Bioscience hypotheses最新文献_第2页

Formation of mitochondrial genome concatemers as an alternative mechanism promoting oncogenic transformation of lymphoid cells 线粒体基因组串联体的形成作为促进淋巴样细胞致癌转化的另一种机制

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2009.07.003

Felipe Bedoya, Peter G. Medveczky

{"title":"Formation of mitochondrial genome concatemers as an alternative mechanism promoting oncogenic transformation of lymphoid cells","authors":"Felipe Bedoya, Peter G. Medveczky","doi":"10.1016/j.bihy.2009.07.003","DOIUrl":"10.1016/j.bihy.2009.07.003","url":null,"abstract":"<div><p><span><span><span>We have previously shown that AIDS-associated lymphomas and lymphoma cell lines<span> contain mitochondrial genome<span> concatemers not present in normal T-lymphocytes. Since cellular </span></span></span>homeostasis<span> and energy production rely heavily on mitochondrial DNA (mtDNA) stability, mutations in the mtDNA have long been linked to the development of various types of cancers. In most of the cases, however, neoplastically transformed cells harbor non-mutated mtDNA. Herein, we propose an alternative mechanism that shows how the formation of mitochondrial genome concatemers may promote oncogenic transformation of normal lymphoid progenitor cells<span> when no mtDNA mutations or </span></span></span>chromosomal aberrations are present. We detected high reactive oxygen species (ROS) levels in the lymphoma samples tested despite no identification of putative mutations in the coding mtDNA. We propose that the formation of atypical mtDNA configurations (i.e. dimers and concatemers) interferes with normal mitochondrial function. Unstable mitochondria lead to abnormal assembly and dysfunction of the </span>oxidative phosphorylation<span> (OXPHOS) complexes, eventually leading to oxidative stress<span> from elevated production of intracellular ROS. ROS have been reported to activate transcription factors associated with cellular proliferation and apoptosis inhibition. Therefore, we hypothesize that formation of mitochondrial genome concatemers can augment endogenous ROS levels capable of promoting oncogenic transformation of normal lymphoid progenitor cells.</span></span></p></div>","PeriodicalId":87894,"journal":{"name":"Bioscience hypotheses","volume":"2 5","pages":"Pages 310-312"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bihy.2009.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28625988","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}

引用次数: 0

A possible mechanism of spontaneous involution of infantile hemangioma 婴儿血管瘤自发复发的可能机制

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2009.01.006

X.J. Yang , J.W. Zheng , Q. Zhou , W.M. Ye , Y.A. Wang , H.G. Zhu , Z.Y. Zhang , L.Z. Wang

引用次数: 1

Mammal aging: Active and passive mechanisms and their medical implications 哺乳动物衰老:主动和被动机制及其医学意义

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2008.12.002

Theodore C. Goldsmith

{"title":"Mammal aging: Active and passive mechanisms and their medical implications","authors":"Theodore C. Goldsmith","doi":"10.1016/j.bihy.2008.12.002","DOIUrl":"10.1016/j.bihy.2008.12.002","url":null,"abstract":"<div><p>This article compares two hypotheses regarding the mechanisms responsible for aging in humans and other mammals. In the <em>passive</em> mechanism, aging is the result of inadequacies in maintenance and repair functions that act to prevent or repair damage from fundamental deteriorative processes. In the <em>active</em> mechanism, a life span management system purposely limits life span by deactivating maintenance and repair processes beyond a species-specific age.</p><p>As described here, the active mechanism provides a much better fit to observational evidence while the passive mechanism provides a much better fit to traditional evolutionary mechanics theory. However, there are many other observations that conflict with traditional theory and consequently a number of alternative evolutionary mechanics theories have been developed since 1962. Several of these alternatives support active life span management and aging theories providing a rationale for active life span management have been developed based on each of those alternatives.</p><p>This issue is very important to our ability to treat age-related diseases and conditions. If indeed the passive mechanism is correct, then efforts should continue to be exerted to find treatments for each different manifestation of aging, independently of the others. If the active concept is valid it is clear that there are, in addition, substantial opportunities for finding agents that generally delay aging and simultaneously ameliorate multiple manifestations of aging.</p><p>In the past, the evolutionary issues have been used as essentially the entire justification for summarily rejecting active theories. Given the public health considerations and the increasing number of issues surrounding evolutionary mechanics theory, this is no longer a reasonable or responsible path.</p></div>","PeriodicalId":87894,"journal":{"name":"Bioscience hypotheses","volume":"2 2","pages":"Pages 59-64"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bihy.2008.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75581030","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}

