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Neural Regeneration Research 2014年第10期9卷 1025-1030页

作者： Luigi Aloe Patrizia Bianchi Alberto De Bellis Marzia Soligo Maria Luisa Rocco cellular biology and Neurobiology Institute National Research Council(CNR) Maria Rosaria Maglione Foundation Onlus NapoliItaly Intitute of Translational pharmacology National Research Council(CNR)

The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

关键词： nerve regeneration spinal cord injury nerve growth factor intranasal delivery blood-brain barrier motor function leptin neuroprotection rats neural regeneration

A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers

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World Journal of Gastroenterology 2010年第46期16卷 5779-5789页

作者： Yasushi Adachi Hiroyuki Yamamoto Hirokazu Ohashi Takao Endo David P Carbone Kohzoh Imai Yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University Department of Internal Medicine Sapporo Shirakabadai Hospital Vanderbilt-Ingram Cancer Center and departments of Medicine and Cell biology Vanderbilt University

Advances in molecular research in cancer have brought new therapeutic strategies into clinical *** new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) *** concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new *** I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human *** this review,we focus on this promising therapeutic target,*** IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI *** studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer *** results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and *** also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical *** mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single *** summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug ***,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcino

关键词： Dominant negative Gastrointestinal cancer Insulin like growth factor-I receptor Monoclonal anti-body Tyrosine kinase inhibitor

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

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National Science Review 2014年第3期1卷 396-412页

作者： Pengyuan Yang Geoffrey J.Markowitz Xiao-Fan Wang Department of pharmacology and Cancer biology Duke University Medical Center CAS Key Laboratory of Infection and Immunity Institute of Biophysics Chinese Academy of Sciences

In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma(HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus(HBV). Transformation of the liver in HBV-associated HCC oten follows from or accompanies long-term symptoms of chronic hepatitis, inlammation and cirrhosis, and viral load is a strong predictor for both incidence and progression of HCC. Besides aiding in transformation, HBV plays a crucial role in modulating the accumulation and activation of both cellular components of the microenvironment,such as immune cells and ibroblasts, and non-cellular components of the microenvironment, such as cytokines and growth factors, markedly inluencing disease progression and prognosis. his review will explore some of these components and mechanisms to demonstrate both underlying themes and the inherent complexity of these interacting systems in the initiation, progression, and metastasis of HBV-positive HCC.

关键词： hepatitis B hepatocellular carcinoma tumor microenvironment leukocytes cytokines growth factors

Retrobulbar administration of purified anti-nerve growth factor in developing rats induces structural and biochemical changes in the retina and cornea

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International Journal of Ophthalmology(English edition) 2021年第2期14卷 209-216页

作者： Luigi Aloe Maria Luisa Rocco Bijorn Omar Balzamino Graziana Esposito Alessandra Micera Institute of Cell biology and Neurobiology CNRLazio 00143RomeItaly Fondazione IRET Ozzano EmiliaBologna 40064Italy Institute of Translational pharmacology CNRLazio 00133RomeItaly Research and Development Laboratory for Biochemical Molecular and Cellular Applications in Ophthalmological ScienceIRCCSFondazione BiettiRome 00182Italy

AIM:To develop an experimental model of endogenous nerve growth factor(NGF)deprivation by retrobulbar administration of purified neutralizing anti-NGF antibodies in young Sprague-Dawley rats and provide further information on NGF expression in the retina and ***:Sixty old pathogen-free Sprague Dawley rats(p14,post-natal days)were treated with repeated retrobulbar injections of neutralizing anti-NGF(2μL,100μg/m L,every 3 d).After 2 wk(p28),retinal and corneal tissues were investigated for morphological,biochemical,and molecular expression of trkANGFR by using Western blotting or *** as well as protein profile expression were also ***:Chronic retrobulbar neutralizing anti-NGF antibodies changed the distribution of trkANGFR immunoreactivity at retinal level,while no changes were detected for global trkANGFR protein *** contrary,the treatment resulted in the increase of corneal trkANGFR *** tissues showed a decreased rhodopsin expression as well as reduced number of both rhodopsin expressing and total retinal cells,as observed after single cell extraction.A decreased expression of ICAM-1,IL-17 and IL-13 as well as an increased expression of IL-21 typified retinal *** significant changes were observed for corneal ***:The reduced availability of endogenous NGF,as produced by chronic retrobulbar anti-NGF administration,produce a quick response from retinal tissues,with respect to corneal ones,suggesting the presence of early compensatory mechanisms to protect retinal networking.

