• International Journal of Oral Biology
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• v.45 no.1
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• pp.1-7
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• 2020

Oral lichen planus (OLP) is a chronic inflammatory disease observed in approximately 0.5-2.2% of the population, and it is recognized as a premalignant lesion that can progress into oral squamous cell carcinoma (OSCC). The rate of malignant transformation is approximately 1.09-2.3%, and the risk factors for malignant transformation are age, female, erosive type, and tongue site location. Malignant transformation of OLP is likely related to the low frequency of apoptotic phenomena. Therefore, apoptosis-related genetic factors, like p53, BCL-2, and BAX are reviewed. Increased p53 expression and altered expression of BCL-2 and BAX were observed in OLP patients, and the malignant transformation rate in these patients was relatively higher. The involvement of microRNA (miRNA) in the malignant transformation of OLP is also reviewed. Because autophagy is involved in cell survival and death through the regulation of various cellular processes, autophagy-related genetic factors may function as factors for malignant transformation. In OLP, decreased levels of ATG9B mRNA and a higher expression of IGF1 were observed, suggesting a reduction in cell death and autophagic response. Activated IGF1-PI3K/AKT/mTor cascade may play an important role in a signaling pathway related to the malignant transformation of OLP to OSCC. Recent research has shown that miRNAs, such as miR-199 and miR-122, activate the cascade, increasing the prosurvival and proproliferative signals.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.12
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• pp.1764-1772
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• 2017

Objective: This study investigated the effects of different dietary energy sources on early postmortem muscle metabolism of finishing pigs. Methods: Seventy-two barrow ($Duroc{\times}Landrace{\times}Yorkshire$, DLY) pigs ($65.0{\pm}2.0kg$) were allotted to three iso-energetic and iso-nitrogenous diets: A (44.1% starch, 5.9% crude fat, and 12.6% neutral detergent fibre [NDF]), B (37.6% starch, 9.5% crude fat, and 15.4% NDF) or C (30.9% starch, 14.3% crude fat, and 17.8% NDF). After the duration of 28-day feeding experiment, 24 pigs (eight per treatment) were slaughtered and the M. longissimus lumborum (LL) samples at 45 min postmortem were collected. Results: Compared with diet A, diet C resulted in greater adenosine triphosphate and decreased phosphocreatine (PCr) concentrations, greater activity of creatine kinase and reduced percentage bound activities of hexokinase (HK), and pyruvate kinase (PK) in LL muscles (p<0.05). Moreover, diet C decreased the phosphor-AKT level and increased the hydroxy-hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) level, as well as decreased the bound protein expressions of HK II, PKM2, and lactate dehydrogenase A (p<0.05). Conclusion: Diet C with the lowest level of starch and the highest levels of fat and NDF could enhance the PCr utilization and attenuate glycolysis early postmortem in LL muscle of finishing pigs.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1657-1662
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• 2012

Fucosyltransferase IV (FUT4) has been implicated in cell adhesion, motility, and tumor progression in human epidermoid carcinoma A431 cells. We previously reported that it promotes cell proliferation through the ERK/MAPK and PI3K/Akt signaling pathways; however, the molecular mechanisms underlying FUT4-induced cell invasion remain unknown. In this study we determined the effect of FUT4 on expression of matrix metalloproteinase (MMP)-12 induced by EGF in A431 cells. Treatment with EGF resulted in an alteration of cell morphology and induced an increase in the expression of MMP-12. EGF induced nuclear translocation of nuclear factor kB (NF-${\kappa}B$) and resulted in phosphorylation of $IkB{\alpha}$ in a time-dependent manner. In addition, ERK1/2 and p38 MAPK were shown to play a crucial role in mediating EGF-induced NF-${\kappa}B$ translocation and phosphorylation of $I{\kappa}B{\alpha}$ when treated with the MAPK inhibitors, PD98059 and SB203580, which resulted in increased MMP-12 expression. Importantly, we showed that FUT4 up-regulated EGF-induced MMP-12 expression by promoting the phosphorylation of ERK1/2 and p38 MAPK, thereby inducing phosphorylation/degradation of $I{\kappa}B{\alpha}$, NF-${\kappa}B$ activation. Base on our data, we propose that FUT4 up-regulates expression of MMP-12 via a MAPK-NF-${\kappa}B$-dependent mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.617-625
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• 2018

Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.

• Journal of Life Science
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• v.29 no.5
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• pp.570-579
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• 2019

Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

• Animal Bioscience
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• v.37 no.1
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• pp.61-73
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• 2024

Objective: The main objective of this study was to define molecular mechanisms associated with thermal stress responses of chickens from commercial broilers (BR, Ross 308), Thai native chickens (NT) and crossbreeds between BR×NT (H75). Methods: Twenty days before reaching specific market age, chickens from each breed were divided into control and thermal-stressed groups. The stressed groups were exposed to a cyclic thermal challenge (35℃±1℃ for 6 h, followed by 26℃±1℃ for 18 h) for 20 days. Control group was raised under a constant temperature of 26℃±1℃. Pectoralis major (n = 4) from each group was collected for transcriptome analysis using HiSeq Illumina and analysis of glycogen and lactate. Gene expression patterns between control and thermal-stressed groups were compared within the same breeds. Results: Differentially expressed transcripts of 65, 59, and 246 transcripts for BR, NT, and H75, respectively, were revealed by RNA-Seq and recognized by Kyoto encyclopedia of genes and genomes database. Pathway analysis underlined altered glucose homeostasis and protein metabolisms in all breeds. The signals centered around phosphatidylinositol 3-kinase (PI3K)/Akt signaling, focal adhesion, and MAPK signaling in all breeds with slight differences in molecular signal transduction patterns among the breeds. An extensive apoptosis was underlined for BR. Roles of AMPK, MAPK signaling and regulation of actin cytoskeleton in adaptive response were suggested for H75 and NT chickens. Lower glycogen content was observed in the breast muscles of BR and NT (p<0.01) compared to their control counterparts. Only BR muscle exhibited increased lactate (p<0.01) upon exposure to the stress. Conclusion: The results provided a better comprehension regarding the associated biological pathways in response to the cyclic thermal stress in each breed and in chickens with different growth rates.

• Journal of Life Science
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• v.29 no.7
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• pp.809-816
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• 2019

The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.683-692
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• 2004

Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.27-35
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• 2012

Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-$3{\beta}$ signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.