引用次数: 7

Oxidative stress and dysregulated Nrf2 activation in the pathogenesis of schizophrenia 氧化应激和Nrf2激活失调在精神分裂症发病机制中的作用

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2008.10.005

Kursad Genc , Sermin Genc

引用次数: 10

Failure of galectin-9 expression by uterine endometrial epithelial cells as a cause for preeclampsia 子宫内膜上皮细胞半凝集素-9表达失败是子痫前期的一个原因

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2009.04.011

Li-Juan Chen , Hao Zhou

{"title":"Failure of galectin-9 expression by uterine endometrial epithelial cells as a cause for preeclampsia","authors":"Li-Juan Chen , Hao Zhou","doi":"10.1016/j.bihy.2009.04.011","DOIUrl":"10.1016/j.bihy.2009.04.011","url":null,"abstract":"<div><p><span>Preeclampsia is a severe pregnancy complication that originates in the placenta and is characterized by shallow trophoblast invasion into the spiral arteries. Immunological imbalances associated with abnormal uterine spiral arteries remodeling during pregnancy have been identified to contribute to the onset and progression of preeclampsia. Interferon (IFN)-γ has a bilateral role in mediating uterine spiral artery remodeling and may lead to preeclampsia under abnormal circumstances. Until recently, the mechanism that regulates the balance between IFN-γ-mediated artery remodeling and IFN-γ-induced </span>Th1 cell<span> activation is ambiguous; but recent studies suggest an important part for galectin-9 in the immune regulation. Therefore, we hypothesize that the galectin-9 expression by uterine endometrial epithelial cells plays a key role in the regulation of the dual function of IFN-γ. Engaging galectin-9 with its receptor on activated Th1 cells causes an inhibitory signal, resulting in apoptosis of Th1 cells and negatively regulates Th1 type immunity. We further hypothesize that failure of galectin-9 expression by endometrial epithelial cells may dampen the endovascular remodeling process and thus result in preeclampsia. This hypothesis proposes a new mechanism in the immunological balance at the uteroplacental interface. Also this hypothesis will help to find out new cause for preeclamspsia and provide new strategy for disease treatment.</span></p></div>","PeriodicalId":87894,"journal":{"name":"Bioscience hypotheses","volume":"2 5","pages":"Pages 306-309"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bihy.2009.04.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89797026","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}

引用次数: 0

CorrespondenceEndothelial-to-mesenchymal transition contributes to hypertrophic scarring 内皮细胞到间质细胞的转化有助于增生性瘢痕形成

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/J.BIHY.2009.01.001

Shunzong Yuan, Wenfeng Yang, Zhifang Li, Hua You, Ren Li, Jia-xiang Xiong

引用次数: 0

The “flip-flop” of aldose reductase gene in diabetic retinopathy and nephropathy 醛糖还原酶基因在糖尿病视网膜病变和肾病中的“翻转”

