• Toxicological Research
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• v.21 no.3
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• pp.195-208
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• 2005

Diabetes is a major cause of morbidity and mortality, and associated with a high risk of atherosclerosis, and liver, kidney, nerve and tissue damage. Defective insulin secretion in pancreas and/or insulin resistance in peripheral tissues is a central component of diabetes. It is well established that, regardless of the degree of muscle insulin resistance, glucose levels in diabetic and non-diabetic individuals are determined by the rate of hepatic glucose production. Moreover recently studies using liver-specific insulin receptor knockout mice show the paramount role of the liver in insulin resistance and diabetes. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. The first major section of this review defines the major insulin-mediated signaling pathways including phosphatidylinositol 3-kinase and mitogen activated protein kinases. The second major section of the review presents a summary and evaluation of methods for determination of the role and function of signaling pathways, including methods for determination of kinase phosphorylation, the use of pharmacological inhibitors of kinase and dominant-negative kinase constructs, and the application of new RNA interference methods.

• Journal of Life Science
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• v.33 no.11
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• pp.859-867
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• 2023

Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.75.1-75
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• 2003

Barely yellow mosaic(BaYMV) and barely mild mosaic (BaMMV) bymoviruses are both transmitted by the soil-inhabiting fungus Polymyxa gramnis, and are responsible for economic losses in barley crops in Asia and Europe. Because chemical control of the vector is ineffective, the losses can only be prevented by growing resistant barley cultivars. The objective of this study is to produce resistant barley plants by transformation with viral coat protein(cp) genes. Resistance tests of T1 plants transformed with the BaYMV CP gene showed that at least four independent lines had clear resistance to BaYMV but two other lines were highly susceptible with severe symptoms. The CP gene was detected in all resistant T1 plants by genomic PCR. Most of T2 progenies derived from the resistant T1 lines also showed resistance. In contrast, only one out of 21 independent T2 lines transformed with the BAMMV CP gene tested showed clear resistance to BaMMV, and others were very susceptible. Further analyses of resistance and CP gene expression are in progress.

• The Plant Pathology Journal
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• v.22 no.4
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• pp.339-347
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• 2006

Riboflavin caused induction of systemic resistance in chickpea against Fusarium wilt and charcoal rot diseases. The dose effect of 0.01 to 20 mM riboflavin showed that 1.0 mM concentration was sufficient for maximum induction of resistance; higher concentration did not increase the effect. At this concentration, riboflavin neither caused cell death of the host plant nor directly affected the pathogen's growth. In time course observation, it was observed that riboflavin treated chickpea plants were inducing resistance 2 days after treatment and reached its maximum level from 5 to 7 days and then decreased. Riboflavin had no effect on salicylic acid(SA) levels in chickpea, however, riboflavin induced plants found accumulation of phenols and a greater activities of phenylalanine ammonia lyase(PAL) and pathogenesis related(PR) protein, peroxidase was observed in induced plant than the control. Riboflavin pre-treated plants challenged with the pathogens exhibited maximum activity of the peroxidases 4 days after treatment. Molecular weight of the purified peroxidase was 42 kDa. From these studies we demonstrated that riboflavin induced resistance is PR-protein mediated but is independent of salicylic acid.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.127-131
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• 2013

Trastuzumab is the first molecular targeting drug to increase the overall survival rate in advanced gastric cancer. However, it has also been found that a high intrinsic or primary trastuzumab resistance exists in some proportion of gastric cancer patients. In order to explore the mechanism of resistance to trastuzumab, firstly we investigated the expression of MUC1 (membrane-type mucin 1) in gastric cancer cells and its relationship with drug-resistance. Then using gene-silencing, we transfected a siRNA of MUC1 into drug-resistant cells. The results showed the MKN45 gastric cell line to be resistant to trastuzumab, mRNA and protein expression of MUC1 being significantly upregulated. After transfection of MUC1 siRNA, protein expression of MUC1 in MKN45cells was significantly reduced. Compared with the junk transfection and blank control groups, the sensitivity to trastuzumab under MUC1 siRNA conditions was significantly increased. These results imply that HER2-positive gastric cancer cell MKN45 is resistant to trastuzumab and this resistance can be cancelled by silencing expression of the MUC1 gene.

