Search

Abstract Idiopathic pulmonary fibrosis is a fatal lung disorder characterized by abnormal deposition of extracellular matrix (ECM), which is secreted by activated myofibroblasts. While the origin of myofibroblasts has been discussed, epithelial-mesenchymal transition (EMT) is being noticed as one of the mechanisms of myofibroblast activation. Recent studies have shown that reactive oxygen species appear to induce not only EMT but also fibrotic progression and maintenance. Therefore, we tested chemicals that have antioxidant capacity as drugs for fibrosis. To evaluate the effects of 4′,6,7-trimethoxyisoflavone (TMF) and catechol (CAT) on EMT and fibrosis, we used an in vitro transforming growth factor (TGF)-β1 or bleomycin-induced model and an in vivo BLM-induced model. The results showed that the co-administration of TMF/CAT ameliorated pulmonary fibrosis by decreasing EMT and ECM accumulation by hindering both Smad and non-Smad TGF-β signalling cascades. Furthermore, significant increases in the number of total immune cells (especially lymphocytes) were observed in BLM-treated animals treated with TMF/CAT. Our findings suggest that co-intervention with TMF/CAT may be a potential treatment for fibrosis.

Abstract This review discusses the effects of short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO) on metabolic diseases, focusing on non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease, and suggests dietary modification as a promising therapeutic strategy. SCFAs, a product of fiber fermentation by microbiota, foster intestinal cell populations, upregulate mucin production, and secure the gut barrier. In contrast, TMAO, a microbiota-produced metabolite from choline, phosphatidylcholine, and l-carnitine, induces atherosclerosis by decreasing cholesterol clearance. An unmanageable abundance of TMAO is potentially harmful to patients with NAFLD owing to its ability to regulate the synthesis and transport of bile acids. The production of SCFAs and TMAO is strongly dependent on the microbial community; therefore, dietary modifications, such as reduction in meat intake, and prebiotic and probiotic consumption that can shape the gut microbiome are considered as promissing therapeutic approaches. This review focuses on well-known prebiotics, such as inulin, fructooligosaccharides, and β-glucan, and probiotics, such as VSL#3 mixture, Lactobacillus rhamnosus GG, Bifidobacterium, and Lactobacillus spp. These additives facilitate microbiota modification, gut homeostasis, intestinal barrier maintenance, and promotion of cholesterol excretion, which may protect the liver from steatosis, inflammation, and fibrosis. Controversial results from previous studies suggest that personalized approaches should be used for dietary modifications.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Beta-glucans, which existed in the cell walls of cereals, bacteria, and fungi, comprise a group of β-d-glucose polysaccharides. We investigated the effects of four kinds of beta-glucan, that are derived from barley, yeast, mushroom, and euglena on wound healing. The migration and viability of keratinocyte or fibroblast were analyzed using the in vitro scratch wound healing assay, invasion assay, MTT assay, and in vivo assay. All the beta-glucans had a significant effect on keratinocyte migration at 20 μM and showed no toxicity on dermal fibroblast. Moreover, treatment of keratinocytes with the beta-glucan derived from the mushroom (Schizophyllum commune) promoted in vivo wound closure. The Integrin/FAK/Src pathway is known to affect cell migration by forming lamellipodia. Beta-glucan from S. commune activates the Integrin/FAK/Src signaling pathway in a time-dependent. Reactive oxygen species are associated with fibroblast differentiation to contract dermal layer and synthesize collagens. We found that fibroblast was activated by increasing NOX4 expression. We propose that beta-glucan derived from mushroom is capable of promoting keratinocyte migration via the induction of FAK/Src phosphorylation there by accelerating wound closure and activating dermal fibroblast differentiation through NADPH oxidase for matrix remodeling.

Big belly seahorse (Hippocampus abdominalis) is a well-known marine organism recognized for its pharmacological value. In this study, peptides derived from natively (Jeju-do, Republic of Korea) farmed seahorses were investigated for their potency on myoblast differentiation and endurance capacitance. Cell viability studies on C2C12 mouse myoblast cells showed that more than 80% of the cells treated with peptides were metabolically active. Morphological observation illustrated the loss of characteristic radial branching towards elongated and well-developed muscle fibers in the peptide-treated C2C12 cells. Immunoblot study on the in vitro translational expression level of key myogenic regulatory proteins (MyoD, MyoG, MyHC) and an in vivo endurance study (using zebrafish as a working model) demonstrated the significance of peptides on the myogenesis process and endurance swimming performance against water flow and gradient, respectively. Collectively, our findings suggest that seahorse-derived peptides can be used as a therapeutic nutrient supplement for improved endurance.

Epithelial-to-mesenchymal transition (EMT) promulgates epithelial cell associated disease-defining characteristics in tumorigenesis and organ fibrosis. Growth factors such as epidermal growth factor and fibroblast growth factor in addition to cytokines such as transforming growth factor-β1 (TGF-β1) is said to play a prominent role in remodeling related pathological events of cancer progression such as invasion, metastasis, apoptosis, EMT, etc. through redox related cellular secondary messengers, in particular the reactive oxygen species (ROS). However, the signaling cascade underlying the redox mechanism and thereby the progression of EMT remains largely unknown. In this study, upon TGF-β1 treatment, we observed an induction in NOX isoforms—NOX2 and NOX4—that have time (early and late) and cellular localization (nucleus and autophagosome co-localized) dependent effects in mediating EMT associated cell proliferation and migration through activation of the focal adhesion kinase (FAK)/SRC pathway in HeLa, human cervical cancer cells. Upon silencing NOX2/4 gene expression and using the SRC inhibitor (AZD0530), progression of TGF-β1 induced EMT related cellular remodeling, extra cellular matrix (ECM) production, cell migration and invasion, got significantly reverted. Together, these results indicate that NOX2 and NOX4 play important, albeit distinct, roles in the activation of cytokine mediated EMT and its associated processes via tyrosine phosphorylation of the FAK/SRC pathway.