Pulmonary alveolar proteinosis: Clinical and morphological overview of a rare disease associated with macrophage dysfunction.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by excessive accumulation of surfactant components in alveolar macrophages, alveoli, and peripheral airways. The accumulation of surfactant is associated with only a minimal inflammatory response but can lead to the development of pulmonary fibrosis. Three clinical forms of PAP are distinguished - primary, secondary and congenital.

Idiopathic Pulmonary Fibrosis: Review of Current Knowledge.

Idiopathic pulmonary fibrosis (IPF) is a severe and currently incurable disease that is associated with irreversible fibrotic remodeling of the lung parenchyma. Pathological remodeling of the lung leads to damage of the alveolo-capillary barrier. There is a reduction in the diffusing capacity of the lungs for respiratory gases.

Histopathological aspects of usual interstitial pneumonia in patients with systemic connective tissue diseases.

Five cases of patients with systemic connective tissue diseases (CTD) who developed connective tissue disease-associated interstitial lung disease (CTD-ILD) with progressive pulmonary fibrosis (PPF) are reported here. Unspecified ILD was diagnosed using high-resolution computed tomography (HRCT). Histologically, all cases were usual interstitial pneumonia (UIP) with findings of advanced (3/5) to diffuse (2/5) fibrosis, with a partially (4/5) to completely (1/5) formed image of a honeycomb lung.

Pulmonary sequestration in adulthood: clinical-morphological study.

Objectives: The aim of the study was to evaluate pulmonary sequestration (PS). We report on location, blood supply, histology, clinical manifestation, and surgical treatment of PS, as well as on postoperative course in patients with PS.

Background: PS is a rare congenital defect of the lower respiratory tract, it represents locus minoris resistentiae of the body.

Histopathological findings in lung biopsies with usual interstitial pneumonia: Definition of a new classification score for histological fibrotic stages.

The objective of this article is to describe and classify usual interstitial pneumonia (UIP) changes according to their relevance in the pathology of the idiopathic pulmonary fibrosis (IPF) process. In a cohort of 50 patients (25♀, 25♂) with UIP findings, the percentage ratio between fibrotic and preserved parts of the lungs was quantified. Three quantitative stages of fibrotic involvement of the lung parenchyma and concomitant changes were defined.

Our experience with solitary fibrous tumors in the chest area.

The article reports on three patients with a solitary fibrous tumor of the chest. The first patient had a tumor in the area of the dome of the right pleural cavity which was radically resected together with the chest wall around its origin. In the second case, the tumor was attached by a vascular pedicle to the lower lobe of the right lung.

Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course.

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection.

Intrapulmonary sequestration with destructive pneumonia and life-threatening hemoptysis in an adult patient: a case report.

The article reports the case of a patient with bronchopulmonary sequestration complicated by destructive actinomycotic inflammation leading to life-threatening hemoptysis. It was an adult patient with the history of repeated right-sided pneumonia the cause of which had not been investigated in detail in the past. Only hemoptysis, which appeared as a complication, led to a closer investigation of the background of repeated right-sided pneumonia.

Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein.

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes.

Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2.

Unlabelled: Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes.

The thioredoxin system: Balancing redox responses in immune cells and tumors.

The thioredoxin (TRX) system is an important contributor to cellular redox balance and regulates cell growth, apoptosis, gene expression, and antioxidant defense in nearly all living cells. Oxidative stress, the imbalance between reactive oxygen species (ROS) and antioxidants, can lead to cell death and tissue damage, thereby contributing to aging and to the development of several diseases, including cardiovascular and allergic diseases, diabetes, and neurological disorders. Targeting its activity is also considered as a promising strategy in the treatment of cancer.

Anti-chemokine antibodies after SARS-CoV-2 infection correlate with favorable disease course.

Unlabelled: Infection by SARS-CoV-2 leads to diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse COVID-19 outcomes. Instead, we discovered that antibodies against specific chemokines are omnipresent after COVID-19, associated with favorable disease, and predictive of lack of long COVID symptoms at one year post infection.

Peroxisomes Are Critical for the Development and Maintenance of B1 and Marginal Zone B Cells but Dispensable for Follicular B Cells and T Cells.

Antioxidant systems maintain cellular redox (oxidation-reduction) homeostasis. In contrast with other key redox pathways, such as the thioredoxin system, glutathione, and NF-E2-related factor 2 (Nrf2), little is known about the function of the redox-sensitive organelle "peroxisome" in immune cells. In this study, we show that the absence of peroxisomes in conditional -deficient mice strikingly results in impaired homeostatic maintenance of innate-like B cells, namely, B1 and marginal zone B cells, which translates into a defective Ab response to Surprisingly, however, follicular B2 cell development, homeostatic maintenance, germinal center reactions, Ab production, class switching, and B cell memory formation were unaffected in -deficient animals.

