Celiac disease (CD) is one of the most common inflammatory diseases of the small intestine which causes abdominal pain, diarrhoea, malabsorption, weight loss, anorexia, and iron deficiency anaemia in humans. It is a human leukocyte antigen (HLA)-linked disorder that is triggered by the gluten and gliadin proteins from wheat and related cereals. The presence of other genetic factors such as HLA-DQ2 and HLA-DQ8 have also been identified for the generation of circulating autoantibodies to the enzyme transglutaminase (TG2). The TG2 enzyme deamidates the gluten peptides and increases their affinity for the HLA-DQ2 or HLA-DQ8, which in turn cause a more vigorous activation of CD4+ T-helper 1 (Th1) cells and trigger the immune response, and such immune cascade eventually leads to intestinal membrane damage and malabsorption. Generally, CD is managed by lifelong gluten-free diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Several pharmacological agents and alternative therapies for treating CD are currently under development and are in clinical trials, The purpose of this review is to highlight the complex involvement of genetics and immunity in CD and to focus on the novel strategies being used for developing adjunct and alternative therapies for the treatment of CD. Biomedical Reviews 2014; 25: 45-58.
乳糜泻(CD)是最常见的小肠炎症性疾病之一，可导致人类腹痛、腹泻、吸收不良、体重减轻、厌食和缺铁性贫血。它是一种人类白细胞抗原(HLA)相关的疾病，由小麦和相关谷物中的麸质和麦胶蛋白引发。其他遗传因素如HLA-DQ2和HLA-DQ8的存在也被确定为产生循环自身抗体转谷氨酰胺酶(TG2)。TG2酶使谷蛋白肽脱酰胺并增加其对HLA-DQ2或HLA-DQ8的亲和力，进而引起CD4+ t -辅助性1 (Th1)细胞更强烈的激活并触发免疫反应，这种免疫级联最终导致肠膜损伤和吸收不良。一般来说，乳糜泻需要终生无谷蛋白饮食。然而，严格遵守无麸质饮食是困难的，并不总是有效的。一些治疗乳糜泻的药物和替代疗法目前正在开发和临床试验中，本综述的目的是强调遗传和免疫在乳糜泻中的复杂参与，并重点介绍用于开发治疗乳糜泻的辅助和替代疗法的新策略。25: 45-58。
{"title":"Celiac disease: Role of genetics and immunity and update on novel strategies for treatment","authors":"E. Sequeira, Ginpreet Kaur, H. Buttar","doi":"10.14748/BMR.V25.1047","DOIUrl":"https://doi.org/10.14748/BMR.V25.1047","url":null,"abstract":"Celiac disease (CD) is one of the most common inflammatory diseases of the small intestine which causes abdominal pain, diarrhoea, malabsorption, weight loss, anorexia, and iron deficiency anaemia in humans. It is a human leukocyte antigen (HLA)-linked disorder that is triggered by the gluten and gliadin proteins from wheat and related cereals. The presence of other genetic factors such as HLA-DQ2 and HLA-DQ8 have also been identified for the generation of circulating autoantibodies to the enzyme transglutaminase (TG2). The TG2 enzyme deamidates the gluten peptides and increases their affinity for the HLA-DQ2 or HLA-DQ8, which in turn cause a more vigorous activation of CD4+ T-helper 1 (Th1) cells and trigger the immune response, and such immune cascade eventually leads to intestinal membrane damage and malabsorption. Generally, CD is managed by lifelong gluten-free diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Several pharmacological agents and alternative therapies for treating CD are currently under development and are in clinical trials, The purpose of this review is to highlight the complex involvement of genetics and immunity in CD and to focus on the novel strategies being used for developing adjunct and alternative therapies for the treatment of CD. Biomedical Reviews 2014; 25: 45-58.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"13 1","pages":"45-58"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83693098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Computational modelling has emerged as a powerful tool to study the behaviour of complex systems. Computer simulation may lead to a better understanding of the function of biological systems and the pathophysiological mechanisms underlying various diseases. In neuroscience, modelling techniques have provided knowledge about the electrical properties of neurons, activity of ion channels, synaptic function, information processing, and signalling pathways. Using simulations and analysis in network models has resulted in greater understanding of the behaviour of neural networks and dynamics of synaptic connectivity. Moreover, the correlation between the neurobiological mechanisms and a cluster of physiological, cognitive, and behavioural phenomena may be explored by the computational modelling of the neuronal systems. In this context, a significant progress has been made in understanding of the neural network architectures including those with a high degree of connectivity between the units, information processing, performance of complex cognitive tasks, integration of brain signals, as well as the dynamic mechanisms and computations implemented in the brain for making goal-directed choices. Computational models are able to explore the interactions between the brain areas which are involved in predictive processes and high-level skills. In this review, the significance of computational modelling in the study of neural networks, decision-making procedure, nerve growth factor signalling, and endocannabinoid system along with its medical applications have been highlighted. Biomedical Reviews 2013; 24: 25-31.
