• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• BMB Reports
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• v.55 no.2
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• pp.98-103
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• 2022

Increased mRNA levels of cancer upregulated gene (CUG)2 have been detected in many different tumor tissues using Affymetrix microarray. Oncogenic capability of the CUG2 gene has been further reported. However, the mechanism by which CUG2 overexpression promotes cancer stem cell (CSC)-like phenotypes remains unknown. With recent studies showing that pyruvate kinase muscle 2 (PKM2) is overexpressed in clinical tissues from gastric, lung, and cervical cancer patients, we hypothesized that PKM2 might play an important role in CSC-like phenotypes caused by CUG2 overexpression. The present study revealed that PKM2 protein levels and translocation of PKM2 into the nucleus were enhanced in CUG2-overexpressing lung carcinoma A549 and immortalized bronchial BEAS-2B cells than in control cells. Expression levels of c-Myc, CyclinD1, and PKM2 were increased in CUG2-overexpressing cells than in control cells. Furthermore, EGFR and ERK inhibitors as well as suppression of Yap1 and NEK2 expression reduced PKM2 protein levels. Interestingly, knockdown of β-catenin expression failed to reduce PKM2 protein levels. Furthermore, reduction of PKM2 expression with its siRNA hindered CSC-like phenotypes such as faster wound healing, aggressive transwell migration, and increased size/number of sphere formation. The introduction of mutant S37A PKM2-green fluorescence protein (GFP) into cells without ability to move to the nucleus did not confer CSC-like phenotypes, whereas forced expression of wild-type PKM2 promoted such phenotypes. Overall, CUG2-induced increase in the expression of nuclear PKM2 contributes to CSC-like phenotypes by upregulating c-Myc and CyclinD1 as a co-activator.

• Journal of Life Science
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• v.25 no.10
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• pp.1081-1090
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• 2015

Diabetes has been one of major health risks in industrialized countries. Allium hookeri is a wild herb distributed in India and Myanmar. The root of the plant has been used as food and medicine in Southeast Asia. We investigated Allium hookeri extract improves type 2 diabetes mellitus in C57BL/KSJ db/db obese mouse. C57BL/KSJ db/db obese mouse arise out of Type 2 diabetes and we treated Allium hookeri methanol extract 400 mg/kg (AH 400), 800 mg/kg (AH 800), positive control group (thiazolidinedine;TZDs) were administered orally for 8weeks. AH treated group normalized lipid enzyme system (triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) and serum glucose, HbA1c and plasma insulin level. AH treated group recovered β-cell damage by hyperglycemia and fatty liver disease. AH treated group significantly up regulated expression of Peroxisome proliferator-activated receptor gamma (PPAR-γ), pyruvate dehydrogenase kinase4 (PDK4), Sterol regulatory element-binding protein 1c (SREBP 1) and fork head box O1 (FOX 01) proteins in C57BL/KSJ db/db obese mouse liver. And we found that AH treated group decreased hepatic malondialdehyde formation in C57BL/KSJ db/db obese mouse liver. These results indicate that Allium hookeri methanol extract might be a potential anti-diabetic agent and could be useful in the treatment of type 2 diabetes mellitus.

• Journal of Nutrition and Health
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• v.44 no.5
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• pp.355-365
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• 2011

This study investigated how dietary fat affects muscle atrophy and lipid metabolism in various muscles during hindlimb immobilization in rats. Twenty-four male Sprague?Dawley rats had their left hindlimb immobilized and were divided into four groups by dietary fat content and composition. The contralateral hindlimb (control) was compared with the immobilized limb in all dietary groups. Rats (n = 6/group) were fed a 4% corn oil diet (CO), 2.6% corn oil + 1.4% fish oil diet (FO), 30% corn oil diet (HCO), or a 30% beef tallow diet (HBT)after their hind limbs were immobilized for 10 days. Data were collected for the gastrocnemius, plantaris and soleus muscles. Muscle atrophy was induced significantly after 10 days of hindlimb immobilization, resulting in significantly decreased muscle mass and total muscle protein content. The protein levels of peroxisome proliferator activated receptor ${\delta}$ (PPAR${\delta}$) in the plantaris, gastrocnemius, and soleus increased following hindlimb immobilization irrespective of dietary fat intake. Interestingly, the PPAR${\delta}$ mRNA level in the plantaris decreased significantly in all groups and that in the FO group was lower than that in the other groups. The soleus PPAR${\delta}$ mRNA level decreased significantly following hindlimb immobilization in the FO group only. Muscle carnitine palmitoyl transferase 1 (mCPT1) mRNA level was not affected by hindlimb immobilization. However, the mCPT1 mRNA level in the FO group was significantly lower in the plantaris but higher in the soleus than that in the other groups. The pyruvate dehydrogenase kinase 4 (PDK4) mRNA level in the plantaris decreased significantly, whereas that in the soleus increased significantly following hindlimb immobilization. The plantaris, but not soleus, PDK4 mRNA level was significantly higher in the FO group than that in the CO group. The increased PPAR${\delta}$ protein level following hindlimb immobilization may have suppressed triglyceride accumulation in muscles and different types of dietary fat may have differentially affected muscle atrophy according to muscle type. Our results suggest that ${\omega}$-3 polyunsaturated fatty acids may suppress muscle atrophy and lipid accumulation by positively affecting the expression level and activity of PPAR${\delta}$ and PPAR${\delta}$-related enzymes, which are supposed to play an important role in muscle lipid metabolism.