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Chemotaxis: new role for Ras revealed

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Protein & Cell 2010年第10期1卷 879-880页

作者： Jianshe Yan Dale Hereld Tian Jin Chemotaxis Signal Section Laboratory of ImmunogeneticsNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockvilleMD 20852USA division of metabolism and health effects National Institute on Alcohol Abuse and AlcoholismNIH5635 Fishers LaneRockvilleMD 20852USA

A recent study of chemotaxis revealed a new role for the proto-oncogene Ras in the social ameba Dictyostelium ***,the directional movement of cells toward chemokines and other chemoattractants,plays critical roles in diverse physiological processes,such as mobilization of immune cells to fight invading microorganisms,targeting of metastatic cancer cells to specific tissues,and guidance of sperm cells to ova during *** work,published in the July 26 issue of The Journal of Cell Biology,was conducted in ***’lab at John Hopkins University and ***’s lab at National Cancer *** research team demonstrated that RasC functions as an upstream regulator of TORC2 and thereby governs the effects of TORC2-PKB signaling on the cytoskeleton and cell migration.

关键词： Hopkins Cancer thereby

Assessment of Neurotoxicity: Use of Glial Fibrillary Acidic Protein as a Biomarker

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Biomedical and Environmental Sciences 1991年第1期4卷 197-206页

作者： JAMES P.O CALLAGHAN Neurotoxicology division Health Effects Research Laboratory U. S Environmental Protection Agency Research Triangle Park

Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes. The hallmark of this response is enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). These observations suggest that GFAP may be a useful biomarker of neurotoxicity. To investigate this possibility, we administered prototype neurotoxicants to experimental animals and assessed the effects of these agents on the tissue content of GFAP, as determined by radioimmunoassay. A review of the background, design, and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity.

关键词： GFAP Use of Glial Fibrillary Acidic Protein as a Biomarker Assessment of Neurotoxicity

Transport mechanism in chemically reactive hybrid nanofluid flow containing gyrotactic micro-organisms over a curved oscillatory surface

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 177-192页

作者： M.NAVEED M.IMRAN T.ASGHAR Z.ABBAS Department of Mathematics Division of Science and TechnologyUniversity of Education Department of Mathematics The Islamia University of Bahawalpur

This paper examines the transport analysis, including both heat transfer and mass transfer, in hybrid nanofluid flow containing gyrotactic microorganisms towards a curved oscillatory surface. The influence of magnetic fields is also inspected in terms of their physical characteristics. To depict the phenomena of transport, modified versions of both Fick's and Fourier's laws are used. Additionally, the characteristics of both heterogeneous and homogeneous chemical reactions are also incorporated. Utilizing a curvilinear coordinate system, the flow problem is formulated as partial differential equations(PDEs)for momentum, concentration, microorganism field, and energy. An analytical solution to the obtained flow equations is achieved utilizing the homotopy analysis method(HAM).The effects of significant flow parameters on the pressure and microorganism fields, velocity, oscillation velocity, concentration, and temperature distributions are shown via graphs. Furthermore, the variations in skin friction, mass transfer rate, heat transfer rate, and local motile number due to different involved parameters are presented in tables and are analyzed in detail. Graphical results indicate that the curves of velocity and temperature fields are enhanced as the values of the solid volume fraction variables *** is also verified that the concentration rate field decreases as the values of the homogeneous reaction strength parameter and the radius of curvature parameter increase, and it increases with the Schmidt number and the heterogeneous reaction strength *** outcomes show a favorable response of the motile number to advanced values of the Peclet number, the Schmidt number, the microorganism difference parameter, and the bio-convective Lewis number.

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Inhibition of DNA-dependent Protein Kinase Catalytic Subunit by Small Molecule Inhibitor NU7026 Sensitizes Human Leukemic K562 Cells to Benzene Metabolite-induced Apoptosis

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第1期33卷 43-50页

作者：游浩孔萌萌王立萍肖潇廖汉林毕卓悦燕虹王红汪春红马强刘燕群毕勇毅 School of Public health Wuhan University School of Medicine Jianghan University School of Pharmaceutical Science Wuhan University Receptor Biology Laboratory Toxicology and Molecular Biology BranchHealth Effects Laboratory DivisionNational Institute for Occupational Safety and Health

Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit （DNA-PKcs） to mediate the cellular response to DNA double strand break （DSB） caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-（morpholin-4-yl）-benzo[h]chomen-4-one （NU7026）, as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.

关键词： benzene DNA-dependent protein kinase catalytic subunit 2-(morpholin-4-yl)- benzo[h]chomen-4-one Akt DNA double strand break

Cord blood zinc status effects on pregnancy outcomes and its relation with maternal serum zinc levels:a systematic review and meta-analysis

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World Journal of Pediatrics 2020年第4期16卷 366-376页

作者： Sevginur Akdas Nuray Yazihan Interdisciplinary Food Metabolism and Clinical Nutrition DepartmentInstitute of Health SciencesAnkara UniversityAnkaraTurkey Department of Pathophysiology Internal Medicine DivisionFaculty of MedicineAnkara UniversityAnkaraTurkey

