• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.337-346
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• 2023

Background: Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated. Methods: We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs. Results: Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-I to LC3-II and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence. Conclusion: Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.

• Journal of Life Science
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• v.33 no.7
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• pp.574-585
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• 2023

Sarcopenia is a leading cause of increased medical and nursing care costs among the elderly. In Korea, preventive measures for sarcopenia are mostly targeted toward the general elderly population without specific diseases. However, it is also necessary to implement measures for elderly individuals living in nursing homes and hospitals, where the prevalence of sarcopenia is high. Currently, computed tomography and/or magnetic resonance imaging are considered standard diagnostic tools. However, their complexity and time-consuming nature make them unsuitable for clinical use. The exact pathophysiological mechanisms of sarcopenia are unclear, as they involve various molecular biological pathways, including decreased exercise, protein and nutrient intake, changes in testosterone and growth hormone, and inflammation. Sarcopenia symptoms can lead to several diseases, such as osteoporosis, fractures, dementia, diabetes, and cardiovascular disease. Vitamin B deficiency is a significant factor in sarcopenia induction, with B vitamins being directly involved in energy and protein metabolism and nerve function. Vitamin B deficiency can lead to neuromuscular and neurogenic disorders, which often overlap with sarcopenia. Suboptimal intake of B vitamins, malabsorption, and anorexia are common among the elderly. This study aims to provide information on the role of water-soluble B vitamins in preventing and controlling muscle mass loss and deterioration among the elderly with sarcopenia. In addition, we discuss the potential of myokines from the B vitamin family in modulating sarcopenia.

• Animal Bioscience
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• v.35 no.10
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• pp.1461-1478
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• 2022

The maintenance of poultry gut health is complex depending on the intricate balance among diet, the commensal microbiota, and the mucosa, including the gut epithelium and the superimposing mucus layer. Changes in microflora composition and abundance can confer beneficial or detrimental effects on fowl. Antibiotics have devastating impacts on altering the landscape of gut microbiota, which further leads to antibiotic resistance or spread the pathogenic populations. By eliciting the landscape of gut microbiota, strategies should be made to break down the regulatory signals of pathogenic bacteria. The optional strategy of conferring dietary fibers (DFs) can be used to counterbalance the gut microbiota. DFs are the non-starch carbohydrates indigestible by host endogenous enzymes but can be fermented by symbiotic microbiota to produce short-chain fatty acids (SCFAs). This is one of the primary modes through which the gut microbiota interacts and communicate with the host. The majority of SCFAs are produced in the large intestine (particularly in the caecum), where they are taken up by the enterocytes or transported through portal vein circulation into the bloodstream. Recent shreds of evidence have elucidated that SCFAs affect the gut and modulate the tissues and organs either by activating G-protein-coupled receptors or affecting epigenetic modifications in the genome through inducing histone acetylase activities and inhibiting histone deacetylases. Thus, in this way, SCFAs vastly influence poultry health by promoting energy regulation, mucosal integrity, immune homeostasis, and immune maturation. In this review article, we will focus on DFs, which directly interact with gut microbes and lead to the production of SCFAs. Further, we will discuss the current molecular mechanisms of how SCFAs are generated, transported, and modulated the pro-and anti-inflammatory immune responses against pathogens and host physiology and gut health.

• Animal Bioscience
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• v.35 no.10
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• pp.1512-1523
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• 2022

Objective: The growth of pigs involves multiple regulatory mechanisms, and modern molecular breeding techniques can be used to understand the skeletal muscle growth and development to promote the selection process of pigs. This study aims to explore candidate lncRNAs and mRNAs related to skeletal muscle growth and development among Duroc pigs with different average daily gain (ADG). Methods: A total of 8 pigs were selected and divided into two groups: H group (high-ADG) and L group (low-ADG). And followed by whole transcriptome sequencing to identify differentially expressed (DE) lncRNAs and mRNAs. Results: In RNA-seq, 703 DE mRNAs (263 up-regulated and 440 down-regulated) and 74 DE lncRNAs (45 up-regulated and 29 down-regulated) were identified. In addition, 1,418 Transcription factors (TFs) were found. Compared with mRNAs, lncRNAs had fewer exons, shorter transcript length and open reading frame length. DE mRNAs and DE lncRNAs can form 417 lncRNA-mRNA pairs (antisense, cis and trans). DE mRNAs and target genes of lncRNAs were enriched in cellular processes, biological regulation, and regulation of biological processes. In addition, quantitative trait locus (QTL) analysis was used to detect the functions of DE mRNAs and lncRNAs, the most of DE mRNAs and target genes of lncRNAs were enriched in QTLs related to growth traits and skeletal muscle development. In single-nucleotide polymorphism/insertion-deletion (SNP/INDEL) analysis, 1,081,182 SNP and 131,721 INDEL were found, and transition was more than transversion. Over 60% of percentage were skipped exon events among alternative splicing events. Conclusion: The results showed that different ADG among Duroc pigs with the same diet maybe due to the DE mRNAs and DE lncRNAs related to skeletal muscle growth and development.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.4
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• pp.73-82
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• 2023