{"title":"Computational modelling: moonlighting on the neuroscience and medicine","authors":"P. Hassanzadeh","doi":"10.14748/BMR.V24.19","DOIUrl":"https://doi.org/10.14748/BMR.V24.19","url":null,"abstract":"Computational modelling has emerged as a powerful tool to study the behaviour of complex systems. Computer simulation may lead to a better understanding of the function of biological systems and the pathophysiological mechanisms underlying various diseases. In neuroscience, modelling techniques have provided knowledge about the electrical properties of neurons, activity of ion channels, synaptic function, information processing, and signalling pathways. Using simulations and analysis in network models has resulted in greater understanding of the behaviour of neural networks and dynamics of synaptic connectivity. Moreover, the correlation between the neurobiological mechanisms and a cluster of physiological, cognitive, and behavioural phenomena may be explored by the computational modelling of the neuronal systems. In this context, a significant progress has been made in understanding of the neural network architectures including those with a high degree of connectivity between the units, information processing, performance of complex cognitive tasks, integration of brain signals, as well as the dynamic mechanisms and computations implemented in the brain for making goal-directed choices. Computational models are able to explore the interactions between the brain areas which are involved in predictive processes and high-level skills. In this review, the significance of computational modelling in the study of neural networks, decision-making procedure, nerve growth factor signalling, and endocannabinoid system along with its medical applications have been highlighted. Biomedical Reviews 2013; 24: 25-31.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"38 1","pages":"25-31"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88954390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Presence of sufficient number of functional glucose responsive β-cells is indispensable for normal glucose homeostasis. Diabetes mellitus is a chronic disease associated with loss or reduction of β-cell mass and not β-cell mass. MicroRNAs are small non-coding RNAs that are involved in different biological processes including development, cell proliferation, stress response, and tumor pathogenesis. MicroRNAs fine-tune the gene expression level post-transcriptionally either by mRNA degradation or translational repression. In the past few years, several miRNAs have been introduced as new critical players for pancreas development, function, and regeneration. Deregulation of several microRNAs is found in animal models of diabetes, as well as in diabetic patients. Therefore, it is essential to understand the roles of these microRNAs in β-cell generation and physiology, as well as the biological consequences of their functional impairment. Biomedical Reviews 2013; 24: 57-65.
{"title":"The roles of micro RNA in pancreas development and regeneration","authors":"Tamara I Rabe, Farnaz Shamsi, A. Mansouri","doi":"10.14748/BMR.V24.22","DOIUrl":"https://doi.org/10.14748/BMR.V24.22","url":null,"abstract":"Presence of sufficient number of functional glucose responsive β-cells is indispensable for normal glucose homeostasis. Diabetes mellitus is a chronic disease associated with loss or reduction of β-cell mass and not β-cell mass. MicroRNAs are small non-coding RNAs that are involved in different biological processes including development, cell proliferation, stress response, and tumor pathogenesis. MicroRNAs fine-tune the gene expression level post-transcriptionally either by mRNA degradation or translational repression. In the past few years, several miRNAs have been introduced as new critical players for pancreas development, function, and regeneration. Deregulation of several microRNAs is found in animal models of diabetes, as well as in diabetic patients. Therefore, it is essential to understand the roles of these microRNAs in β-cell generation and physiology, as well as the biological consequences of their functional impairment. Biomedical Reviews 2013; 24: 57-65.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"8 1","pages":"57-64"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75349558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There is a need of biomarkers to detect early joint inflammation and destruction of cartilage in different types of arthritis. YKL-40, a 39 kD heparin- and chitin-binding secreted glycoprotein (also known as cartilage gp39), was recently discovered. Its exact biological function is still unclear. Specific receptors for YKL-40 have not been identified yet. The clinical significance of YKL-40 as a biomarker is discussed in different aspects. High level of YKL-40 was found in various human diseases associated with inflammatory and neoplastic processes. The review highlights the information available about YKL-40 and its significance in inflammatory joint diseases. We suggest that this glycoprotein might have a promising value as a novel biomarker and could provide additional evidence for inflammation activity in different types of arthritis. Biomedical Reviews 2013, 24: 49-56.
