Korea Research Institute of Bioscience and Biotechnology
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Tryptophanyl-tRNA synthetase as a potential therapeutic target
No full textTryptophanyl-tRNA synthetase (WRS) is an essential enzyme that catalyzes the ligation of tryptophan (Trp) to its cognate tRNAtrp during translation via aminoacylation. Interestingly, WRS also plays physiopathological roles in diseases including sepsis, cancer, and autoimmune and brain diseases and has potential as a pharmacological target and therapeutic. However, WRS is still generally regarded simply as an enzyme that produces Trp in polypeptides; therefore, studies of the pharmacological effects, therapeutic targets, and mechanisms of action of WRS are still at an emerging stage. This review summarizes the involvement of WRS in human diseases. We hope that this will encourage further investigation into WRS as a potential target for drug development in various pathological states including infection, tumorigenesis, and autoimmune and brain diseases.
The development of a functional human small intestinal epithelium model for drug absorption
No full textAdvanced technologies are required for generating human intestinal epithelial cells (hIECs) harboring cellular diversity and functionalities to predict oral drug absorption in humans and study normal intestinal epithelial physiology. We developed a reproducible two-step protocol to induce human pluripotent stem cells to differentiate into highly expandable hIEC progenitors and a functional hIEC monolayer exhibiting intestinal molecular features, cell type diversity, and high activities of intestinal transporters and metabolic enzymes such as cytochrome P450 3A4 (CYP3A4). Functional hIECs are more suitable for predicting compounds metabolized by CYP3A4 and absorbed in the intestine than Caco-2 cells. This system is a step toward the transition from three-dimensional (3D) intestinal organoids to 2D hIEC monolayers without compromising cellular diversity and function. A physiologically relevant hIEC model offers a novel platform for creating patient-specific assays and support translational applications, thereby bridging the gap between 3D and 2D culture models of the intestine.
Anti-inflammatory and antioxidant effects of Soroseris hirsuta extract by regulating iNOS/NF-κB and NRF2/HO-1 pathways in murine macrophage RAW 264.7 cells
No full textUntil now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.
Establishment of a chicken challenge model of fowl adenovirus serotype-4 for vaccine verification
No full textFowl adenovirus serotype-4 (FAdV-4) infection, also known as hydropericardium-hepatitis syndrome (HHS), is one of the most prevalent diseases in the Korean poultry industry. Therefore, an effective vaccination against FAdV-4 should be developed for prevention of HHS infection. However, a standard animal model with significant pathologic characteristics has not been established for evaluation of HHS vaccine efficacy. In this study, we comparatively evaluated FAdV-4 pathogenicity from specific-pathogen-free (SPF) chickens using FAdV-4 strain (ADL091024) isolated in laying chickens in Korea according to chicken age, passage number and virus titers. In brief, FAdV-4 passaged four times in yolk sac of SPF eggs with the highest viral titers could induce the most severe clinical signs in 1-day-old chickens, similar to natural HHS outbreaks. Furthermore, the efficacy of a newly developed attenuated live FAdV-4 vaccine candidate was successfully determined using the established 1-day-old SPF chickens. There was no significant pathogenicity based on the criteria such as mortality, body weight, gross lesions, histological lesions and virus detection rates in the vaccination and non-challenge control groups. However, the challenge group without vaccination showed significant pathogenicity including hepatic necrosis, histological lesion scores in the liver and heart, virus replication and decreased body weight gain. In conclusion, the chicken challenge model established in this report was proposed for consistent and reliable evaluation of FAdV-4 vaccine efficacy.
Lycopene improves in vitro development of porcine embryos by reducing oxidative stress and apoptosis
No full textIn vitro culture (IVC) for porcine embryo development is inferior compared to in vivo development because oxidative stress can be induced by the production of excessive reactive oxygen species (ROS) under high oxygen tension in the in vitro environment. To overcome this problem, we investigated the effect of lycopene, an antioxidant carotenoid, on developmental competence and the mechanisms involved in mitochondria-dependent apoptosis pathways in porcine embryos. In vitro fertilized (IVF) embryos were cultured in IVC medium supplemented with 0, 0.02, 0.05, 0.1, or 0.2 μM lycopene. The results indicate that 0.1 μM lycopene significantly increased the rate of blastocyst formation and the total cell numbers, including trophectoderm cell numbers, on Day In terms of mitochondria-dependent apoptosis, IVF embryos treated with 0.1 μM lycopene exhibited significantly decreased levels of ROS, increased mitochondrial membrane potential, and decreased expression of cytochrome c on Days 2 and Furthermore, 0.1 μM lycopene significantly decreased the number and percentage of caspase 3-positive and apoptotic cells in Day-6 blastocysts. In addition, Day-2 embryos and Day-6 blastocysts treated with 0.1 μM lycopene showed significantly reduced mRNA expression related to antioxidant enzymes (SOD1, SOD2, CATALASE) and apoptosis (BAX/BCL2L1 ratio). These results indicate that lycopene supplementation during the entire period of IVC enhanced embryonic development in pigs by regulating oxidative stress and mitochondria-dependent apoptosis.
A combination of Olea europaea leaf extract and Spirodela polyrhiza extract alleviates atopic dermatitis by modulating immune balance and skin barrier function in a 1-chloro-2,4-dinitrobenzene-induced murine model
No full textBackground: Atopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied.
Purpose: In this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice.
