• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.207-216
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• 2021

Supplement of high-protein food plays an important role in improving the symptoms of malnutrition and the immune capacity of the body, but the association of high-protein diet and gut microbiota remained unaddressed. Here, we systematically analyzed the internal organs and gut microbiota in C57(WT) or PD-1H-depleted (KO) mice (T cells were activated) fed with pupae or feed for six weeks. We observed that the body weight gain in the mice fed with pupae increased less significantly than that of the feed group, while the villi and small intestine lengths in the pupa group were reduced compared with that of mice given feed. However, the average body weight of the KO mice increased compared with that of the WT mice fed with pupae or feed. Pupae increased the concentration of blood glucose in WT, but not in KO mice. Moreover, in the feed group, there was no difference in the weight of the internal organs between the WT and KO mice, but in the pupae-fed group, liver weight was decreased and spleen weight was increased compared with that of KO mice. The amounts/plural/amounts of Melainabacteria, Chloroflexi, and Armatimonadetes were specifically upregulated by pupae, and this upregulation was weakened or eliminated by PD-1H depletion. Some bacteria with high abundance in the feed-fed KO mice, such as Deferribacteres, Melainabacteria, Acidobacteria, Bacteroidetes, Spirochaetes and Verrucomicrobia, were decreased in pupae-fed KO mice, and Proteobacteria and Deinococcus were specifically enriched in pupae-fed KO mice. Bacteroidetes, Firmicutes and Akkermansia were associated with weight loss in the pupae-fed group while Lachnospiraceae and Anaerobiospirillum were related glucose metabolism and energy consumption. Based on high-throughput sequencing, we discovered that some gut bacteria specifically regulated the metabolism of a high-protein diet, and PD-1H deficiency improved life quality and sustained blood glucose. Moreover, PD-1H responses to high-protein diet through modulating the type and quantity of gut bacteria. These findings provide evidence about the association among gut microbiota, T cell activation (for PD-1H depletion) and high-protein diet metabolism, have important theoretical significance for nutrition and health research.

• Journal of Life Science
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• v.31 no.6
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• pp.595-602
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• 2021

Human intestinal microbiota play an important role in the regulation of the host's metabolism. There is a close pathological and physiological interaction between dysbiosis of the intestinal microflora and obesity and metabolic syndrome. Akkermansia muciniphila, which was recently isolated from human feces, accounts for about 1-4% of the intestinal microbiota population. The use of A. muciniphila- derived external membrane protein Amuc_1100 and extracellular vesicles (EVs) could be a new strategy for the treatment of obesity. A. muciniphila is considered a next-generation probiotic (NGP) for the treatment of metabolic disorders, such as obesity. Faecalibacterium prausnitzii accounts for about 5% of the intestinal microbiota population in healthy adults and is an indicator of gut health. F. prausnitzii is a butyrate-producing bacterium, with anti-inflammatory effects, and is considered an NGP for the treatment of immune diseases and diabetes. Postbiotics are complex mixtures of metabolites contained in the cell supernatant secreted by probiotics. Parabiotics are microbial cells in which probiotics are inactivated. Paraprobiotics and postbiotics have many advantages over probiotics, such as clear chemical structures, safe dose parameters, and a long shelf life. Thus, they have the potential to replace probiotics. The most natural strategy to restore the imbalance of the intestinal ecosystem normally is to use NGPs among commensal bacteria in the gut. Therefore, it is necessary to develop new foods or drugs such as parabiotics and postbiotics using NGPs.

• Journal of Life Science
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• v.32 no.2
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• pp.175-188
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• 2022

Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IK_Ca channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI₂. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

• Fisheries and Aquatic Sciences
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• v.25 no.11
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• pp.579-586
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• 2022

Research on the potential biological activity of red alga Symphyocladia spp. has been limited to Symphyocladia latiuscula, which is widely used as a food ingredient in Korea. Here, we examined the biological activity of another species, Symphyocladia linearis, which is found in Korea and was reported as a new species in 2013. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antibacterial properties of a 70% ethanol extract of S. linearis. Antioxidant activity, which was evaluated using radical scavenging assays, revealed half maximal inhibitory concentration values for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) of 34.57 and 11.70 ㎍/mL algal extract, respectively. Anti-inflammatory activity of the S. linearis ethanolic extract was evaluated using RAW 264.7 cells by measuring the inhibition of lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. The potential cytotoxicity of NO and PGE₂ was first examined, confirming no toxicity at concentrations ranging from 10-100 ㎍/mL. NO production was inhibited 61.1% and 78.0% at 50 and 100 ㎍/mL S. linearis extract, respectively; and PGE₂ production was inhibited 69.1%, 83.2%, and 94.8% at 25, 50, and 100 ㎍/mL S. linearis extract, respectively. Thus, the S. linearis extract showed very strong efficacy against PGE₂ production. The cellular production of reactive oxygen species, measured using 2',7'-dichlorofluorescin diacetate fluorescence, was inhibited 48.8% by the addition of 100 ㎍/mL S. linearis extract. Antibacterial activity was evaluated using the disc diffusion method and minimum inhibitory concentration (MIC). S. linearis was effective only against gram-positive bacteria, exhibiting antibacterial activity against Staphylococcus aureus with a MIC of 256 ㎍/mL extract and against Bacillus cereus with a MIC of 1,024 ㎍/mL extract. Based on these results, we infer that a 70% ethanolic extract of S. linearis possesses strong anti-inflammatory properties, and therefore has the potential to be used in the prevention and treatment of inflammatory and immune diseases.