{"title":"YKL-40 in health and disease: a challenge for joint inflammation","authors":"M. Kazakova, V. Sarafian","doi":"10.14748/BMR.V24.21","DOIUrl":"https://doi.org/10.14748/BMR.V24.21","url":null,"abstract":"There is a need of biomarkers to detect early joint inflammation and destruction of cartilage in different types of arthritis. YKL-40, a 39 kD heparin- and chitin-binding secreted glycoprotein (also known as cartilage gp39), was recently discovered. Its exact biological function is still unclear. Specific receptors for YKL-40 have not been identified yet. The clinical significance of YKL-40 as a biomarker is discussed in different aspects. High level of YKL-40 was found in various human diseases associated with inflammatory and neoplastic processes. The review highlights the information available about YKL-40 and its significance in inflammatory joint diseases. We suggest that this glycoprotein might have a promising value as a novel biomarker and could provide additional evidence for inflammation activity in different types of arthritis. Biomedical Reviews 2013, 24: 49-56.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"94 1 1","pages":"49-56"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91079309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Efferent innervation of the inner ear is extensively studied but the whole model revealing the development of efferent synapses is not clear yet. In mammals the lateral and medial olivocochlear systems are known as the source of efferent fibers. The lateral olivocochlear system innervates the ipsilateral cochlea, terminating on the dendrites beneath the inner hair cells (IHCs), the dendrites being spiral ganglion neuron compounds. The medial olivocochlear system is involved in forming synapses directly on the outer hair cells (OHCs). To reach the final targets efferent axons use the afferent fibers as a scaffold. Efferent synaptogenesis occurs just before the onset of hearing. At P0 in rats we observed synaptic-like contacts lacking typical features. At P3 the synapses were immature. At P4-P5 efferent contacts with IHCs were clearly defined. At P6-P7 the efferent terminals were larger with distinct synaptic vesicles. During maturation, at P8-P10, the number of efferent synapses at the base of the ICHs reduced alongside with a decrease in the synaptic cisternae. After P12 efferent terminals formed axodendritic synapses below IHCs and large axosomatic synapses on OHCs. The innervation of OHCs underwent two stages, i.e. transitional with simultaneous innervation of IHCs and OHCs and a final OHC-targeted innervation. These results support the idea for a waiting period of efferent innervation before its final establishment in adult organ of Corti. We also summarize the role of neurotrophic factors, specific neurotransmitter systems, their receptors and transporters for refinement of cochlear efferent innervation. Biomedical Reviews 2013; 24: 33-48.