关键词： anti-nerve growth factor trk^(ANGFR) retina cornea photoreceptors tissue response

Pharmacological potential of Populus nigra extract as antioxidant,anti-inflammatory,cardiovascular and hepatoprotective agent

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Asian Pacific Journal of Tropical Biomedicine 2013年第9期3卷 697-704页

作者： Nadjet Debbache-Benaida Dina Atmani-Kilani Valerie Barbara Schini-Keirth Nouredine Djebbli Djebbar Atmani Laboratory of Applied Biochemistry Faculty of Nature and Life ScienceUniversity A.Mira pharmacology and physical-chemistry of cellular and molecular interactions UMR CNRS 7213Faculty of PharmacyUniversity Louis Pasteur of Strasbourg Department of biology Faculty of SciencesUniversity of Mostaganem

Objective:To evaluate antioxidant,anti-inflammatory,hepatoprotective and vasorelaxant activities of Pupulus nigra flower buds ethanolic ***:Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw *** from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver *** effect was estimated in endothelium-intact and-nibbed rings of porcine coronary arteries precontracted with high concentration of ***:The results showed a moderate antioxidant activity(40%),but potent anti-inflammatory activity(49.9%)on carrageenan-induced mice paw edema,and also as revealed by histopathologic examination,complete protection against AlCl_3-induced hepatic *** effects of the same exlracl on vascular preparation from porcine aorta precontracted with high concentration of U466I9 were considerable at 10^(-1)g/L,and comparable(P>0.05)between endothelium-intact(67.74%,IC_(50)0.04 mg/ml.)and-rubbed(72.72%,IC_(50)=0.075 mg/ml,)aortic ***:The extract exerted significant anti-inflammatory,hepatoprotective and vasorelaxant activities,the latter being cndothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties,probably related to an inhibition of Ca^(2+)influx.

关键词： Populus nigra Polyphenols Anti-inflammatory activity Hepatoprotection Vasorelaxation

Trivalent Chromium Modulates Hexosamine Biosynthesis Pathway Transcriptional Activation of Cholesterol Synthesis and Insulin Resistance

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Open Journal of Endocrine and Metabolic Diseases 2013年第4期3卷 1-8页

作者： Brent A. Penque Lixuan Tackett Jeffrey S. Elmendorf departments of cellular and Integrative Physiology and Biochemistry and Molecular biology Centers for Diabetes Research and Membrane Biosciences Indiana University School of Medicine Indianapolis USA

Trivalent chromium has long been recognized to benefit carbohydrate and lipid metabolism. Given emerging evidence that suggests chromium improves insulin sensitivity through the maintenance of an optimal level of plasma membrane (PM) cholesterol, we delineated the role of this micronutrient in attenuating hyperinsulinemia-induced cholesterol biosynthesis and insulin resistance. Exposing 3T3-L1 adipocytes to physiological hyperinsulinemia (500 pM 12 h), resulted in a marked impairment in insulin-stimulated glucose transport. Concurrent treatment with chromium in the picolinate form (CrPic, 10 nM 16 h) prevented against glucose transport dysfunction. Insulin signaling was neither impaired by hyperinsulinemia nor amplified by chromium to promote this protective action. Instead, it was found that hyperinsulinemia promoted an increase in PM cholesterol content that was observed to impair the acute ability of insulin to stimulate GLUT4 redistribution to the PM. Chromium prevented against the accumulation of PM cholesterol. Mechanistically, hyperinsulinemia promoted increases in O-GlcNAc modification of specificity protein 1 (Sp1), known to engage a cholesterolgenic response. Subsequent chromatin immunoprecipitation and luciferase assays revealed that hyperinsulinemia increased the binding affinity of Sp1 to the promoter region of Hmgcr, encoding 3-hydroxy 3-methyl-glutaryl-CoA reductase (HMGR), as well as HMGR promoter activity. This resulted in gains in mRNA and protein content of HMGR, with resulting elevations in PM cholesterol content. Moreover, treatment with chromium prevented this transcriptional response. Together, these data suggest a mechanism whereby CrPic affords glycemic health through inhibition of a transcriptional cholesterolgenic program detrimental to insulin action.