• Journal of Life Science
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• v.32 no.3
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• pp.256-262
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• 2022

Oxysterols are oxygenated metabolites of cholesterol generated by serial enzymatic reactions during bile acid synthesis. Similar to cholesterol, oxysterols move rapidly to the intracellular region and modulate various cellular processes, such as immune cell responses, lipid metabolism, and cholesterol homeostasis. Different nuclear transcription factors, such as glucocorticoid, estrogen, and liver X receptors, can be modulated by oxysterols in multiple tissues. The most abundant oxysterol, 27-hydroxycholesterol (27-OHC), is a well-known selective modulator that can either activate or suppress estrogen receptor activity in a tissue-specific manner. The contribution of 27-OHC in atherosclerosis development is apparent because a large amount of it is found in atherosclerotic plaques, accelerating the transformation of macrophages into foam cells that uptake extracellular modified lipids. According to previous studies, however, there are opposing opinions about how 27-OHC affects lipid and cholesterol metabolism in metabolic organs, including the liver and adipose tissue. In particular, the effects of 27-OHC on lipid metabolism are entirely different between in vitro and in vivo conditions, suggesting that understanding the physiology of this oxysterol requires a sophisticated approach. This review summarizes the potential effects of 27-OHC in atherosclerosis and metabolic syndromes with a special discussion of its role in metabolic tissues.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.50 no.2
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• pp.119-129
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• 2024

The cutaneous lymphatic system in humans plays a crucial role in draining interstitial fluid and activating the immune system. Environmental factors, such as ultraviolet light and natural aging, often affect structural changes of such lymphatic vessels, causing skin dysfunction. However, some limitations still exist because of no alternatives to animal testing. To better understand the skin lymphatic system, a biomimetic microfluidic platform, skin-lymph-on-a-chip, was fabricated to develop a novel in vitro skin lymphatic model of humans and to investigate the molecular and physiological changes involved in lymphangiogenesis, the formation of lymphatic vessels. Briefly, the platform involved co-culturing differentiated primary normal human epidermal keratinocytes (NHEKs) and dermal lymphatic endothelial cells (HDLECs) in vitro. Based on our system, Lymphanax^TM, which is a condensed Panax ginseng root extract obtained through thermal conversion for 21 days, was applied to evaluate the lymphangiogenic effect, and the changes in molecular factors were analyzed using a deep-learning-based algorithm. Lymphanax^TM promoted healthy lymphangiogenesis in skin-lymphon-a-chip and indirectly affected HDELCs as its components rarely penetrated differentiated NHEKs in the chip. Overall, this study provides a new perspective on Lymphanax^TM and its effects using an innovative in vitro system.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.298-305
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• 2023

Burkitt's lymphoma is a distinct subtype of non-Hodgkin's lymphoma originating from B-cells that is notorious for its aggressive growth and association with immune system impairments, potentially resulting in rapid and fatal outcomes if not addressed promptly. Optimizing the use of Food and Drug Administration-approved medications, such as combining known safe drugs, can lead to time and cost savings. This method holds promise in accelerating the progress of novel treatments, ultimately facilitating swifter access for patients. This study explores the potential of a dual-targeted therapeutic strategy, combining the bruton tyrosine kinase-targeting drug Ibrutinib and the epidermal growth factor receptor/human epidermal growth factor receptor-2-targeting drug Lapatinib. Ramos and Daudi cell lines, well-established models of Burkitt's lymphoma, were used to examine the impact of this combination therapy. The combination of Ibrutinib and Lapatinib inhibited cell proliferation more than using each drug individually. A combination treatment induced apoptosis and caused cell cycle arrest at the S and G2/M phases. This approach is multifaceted in its benefits. It enhances the efficiency of the drug development timeline and maximizes the utility of currently available resources, ensuring a more streamlined and resource-effective research process.

• IMMUNE NETWORK
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• v.22 no.4
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• pp.34.1-34.19
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• 2022

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)₂D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.32.1-32.15
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• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.281-292
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• 2023

Background and Objectives: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy. Methods and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM. Conclusions: To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.