1.Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities.
Protein & Cell 2015;6(2):88-100
Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replication, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells. Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy. During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.
Carcinogenesis
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genetics
;
metabolism
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Homeostasis
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Humans
;
Iron
;
metabolism
;
Neoplasms
;
genetics
;
metabolism
;
pathology
;
Signal Transduction
2.MicroRNAs: a new ray of hope for diabetes mellitus.
Munish KUMAR ; Sayantan NATH ; Himanshu K PRASAD ; G D SHARMA ; Yong LI
Protein & Cell 2012;3(10):726-738
Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.
Animals
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Diabetes Complications
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genetics
;
metabolism
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Diabetes Mellitus
;
genetics
;
metabolism
;
Glucose
;
metabolism
;
Homeostasis
;
genetics
;
Humans
;
Insulin
;
metabolism
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MicroRNAs
;
biosynthesis
;
genetics
;
metabolism
3.How Long Can We Live?.
Journal of the Korean Geriatrics Society 1999;3(4):1-10
Potential maximum life span of humans is estimated around 115-120 years by Cutler. His estimate agrees with an earlier observation by Buffon who claimed that animals tended to live six times the period needed to complete their growth. As humans reach their skeletal maturity at approximately 20 years. Life span has not changed throughout recorded history. Life expectany, the actual average survival for certain given population has increased thanks to social, economic and medical advances. There are two basic levels of biological explanations on aging: macrobiological and microbiological. Macrobiological explanation includes homeostasis, immune system, endocrine, lifestyle, nutrition and environment. Microbiological explanation includes cellular clock theory, free radical theory and metabolic theory with nutrition and antioxidants. Recent advances of genetics opened new era on telomere and telemorase. Gene therapy is applied mainly at the laboratory or limited as local use under investigation. Although the results are encouraging at the laboratory, application for clinical purpose will need tremendous thorough trial and errors.
Aging
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Animals
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Antioxidants
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Genetic Therapy
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Genetics
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Homeostasis
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Humans
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Immune System
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Life Style
;
Telomere
4.A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis.
Tengfei MA ; Liyuan ZHAO ; Jie ZHANG ; Ruofeng TANG ; Xin WANG ; Nan LIU ; Qian ZHANG ; Fengyang WANG ; Meijiao LI ; Qian SHAN ; Yang YANG ; Qiuyuan YIN ; Limei YANG ; Qiwen GAN ; Chonglin YANG
Protein & Cell 2022;13(3):180-202
Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.
Animals
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Caenorhabditis elegans/metabolism*
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Cation Transport Proteins/genetics*
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Homeostasis
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Mitochondria/metabolism*
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Zinc/metabolism*
5.Progress on epigenetic regulation of iron homeostasis.
Lingyan DUAN ; Xiangju YIN ; Hong'en MENG ; Xuexian FANG ; Junxia MIN ; Fudi WANG
Journal of Zhejiang University. Medical sciences 2020;49(1):58-70
Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1(), transferrin receptor 1(), transferrin receptor 2(), ferroportin(), hepcidin(), hemojuvelin() and . Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of , and bone morphogenetic protein 6 () genes result in inhibitory effect on the expression of these iron-related gene. In addition, histone deacetylase (HADC) suppresses gene expression. On the contrary, HADC inhibitor upregulates gene expression. Additional reports showed that miRNA can also modulate iron absorption, transport, storage and utilization via downregulation of and other genes. It is noteworthy that some key epigenetic regulatory enzymes, such as DNA demethylase TET2 and histone lysine demethylase JmjC KDMs, require iron for the enzymatic activities. In this review, we summarize the recent progress of DNA methylation, histone acetylation and miRNA in regulating iron metabolism and also discuss the future research directions.
Epigenesis, Genetic
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Gene Expression Regulation
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genetics
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Homeostasis
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Humans
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Iron
;
metabolism
;
Receptors, Transferrin
6.Progress in the regulation of energy metabolic homeostasis by the SWI/SNF complex subunit Baf60a.
Mengyi XU ; Shiyao ZHANG ; Wenxiang ZHANG ; Chang LIU ; Siyu CHEN
Chinese Journal of Biotechnology 2021;37(2):500-512
Metabolic syndrome is a global chronic epidemic. Its pathogenesis is determined by genetic and environmental factors. Epigenetic modification is reported to regulate gene expression without altering its nucleotide sequences. In recent years, epigenetic modification is sensitively responded to environmental signals, further affecting the gene expression and signaling transduction. Among these regulators, chromatin remodeling SWI/SNF (SWItch/Sucrose non fermentable, SWI/SNF) complex subunit Baf60a plays an important role in maintaining energy homeostasis in mammals. In this paper, we described the pathophysiological roles of Baf60a in maintaining the balance of energy metabolism, including lipid metabolism, cholesterol metabolism, urea metabolism, as well as their rhythmicity. Therefore, in-depth understanding of Baf60a-orchestrated transcriptional network of energy metabolism will provide potential therapeutic targets and reliable theoretical supports for the treatment of metabolic syndrome.
