And Main Measures: In this prospective, observational, multicenter analysis of comorbidities, the clinical data, additional examinations and severity of CAP were measured by the PSI and functional status by the BI.

Asthma in older people hospitalized with influenza in Spain: A case-control study.

Background: Influenza infection is an exacerbating factor for asthma, and its prevention is critical in older patients with asthma.

Objective: This study investigated the association between asthma and influenza-related hospitalization, in Spain, of patients ages ≥ 65 years and their clinical evolution.

Methods: A multicenter case-control study was carried out in 20 Spanish hospitals during the 2013-2014 and 2014-2015 influenza seasons.

Asthma and influenza vaccination in elderly hospitalized patients: Matched case-control study in Spain.

Objectives: Influenza infection is an exacerbating factor for asthma, and its prevention is critical in managing asthmatic patients. We investigated the effect of influenza vaccination on asthmatic and non-asthmatic patients hospitalized with laboratory-confirmed influenza in Spain.

Methods: We made a matched case-control study to assess the frequency of hospitalization for influenza in people aged ≥65 years.

Mesothelial-to-mesenchymal transition as a possible therapeutic target in peritoneal metastasis of ovarian cancer.

Peritoneal dissemination is the primary metastatic route of ovarian cancer (OvCa), and is often accompanied by the accumulation of ascitic fluid. The peritoneal cavity is lined by mesothelial cells (MCs), which can be converted into carcinoma-associated fibroblasts (CAFs) through mesothelial-to-mesenchymal transition (MMT). Here, we demonstrate that MCs isolated from ascitic fluid (AFMCs) of OvCa patients with peritoneal implants also undergo MMT and promote subcutaneous tumour growth in mice.

Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions.

Peritoneal adhesions (PAs) are fibrotic bands formed between bowel loops, solid organs, and the parietal peritoneum, which may appear following surgery, infection or endometriosis. They represent an important health problem with no effective treatment. Mesothelial cells (MCs) line the peritoneal cavity and undergo a mesothelial-to-mesenchymal transition (MMT) under pathological conditions, transforming into myofibroblasts, which are abundant in peritoneal fibrotic tissue.

Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis.

Peritoneal dialysis (PD) is a form of renal replacement therapy whose repeated use can alter dialytic function through induction of epithelial-mesenchymal transition (EMT) and fibrosis, eventually leading to PD discontinuation. The peritoneum from Cav1-/- mice showed increased EMT, thickness, and fibrosis. Exposure of Cav1-/- mice to PD fluids further increased peritoneal membrane thickness, altered permeability, and increased the number of FSP-1/cytokeratin-positive cells invading the sub-mesothelial stroma.

A pathogenetic role for endothelin-1 in peritoneal dialysis-associated fibrosis.

In patients undergoing peritoneal dialysis (PD), chronic exposure to nonphysiologic PD fluids elicits low-grade peritoneal inflammation, leading to fibrosis and angiogenesis. Phenotype conversion of mesothelial cells into myofibroblasts, the so-called mesothelial-to-mesenchymal transition (MMT), significantly contributes to the peritoneal dysfunction related to PD. A number of factors have been described to induce MMT in vitro and in vivo, of which TGF-β1 is probably the most important.

Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis.

Peritoneal dissemination is a frequent metastatic route for cancers of the ovary and gastrointestinal tract. Tumour cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity. Metastases are influenced by carcinoma-associated fibroblasts (CAFs), a cell population that derives from different sources.

Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.

Vascular endothelial growth factor (VEGF) is up-regulated during mesothelial to mesenchymal transition (MMT) and has been associated with peritoneal membrane dysfunction in peritoneal dialysis (PD) patients. It has been shown that normal and malignant mesothelial cells (MCs) express VEGF receptors (VEGFRs) and co-receptors and that VEGF is an autocrine growth factor for mesothelioma. Hence, we evaluated the expression patterns and the functional relevance of the VEGF/VEGFRs/co-receptors axis during the mesenchymal conversion of MCs induced by peritoneal dialysis.

Inhibition of transforming growth factor-activated kinase 1 (TAK1) blocks and reverses epithelial to mesenchymal transition of mesothelial cells.

