Biomedical Reviews最新文献

{"title":"Electron microscopist’s view of the Alzheimer’s plaque","authors":"K. Dikranian","doi":"10.14748/BMR.V23.25","DOIUrl":"https://doi.org/10.14748/BMR.V23.25","url":null,"abstract":"Alzheimer's disease (AD) is characterized by extracellular aggregation and deposition of Amyloid-beta peptide in the form of diffuse and fibrillar plaques. More than 50 years ago electron microscopic studies in humans have characterized the structure of the amyloid plaque and neurofibrillary tangles. More recently animal models of AD-type amyloidosis have provided excellent opportunities to study plaque structure during the development and expression of AD-type pathology. Ultrastructural data from a variety of transgenic mice overexpressing mutant amyloid precursor proteins, mutant presenilins, with or without human ApoE knock-in isoforms, are highly comparable to classical electron microscopic findings in AD. This review is an attempt to evaluate, from an electron microscopist’s point of view, the structural identity of AD type pathology, and the mature amyloid plaque in particular. Biomedical Reviews 2012; 23: 9-17.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"22 5-6 1","pages":"9-17"},"PeriodicalIF":0.0,"publicationDate":"2012-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77207080","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}

{"title":"Tissue engineering and growth factors: updated evidence","authors":"P. Hassanzadeh","doi":"10.14748/BMR.V23.26","DOIUrl":"https://doi.org/10.14748/BMR.V23.26","url":null,"abstract":"In difficult-to-treat disorders, the traditional pharmacological agents or medical devices alleviate the symptoms but do not reverse the condition. In recent years, the increasing interest into the field of tissue engineering has generated different strategies for tissue growth in vitro or the enhanced repair of damaged tissues in vivo. The core approach of tissue engineering for either therapeutic or diagnostic applications is the ability to exploit living cells in a variety of ways. In this context, identification of the ideal cells and development of biomaterials including the scaffolds for potential applications in the repair, replacement, or regeneration of damaged tissues appear crucial. Meanwhile, successful tissue engineering is often dependent on the delivery of growth factors to the regenerating tissues. Growth factors are multifunctional peptides which play fundamental roles in a wide variety of physiological processes including cell proliferation, chemotaxis, intercellular signalling, angiogenesis and the formation of extracellular matrix, also the re-establishment of tissue integrity. In order to mimic the endogenous profile of growth factor production during the natural tissue morphogenesis or regeneration, the sophisticated mechanisms of growth factor delivery should be developed. This review highlights the general aspects of tissue engineering along with the approaches taken to incorporate growth factors within the biomaterials and their delivery to injured tissue. Biomedical Reviews 2012; 23: 19-35.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"24 1","pages":"19-35"},"PeriodicalIF":0.0,"publicationDate":"2012-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85407304","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}

{"title":"Homage to Rita Levi-Montalcini, the queen of modern neuroscience","authors":"G. Chaldakov, L. Aloe","doi":"10.14748/BMR.V23.24","DOIUrl":"https://doi.org/10.14748/BMR.V23.24","url":null,"abstract":"The first cell growth factor, nerve growth factor (NGF), was discovered by Rita Levi-Montalcini (RLM) in the early 1950's in Washington University in Saint Louis, Missouri, USA. Originally identified as neurite outgrowth-stimulating factor, later studies revealed that non-neuronal cells, including immune cells, endothelial cells, cardiomyocytes, pancreatic beta cells, prostate epithelial cells and adipose tissue cells, are also targets for and/or sources of NGF. Nerve growth factor is well recognized at present to mediate multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other members of the neurotrophin family are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, ranging from Alzheimer's and other neurodegenerative diseases to atherosclerosis and other cardiometabolic diseases. Recent studies demonstrated the therapeutic potentials of NGF in these diseases including ocular and cutaneous diseases. Whereas NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, and urinary bladder syndromes. Here we briefly describe (i) the \"unpredictable\" ideogenesis of the discovery of NGF, and (ii) our scientific and human experience working in RML's laboratory for 15 years (GNC) and over 40 years (LA). Biomedical Reviews 2012; 23: 1-7.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"19 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2012-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77020950","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}

{"title":"Pathogenesis of amyotrophic lateral sclerosis","authors":"M. Kuźma-Kozakiewicz","doi":"10.14748/BMR.V22.31","DOIUrl":"https://doi.org/10.14748/BMR.V22.31","url":null,"abstract":"Amyotrophic lateral sclerosis is a devastating neurodegenerative disease affecting both upper and lower motor neuron. Despite extensive research the primary cause of the disease has not been indentified and the causative treatment is lacking. The present article describes mechanisms involved in the disease development and progression, including oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, RNA processing, alterations of cytoskeleton functions and axonal transport, glial cell involvement and programmed cell death. Biomedical Reviews 2011; 22: 7-14.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"75 1","pages":"7-14"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74143223","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}

