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Increased DNA binding activity of NF-κB,STAT-3,SMAD3 and AP-1 in acutely damaged liver

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World Journal of Gastroenterology 2006年第37期12卷 5995-6001页

作者： adriana.salazar-montes Luis Ruiz-Corro Ana Sandoval-Rodriguez Alberto Lopez-Reyes Juan Armendariz-Borunda Institute of Molecular Biology in Medicine and Gene Therapy CUCS University of Guadalajara Apdo. Postal 2-123 Guadalajara 44281 Jal Mexico Institute of Molecular Biology in Medicine and Gene Therapy CUCS University of Guadalajara Apdo.Postal 2-123 Guadalajara 44281 Jal Mexico OPD Hospital Civil de Guadalajara Guadalajara Jal Mexico

AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.

关键词： Hepatic regeneration Transcription factor Gene regulation

New gene therapy strategies for hepatic fibrosis

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World Journal of Gastroenterology 2015年第13期21卷 3813-3825页

作者： adriana M salazar-montes Luis D Hernández-Ortega Martha S Lucano-Landeros Juan Armendariz-Borunda Department of Molecular Biology and Genomics Institute for Molecular Biology and Gene TherapyUniversity of GuadalajaraGuadalajaraJalisco 44281México

The liver is the largest internal organ of the body, which may suffer acute or chronic injury induced by many factors, leading to cirrhosis and hepatocarcinoma. Cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure, regenerative nodules and fibrotic tissue. Cirrhosis is associated with a high co-morbidity and mortality without effective treatment, and much research has been aimed at developing new therapeutic strategies to guarantee recovery. Liver-based gene therapy has been used to downregulate specific genes, to block the expression of deleterious genes, to delivery therapeutic genes, to prevent allograft rejection and to augment liver regeneration. Viral and non-viral vectors have been used, with viral vectors proving to be more efficient. This review provides an overview of the main strategies used in liver-gene therapy represented by non-viral vectors, viral vectors, novel administration methods like hydrodynamic injection, hybrids of two viral vectors and blocking molecules, with the hope of translating findings from the laboratory to the patient′s bed-side.

关键词： Gene therapy Hepatic fibrosis Viral vectors Non-vi

Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine

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World Journal of Gastroenterology 2013年第47期19卷 9020-9033页

作者： Daniela Gordillo-Bastidas Edén Oceguera-Contreras adriana.salazar-montes Jaime González-Cuevas Luis Daniel Hernández-Ortega Juan Armendáriz-Borunda nstitute of Molecular Biology in Medicine and Gene Therapy/CUCS University of GuadalajaraGuadalajaraJalisco 44100México

AIM:To determine the molecular mechanisms involved in experimental hepatic fibrosis prevention by caffeine(CFA).METHODS:Liver fibrosis was induced in Wistar rats by intraperitoneal thioacetamide or bile duct ligation and they were concomitantly treated with CFA(15 mg/kg per day).Fibrosis and inflammatory cell infiltrate were evaluated and classified by Knodell *** infiltrate was quantified by immunohistochemistry(anti-CD11b).Gene expression was analyzed by quantitative reverse transcription-polymerase chain reaction for collagenⅠ?(Col-1),connective tissue growth factor(CTGF),transforming growth factorβ1(TGF-β1),tumor necrosis factor alpha(TNF-α),interleukin-1(IL-1),IL-6,superoxide dismutase(SOD)and catalase(CAT).Activation of Nrf2 and Snail-1 was analyzed by ***-αexpression was proved by enzyme-linked immunosorbant assay,CAT activity was performed by ***:CFA treatment diminished fibrosis index in treated *** Knodell index showed both lower fibrosis and *** of profibrogenic genes CTGF,Col-1 and TGF-β1 and proinflammatory genes TNF-α,IL-6 and IL-1 was substantially diminished with CFA treatment with less CD11b positive *** lower values of transcriptional factor Snail-1 were detected in CFA treated rats compared with cirrhotic rats without treatment;in contrast Nrf2was increased in the presence of *** of SOD and CAT was greater in animals treated with CFA showing a strong correlation between mRNA expression and enzyme ***:Our results suggest that CFA inhibits the transcriptional factor Snail-1,down-regulating profibrogenic genes,and activates Nrf2 inducing antioxidant enzymes system,preventing inflammation and fibrosis.