Animals
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Energy Metabolism/genetics*
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Homeostasis
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Lipid Metabolism
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Signal Transduction
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Transcription Factors/metabolism*
7.Role of transcription factor acetylation in the regulation of metabolic homeostasis.
Joo-Man PARK ; Seong-Ho JO ; Mi-Young KIM ; Tae-Hyun KIM ; Yong-Ho AHN
Protein & Cell 2015;6(11):804-813
Post-translational modifications (PTMs) of transcription factors play a crucial role in regulating metabolic homeostasis. These modifications include phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, and O-GlcNAcylation. Recent studies have shed light on the importance of lysine acetylation at nonhistone proteins including transcription factors. Acetylation of transcription factors affects subcellular distribution, DNA affinity, stability, transcriptional activity, and current investigations are aiming to further expand our understanding of the role of lysine acetylation of transcription factors. In this review, we summarize recent studies that provide new insights into the role of protein lysine-acetylation in the transcriptional regulation of metabolic homeostasis.
Acetylation
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Animals
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Diabetes Mellitus, Type 2
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metabolism
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Homeostasis
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genetics
;
physiology
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Humans
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Protein Processing, Post-Translational
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genetics
;
physiology
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Transcription Factors
;
metabolism
8.Pulmonary surfactant homeostasis associated genetic abnormalities and lung diseases.
Xiaojing JIANG ; Xiuzhu SUN ; Weihua DU ; Haisheng HAO ; Xueming ZHAO ; Dong WANG ; Huabin ZHU ; Yan LIU
Chinese Journal of Medical Genetics 2016;33(4):564-568
Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
ATP-Binding Cassette Transporters
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genetics
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DNA-Binding Proteins
;
genetics
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Homeostasis
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Humans
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Lung Diseases
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genetics
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Pulmonary Surfactant-Associated Protein C
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genetics
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Pulmonary Surfactants
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metabolism
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Transcription Factors
9.Relationship between vitamin D and autism spectrum disorder.
Xiao-Yan DUAN ; Fei-Yong JIA ; Hui-Yi JIANG
Chinese Journal of Contemporary Pediatrics 2013;15(8):698-702
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with multiple genetic and environmental risk factors. The interplay between genetic and environmental factors has become the subject of intensified research in the last several years. Vitamin D deficiency has recently been proposed as a possible environmental risk factor for ASD. Vitamin D has a unique role in brain homeostasis, embryogenesis and neurodevelopment, immunological modulation (including the brain's immune system), antioxidation, antiapoptosis, neural differentiation and gene regulation. Children with ASD had significantly lower serum levels of 25-hydroxy vitamin D than healthy children.Therefore vitamin D deficiency during pregnancy and early childhood may be an environmental trigger for ASD.
Child Development Disorders, Pervasive
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etiology
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genetics
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Embryonic Development
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Homeostasis
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Humans
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Vitamin D
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physiology
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Vitamin D Deficiency
;
complications
10.Chinese medicinal formulae treat inflammatory bowel diseases through maintaining gut flora homeostasis.
China Journal of Chinese Materia Medica 2022;47(22):5997-6004
Inflammatory bowel disease(IBD) is a chronic and recurrent inflammatory disorder of the gut, including Crohn's disease(CD) and ulcerative colitis(UC). The occurrence and development of IBD involves multiple pathogenic factors, and the dybiosis of gut flora is recognized as an important pathogenic mechanism of IBD. Therefore, restoring and maintaining the balance of gut flora including bacteria and fungi has become an effective option for IBD treatment. Based on the theoretical basis of the interaction between gut flora and IBD, this paper followed the principle of clinical syndrome differentiation for IBD therapy by traditional Chinese medicine(TCM), and summarized several Chinese medicinal formulae commonly used in IBD patients with large intestine damp-heat syndrome, intermingled heat and cold syndrome, spleen deficiency and dampness accumulation syndrome, spleen and kidney yang deficiency syndrome, liver stagnation and spleen deficiency syndrome, and severe heat poisoning syndrome. The therapeutic and regulatory effects of Shaoyao Decoction, Qingchang Suppository, Wumei Pills, Banxia Xiexin Decoction, Shenling Baizhu Powder, Lizhong Decoction, Sishen Pills, Tongxie Yaofang, Baitouweng Decoction, Gegen Qinlian Decoction, and Houttuyniae Herba prescriptions on gut flora of IBD patients were emphasized as well as the mechanisms. This study found that Chinese medicinal formulae increased the abundance of Bacteroidetes, Bifidobacteria, Lactobacillus, and other beneficial bacteria producing short-chain fatty acids, and reduced the abundance of Enterobacteriaceae and other harmful bacteria to restore the balance of gut flora, thus treating IBD. Confronting the recalcitrance and high recurrence of IBD, Chinese medicinal formulae provide new opportunities for IBD treatment through intervening dysbiosis of gut flora.
Humans
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Gastrointestinal Microbiome
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Inflammatory Bowel Diseases/drug therapy*
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Dysbiosis/drug therapy*
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Colitis, Ulcerative/drug therapy*
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Bacteria/genetics*
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Homeostasis
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China