{"title":"A linkage of mind and brain: Sir John Eccles and modern dualistic interactionism","authors":"Danko D. Georgiev","doi":"10.14748/BMR.V22.38","DOIUrl":"https://doi.org/10.14748/BMR.V22.38","url":null,"abstract":"Our minds, constituted by conscious experiences, are both the most familiar and most mysterious aspect of our lives. Despite the large amount of clinical evidence suggesting an intimate relationship between the brain function and the mind, the nature of this relationship remains poorly understood. In this Commentary we discuss some of the problems faced by the classical mind-brain identity theory and explain how the quantum dualistic interactionism proposed by Sir John Eccles could resolve these problems. Biomedical Reviews 2011; 22: 81-84.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"175 1","pages":"81-84"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79719499","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}

{"title":"Metallosis: metal ion release from metal-on-metal joint surface replacement - current concerns and future problems","authors":"S. R. Manning","doi":"10.14748/BMR.V22.35","DOIUrl":"https://doi.org/10.14748/BMR.V22.35","url":null,"abstract":"Since its innovation, joint replacement surgery has offered relief from the pain and functional limitation of destructive or degenerate joint disease. The search for the ideal material continues over 120 years later. Recently, using metal-on-metal bearings for younger patients has become the trend to avoid excess wear in high demand patients in the hope of reducing the need to revision surgery. Initial evidence suggested these prostheses offered a durable, functional safe joint that was less likely to be revised than the standard metal and polyethylene joint. A body of evidence is growing rapidly to suggest that metal-on-metal joints are associated with local tissue reactions - metallosis - cellular toxicity, increased serum metal ion concentrations, organ deposition of metal ions, higher rather than lower rates of revision surgery and no functional advantage over any other type of joint replacement. We will consider the reasons for metal ion release; the cellular, local tissue and systemic effects of metal ions and the patient risk and presentation. From the evidence reviewed, serious consideration should be given to the future use of metal-on-metal joint bearings and a suggested follow up plan for patients with such joints is identified and reproduced. Biomedical Reviews 2011; 22: 57-64.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"1 1","pages":"57-64"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88341152","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}

{"title":"From bone marrow to brain: stem cells in neuroprotection, plasticity, and neuroregeneration","authors":"M. Penkowa","doi":"10.14748/BMR.V22.30","DOIUrl":"https://doi.org/10.14748/BMR.V22.30","url":null,"abstract":"At present, curative therapies for neurological diseases are limited, even though they are prevalent worldwide. So far, molecular strategies developed for brain disorders act through one single molecular mechanism, yet, these diseases are multifactorial and highly complex, as to why a successful therapy likely calls for a more multifaceted and cell-based approach. The bone marrow contains a mixed stem and progenitor cell population including hematopoietic stem cells (HSC) and mesenchymal stromal stem cells (MSC), which are potential endogenous candidates for cell-based therapy in various brain disorders like stroke, trauma, and neurodegeneration. Unlike the neural stem cells (NSC), bone marrow HSC are readily isolated, mobilized and expanded by means of treatment with granulocyte-colony stimulating factor (G-CSF) and CXCR4-antagonist plerixafor. Once in the blood circulation, the cells preferentially home to injured tissues including the brain. Bone marrow cells may convey neuroprotection, plasticity, and neuroregeneration by different mechanisms of action, which include either transdifferentiation or cell-cell fusion with resident brain cells. Bone marrow cells also benefit the injured brain by secreting bioactive factors, which in a paracrine manner convey intrinsic repair and enhance neurogenesis. Furthermore, transplanted MSC may activate the astrocytes leading to increased glial secretion of neurotrophic growth factors and enhanced proliferation and migration of the resident NSC. These neuroregenerative mechanisms of action are not mutually exclusive, in fact they may provide a multifaceted therapeutic approach, which is requested in order to move neurorestorative and protective strategies into the clinic. Biomedical Reviews 2011; 22: 1-6.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"18 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86470272","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}

{"title":"towards pragmatic and functional unit of mind-and-brain in rEsponsE to danko gEorgiEv's \"a linkagE of mind and brain: sir john EcclEs and modErn dualistic intEractionism\"","authors":"Rayito Rivera-Hernández, D. Stoyanov","doi":"10.14748/BMR.V22.39","DOIUrl":"https://doi.org/10.14748/BMR.V22.39","url":null,"abstract":"Consciousness is an enigma, perhaps the greatest enigma of philosophy of science. It can be described as a multilevel phenomenon, where transition (from unconsciousness to consciousness) is not a compromise OFF/ON in neuronal activity, but involves a complex change in nerve function, which is mediated by the environment. For the analysis of consciousness, the Australian philosopher David J. Chalmers distinguishes the easy problem of the hard problem of consciousness. The easy problem to analyze issues such as discrimination between sensory stimuli, the integration of information to guide behavior, verbalization of internal states, the integration of sensory information with past experience, how to focus attention, and what distinguishes waking from sleep. On the other hand, the \"hard problem\" of consciousness is to explain how the physical brain gives rise to consciousness. This analysis deals with the latter. Biomedical Reviews 2011; 22: 85-89.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"20 1","pages":"85-89"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83189167","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}