Methods: Atopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil:acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated.
Results: The OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCB-induced atopic dermatitis. It also significantly reduced the number of CD4+, CD8+, and CD4+/CD69+ T cells; immunoglobulin E-producing B cells (CD23+/B220+) in the axillary lymph nodes; CD3+ T-cell eosinophils (chemokine-chemokine receptor 3+/CD11b+) in the skin; and CD3+ T cells, immunoglobulin E-producing B cells (CD23+/B220+), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-γ in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine-chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions.
Conclusion: Taken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.
Omics in gut microbiome analysis
No full textOur understanding of the interactions between microbial communities and their niche in the host gut has improved owing to recent advances in environmental microbial genomics. Integration of metagenomic and metataxonomic sequencing data with other omics data to study the gut microbiome has become increasingly common, but downstream analysis after data integration and interpretation of complex omics data remain challenging. Here, we review studies that have explored the gut microbiome signature using omics approaches, including metagenomics, metataxonomics, metatranscriptomics, and metabolomics. We further discuss recent analytics programs to analyze and integrate multi-omics datasets and further utilization of omics data with other advanced techniques, such as adaptive immune receptor repertoire sequencing, microbial culturomics, and machine learning, to evaluate important microbiome characteristics in the gut.
Alnus hirsuta (Spach) Rupr. attenuates airway inflammation and mucus overproduction in a murine model of ovalbumin-challenged asthma
No full textAlnus hirsuta (Spach) Rupr. (AH), a member of the Betulaceae family, is widely used in Eastern Asia of as a source of medicinal compounds for the treatment of hemorrhage, diarrhea, and alcoholism. In this study, we investigated the protective effects of a methanolic extract of AH branches against airway inflammation and mucus production in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in an ovalbumin (OVA)-challenged allergic asthma mouse model. Female BALB/c mice were injected with OVA (40 μg) and aluminum hydroxide (2 mg) on days 0 and 14 to induce allergic airway inflammation. The mice were then challenged with 1% OVA from days 21？23. Mice were treated with AH (50 and 100 mg/kg/day; 2% DMSO) or dexamethasone (positive control; 3 mg/kg/day) from days 18？23. AH treatment effectively attenuated airway resistance/hyperresponsiveness and reduced levels of T helper type 2 (Th2) cytokines, eotaxins, and number of inflammatory cells in bronchoalveolar lavage fluid, and immunoglobulin E in serums of OVA-challenged mice. In histological analysis, AH treatment significantly inhibited airway inflammation and mucus production in OVA-challenged mice. AH treatment downregulated the phosphorylation of I kappa B-alpha, p65 nuclear factor-kappa B (p65NF-κB), and mitogen-activated protein kinases with suppression of mucin 5AC (MUC5AC) in lung tissue. Moreover, AH treatment decreased the levels of pro-inflammatory cytokines and Th2 cytokines, as well as MUC5AC expression, and inhibited the phosphorylation of p65NF-κB in TNF-α-stimulated NCI-H292 cells. These results indicate that AH might represent a useful therapeutic agent for the treatment of allergic asthma.
Lipid metabolism and ferroptosis
No full textFerroptosis is a type of iron-dependent regulated necrosis induced by lipid peroxidation that occurs in cellular membranes. Among the various lipids, polyunsaturated fatty acids (PUFAs) associated with several phospholipids, such as phosphatidylethanolamine (PE) and phosphatidylcholine (PC), are responsible for ferroptosis-inducing lipid peroxidation. Since the de novo synthesis of PUFAs is strongly restricted in mammals, cells take up essential fatty acids from the blood and lymph to produce a variety of PUFAs via PUFA biosynthesis pathways. Free PUFAs can be incorporated into the cellular membrane by several enzymes, such as ACLS4 and LPCAT3, and undergo lipid peroxidation through enzymatic and non-enzymatic mechanisms. These pathways are tightly regulated by various metabolic and signaling pathways. In this review, we summarize our current knowledge of how various lipid metabolic pathways are associated with lipid peroxidation and ferroptosis. Our review will provide insight into treatment strategies for ferroptosis-related diseases.
The mitochondrial genome of hydrothermal vent barnacle Eochionelasmus coreana (Cirripedia: Thoracica) from the Indian Ocean
No full textBalanomorph Eochionelasmus species are hydrothermal vent endemic barnacles. In the genus Eochionelasmus, three species are known to date and they distribute at three different vent fields in Pacific and Indian Oceans, E. ohtai in the Southwest Pacific Ocean, E. paquensis in the East Pacific Ocean, and E. coreana in the Indian Ocean. Therefore, Eochionelasmus species are considered to be a meaningful model taxon to elucidate the evolutionary history of vent organism in relation to geotectonic events. Here, we characterized the partial mitogenome of a newly described vent barnacle Eochionelasmus coreana Chan et al., 2020 from the Solitaire vent field in the Indian Ocean. The length of mitogenome was 16,804？bp with 64.0% AT content. Its gene content and organization was identical to those of E. ohtai. There was one significant part in the mitogenome of E. coreana, which was a long intergenic region over 2？kb found between tRNAPro and tRNAThr. The phylogenetic tree suggested the monophyly of E. ohtai and E. coreana with high supporting values. In the future, additional mitogenome analysis of the last Eochionelasmus species, E. paquensis, could expand our understanding about the speciation and global distribution of Eochionelasmus species.