• Biomolecules & Therapeutics
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• v.25 no.1
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• pp.1-3
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• 2017

• Journal of Veterinary Science
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• v.24 no.6
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• pp.82.1-82.12
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• 2023

Background: The current conventional serotyping based on antigen-antisera agglutination could not provide a better understanding of the potential pathogenicity of Salmonella enterica subsp. enterica serovar Brancaster. Surveillance data from Malaysian poultry farms indicated an increase in its presence over the years. Objective: This study aims to investigate the virulence determinants and antimicrobial resistance in S. Brancaster isolated from chickens in Malaysia. Methods: One hundred strains of archived S. Brancaster isolated from chicken cloacal swabs and raw chicken meat from 2017 to 2022 were studied. Two sets of multiplex polymerase chain reaction (PCR) were conducted to identify eight virulence genes associated with pathogenicity in Salmonella (invasion protein gene [invA], Salmonella invasion protein gene [sipB], Salmonella-induced filament gene [sifA], cytolethal-distending toxin B gene [cdtB], Salmonella iron transporter gene [sitC], Salmonella pathogenicity islands gene [spiA], Salmonella plasmid virulence gene [spvB], and inositol phosphate phosphatase gene [sopB]). Antimicrobial susceptibility assessment was conducted by disc diffusion method on nine selected antibiotics for the S. Brancaster isolates. S. Brancaster, with the phenotypic ACSSuT-resistance pattern (ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracycline), was subjected to PCR to detect the corresponding resistance gene(s). Results: Virulence genes detected in S. Brancaster in this study were invA, sitC, spiA, sipB, sopB, sifA, cdtB, and spvB. A total of 36 antibiogram patterns of S. Brancaster with a high level of multidrug resistance were observed, with ampicillin exhibiting the highest resistance. Over a third of the isolates displayed ACSSuT-resistance, and seven resistance genes (β-lactamase temoneira [bla_TEM], florfenicol/chloramphenicol resistance gene [floR], streptomycin resistance gene [strA], aminoglycoside nucleotidyltransferase gene [ant(3")-Ia], sulfonamides resistance gene [sul-1, sul-2], and tetracycline resistance gene [tetA]) were detected. Conclusion: Multidrug-resistant S. Brancaster from chickens harbored an array of virulence-associated genes similar to other clinically significant and invasive non-typhoidal Salmonella serovars, placing it as another significant foodborne zoonosis.

• Mycobiology
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• v.45 no.2
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• pp.101-104
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• 2017

We identified two genes related to fungicide resistance in Fusarium fujikuroi through random mutagenesis. Targeted gene deletions showed that survival factor 1 deletion resulted in higher sensitivity to fungicides, while deletion of the gene encoding F-box/WD-repeat protein increased resistance, suggesting that the genes affect fungicide resistance in different ways.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10597-10601
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• 2015

Up-regulation of multidrug resistance-associated protein 1 (MRP1) is regarded as one of the main causes for multidrug resistance (MDR) of tumor cells, leading to failure of chemotherapy-based treatment for a multitude of cancers. However, whether silencing the overexpressed MRP1 is sufficient to reverse MDR has yet to be validated. This study demonstrated that RNAi-based knockdown of MRP1 reversed the increased efflux ability and MDR efficiently. Two different short haipin RNAs (shRNAs) targeting MRP1 were designed and inserted into pSilence-2.1-neo. The shRNA recombinant plasmids were transfected into cis-dichlorodiamineplatinum-resistant A549 lung (A549/DDP) cells, and then shRNA expressing cell clones were collected and maintained. Real time PCR and immunofluorescence staining for MRP1 revealed a high silent efficiency of these two shRNAs. Functionally, shRNA-expressing cells showed increased rhodamine 123 retention in A549/DDP cells, indicating reduced efflux ability of tumor cells in the absence of MRP1. Consistently, MRP1-silent cells exhibited decreased resistance to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and DDP, suggesting reversal of MDR in these tumor cells. Specifically, MRP1 knockdown increased the DDP-induced apoptosis of A549/DDP cells by increased trapping of their cell cycling in the G2 stage. Taken together, this study demonstrated that RNAi-based silencing of MRP1 is sufficient to reverse MDR in tumor cells, shedding light on possible novel clinical treatment of cancers.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.