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2008.11.002

Pablo R. Olmos , Valeska Vollrath , Verónica Irribarra

{"title":"The “flip-flop” of aldose reductase gene in diabetic retinopathy and nephropathy","authors":"Pablo R. Olmos , Valeska Vollrath , Verónica Irribarra","doi":"10.1016/j.bihy.2008.11.002","DOIUrl":"10.1016/j.bihy.2008.11.002","url":null,"abstract":"<div><h3>Retinopathy and nephropathy – current view</h3><p>The Kumamoto and UKPDS studies of type-2 diabetes demonstrated that high glucose mean faster worsening for both diabetic retinopathy and nephropathy. However, why so many type-2 diabetics develop nephropathy but no retinopathy? Why so many type-2 diabetics have severe retinopathy and little or no nephropathy? The answer may be genetic susceptibility.</p></div><div><h3>Hypothesis: the “flip-flop” effect of aldose reductase gene</h3><p>When the CC genotype (high aldose reductase<span> expression) of the (−106) polymorphism of the aldose reductase gene was linked to enhanced retinal susceptibility to hyperglycemia, it was expected that it would also accelerate nephropathy. As the case was the opposite, we now hypothesize that in the kidney, higher aldose reductase activity reduces susceptibility to hyperglycaemia by means of shifting glucose away from the synthesis of Transforming Growth Factor-Beta (TGF-β), a stimulator of mesangial expansion – the landmark of diabetic nephropathy. As the CT & TT genotypes (lower expression of aldose reductase) have effects that are the opposite of those of CC genotype, i.e. retinopathy-protection & nephropathy proneness, we have coined the term “flip-flop”, an acronym taken from electronics, meaning a system that is bi-stable.</span></p></div><div><h3>If the “flip-flop” was confirmed – what then?</h3><p>Those diabetics who are retinopathy-protected & nephropathy-prone (CT & TT), should not be given aldose reductase inhibitors<span> (which could worsen nephropathy) but the new breed of TGF-β inhibitors. This might be a first step towards “genetic individualization of diabetes therapy”.</span></p></div>","PeriodicalId":87894,"journal":{"name":"Bioscience hypotheses","volume":"2 2","pages":"Pages 92-99"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bihy.2008.11.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81118368","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}

引用次数: 0

Valproic acid reduces the ability of neutrophils to fight infection in epileptic patients 丙戊酸降低了癫痫患者中性粒细胞抵抗感染的能力

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2009.05.005

Min Zhang , Yi Wang , Xiao-chuan Wang

{"title":"Valproic acid reduces the ability of neutrophils to fight infection in epileptic patients","authors":"Min Zhang , Yi Wang , Xiao-chuan Wang","doi":"10.1016/j.bihy.2009.05.005","DOIUrl":"10.1016/j.bihy.2009.05.005","url":null,"abstract":"<div><p><span>Valproic acid (VPA) is well established as a first-line and widely used antiepileptic agent. It is well tolerated in most patients and the main issues of concern of VPA are hematological toxicity, tertogenicity and idiosyncratic hepatotoxicity. Recently, researches have showed that VPA monotherapy could cause immunological function disorder, characterized that VPA monotherapy induced imbalance of oxidative/antioxidative status. Measures of oxidative stress<span><span> were elevated while the antioxidative agent like Reduced glutathione (GSH) was degraded. Besides, antioxidants vitamin C and </span>vitamin E<span> can protect hepatocyte from VPA toxicity. In addition, in a eukaryon, social amoeba<span> dictyostelium discoideum, VPA inhibit the chemotactic cell movement and endocytosis/exocytosis by attenuating its </span></span></span></span>phospholipid<span><span> signaling. Neutrophil is an important composition of </span>innate immunity<span>, it works mainly through phagocytosis and oxidization. The phagocytosis and oxidization activity are the basic and primitive function of neutrophils which are mimic to that of a eukaryon. Herein, we hypothesize that VPA, may have unexpected effects on the endocytic and oxidative function of neutrophil. The potential unfavorable subsequent events in the individuals with VPA treatment would be in the increased episodes of infection. Any agent to boost neutrophlic endocytic and antioxidative function may be helpful to the epileptic patients.</span></span></p></div>","PeriodicalId":87894,"journal":{"name":"Bioscience hypotheses","volume":"2 5","pages":"Pages 316-318"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bihy.2009.05.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83858905","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}

引用次数: 4

Paclitaxel may inhibit autoimmune diseases by sparing or increasing the number of CD4(+) CD25(+) regulatory T cells 紫杉醇可能通过减少或增加CD4(+) CD25(+)调节性T细胞的数量来抑制自身免疫性疾病

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2008.11.006

Aqeel Javeed , Muhammad Ashraf , Muhammad Mahmood Mukhtar

引用次数: 0

Aging of mesenchymal stem cells is a root cause of vascular calcification 间充质干细胞老化是血管钙化的根本原因

Bioscience hypotheses Pub Date : 2009-01-01 DOI: 10.1016/j.bihy.2009.03.009

Fang Xin, Siming Guan

引用次数: 0