{"title":"G protein-coupled sphingosine-1-phosphate receptors: potential molecular targets for angiogenic and anti-angiogenic therapies","authors":"N. Takuwa, Y. Okamoto, K. Yoshioka, Y. Takuwa","doi":"10.14748/BMR.V22.32","DOIUrl":"https://doi.org/10.14748/BMR.V22.32","url":null,"abstract":"Sphingosine-1-phosphate (S1P) is a plasma lipid mediator with pleiotropic activities; it is constitutively produced in red blood cells and vascular endothelial cells through phosphorylation of sphingosine by one of two S1P synthesizing enzymes, sphingosine kinase 1 and 2 (SphK 1, 2), and exported into plasma to bind to high density lipoprotein and albumin. Sphingosine-1-phosphate acts through five members of the G protein-coupled S1P receptors (S1PR1-S1PR5) to exert diverse actions, which include vascular maturation in embryonic stage and postnatal angiogenesis, maintenance of functional integrity of vascular endothelium, regulation of vascular tonus, and lymphocyte trafficking. Sphingosine-1-phosphate is unique in its ability to regulate cell migration either positively or negatively by acting through different receptor subtypes. S1PR1 and S1PR3 mediate chemotactic cell migration toward S1P via Gi/Rac pathway, whereas S1PR2 mediates S1P inhibition of chemotaxis via G12/13/Rho-dependent inhibition of Rac. Sphingosine-1-phosphate positively or negatively regulates tumor cell migration, invasion in Matrigel, and hematogenous metastasis in manners strictly dependent on S1P receptor subtypes expressed in tumor cells. S1PR1 (and S1PR3) also mediates activation of Gi/phosphatidylinositol 3-kinase (PI3K)/Akt and stimulation of cell proliferation/survival, whereas S1PR2 could mediate suppression of cell proliferation/survival through G12/13/Rho/Rho kinase/PTEN-dependent Akt inhibition. S1PR1 (and S1PR3) expressed in endothelial cells mediates angiogenic action of S1P by stimulating endothelial cell migration, proliferation and tube formation. In a mouse model of hindlimb ischemia after femoral artery resection, repeated local administration or sustained delivery of S1P, or transgenic overexpression of SphK1, accelerates post-ischemic angiogenesis, through the S1P actions on both endothelial cells and bone marrow-derived myeloid cells (BMDCs). In tumor cells, SphK1 is upregulated especially in advanced stages, through mechanisms involving both activating Ras mutation and hypoxia, which leads to increased S1P production and also decreased cellular content of pro-apoptotic sphingolipid ceramide, a metabolic precursor of S1P. Apoptotic tumor cells also produce S1P through SphK2 activation, thus implicated in tumor angiogenesis by acting on endothelial cells through S1PR1/S1PR3, as well as tumor-infiltrating macrophages and BMDCs. Inhibition of S1PR1 function by either an anti-S1P antibody or FTY720 inhibits tumor angiogenesis and tumor growth. Differently from S1PR1, S1PR2 expressed in host cells mediates inhibition of tumor angiogenesis and tumor growth, through mechanisms involving the suppression of endothelial cell migration, proliferation and tube formation, and inhibition of BMDC recruitment to tumor stroma with suppressed expression of pro-angiogenic factor and matrix metalloprotease 9. These findings provide the molecular basis for S1P receptor subty","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"13 1","pages":"15-29"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90910131","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}

{"title":"REGULATION OF GLUCOSE METABOLISM BY CENTRAL INSULIN ACTION","authors":"H. Inoue","doi":"10.14748/BMR.V22.33","DOIUrl":"https://doi.org/10.14748/BMR.V22.33","url":null,"abstract":"Insulin has been known to act on the hypothalamus, in particular the arcuate nucleus, in the central nervous system. Such central insulin action is not only involved in the regulation of energy metabolism via the regulation of food intake and heat production, but also plays an important role in glucose metabolism by regulating hepatic glucose production and glucose uptake by skeletal muscles. Studies on the intracerebroventricular administration of PI-3K inhibitors or sulfonylureas have demonstrated that hyperpolarization of agouti-related protein neurons induced by the activation of PI-3K signaling/KATP channels in the hypothalamic arcuate nucleus plays an important role in the suppression of hepatic glucose production mediated by central insulin action. Cutting of the vagus nerve overrides the suppression of hepatic glucose production by intracerebroventricular insulin administration, which suggests the involvement of autonomic nerves in central insulin action in the liver. The central insulin action-mediated suppression of hepatic glucose production is associated with decreased gene expression of enzymes involved in hepatic gluconeogenesis, and both increased interleukin-6 expression in hepatic non-parenchymal cells induced by central insulin action and associated activation of hepatic STAT3 play an important role in the suppression of gene expression of hepatic gluconeogenesis-related enzymes. In animal models of obesity and insulin resistance, the central insulin action-mediated hepatic glucose production control mechanism is impaired in both the hypothalamus and liver. Increased hepatic gluconeogenesis in obesity and type-2 diabetes has been attributed to impaired hepatic insulin signaling and increased expression of enzymes involved in hepatic gluconeogenesis due to hyperglycemia, but may also be partially attributed to the impairment of the central insulin action-mediated suppression of hepatic gluconeogenesis. Biomedical Reviews 2011; 22: 31-39.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"65 1","pages":"31-39"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83986575","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}