关键词： 3T3-L1 Adipocytes GLUT4 HMG-CoA Reductase Hyperinsulinemia Sp1

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生命的印迹：在一个被污染的世界中生活

环境与职业医学 2013年第2期30卷 157-159页

作者： David Crews Andrea C.Gore 汪源王晓宇张晶郑轻舟金泰廙 Section of Integrative biology Institute for cellular and Molecular biology Division of pharmacology and Toxicology University of Texas at AustinAustinTexasUSA

[背景]由于人为的化学污染,先天遗传和后天环境之间的关联需要重新进行认定。尽管污染整治行动已经在局部地域开展起来,但在全球层面上,这基本不可能。污染物会通过人群迁徙、食物链传递以及空气和水流而扩散,甚至能累及以前从未直接受... 详细信息

[背景]由于人为的化学污染,先天遗传和后天环境之间的关联需要重新进行认定。尽管污染整治行动已经在局部地域开展起来,但在全球层面上,这基本不可能。污染物会通过人群迁徙、食物链传递以及空气和水流而扩散,甚至能累及以前从未直接受到过这些环境危害暴露的地区。在认识并接受这一全球性变化的同时,我们必须做进一步研究并考虑各种可能作为后果的适应状态。[目的]综合各种有关环境污染研究的学科,提出了一种范式转换,以证明污染分布广泛性且不能在全球层面上进行治理。[讨论]必须投入更多的综合性及跨学科研究,因为这样的研究才能明确阐释相关过程的因果机制和功能性结果如何在各级生物组织产生作用,同时揭示各级之间的关系。[结论]要预测和了解未来,我们必须更多研究可能发生的事,较少研究已经发生的事。这样我们才能明白祖先的环境暴露如何在其个体和后代层面起作用,影响生命周期的方方面面。

关键词：内分泌干扰物表观遗传学进化生物学可遗传的后天效应先天效应

Minimally manipulated autologous adherent bone marrow cells (ABMCs):a promising cell therapy of spinal cord injury

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Neural Regeneration Research 2015年第7期10卷 1058-1060页

作者： Kamana Misra Hatem E.Sabaawy Celvive Inc. departments of Neuroscience and Cell biology RBHS-Robert Wood Johnson Medical School Rutgers University cellular and Molecular pharmacology and MedicineRBHS-Robert Wood Johnson Medical School Rutgers University Rutgers Cancer Institute of New Jersey Rutgers University

Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorr... 详细信息

关键词： bone cell Minimally manipulated autologous adherent bone marrow cells a promising cell therapy of spinal cord injury ABMCs MSCs

Upregulation of PIP3-Dependent Rac Exchanger 1(P-Rex1) Promotes Prostate Cancer Metastasis

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生物物理学报 2009年第S1期25卷 229-229页

作者： Mikio Hoshino Dennis W.Wolff Margaret A.Scofield Frank J.Dowd Department of Biochemistry and cellular biology National Institute of Neuroscience National Center of Neurology and Psychiatry Kyoto Japan departments of pharmacology Creighton University School of Medicine Omaha NE 68178 USA

Excessive activation of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation

关键词： PIP P-Rex1 Promotes Prostate Cancer Metastasis Upregulation of PIP3-Dependent Rac Exchanger 1