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The progression of Crohn's disease to intestinal stricture formation is poorly controlled and the pathogenesis is unclear, although increased smooth muscle mass is present. Earlier, stricture formation was described in in the rat model of TNBS-induced colitis, now re-examined for early cellular features of stricture development. While inflammation of the mid-descending colon typically resolved, a subset showed characteristic stricturing by Day 16, with an inflammatory infiltrate in the neuromuscular layers that included eosinophils, CD3-positive T cells and CD68-positive macrophages. Closer study identified CD163-positive, CD206-positive and arginase-positive cells indicative of a M2 macrophage phenotype. Stricturing involved ongoing proliferation of intestinal smooth muscle cells (ISMC) with expression of PDGF-Rβ and progressive loss of phenotypic markers, and stable expression of HIF-1α. In parallel, collagen I and III showed a selective and progressive increase over time. A culture model of the stricture phenotype of ISMC showed stable HIF-1α expression that promoted growth and improved both survival and growth in models of experimental ischemia. This phenotype was hyperproliferative to serum and PDGF-BB and unresponsive to TGFβ, a prominent cytokine of M2 macrophages, compared to control ISMC. This rat model of stricturing identified a hyperplastic phenotype of ISMC, uniquely adapted to an ischemic environment to drive expansion of the smooth muscle layers. Identification of key cellular processes reveals new targets for interventions in intestinal fibrosis.Interfaces between soft tissue and bone are characterized by transitional gradients in composition and structure that mediate substantial changes in mechanical properties. For interfacial tissue engineering, scaffolds with mineral gradients have shown promise in controlling osteogenic behavior of seeded bone marrow stromal cells (bMSCs). Previously, we have demonstrated a 'top-down' method for creating monolithic bone-derived scaffolds with patterned mineral distributions similar to native tissue. In the present work, we evaluated the ability of these scaffolds to pattern osteogenic behavior in bMSCs in basic, osteogenic, and chondrogenic biochemical environments. Immunohistochemical (IHC) and histological stains were used to characterize cellular behavior as a function of local mineral content. Alkaline phosphatase, an early marker of osteogenesis, and osteocalcin, a late marker of osteogenesis, were positively correlated with mineral content in basic, osteogenic, and chondrogenic media. The difference in bMiological structures, interfacial tissues present unique challenges for tissue engineering. Here, we demonstrate that material-derived cues can spatially pattern osteogenic behavior in bone marrow stromal cells (bMSCs). Specifically, we observed that when the bMSCs are cultured on bone-derived scaffolds with mineral gradients, cells in contact with higher mineral content display osteogenic behavior at earlier times than those on the unmineralized substrate. The ability to pattern the cellular complexity found in native interfaces while maintaining biologically relevant structures is a key step towards creating engineered tissue interfaces.Pharmaceutical drugs are among the most used chemicals, for human and veterinary medicines, aquaculture and agriculture. Pharmaceuticals are biologically active molecules, having also environmental persistence, thereby exerting biological effects on non-target species. Among the most used pharmaceuticals, one may find salicylic acid (SA), a non-steroid anti-inflammatory drugs (NSAIDs), and acetazolamide (ACZ), a diuretic drug that acts by inhibiting the activity of carbonic anhydrase (CA). In this work, single and combined effects of SA and ACZ were assessed in the aquatic macrophyte Lemna gibba L., focusing on physiological parameters, namely photosynthetic pigments, (chlorophyll a, b and total (Chl a, b and TChl) as well as carotenoids (Car)). In addition, chemical biomarkers, namely, glutathione S-transferases (GSTs), catalase (CAT) and carbonic anhydrase (CA) activities, were also determined. The highest concentrations of ACZ, caused a decrease in the contents of all chlorophylls; this effect was however reverted by SA exposure. Both ACZ and SA levels caused a decrease in CA activity. Nevertheless, when in combination, this inhibition was not observed in plants exposed to the lowest concentration of these drugs. In conclusion, both pharmaceuticals have the capacity to cause alterations in L. gibba enzymatic activity and photosynthetic pigments content. Additionally, SA seems to exert a protective effect on this species against deleterious effects caused by ACZ.Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to more than 200 countries or territories. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. this website Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood laboratory profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.
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