{"title":"Postnatal development of the inner ear efferent innervation in mammals","authors":"E. Ivanov, Svetla P. Doseva, N. Lazarov","doi":"10.14748/BMR.V24.20","DOIUrl":"https://doi.org/10.14748/BMR.V24.20","url":null,"abstract":"Efferent innervation of the inner ear is extensively studied but the whole model revealing the development of efferent synapses is not clear yet. In mammals the lateral and medial olivocochlear systems are known as the source of efferent fibers. The lateral olivocochlear system innervates the ipsilateral cochlea, terminating on the dendrites beneath the inner hair cells (IHCs), the dendrites being spiral ganglion neuron compounds. The medial olivocochlear system is involved in forming synapses directly on the outer hair cells (OHCs). To reach the final targets efferent axons use the afferent fibers as a scaffold. Efferent synaptogenesis occurs just before the onset of hearing. At P0 in rats we observed synaptic-like contacts lacking typical features. At P3 the synapses were immature. At P4-P5 efferent contacts with IHCs were clearly defined. At P6-P7 the efferent terminals were larger with distinct synaptic vesicles. During maturation, at P8-P10, the number of efferent synapses at the base of the ICHs reduced alongside with a decrease in the synaptic cisternae. After P12 efferent terminals formed axodendritic synapses below IHCs and large axosomatic synapses on OHCs. The innervation of OHCs underwent two stages, i.e. transitional with simultaneous innervation of IHCs and OHCs and a final OHC-targeted innervation. These results support the idea for a waiting period of efferent innervation before its final establishment in adult organ of Corti. We also summarize the role of neurotrophic factors, specific neurotransmitter systems, their receptors and transporters for refinement of cochlear efferent innervation. Biomedical Reviews 2013; 24: 33-48.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"47 1","pages":"33-48"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91137136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thanks to a never-before detailed view of the human genome, the last decade has brought to light the notion of DNA copy number variation (CNV) as the pivotal force contributing to population genomic diversity and evolution. It is as well clear now that cancer typically results in loosened control over genomic integrity and that the acquisition of somatic copy number alterations (SCNAs), whether confined to specific genes or affecting entire chromosome arms, is likely to be a fundamental prerequisite to the adaptive pressure that drives oncogenesis. This review gives a brief overview of key developments in genome-wide SCNA profiling, with specific emphasis on array-based techniques and deep-sequencing, which indeed enabled us to identify the large majority of genomic regions undergoing frequent alteration in human cancers and defining recognizable clinical phenotype. Alongside with the prospective to take advantage for future personalized precision medicine, high-throughput SCNA analysis have already proven diagnostic and prognostic potential, particularly for those clinically unpredictable and therapy-refractory tumors, such us cutaneous melanoma. Biomedical Reviews 2013; 24: 11-24.
{"title":"GENOME-WIDE PROFILING OF COPY NUMBER ALTERATIONS IN CANCER: FOCUS ON MELANOMA","authors":"L. Pasini","doi":"10.14748/BMR.V24.18","DOIUrl":"https://doi.org/10.14748/BMR.V24.18","url":null,"abstract":"Thanks to a never-before detailed view of the human genome, the last decade has brought to light the notion of DNA copy number variation (CNV) as the pivotal force contributing to population genomic diversity and evolution. It is as well clear now that cancer typically results in loosened control over genomic integrity and that the acquisition of somatic copy number alterations (SCNAs), whether confined to specific genes or affecting entire chromosome arms, is likely to be a fundamental prerequisite to the adaptive pressure that drives oncogenesis. This review gives a brief overview of key developments in genome-wide SCNA profiling, with specific emphasis on array-based techniques and deep-sequencing, which indeed enabled us to identify the large majority of genomic regions undergoing frequent alteration in human cancers and defining recognizable clinical phenotype. Alongside with the prospective to take advantage for future personalized precision medicine, high-throughput SCNA analysis have already proven diagnostic and prognostic potential, particularly for those clinically unpredictable and therapy-refractory tumors, such us cutaneous melanoma. Biomedical Reviews 2013; 24: 11-24.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"22 1","pages":"11-24"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84403413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The primary cilium was recognised in the late 19th century. Conclusive evidence of its existence required the advent of the electron microscope (1950s-1960s), after which its comparison with motile cilia of the (9 + 2) variety was made by Sorokin. Although a small group of devotees researched the primary cilium from this period until the late 1990s, its function as a sensor (previously advocated by Tony Poole) was established because it produced Ca 2+ transients in intracellular signalling. The pathobiological consequences of ciliary agenesis or dysfunction was emphasised in the mid 1990s. But it was only after the recognition that agenesis could be due to mutations in intraflagellar transport proteins several years later that the pathological sequelae were appreciated. Since the early 2000s, the primary cilium has now been implicated as having many functions in cellular behaviour and development, such that disorder in this almost ubiquitous organelle in many tissues of the body leads to an astonishingly wide range of symptoms, from polycystic kidney disease to Alzheimer's. This organelle, dismissed as vestigial or rudimentary by most cell biologists for well over a century, can no longer be ignored in almost any medical and development condition. There is also very much more to learn about the biology of this fascinating organelle. Biomedical Reviews 2013; 24: 1-7.
