Acute respiratory distress syndrome (ARDS) is the most advanced form of acute lung injury (ALI). This is characterized by bilateral pulmonary infiltrates and severe hypoxemia. According to Berlin definition of ARDS, this is defined based on the timings, radiographic changes, edema formation, and severity on the PaO/FiO ratio. During ARDS, the loss of integrity of the epithelium causes the septic shock. The degree of epithelial injury is the major prognostic marker of ARDS. In addition to this, inflammatory cell migration, fibro-proliferation, and activation of apoptosis also play an important role in the pathophysiology of ARDS. The alveolar epithelial cell is the prime target during injury where this cell either undergo apoptosis or epithelial-mesenchymal transition (EMT). Injury to the AECs triggers the changes in the DNA fragmentation and activation of certain apoptotic markers such as caspases at the same time some cells undergo biochemical changes and loses its epithelial morphology as well epithelial biomarkers and gain mesenchymal biomarkers and morphology. In both the cases, the fibrinolytic system plays an important role in maintaining the integrity of the disease process efficiently. This review highlights the research evidence of apoptosis and EMT in lung development, injury and its prognosis in ARDS thereby to develop an effective strategy for the treatment of ARDS.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including haemostasis and anti-bacterial activity are essential for successful wound healing, however, the design of an ideal material is still challenging. Herein, we...

Cells respond to many stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a proinflammatory senescence-associated secretory phenotype. The heterogeneity of senescent cells (SnCs) and senescence-associated secretory phenotype are vast, yet ill characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and their detection a priority. The Cellular Senescence Network (SenNet), a National Institutes of Health Common Fund initiative, was established to address this need. The goal of SenNet is to map SnCs across the human lifespan to advance diagnostic and therapeutic approaches to improve human health. State-of-the-art methods will be applied to identify, define and map SnCs in 18 human tissues. A common coordinate framework will integrate data to create four-dimensional SnC atlases. Other key SenNet deliverables include innovative tools and technologies to detect SnCs, new SnC biomarkers and extensive public multi-omics datasets. This Perspective lays out the impetus, goals, approaches and products of SenNet.

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Oral nicotine pouches (ONPs) are a modern form of smokeless tobacco products sold by several brands in the U.S., which comprise a significant portion of non-combustible nicotine-containing product (NCNP) sales to date. ONPs are available in various flavors and may contain either tobacco-derived nicotine (TDN) or tobacco-free nicotine (TFN). The growth in popularity of these products has raised concerns that flavored ONPs may cause adverse oral health effects and promote systemic toxic effects due to nicotine and other ONP by-products being absorbed into the circulatory system through oral mucosa. We hypothesized that flavored ONPs are unsafe and likely to cause oral and pulmonary inflammation in oral and respiratory epithelial cells. Before analyzing the effects of ONPs, we first classified ONPs sold in the U.S. based on their flavor and the flavor category to which they belonged using a wheel diagram. Human gingival epithelial cells (HGEP) were treated with flavored ONP extracts of tobacco (original, smooth), menthol (wintergreen and cool cider), and fruit flavor (americana and citrus), each from the TDN and TFN groups. The levels of ONP-induced inflammatory cytokine release (TNF-α, IL-6, and IL-8) by ELISA, cellular reactive oxygen species (ROS) production by CellRox Green, and cytotoxicity by lactate dehydrogenase (LDH) release assay in HGEP cells were assessed. Flavored ONP extracts elicited differential toxicities in a dose- and extract-dependent manner in HGEP cells 24 h post-treatment. Both fruit TDN and TFN extracts resulted in the greatest cytotoxicity. Tobacco- and fruit-flavored, but not menthol-flavored, ONPs resulted in increased ROS production 4 h post-treatment. Flavored ONPs led to differential cytokine release (TNF-α, IL-6, and IL-8) which varied by flavor (menthol, tobacco, or fruit) and nicotine (TDN vs. TFN) 24 h post-treatment. Menthol-flavored ONPs led to the most significant TNF-α release; fruit TFN resulted in the most significant IL-6 release; and fruit TDN and tobacco TFN led to the highest release of IL-8. Subsequently, human bronchial epithelial cells (16-HBE and BEAS-2B) were also treated with flavored ONP extracts, and similar assays were evaluated. Here, the lowest concentration treatments displayed increased cytotoxicity. The most striking response was observed among cells treated with spearmint and tobacco flavored ONPs. Our data suggest that flavored ONPs are unsafe and likely to cause systemic and local toxicological responses during chronic usage.