• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.202-208
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• 2004

Diabetes mellitus is a complex metabolic derangement with hyperglycaemia being the most characteristic symptom of diabetes. Hyperglycaemia can be caused by an increase in the rate of glucose production by the liver or by a decrease in the rate of glucose use by peripheral tissues. Impaired glucose transport is one of the major factors contributing to insulin resistance in type 2 diabetic patients. The ability of insulin to mediate tissue glucose uptake is a critical step in maintaining glucose homeostasis and in clearing the post-prandial glucose load. Glucose transport is mediated by specific carriers called glucose transporters (GLUTs). In this article, the functional importance and molecular mechanisms of insulin-induced glucose transport and development of hypoglycaemic agents which increase glucose transport are reviewed.

• BMB Reports
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• v.42 no.7
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• pp.421-426
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• 2009

Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.

• Toxicological Research
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• v.25 no.2
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• pp.59-69
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• 2009

Metabolomics which deals with the biological metabolite profile produced in the body and its relation to disease state is a relatively recent research area for drug discovery and biological sciences including toxicology and pharmacology. Metabolomics, based on analytical method and multivariate analysis, has been considered a promising technology because of its advantage over other toxicogenomic and toxicoproteomic approaches. The application of metabolomics includes the development of biomarkers associated with the pathogenesis of various diseases, alternative toxicity tests, high-throughput screening (HTS), and risk assessment, allowing the simultaneous acquisition of multiple biochemical parameters in biological samples. The metabolic profile of urine, in particular, often shows changes in response to exposure to xenobiotics or disease-induced stress, because of the biological system's attempt to maintain homeostasis. In this review, we focus on the most recent advances and applications of metabolomics in toxicological research.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.2
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• pp.113-118
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• 2020

Hepatic stellate cells (HSCs) play essential roles in normal and pathophysiological function in liver. In steady state, HSCs contribute to retinoid storage, immune tolerance, and extracellular matrix (ECM) homeostasis. Upon liver injury, they become activated and lead to morphological and functional changes. Studies have demonstrated that activation of HSCs by various stimuli such as toxins, microbial infection, or metabolic overload can promote the fibrotic changes in liver by production of ECM. Herein, we provide current knowledge about the basic characteristics of HSCs and the mechanism by which they are activated.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.85-90
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• 2017

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.19-28
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• 2018

Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling. Furthermore, we summarize the potential therapeutic approaches of targeting glutamine metabolism for the treatment of numerous types of cancer.

• BMB Reports
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• v.50 no.6
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• pp.299-307
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• 2017

Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology.

• Sleep Medicine and Psychophysiology
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• v.12 no.1
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• pp.17-22
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• 2005

Sleep-disordered breathing (SDB) is associated with increased cardiovascular and cerebrovascular morbidity. Epidemiological and clinic-based studies have shown that SDB is related to impaired glucose tolerance and increased insulin resistance, independent of obesity. Despite of a consistent association between SDB and impaired glucose-insulin metabolism, the mechanism underlying this relationship has not been fully elucidated. It is recognized that hypoxemia and hypercapnia that occur in SDB provoke sympathetic nervous activity and catecholamine, epinephrine and norepinephrine, and cortisol are released. Sympathetic hyperactivity and increased catecholamines can impair glucose homeostasis by increasing glycogenolysis and gluconeogenesis, which can result in increased circulating insulin levels and increased risk of insulin resistance. A prospective study is needed to investigate the causal relationship between SDB and impaired glucose-insulin metabolism in a healthy population without diabetes, hypertension and obesity as etiologic risk factors.

• Journal of Integrative Natural Science
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• v.10 no.3
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• pp.119-124
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• 2017

Glucagon-like peptide 2 receptor, a GPCR, binds with the glucagon-like peptide, GLP-2 and regulates various metabolic functions in the gastrointestinal tract. It plays an important role in the nutrient homeostasis related to nutrient assimilation by regulating mucosal epithelium. GLP-2 receptor affects the cellular response to external injury, by controlling the intestinal crypt cell proliferation. As they are therapeutically attractive towards diseases related with the gastrointestinal tract, it becomes essential to analyse their structural features to study the pathophysiology of the diseases. As the three dimensional structure of the protein is not available, in this study, we have performed the homology modelling of the receptor based on single- and multiple template modeling. The models were subjected to model validation and a reliable model based on the validation statistics was identified. The predicted model could be useful in studying the structural features of GLP-2 receptor and their role in various diseases related to them.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.411-430
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• 2021

Irritable bowel syndrome (IBS) is a frequently diagnosed gastrointestinal (GI) disorder characterized by recurrent abdominal pain, bloating, and changes in the stool form or frequency without any structural changes and overt inflammation. It is not a life-threatening condition but causes a considerable level of discomfort and distress. Among the many pathophysiologic factors, such as altered GI motility, visceral hypersensitivity, and low-grade mucosal inflammation, as well as other immunologic, psychologic, and genetic factors, gut microbiota imbalance (dysbiosis), which is frequently found in IBS, has been highlighted as an etiology of IBS. Dysbiosis may affect gut mucosal homeostasis, immune function, metabolic regulation, and even visceral motor function. As diet is shown to play a fundamental role in the gut microbiota profile, this review discusses the influence of diet on IBS occurring through the modulation of gut microbiota. Based on previous studies, it appears that dietary modulation of the gut microbiota may be effective for the alleviation of IBS symptoms and, also an effective IBS management strategy based on the underlying mechanism; especially because, IBS currently has no specific treatment owing to its uncertain etiology.