{"title":"\"Rediscovery\" of a forgotten organelle, the primary cilium: the root cause of a plethora of disorders","authors":"D. Wheatley","doi":"10.14748/BMR.V24.16","DOIUrl":"https://doi.org/10.14748/BMR.V24.16","url":null,"abstract":"The primary cilium was recognised in the late 19th century. Conclusive evidence of its existence required the advent of the electron microscope (1950s-1960s), after which its comparison with motile cilia of the (9 + 2) variety was made by Sorokin. Although a small group of devotees researched the primary cilium from this period until the late 1990s, its function as a sensor (previously advocated by Tony Poole) was established because it produced Ca 2+ transients in intracellular signalling. The pathobiological consequences of ciliary agenesis or dysfunction was emphasised in the mid 1990s. But it was only after the recognition that agenesis could be due to mutations in intraflagellar transport proteins several years later that the pathological sequelae were appreciated. Since the early 2000s, the primary cilium has now been implicated as having many functions in cellular behaviour and development, such that disorder in this almost ubiquitous organelle in many tissues of the body leads to an astonishingly wide range of symptoms, from polycystic kidney disease to Alzheimer's. This organelle, dismissed as vestigial or rudimentary by most cell biologists for well over a century, can no longer be ignored in almost any medical and development condition. There is also very much more to learn about the biology of this fascinating organelle. Biomedical Reviews 2013; 24: 1-7.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"8 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86564141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this volume of Biomedical Reviews Denys Wheatley presents a short review "Rediscovery" of a forgotten organelle, the primary cilium: the root cause of a plethora of disorders . Dr Wheatley has extensively published cilium-related research papers, reviews and book chapters. Quite naturally has been an advocate for attracting scientific interest to this beautiful biological structure for decades. Therefore he is well suited to provide a world-class view on this scientific problem. He does that in an elegant manner in his review, and states the future direction of research into the ubiquitous nature and involvement of this organelle in health and disease. Biomedical Reviews 2013; 24: 9-10.
{"title":"SOS for SOC: the renaissance of a seemingly ubiquitous organelle","authors":"G. Chaldakov, K. Dikranian","doi":"10.14748/BMR.V24.17","DOIUrl":"https://doi.org/10.14748/BMR.V24.17","url":null,"abstract":"In this volume of Biomedical Reviews Denys Wheatley presents a short review \"Rediscovery\" of a forgotten organelle, the primary cilium: the root cause of a plethora of disorders . Dr Wheatley has extensively published cilium-related research papers, reviews and book chapters. Quite naturally has been an advocate for attracting scientific interest to this beautiful biological structure for decades. Therefore he is well suited to provide a world-class view on this scientific problem. He does that in an elegant manner in his review, and states the future direction of research into the ubiquitous nature and involvement of this organelle in health and disease. Biomedical Reviews 2013; 24: 9-10.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"38 1","pages":"9-10"},"PeriodicalIF":0.0,"publicationDate":"2013-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76647171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The human genome project's big promise was that it could improve our understanding of the pathogenesis and therapy of diseases. However, the genes have been found to account for only about 10% of diseases, and the remaining causes appear to be from environmental exposures, hence the exposure science (exposome concept) emerges. Indeed, Homo sapiens is exposed to an overwhelming number of chemical contaminants circulating every day in the air, water, food, and general environment. The body is a well-equipped entity with capabilities to excrete water-soluble pollutants, but not as well-equipped to excrete some of the lipid-soluble xenobiotics. Here we present data that adipose tissue may be an important participant in the environmental molecular toxicology. Numerous evidence demonstrates that the exposure to persistent organic pollutants may contribute to the pathogenesis of obesity and its related diseases. Noteworthy, these pollutants accumulate mainly in the adipose tissue. And xenobiotic-metabolizing cytochromes p450 (CYP) are expressed in adipose tissue, where CYP1A1 and CYP1B1 can bioactivate carcinogenic polycyclic aromatic hydrocarbons and xenoestrogens. Altogether, the present review highlights an adipocentric approach in molecular toxicology. It is conceptualized as adipotoxicology, that is, the study of accumulation, metabolism, and release of xenobiotics in adipose tissue in health and disease. Biomedical Reviews 2012; 23: 53-60.
