The First Potentially Causal Genetic Variant Documented in a Polish Woman with Multiple Cavernous Malformations of the Brain.

Cerebral cavernous malformations (CCMs) are relatively common in the central nervous system. They occur in two forms, sporadic and familial (FCCMs). Three genes are recognized to be associated with FCCM, including , , and , the latter also called .

Human Lung Organoids-A Novel Experimental and Precision Medicine Approach.

The global burden of respiratory diseases is very high and still on the rise, prompting the need for accurate models for basic and translational research. Several model systems are currently available ranging from simple airway cell cultures to complex tissue-engineered lungs. In recent years, human lung organoids have been established as highly transferrable three-dimensional in vitro model systems for lung research.

Editorial of Special Issue "Molecular Mechanisms of Allergy and Asthma 2.0".

Similarly to the previous Special Issue entitled "Molecular Mechanisms of Allergy and Asthma" [...

Identification of extracellular vesicle microRNA signatures specifically linked to inflammatory and metabolic mechanisms in obesity-associated low type-2 asthma.

Rationale And Objective: Plasma extracellular vesicles (EVs) represent a vital source of molecular information about health and disease states. Due to their heterogenous cellular sources, EVs and their cargo may predict specific pathomechanisms behind disease phenotypes. Here we aimed to utilize EV microRNA (miRNA) signatures to gain new insights into underlying molecular mechanisms of obesity-associated low type-2 asthma.

Increased oxidative stress response in circulating blood of systemic sclerosis patients - relation to disease characteristics and inflammatory blood biomarkers.

Background: Systemic sclerosis (SSc) is a rare connective tissue disorder of unknown etiology characterized by organ fibrosis and microcirculation dysfunction. Emerging evidence suggests that SSc is related to increased oxidative stress, which contributes to further tissue and vascular damage.

Methods: Oxidative stress response in the peripheral blood was assessed in patients with SSc (n = 55) and well-matched controls (n = 44) using real-time monitoring of protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay.

Decoding the role of fatty acids and their metabolites in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and life‑threatening interstitial lung disease of familial or sporadic onset. The incidence and prevalence of IPF range from 0.09 to 1.

The emerging role of extracellular vesicles as communicators between adipose tissue and pathologic lungs with a special focus on asthma.

Extracellular vesicles (EVs) gain increasing attention due to their (patho-)physiological role in intercellular signaling, specifically in the communication between distant organs. Recent studies highlight a connection between the adipose tissue (AT) and the lung via (immuno-)modulatory EVs in disorders such as obesity-associated asthma and lung cancer-associated cachexia. Although lung cancer-derived EVs induce lipolysis and myotube atrophy in vivo, pathogenic effects were also reported in the opposite direction with the involvement of AT-derived EVs in cancer-promoting responses and potentially in asthma development.

Diverse functions of apolipoprotein A-I in lung fibrosis.

Apolipoprotein A-I (apoA-I) mediates reverse cholesterol transport (RCT) out of cells. In addition to its important role in the RTC, apoA-I also possesses anti-inflammatory and antioxidative functions including the ability to activate inflammasome and signal via toll-like receptors. Dysfunctional apoA-I or its low abundance may cause accumulation of cholesterol mass in alveolar macrophages, leading to the formation of foam cells.

Intranasal administration of Acinetobacter lwoffii in a murine model of asthma induces IL-6-mediated protection associated with cecal microbiota changes.

Background: Early-life exposure to certain environmental bacteria including Acinetobacter lwoffii (AL) has been implicated in protection from chronic inflammatory diseases including asthma later in life. However, the underlying mechanisms at the immune-microbe interface remain largely unknown.

Methods: The effects of repeated intranasal AL exposure on local and systemic innate immune responses were investigated in wild-type and Il6 , Il10 , and Il17 mice exposed to ovalbumin-induced allergic airway inflammation.

Timing of Blood Sample Processing Affects the Transcriptomic and Epigenomic Profiles in CD4 T-cells of Atopic Subjects.

Optimal pre-analytical conditions for blood sample processing and isolation of selected cell populations for subsequent transcriptomic and epigenomic studies are required to obtain robust and reproducible results. This pilot study was conducted to investigate the potential effects of timing of CD4 T-cell processing from peripheral blood of atopic and non-atopic adults on their transcriptomic and epigenetic profiles. Two heparinized blood samples were drawn from each of three atopic and three healthy individuals.