Peritoneal fibrosis is a frequent complication of peritoneal dialysis following repeated low grade inflammatory and pro-fibrotic insults. This pathological process may lead to ultrafiltration failure and eventually to the discontinuing of the therapy. Fibrosis is linked to epithelial to mesenchymal transition (EMT) of the peritoneal mesothelial cells, which acquire invasive and fibrogenic abilities.

Blocking TGF-β1 protects the peritoneal membrane from dialysate-induced damage.

During peritoneal dialysis (PD), mesothelial cells undergo mesothelial-to-mesenchymal transition (MMT), a process associated with peritoneal-membrane dysfunction. Because TGF-β1 can induce MMT, we evaluated the efficacy of TGF-β1-blocking peptides in modulating MMT and ameliorating peritoneal damage in a mouse model of PD. Exposure of the peritoneum to PD fluid induced fibrosis, angiogenesis, functional impairment, and the accumulation of fibroblasts.

p38 maintains E-cadherin expression by modulating TAK1-NF-kappa B during epithelial-to-mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells is a pathological process that occurs during peritoneal dialysis. EMT leads to peritoneal fibrosis, ultrafiltration failure and eventually to the discontinuation of therapy. Signaling pathways involved in mesothelial EMT are thus of great interest, but are mostly unknown.

Low-GDP peritoneal dialysis fluid ('balance') has less impact in vitro and ex vivo on epithelial-to-mesenchymal transition (EMT) of mesothelial cells than a standard fluid.

Background: Peritoneal membrane deterioration during peritoneal dialysis (PD) is associated with epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MC), which is believed to be mainly due to glucose degradation products (GDPs) present in PD solutions. Here we investigate the impact of GDPs in PD solutions on the EMT of MC in vitro and ex vivo.

Methods: For in vitro studies, omentum-derived MC were incubated with standard PD fluid or low-GDP solution diluted 1:1 with culture medium.

PPAR-γ agonist rosiglitazone protects peritoneal membrane from dialysis fluid-induced damage.

Exposure to non-physiological solutions during peritoneal dialysis (PD) produces structural alterations to the peritoneal membrane and ultrafiltration dysfunction. The high concentration of glucose and glucose degradation products in standard PD fluids induce a local diabetic environment, which leads to the formation of advanced glycation end products (AGEs) that have an important role in peritoneal membrane deterioration. Peroxisome proliferator-activated receptor γ (PPAR-γ) agonists are used to treat type II diabetes and they have beneficial effects on inflammation, fibrosis, and angiogenesis.

BMP-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure.

Background: During peritoneal dialysis (PD), mesothelial cells (MC) undergo an epithelial-to-mesenchymal transition (EMT), and this process is associated with peritoneal membrane (PM) damage. Bone morphogenic protein-7 (BMP-7) antagonizes transforming growth factor (TGF)-beta1, modulates EMT and protects against fibrosis. Herein, we analysed the modulating role of BMP-7 on EMT of MC in vitro and its protective effects in a rat PD model.

Cyclooxygenase-2 mediates dialysate-induced alterations of the peritoneal membrane.

During peritoneal dialysis (PD), exposure of the peritoneal membrane to nonphysiologic solutions causes inflammation, ultimately leading to altered structure and function. Myofibroblasts, one of the cell types that contribute to dysfunction of the peritoneal membrane, can originate from mesothelial cells (MCs) by epithelial-to-mesenchymal transition (EMT), a process that has been associated with an increased rate of peritoneal transport. Because cyclooxygenase-2 (COX-2) is induced by inflammation, we studied the role of COX-2 in the deterioration of the peritoneal membrane.

Epithelial-to-mesenchymal transition of peritoneal mesothelial cells is regulated by an ERK/NF-kappaB/Snail1 pathway.

Epithelial-to-mesenchymal transition (EMT) occurs in fibrotic diseases affecting the kidney, liver and lung, and in the peritoneum of patients undergoing peritoneal dialysis. EMT in the peritoneum is linked to peritoneal membrane dysfunction, and its establishment limits the effectiveness of peritoneal dialysis. The molecular regulation of EMT in the peritoneum is thus of interest from basic and clinical perspectives.