{"title":"Adipotoxicology of obesity and related diseases","authors":"S. Yanev, G. Chaldakov","doi":"10.14748/BMR.V23.28","DOIUrl":"https://doi.org/10.14748/BMR.V23.28","url":null,"abstract":"The human genome project's big promise was that it could improve our understanding of the pathogenesis and therapy of diseases. However, the genes have been found to account for only about 10% of diseases, and the remaining causes appear to be from environmental exposures, hence the exposure science (exposome concept) emerges. Indeed, Homo sapiens is exposed to an overwhelming number of chemical contaminants circulating every day in the air, water, food, and general environment. The body is a well-equipped entity with capabilities to excrete water-soluble pollutants, but not as well-equipped to excrete some of the lipid-soluble xenobiotics. Here we present data that adipose tissue may be an important participant in the environmental molecular toxicology. Numerous evidence demonstrates that the exposure to persistent organic pollutants may contribute to the pathogenesis of obesity and its related diseases. Noteworthy, these pollutants accumulate mainly in the adipose tissue. And xenobiotic-metabolizing cytochromes p450 (CYP) are expressed in adipose tissue, where CYP1A1 and CYP1B1 can bioactivate carcinogenic polycyclic aromatic hydrocarbons and xenoestrogens. Altogether, the present review highlights an adipocentric approach in molecular toxicology. It is conceptualized as adipotoxicology, that is, the study of accumulation, metabolism, and release of xenobiotics in adipose tissue in health and disease. Biomedical Reviews 2012; 23: 53-60.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"365 1","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"2012-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75450896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The adult mammalian cochlea receives dual afferent innervation: the inner hair cells (IHCs) are innervated exclusively by type I spiral ganglion neurons (SGNs), whereas the outer hair cells (OHCs) are innervated by type II SGNs. We have characterized the reorganization and morphology of this dual afferent innervation pattern as it is established in the developing rat cochlea. Before the cochlear afferent innervation reaches a mature configuration, there is an initial mismatch, where both populations of SGNs innervate both types of sensory hair cells: during the first postnatal week in the rat cochlea, type I SGN innervation is eliminated from the OHC and type II SGN innervation is eliminated from the IHC. This reorganization occurs during the first two postnatal weeks just before the onset of hearing. Our data reveal distinct phases in the development of the afferent innervation of the organ of Corti: neurite refinement, with a formation of the outer spiral bundles innervating outer hair cells; neurite retraction and synaptic pruning to eliminate type I SGN innervation of OHCs, while retaining their supply to IHCs. Such a reorganization also makes the cochlea a model system for studying CNS synapse development, plasticity and elimination. The present article summarizes the recent progress in our understanding of the afferent innervation of the cochlea. Biomedical Reviews 2012; 23: 37-52.
{"title":"Postnatal development of the afferent innervation of the mammalian cochlea","authors":"E. Ivanov, N. Lazarov","doi":"10.14748/BMR.V23.27","DOIUrl":"https://doi.org/10.14748/BMR.V23.27","url":null,"abstract":"The adult mammalian cochlea receives dual afferent innervation: the inner hair cells (IHCs) are innervated exclusively by type I spiral ganglion neurons (SGNs), whereas the outer hair cells (OHCs) are innervated by type II SGNs. We have characterized the reorganization and morphology of this dual afferent innervation pattern as it is established in the developing rat cochlea. Before the cochlear afferent innervation reaches a mature configuration, there is an initial mismatch, where both populations of SGNs innervate both types of sensory hair cells: during the first postnatal week in the rat cochlea, type I SGN innervation is eliminated from the OHC and type II SGN innervation is eliminated from the IHC. This reorganization occurs during the first two postnatal weeks just before the onset of hearing. Our data reveal distinct phases in the development of the afferent innervation of the organ of Corti: neurite refinement, with a formation of the outer spiral bundles innervating outer hair cells; neurite retraction and synaptic pruning to eliminate type I SGN innervation of OHCs, while retaining their supply to IHCs. Such a reorganization also makes the cochlea a model system for studying CNS synapse development, plasticity and elimination. The present article summarizes the recent progress in our understanding of the afferent innervation of the cochlea. Biomedical Reviews 2012; 23: 37-52.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"11 1","pages":"37-52"},"PeriodicalIF":0.0,"publicationDate":"2012-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87206649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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