Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer activator of transcription 3 (STAT3) protein activated in lung fibroblasts alveolar type II cells (ATII), thereby contributing to IPF. Although activation Janus kinase 2 (JAK2) has been implicated proliferative disorders, its role IPF unknown. aim this study was analyze JAK2 IPF, determine whether JAK2/STAT3 inhibition a potential therapeutic...

Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on vessels is unknown. Here we analyzed the contribution of PH patients with IPF and potential mechanism implicated. arteries, lung tissue serum control subjects (n = 20), 20) were used study expression localization IL-11Rα. Two models bleomycin-induced Tie2-GFP transgenic mice evaluate endothelial cells artery remodeling. The...

Inflammasome activation is one of the first steps in initiating innate immune responses. In this work, we studied inflammasomes airways critically ill COVID-19 patients and effects N-acetylcysteine (NAC) on inflammasomes. Tracheal biopsies were obtained from without no respiratory disease (control, n = 32), SARS-CoV-2 B.1 variant (n 31), B.1.1.7 VOC alpha 20) patients. Gene expression protein measured by RT-qPCR immunohistochemistry. Macrophages bronchial epithelial cells stimulated with...

There is a pressing medical need for improved treatments in skin fibrosis including keloids and hypertrophic scars (HTS). This study aimed to characterize the role of phosphodiesterase 4 (PDE4), specifically PDE4B fibrotic remodeling vitro vivo. In vitro, effects PDE4A-D (Roflumilast) or (siRNA) inhibition on TGFβ1-induced myofibroblast differentiation dedifferentiation were studied normal (NHDF) keloid (KF) human dermal fibroblasts. vivo, PDE4 HOCl-induced mice was addressed preventive...

Exposure to solar radiation can cause a range of skin damage, including sunburn, erythema, carcinogenesis, the release reactive oxygen species (ROS), inflammation, DNA and photoaging. Other wavelengths beyond UVB, such as UVA, blue light, infrared radiation, also contribute harmful effects radiation. Reconstructed full-thickness human has potential serve effective predictive in vitro tools for evaluating on skin. The aim this work was evaluate damaging model terms viability, photoaging,...

Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates receive are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid chronic rhinosinusitis. The objective this work was analyze previously unexplored role on vitro and vivo models. MUC1-CT expression measured real time PCR, western blot, immunohistochemistry...

N-Acetyl-l-cysteine (NAC) acts as a precursor of the tripeptide glutathione (GSH), one principal cell mechanisms for reactive oxygen species (ROS) detoxification. Chronic obstructive pulmonary disease (COPD) is associated with enhanced inflammatory response and oxidative stress NAC has been used to suppress various pathogenic processes in this disease. Studies show that effects are dose-dependent, it appears efficient doses vitro usually higher than achieved vivo plasma concentrations....

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer widespread use, paclitaxel also damages healthy tissues, including skin. However, mechanisms that drive these skin adverse events are not clearly understood. In present study, we demonstrated, by using both primary epidermal keratinocytes (NHEK) 3D epidermis model, impairs different cellular...

Idiopathic pulmonary fibrosis (IPF) associated to hypertension (PH) portends a poor prognosis, characterized by lung parenchyma and artery remodeling. Serum levels of Interleukin 11 (IL-11) are elevated in IPF-PH patients contributes remodeling PH. However, the effect current approved therapies against IPF induced IL-11 is unknown. The aim this study analyze effects nintedanib pirfenidone on endothelial smooth muscle cell vitro. Our results show that (NTD) (PFD) ameliorates mesenchymal...

Abstract Background Epidermal remodeling and hypertrophy are hallmarks of skin fibrotic disorders, keratinocyte to mesenchymal (EMT)-like transformations drive epidermis alteration in fibrosis such as keloids hypertrophic scars (HTS). While phosphodiesterase 4 (PDE4) inhibitors have shown effectiveness various their role is not fully understood. This study aimed explore the specific PDE4B epidermal seen fibrosis. Methods In vitro experiments examined effects inhibiting PDE4A-D (with...

Background and Purpose IL‐11 is a member of the IL‐6 family cytokine initially considered as haematopoietic cytoprotective factor. Recent evidence indicates that promotes lung fibrosis pulmonary hypertension in animal models elevated tissue patients with hypertension. Fibrocytes are bone marrow‐derived circulating cells participate hypertension, but role on fibrocytes unknown. We investigated system fibrocyte activation different vitro vivo associated Experimental Approach Human were...

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent. Despite its widespread use, it damages healthy tissues such as skin. The goal of this study was to prove that the real impact paclitaxel-induced skin toxicity could be underestimated because adverse events might appear asymptomatic.Gynecological cancer patients were recruited. Skin parameters measurements taken after three and six paclitaxel cycles. Measurements conducted using specific probes which measure hydration,...

IL-11 is linked to fibrotic diseases, but its role in pulmonary hypertension unclear. We examined IL-11's involvement idiopathic arterial (iPAH). Using samples from control (n = 20) and iPAH 6) subjects, we assessed IL-11Rα expression localization through RT-qPCR, ELISA, immunohistochemistry, immunofluorescence. A monocrotaline-induced PAH model helped evaluate the impact of siRNA-IL-11 on artery remodeling PH. The effects recombinant human smooth muscle cell (HPASMC) proliferation,...

Solar radiation can cause damage to the skin, leading various adverse effects such as sunburn, reactive oxygen species production, inflammation, DNA damage, and photoaging. To study potential of photoprotective agents, full-thickness skin models are increasingly being used in vitro tools. One promising approach photoprotection involves targeting redox-sensitive transcription factor Nrf2, which is responsible for regulating cellular defense mechanisms, including antioxidant response,...

Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. Currently, no therapy can improve survival of patients diagnosed with this disease. IL-11 molecular pathway is over-expressed proliferative disorders, however, its role PH- associated IPF unknown. The aim study was to evaluated the expression or without PH. Also we hypothesized that stimulation artery smooth muscle cells (PASMCs) and human microvascular endothelial (HMVEC-L) induced transformation...

<b>Background:</b> Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible form of fibrotic interstitial lung disease. MUC1, membrane-bound O-glycoprotein, considered as oncogenic molecule by altering signaling pathways involved in cellular processes related to IPF. In previous studies we have observed an up-regulation MUC1 its phosphorylated forms IPF tissue. However the exact participation currently unknown. <b>Objective:</b> To analyze mechanism MUC1-induced...

Delayed-type hypersensitivity (DTH) is caused by a broad number of drugs used in clinic, and antineoplastic show an elevated proportion DTH, which potentially affects the quality life patients. Despite serious problem negative economic impact deriving from market withdrawal such high hospitalization costs, nowadays, there are no standard validated methods vitro or vivo to evaluate sensitizing potential preclinical phase. Enhanced predictions safety evaluations really important, for that...