The role of tumor-associated macrophages in solid malignancies - an overview of current knowledge.

Tumor-associated macrophages are an important part of the tumor microenvironment. The presence of certain populations of macrophages within tumor tissue may be associated with either better or worse disease prognosis. The study of these cells is currently receiving a great deal of attention, with the most important topics of investigation raised being: the typification of subpopulations of tumor-associated macrophages; identification of the prognostic significance of population density and distribution of macrophages in the tumor microenvironment; ways to influence macrophage activity, migration and differentiation within the tumor.

Differential sensitivity of inflammatory macrophages and alternatively activated macrophages to ferroptosis.

Acumulation of oxidized membrane lipids ultimately results in ferroptotic cell death, which can be prevented by the selenoenzyme glutathione peroxidase 4 (Gpx4). In vivo conditions promoting ferroptosis and susceptible cell types are still poorly defined. In this study, we analyzed the conditional deletion of Gpx4 in mice specifically in the myeloid cell lineages.

Redox regulation of immunometabolism.

Metabolic pathways and redox reactions are at the core of life. In the past decade(s), numerous discoveries have shed light on how metabolic pathways determine the cellular fate and function of lymphoid and myeloid cells, giving rise to an area of research referred to as immunometabolism. Upon activation, however, immune cells not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system, which in turn supports metabolic reprogramming.

The thioredoxin-1 inhibitor Txnip restrains effector T-cell and germinal center B-cell expansion.

Thioredoxin-1 (Trx1) is a vital component for cellular redox homeostasis. In T cells, Trx1 donates electrons for the de novo synthesis of deoxyribonucleotides to allow rapid cell proliferation. The Trx-interacting protein (Txnip) binds to the reduced Trx1 and inhibits its activity.

Electrophilic Nrf2 activators and itaconate inhibit inflammation at low dose and promote IL-1β production and inflammatory apoptosis at high dose.

Controlling inflammation is critical for preventing many diseases including cancer, autoimmune disorders and hypersensitivity reactions. NF-E2-related factor 2 (Nrf2) is a key transcription factor that controls the cellular antioxidant and cytoprotective response. Moreover, Nrf2 has been implicated in the regulation of inflammatory processes, although the ultimate mechanism by which this is achieved is unknown.

Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization.

Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype.

Cyclopentenone Prostaglandins and Structurally Related Oxidized Lipid Species Instigate and Share Distinct Pro- and Anti-inflammatory Pathways.

Oxidized lipids play a critical role in a variety of diseases with two faces: pro- and anti-inflammatory. The molecular mechanisms of this Janus-faced activity remain largely unknown. Here, we have identified that cyclopentenone-containing prostaglandins such as 15d-PGJ2 and structurally related oxidized phospholipid species possess a dual and opposing bioactivity in inflammation, depending on their concentration.

Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip.

Antioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how such systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role in T cells, the murine Trx1 system is dispensable for steady-state myeloid-cell hematopoiesis due to their capacity to tap the glutathione/glutaredoxin pathway for DNA biosynthesis.

Maternal obstructive sleep apnea and neonatal birth outcomes in a population based sample.

Objective: Evaluate the association of OSA with birth outcomes including the risk of congenital anomalies and the need for a higher level of clinical care at delivery.

Methods: Population-based study that linked newborn records with maternal records. Data from 95 perinatal centers across all geographic census divisions of the U.

B1 and Marginal Zone B Cells but Not Follicular B2 Cells Require Gpx4 to Prevent Lipid Peroxidation and Ferroptosis.

Aerobic organisms need to maintain cellular redox homeostasis. Glutathione peroxidase-4 (Gpx4) has the unique ability to protect cells against lipid peroxidation. Here, we show that Gpx4 is absolutely required to prevent ferroptosis during development, maintenance, and responses of innate-like B cells, namely, the B1 and marginal zone (MZ) B cells.

Development and Validation of a Risk Prediction Model for Cesarean Delivery After Labor Induction.

The goal of the study was to develop and validate a prediction model for cesarean delivery after labor induction that included factors known before the start of induction, unlike prior studies that focused on characteristics at the time of induction. Using 17,370 term labor inductions without documented medical indications occurring at 14 U.S.