Background The association between maternal and cord blood zinc level and pregnancy outcomes remains *** present study aims to assess whether maternal blood zinc level represents cord blood zinc level *** In this meta-analysis,systematic search was performed in PubMed,Web of Science,and Scopus databases for relevant available English articles which included mean and standard deviation values of cord blood zinc level up to April *** the assessment of the relation between cord blood zinc level and pregnancy outcomes,the pooled standard mean difference with 95%confidence interval(CI)was used and 23 studies were *** Cumulative analysis showed that cord blood zinc level was found significantly decreased in pregnancies with complications compared with healthy pregnancy controls[REM:P=0.0007,mean difference−7.9(−12.48,−3.31)].For further analysis,maternal serum zinc level status was determined from same studies to compare with cord blood levels and subgroups were detected as“Preterm”,“Preeclampsia”,“Small for gestational age/Intrauterine growth restriction and Low birth weight”.It was observed that cord blood zinc levels in subgroup analysis were also decreased and/or tend to be decreased compared to healthy pregnancies,except for preeclampsia ***,a correlation was seen between cord blood and maternal blood zinc level status(R=0.4365,95%CI−0.530,0.756;P=0.0351).Conclusion It was thought that cord blood zinc level might tend to decrease more than maternal serum zinc level in the pathological conditions during pregnancies.

关键词： Intrauterine growth restriction Preeclampsia Pregnancy Preterm Zinc

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

Adverse effects of androgen deprivation therapy in men with prostate cancer： a focus on metabolic and cardiovascular complications

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Asian Journal of Andrology 2012年第2期14卷 222-225页

作者： Lauren Collins Shehzad Basaria Department of Medicine Division of Endocrinology and MetabolismBoston University School of MedicineBostonMA 02118USA

Prostate cancer （PCa） is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy （ADT） is used in the management of locally advanced （improves survival） and metastatic （improves pain and quality of life） PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.

关键词： androgen deprivation therapy cardiovascular disease diabetes hypogonadism prostate cancer

Tyrosine Hydroxylase as a Target for Deltamethrin in the Nigrostriatal Dopaminergic Pathway

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Biomedical and Environmental Sciences 2006年第1期19卷 27-34页

作者： GONG-PING LIU QIANG MA NIAN SHI Department of Toxicology MOE key Laboratory of Environmental and Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei China Receptor Biology Laboratory Toxicology and Molecular Biology Branch Health Effects Laboratory Division National Institute for Occupational Safety and Health Centers for Disease Control and Prevention Morgantown WV 26505 USA

Objective To study the effects of deltamethrin on tyrosine hydroxylase in nigrostriatum of male rats. Methods Sprague-Dawley rats were daily treated with deltamethrin at 6.25 or 12.5 mg/kg body weight by gavage for 10 days. Then HPLC-fluorescence detection was used to analyze the contents of dopamine （DA）, 3,4-dihydmxyphenylacetic acid （DOPAC） and homoranillic acid （HVA） in substantial nigra and striatum. The activities of tyrosine hydroxylase （TH） were also detected by HPLC-fluorescence detection. TH mRNA or TH protein levels were measured by RT-PCR and immunohistochemistry method. Results The content of DA in stfiatum was significantly decreased by the treatments, suggesting an inhibition of DA synthesis by deltamethrin. The contents of DA metabolites DOPAC and HVA increased, indicating increased dopamine turnover. Furthermore, deltamethrin significantly decreased the activity, as well as the mRNA and protein levels of TH. Conclusions These findings reveal a novel aspect of deltamethfin neurotoxicity and suggest tyrosine hydroxylase as a molecular target of deltamethin on dopamine metabolism in the nigrostriatal pathway.

关键词： Deltamethrin Nigrostriatum Dopamine Tyrosine hydroxylase Parkinson's disease

Combination therapy with saxagliptin and vitamin D for the preservation ofβ-cell function in adult-onset type 1 diabetes:a multi-center,randomized,controlled trial

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2354-2362页

作者： Xiang Yan Xia Li Bingwen Liu Jiaqi Huang Yufei Xiang Yuhang Hu Xiaohan Tang Ziwei Zhang Gan Huang Zhiguo Xie Houde Zhou Zhenqi Liu Xiangbing Wang Richard David Leslie Zhiguang Zhou National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology(Central South University)Ministry of Educationand Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina division of Endocrinology and metabolism Department of MedicineUniversity of Virginia Health SystemCharlottesvilleVAUSA division of Endocrinology Metabolism and NutritionRutgers University-Robert Wood Johnson Medical SchoolNew BrunswickNJUSA Centre for Immunobiology Blizard InstituteQueen Mary University of LondonLondonUK

Disease modifying therapies aiming to preserveβ-cell function in patients with adult-onset autoimmune type 1 diabetes are ***,we conducted a multi-centre,randomized,controlled trial to assess theβ-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 *** this 3-arm trial,301 participants were randomly assigned to a 24-month course of the conventional therapy(metformin with or without insulin)or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional *** primary endpoint was the change from baseline to 24 months in the fasting *** secondary endpoints included the area under the concentration-time curve(AUC)for C-peptide level in a 2-h mixed-meal tolerance test,glycemic control,total daily insulin use and safety,*** primary endpoint was not achieved in saxagliptin plus vitamin D group(P=0.18)and saxagliptin group(P=0.26).However,compared with the conventional therapy,2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D(-276 pmol/L vs.-419 pmol/L;P=0.01),and not to the same degree with saxagliptin alone(-314 pmol/L;P=0.14).Notably,for participants with higher glutamic acid decarboxylase antibody(GADA)levels,the decline ofβ-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group(P=0.001).Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic *** conclusion,the combination of saxagliptin and vitamin D preserves pancreaticβ-cell function in adult-onset autoimmune type 1 diabetes,an effect especially efficacious in individuals with higher GADA *** results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes.(*** identifier:NCT024

关键词： vitamin alone treatment