The human lung harbors a large population of resident memory T cells (Trm cells). These are perfectly positioned to mediate rapid protection against respiratory pathogens such as influenza virus, highly contagious pathogen that continues be major public health burden. Animal models show influenza-specific CD8+ Trm indispensable for crossprotection pulmonary infection with different virus strains. However, it is not known whether present within the have same critical role in modulating course...

We report that antibodies can be spontaneously loaded in functionalized mesoporous silica (FMS) with superhigh density (0.4−0.8 mg of antibody/mg FMS) due to their comprehensive noncovalent interaction. The loading and interaction between FMS allow long-lasting local release the immunoregulatory molecules from under physiological conditions. Preliminary data indicate FMS-anti-CTLA4 antibody injected directly into a mouse melanoma induces much greater extended inhibition tumor growth than...

Abstract Increasing evidence highlights that senescence plays an important role in idiopathic pulmonary fibrosis ( IPF ). This study delineates the specific contribution of mitochondria and superoxide they form to senescent phenotype lung fibroblasts from patients ‐ LF s). Primary cultures s exhibited intensified DNA damage response DDR ) were more than age‐matched control donors (Ctrl‐ Furthermore, mitochondrial dysfunction, exemplified by increases superoxide, , stress activation mTORC 1....

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause with median survival only 3 years. Other investigators and we have shown that fibroblasts derived from IPF lungs display characteristics senescent cells, dysregulated activation the transcription factor signal transducer activator (STAT3) correlates progression. The question whether STAT3 involved in fibroblast senescence remains unanswered. We hypothesized inhibiting after oxidant-induced would attenuate...

We have previously reported arterial remodelling in patients with idiopathic pulmonary fibrosis (IPF) and suggested that endothelial-to-mesenchymal transition (EndMT) might be central to these changes. This study aims provide evidence for active EndMT IPF patients.Lung resections from 13 15 normal controls (NCs) were immunostained biomarkers: vascular endothelial cadherin (VE-cadherin), neural (N-cadherin), S100A4 vimentin. Pulmonary arteries analysed markers by using computer-...

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that prevalent in individuals >50 years of age, with median survival 3-5 and limited therapeutic options. The characterized by collagen deposition remodeling the parenchyma process thought to be driven collagen-expressing immune structural cells. G-protein coupled C-X-C chemokine receptor 4, CXCR4, candidate target for IPF owing its role recruitment CXCR4+ fibrocytes from bone marrow tissue increased expression levels...

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive accumulation of fibroblasts (LFs) and collagen in the parenchyma. The mechanisms that underlie IPF pathophysiology are thought to reflect repeated alveolar epithelial injury leading an aberrant wound repair response. Recent work has shown IPF-LFs display increased characteristics senescence including growth arrest senescence-associated secretory phenotype (SASP) suggesting senescent LFs contribute...

Senescence and mitochondrial stress are mutually reinforcing age-related processes that contribute to idiopathic pulmonary fibrosis (IPF); a lethal disease manifests primarily in the elderly. Whilst evidence is accumulating GMP-AMP synthase (cGAS) crucial perpetuating senescence by binding damaged DNA released into cytosol, its role IPF not known. The present study examines contributions of cGAS self lung fibroblasts from patients (IPF-LFs) age-matched controls (Ctrl-LFs). immunoreactivity...

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible fibrotic interstitial lung disease. We performed size-based quantitation of arterial remodelling in IPF and examined the role endothelial-to-mesenchymal transition (EndMT) effects on physiology.Resected tissues from 11 normal controls (NCs), 13 patients were differentially stained using Movat Pentachrome technique. Size-based classification for arteries was conducted NC tissues. For each artery, size, luminal diameter,...

Abstract Fibulin-1 is an extracellular matrix (ECM) protein, levels of which are elevated in serum and lung tissue from patients with idiopathic pulmonary fibrosis compared to healthy volunteers. Inhibition fibulin-1C, one four fibulin-1 isoforms, reduced proliferation wound healing human airway smooth muscle (ASM) cells. This study identified the bioactive region/s fibulin-1C promotes fibrosis. Seven peptides were synthesized used pre-coat culture plates before derived ASM cells fibroblasts...

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease involving degenerative breathing capacity. Fibrotic driven by dysregulation in mechanical forces at the organ, tissue, and cellular level. While it known that, certain pathologies, diseased cells are stiffer than healthy cells, not if fibroblasts derived from patients with IPF their normal counterparts. Using patient-derived cell cultures, we measured stiffness of individual via high-resolution force maps using atomic microscopy....