Purpose : Cymbopogon citratus, also known as lemongrass, has widely spread around the world and its essential oil is usually applied in food, perfume, and other industrial purposes. In addition, C. citratus has also been used for the treatment of inflammation, digestive disorders, and diabetes in traditional medicine. In this study, the antioxidative activity of C. citratus ethanol extract (CCEE) was analyzed in RAW 264.7 cells through the induction of one of phase II enzymes, heme oxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor (Nrf)2, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt. Methods : The antioxidative activity of CCEE against oxidative stress and its underlying molecular mechanisms were analyzed by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results : The results exhibited that CCEE potently attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS levels in a dose-dependent manner without any cytotoxicity. CCEE treatment significantly induced the expression of HO-1 which is known for its antioxidative capacity. In addition, CCEE treatment significantly upregulated the expression of Nrf2, a corresponding transcription factor for the regulation of antioxidative enzymes, which was in accordance with the HO-1 overexpression. MAPK and PI3K/Akt were also evaluated for their important roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, the potent HO-1 expression was mediated by not extracellular regulated kinase (ERK), c-Jun NH2 terminal kinase (JNK), p38, but phosphoinositide 3-kinase (PI3K) phosphorylation. To confirm the antioxidative activity of CCEE-induced HO-1 expression, oxidative damage was initiated by t-BHP and attenuated by CCEE treatment, which was identified by HO-1 selective inhibitor and inducer. Conclusion : Consequently, CCEE potently induced the HO-1-mediated antioxidative potential through the modulation of Nrf2 and PI3K/Akt signaling pathways in RAW 264.7 cells. These results suggest that CCEE could be a promising strategy for the mitigation against cellular oxidative damage.

• Animal Bioscience
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• v.36 no.12
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• pp.1775-1784
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• 2023

Objective: The aim of this study was to reveal the role and regulatory mechanism of miR-188-5p in the proliferation and differentiation of goat muscle satellite cells. Methods: Goat skeletal muscle satellite cells isolated in the pre-laboratory were used as the test material. First, the expression of miR-188-5p in goat muscle tissues at different developmental stages was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, miR-188-5p was transfected into goat skeletal muscle satellite cells by constructing mimics and inhibitors of miR-188-5p, respectively. The changes of differentiation marker gene expression were detected by qPCR method. Results: It was highly expressed in adult goat latissimus dorsi and leg muscles, goat fetal skeletal muscle, and at the differentiation stage of muscle satellite cells. Overexpression and interference of miR-188-5p showed that miR-188-5p inhibited the proliferation and promoted the differentiation of goat muscle satellite cells. Target gene prediction and dual luciferase assays showed that miR-188-5p could target the 3'untranslated region of the calcium/calmodulin dependent protein kinase II beta (CAMK2B) gene and inhibit luciferase activity. Further functional studies revealed that CAMK2B promoted the proliferation and inhibited the differentiation of goat muscle satellite cells, whereas si-CAMK2B restored the function of miR-188-5p inhibitor. Conclusion: These results suggest that miR-188-5p inhibits the proliferation and promotes the differentiation of goat muscle satellite cells by targeting CAMK2B. This study will provide a theoretical reference for future studies on the molecular mechanisms of skeletal muscle development in goats.

• Journal of Life Science
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• v.34 no.6
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• pp.418-425
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• 2024

Solid tumors are heterogeneous populations of multiple cell types. While the majority of the cells that comprise cancer are unable to divide, cancer stem cells have self-renewal and differentiation properties. Normal stem cell pathways that control self-renewal are overactivated in cancer stem cells, making cancer stem cells important for cancer cell expansion and progression. Dick first proposed the definition of cancer stem cells in acute myeloid leukemia, according to which cancer stem cells can be classified based on the expression of cell surface markers. Cancer stem cells maintain their potential in the tumor microenvironment. Multiple cell types in the tumor microenvironment maintain quiescent cancer stem cells and serve as regulators of cancer growth. Since current cancer treatments target proliferative cells, quiescent state cancer stem cells that are resistant to treatment increase the risk of recurrence or metastasis. Various signals of the tumor microenvironment induce changes to become a tumor-supportive environment by remodeling the vasculature and extracellular matrix. To effectively treat cancer, cancer stem cells and the tumor microenvironment must be targeted. Therefore, it is important to understand how the tumor microenvironment induces reprogramming of the immune response to promote cancer growth, immune resistance, and metastasis. In this review, we discuss the cellular and molecular mechanisms that can enhance immunosuppression in the tumor microenvironment.

• Journal of The Korean Society of Integrative Medicine
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• v.12 no.1
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• pp.1-10
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• 2024

Purpose: Lycopene is abundantly contained in Tomatoes and is known for diverse biological activities such as antioxidant, anti-inflammatory, and anticancer effects. In this study, the antioxidative potential of lycopene was investigated through the induction of hemeoxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor2 (Nrf2) and upstream signaling molecules, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Aktin RAW 264.7 cells. Methods: The antioxidative potential of lycopene against oxidative stress and its molecular mechanisms were determined by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results: Lycopene treatment significantly attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS formation in a dose-dependent manner without any cytotoxicity. In addition, 50 µM of lycopene for 6 h treatment induced potent HO-1 expression and its transcription factor, Nrf2. MAPK and PI3K/Aktwere also analyzed due to their critical roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, phosphorylation of extracellular regulated kinase (ERK) was significantly induced by lycopene treatment while the activated status of c-Jun NH2-terminal kinase (JNK), p38, and Akt, were not given any effect. To confirm the antioxidative mechanism of HO-1 mediated by ERK activation, each selective inhibitor was employed in a protection assay, in which oxidative damage occurred by t-BHP. Lycopene, SnPP, and CoPP treatments reflected accelerated HO-1 expression could be a protective role against oxidative damage-initiated cell death. A selective inhibitor for ERK significantly inhibited the lycopene-induced cytoprotective effect but selective inhibitors for other signaling molecules did not attenuate the rate of t-BHP-induced cell death. Conclusion: In conclusion, lycopene potently scavenged intracellular ROS formation and enhanced the HO-1 mediated antioxidative potential through the modulation of Nrf2, MAPK signaling pathway in RAW 264.7 cells.

• BMB Reports
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• v.56 no.12
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• pp.663-668
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• 2023

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRP-induced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage.