Wear and Tear of the Intestinal Visceral Musculature by Intrinsic and Extrinsic Factors

The gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood. Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as ′sprout′, ′discontinuity′, ′furcation′, and ′crossover′ of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissue-damaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well. Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.

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Natural naphthoquinones isolated from Lithospermum erythrorhizon suppress dextran sulfate sodium-induced murine experimental colitis

10.1101/830224 ◽

2019 ◽

Author(s):

Wenxue Sun ◽

Hongwei Han ◽

Zhaoyue Wang ◽

Zhongling Wen ◽

Minkai Yang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Active Sites ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Docking Simulation ◽

Disease Activity Index ◽

Experimental Colitis ◽

Intragastric Administration ◽

Underlying Mechanisms

AbstractThe purpose of this study was to explore the effects of natural shikonin and its derivatives on mice experimental colitis induced by dextran sulfate sodium, and to investigate the underlying mechanisms in vivo. Our results suggested that, intragastric administration of single compound like shikonin and its derivatives contributed to attenuating symptoms of malignant induced by DSS. Meanwhile, shikonin or its derivatives could also remarkably reduce the disease activity index and histopathological scores, suppress the levels of pro-inflammatory cytokines (including IL-6, IL-1β and TNF-α), while increase that of inflammatory cytokine IL-10 in serum. Additionally, both shikonin and alkanin were found to restrain the levels of COX-2, MPO and iNOS in serum and colonic tissues. Moreover, western blotting results demonstrated that shikonin and its derivatives could inhibit the activation of the NLRP3 inflammasome and the NF-κB signaling pathway, relieve the DSS-induced disruption of colonic epithelial tight junction (TJ) in colonic tissues. Further, docking simulation had been performed to prove that shikonin and its derivatives could bind to the active sites of NLRP3 inflammasome and the NF-κB to generate an effective inflammatory effect. Taken together, our experimental data can provide some evidence for the potential use of shikonin and its derivatives to treat the inflammatory bowel disease (IBD).

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Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052621 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2621

Author(s):

César Fernández-de-las-Peñas ◽

Domingo Palacios-Ceña ◽

Víctor Gómez-Mayordomo ◽

María L. Cuadrado ◽

Lidiane L. Florencio

Keyword(s):

Reference Points ◽

Extrinsic Factors ◽

Multiple Systems ◽

Relapsing Remitting ◽

Underlying Mechanisms ◽

Intrinsic And Extrinsic Factors

The pandemic of the coronavirus disease 2019 (COVID-19) has provoked a second pandemic, the “long-haulers”, i.e., individuals presenting with post-COVID symptoms. We propose that to determine the presence of post-COVID symptoms, symptoms should appear after the diagnosis of SARS-CoV-2 infection; however, this situation has some problems due to the fact that not all people infected by SARS-CoV-2 receive such diagnosis. Based on relapsing/remitting nature of post-COVID symptoms, the following integrative classification is proposed: potentially infection related-symptoms (up to 4–5 weeks), acute post-COVID symptoms (from week 5 to week 12), long post-COVID symptoms (from week 12 to week 24), and persistent post-COVID symptoms (lasting more than 24 weeks). The most important topic is to establish the time reference points. The classification also integrates predisposing intrinsic and extrinsic factors and hospitalization data which could promote post-COVID symptoms. The plethora of symptoms affecting multiple systems exhibited by “long-haulers” suggests the presence of different underlying mechanisms.

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TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

10.1101/714931 ◽

2019 ◽

Author(s):

Ju-Hyun An ◽

Woo-Jin Song ◽

Qiang Li ◽

Min-Ok Ryu ◽

A-Ryung Nam ◽

...

Keyword(s):

Extracellular Vesicles ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Qrt Pcr ◽

Tnf Α ◽

Key Factor ◽

Ifn Γ ◽

Underlying Mechanisms ◽

Factor Α ◽

Necrosis Factor

AbstractMesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, n = 6-8/group) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, qRT-PCR, western blot, and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs in the colon.

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