Abstract Background CXCR4, a transmembrane-receptor located on epithelial cells that is activated by CXCL12, may have role in IPF via migration of CXCR4 + fibrocytes to the lung. However, its expression has not been fully characterised idiopathic pulmonary fibrosis (IPF) or other fibrotic interstitial lung diseases (ILDs). CXCL12 constitutively expressed bone marrow, and levels regulate control this signalling pathway. The aim study was profile tissue peripheral circulation patients with...

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and poor prognosis. In IPF, aberrant extracellular matrix production by activated, hyperproliferative fibroblasts drives progression but the exact mechanisms which this occurs remains undefined. The transcription factor nuclear kappa-B (NF-ĸB) has been suggested as potential therapeutic target in IPF therefore aim study was to investigate efficacy ACT001, an NF-ĸB inhibitor, on primary derived from...

In lung injury and disease, including idiopathic pulmonary fibrosis (IPF), extravascular factor X is converted into Xa (FXa), a coagulant protease with fibrogenic actions. Extracellular annexin A2 binds to FXa, augmenting activation of the protease-activated receptor-1 (PAR-1). this study, contribution in was investigated. Annexin immunoreactivity observed regions fibrosis, those associated fibroblasts tissue IPF patients. Furthermore, detected conditioned media an EGTA membrane wash human...

Pathological changes in the biomechanical environment are implicated progression of idiopathic pulmonary fibrosis (IPF). Stiffened matrix augments fibroblast proliferation and differentiation activates TGF-β1 (transforming growth factor-β1). impairs synthesis antifibrogenic lipid mediator prostaglandin E2 (PGE2) reduces expression rate-limiting prostanoid biosynthetic enzyme cyclooxygenase-2 (COX-2). We now show that E synthase (PTGES), final PGE2 pathway, is expressed at lower levels lungs...

Introduction Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic lung condition with poor prognosis. Matrix metalloproteinase-7 (MMP7) protein secreted by epithelial cells in IPF lungs. It not known if MMP7 expression correlates changes tissue. Methods Tissue samples from apices and bases were obtained 20 patients 14 non-diseased control (NDC) donors. In formalin-fixed paraffin-embedded sections, histological assessment of was performed; overall positivity assessed...

Background: We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim quantify drivers of EndMT IPF compared normal controls (NCs). Methods: Lung resections from thirteen and eleven NCs were immunohistochemically stained for drivers, including TGF-β1, pSmad-2/3, Smad-7, β-catenin. Intima, media, adventitia analysed expression each driver arteries....

Cyclophosphamide (CTX) is often used to create a "window" for more effective therapeutic tumor vaccination. According commonly applied protocol, we injected 2 mg CTX intraperitoneally mice with small (2 3 mm diameter) or large (5 7 mm, and in one experiment 8 10 subcutaneously growing tumors from the SW1 clone of K1735 melanoma, euthanized 4 days later studied composition lymphoid cells by flow cytometry both spleens tumors. Administration increased percentage CD3, CD4, CD8 increase being...

Abstract For immunotherapy to become more effective, there is a need maximize the antitumor response at tumor site as well eliminate cell variants that lack given antigen or ability present it. We have previously shown wild-type (WT) cells from K1735 melanoma (K1735-WT) are rejected following vaccination with (K1735-1D8) transfected express scFv anti-CD137 monoclonal antibody 1D8, and CD4+ T natural killer (NK) needed for this rejection. now show tumors harvested 4 10 days after mice had...

Abstract The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels lung tissue sera from IPF patients to establish the mechanism its on fibroblasts (LFs). immunoreactivity was detected regions including (n = 7). Serum activity were also higher 18) than controls (P <...

Transforming growth factor-beta (TGF-β) is a major mediator of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). However, therapeutic global inhibition TGF-β limited by unwanted immunosuppression and mitral valve defects. We performed an extensive literature search to uncover little-known connection between signalling casein kinase (CK) activity. have examined the abundance CK1 delta epsilon (CK1δ/ε) in lung tissue from IPF patients non-diseased controls, investigated whether...

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Summary Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator‐induced injury, cardiopulmonary bypass, ischaemia‐reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety efficacy an open‐lung protective ventilation strategy aimed at reducing injury. enrolled adult scheduled undergo bilateral sequential transplantation, randomly assigned them either a control group (volume‐controlled with...