Increased Oxidative Stress in Asthma-Relation to Inflammatory Blood and Lung Biomarkers and Airway Remodeling Indices.

Airway inflammation in asthma is related to increased reactive oxygen species generation, potentially leading to tissue injury and subsequent airway remodeling. We evaluated oxidative stress in peripheral blood from asthmatic subjects (n = 74) and matched controls (n = 65), using recently developed real-time monitoring of the protein hydroperoxide (HP) formation by the coumarin boronic acid (CBA) assay. We also investigated the relation of the systemic oxidative stress response in asthma to disease severity, lung function, airway remodeling indices (lung computed tomography and histology), and blood and bronchoalveolar lavage fluid (BAL) inflammatory biomarkers.

Short-Chain Fatty Acids Augment Differentiation and Function of Human Induced Regulatory T Cells.

Regulatory T cells (Tregs) control immune system activity and inhibit inflammation. While, in mice, short-chain fatty acids (SCFAs) are known to be essential regulators of naturally occurring and in vitro induced Tregs (iTregs), data on their contribution to the development of human iTregs are sparse, with no reports of the successful SCFAs-augmented in vitro generation of fully functional human iTregs. Likewise, markers undoubtedly defining human iTregs are missing.

A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms.

Objectives: Protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.5% in the general population and 3% in subjects with a first-time deep vein thrombosis (DVT). Here we report a series of 14 PC-deficient Polish patients with comprehensive clinical and molecular characteristics, including long-term follow-up data and a deep mutational analysis of the PROC gene.

Local and Systemic Production of Pro-Inflammatory Eicosanoids Is Inversely Related to Sensitization to Aeroallergens in Patients with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by overproduction of the pro-inflammatory eicosanoids. Although immunoglobulin E-mediated sensitization to aeroallergens is common among AERD patients, it does not belong to the defining disease characteristics. In this study of 133 AERD patients, we sought to find a relationship between sensitization to aeroallergens and local (leukotriene E, prostaglandin E and prostaglandin D) and/or systemic (leukotriene E) production of arachidonic acid metabolites.

Side-Directed Release of Differential Extracellular Vesicle-associated microRNA Profiles from Bronchial Epithelial Cells of Healthy and Asthmatic Subjects.

Extracellular vesicles (EVs) are released by virtually all cells and may serve as intercellular communication structures by transmitting molecules such as proteins, lipids, and nucleic acids between cells. MicroRNAs (miRNAs) are an abundant class of vesicular RNA playing a pivotal role in regulating intracellular processes. In this work, we aimed to characterize vesicular miRNA profiles released in a side-directed manner by bronchial epithelial cells from healthy and asthmatic subjects using an air-liquid interface cell culture model.

Editorial of Special Issue "Molecular Mechanisms of Allergy and Asthma".

This Special Issue aggregates several high-quality original articles written by renowned researchers [...

Differential Regulation of Interferon Signaling Pathways in CD4 T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype.

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.

Epigenetic Mechanisms in Allergy Development and Prevention.

There has been a substantial increase in the incidence and the prevalence of allergic disorders in the recent decades, which seems to be related to rapid environmental and lifestyle changes, such as higher exposure to factors thought to exert pro-allergic effects but less contact with factors known to be associated with protection against the development of allergies. Pollution is the most remarkable example of the former, while less contact with microorganisms, lower proportion of unprocessed natural products in diet, and others resulting from urbanization and westernization of the lifestyle exemplify the latter. It is strongly believed that the effects of environmental factors on allergy susceptibility and development are mediated by epigenetic mechanisms, i.

Extracellular Vesicles and Asthma-More Than Just a Co-Existence.

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases.

The Hygiene Hypothesis and New Perspectives-Current Challenges Meeting an Old Postulate.

During its 30 years history, the Hygiene Hypothesis has shown itself to be adaptable whenever it has been challenged by new scientific developments and this is a still a continuously ongoing process. In this regard, the mini review aims to discuss some selected new developments in relation to their impact on further fine-tuning and expansion of the Hygiene Hypothesis. This will include the role of recently discovered classes of innate and adaptive immune cells that challenges the old Th1/Th2 paradigm, the applicability of the Hygiene Hypothesis to newly identified allergy/asthma phenotypes with diverse underlying pathomechanistic endotypes, and the increasing knowledge derived from epigenetic studies that leads to better understanding of mechanisms involved in the translation of environmental impacts on biological systems.