关键词： Liver fibrosis Caffeine Thioacetamide Bile duct ligation Profibrogenic genes Proinflammatory cytokines Antioxidant enzymes

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi James D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Evaluation of hypoxia inducible factor targeting pharmacological drugs as antileishmanial agents

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Asian Pacific Journal of Tropical Medicine 2016年第7期9卷 633-638页

作者： Marina Dal’Bo Pelegrini Juliana Biar Pereira Solange dos Santos Costa Myriam Janeth salazar Terreros adriana Degrossoli Selma Giorgio Department of Animal Biology Biology InstituteUniversidade Estadual de CampinasCampinasSao PauloBrazil

Objective:To evaluate whether hypoxia inducible factor(HIF-1α) targeting pharmacological drugs,echinomycin,resveratrol and CdCl_2 which inhibit HIF-1α stimulation,and mimosine,which enhances the stability of HIF-1α present antileishmanial ***:The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous ***:Resveratrol and CdCl_2 reduced the parasite load [IC50,(27.3±2.25) μM and(24.8±0.95) μM,respectively].The IC50 value of echinomycin was(22.7±7.36) nM and mimosine did not alter the parasite load in primary *** macrophage viability IC50 values for resveratrol,echinomycin and CdCl_2 and mimosine were >40 μM,>100 nM,> 200 μM and>2 000 μM,*** vivo no differences between cutaneous lesions from control,resveratrol-and echinomycin-treated Balb/c mice were ***:Resveratrol,echinomycin and CdCl_2 reduce parasite survival in *** HIF-1α targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies.

关键词： Leishmaniosis Hypoxia inducible factor Resveratrol Echinomycin CdCl2 Mimosine

Spectral square moments of a resonance sum for Maass forms

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Frontiers of Mathematics in China 2017年第5期12卷 1183-1200页

作者： Nathan salazar Yangbo YE Department of Mathematics The University of Iowa Iowa City Iowa 52242-1419 USA

Let f be a Maass cusp form for Г0（N） with Fourier coefficients 1 k2. λf（n） and Laplace eigenvalue 1/4 ＋k2 For real α≠0 and β 〉 0, consider the sum Sx（f; α,β） = ∑n λf（n）e（αnβ）φ（n/X）, where φ is a smooth function of compact support. We prove bounds for the second spectral moment of Sx （f;α, β）, with the eigenvalue tending towards infinity. When the eigenvalue is sufficiently large, we obtain an average bound for this sum in terms of X. This implies that if f has its eigenvalue beyond X1/2＋ε, the standard resonance main term for Sx（f; ±2√q 1/2）, q ∈Z＋, cannot appear in general. The method is adopted from proofs of subconvexity bounds for Rankin-Selberg L-functions for GL（2） × GL（2）. It contains in particular a proof of an asymptotic expansion of a well-known oscillatory integral with an enlarged range of Kε≤ L≤ K1-ε. The same bounds can be proved in a similar way for holomorphie cusp forms.

关键词： Cusp form Maass form Fourier coefficient of cusp form Kuznetsovtrace formula resonance sum first derivative test weighted stationary phase

Linear viscoelastic behavior of asphalt binders and mixtures containing very high percentages of reclaimed asphalt pavement

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Frontiers of Structural and Civil Engineering 2023年第8期17卷 1211-1227页

作者： Reza IMANINASAB Luis LORIA-salazar Alan CARTER Construction Engineering Department École de Technologie Supérieure(ÉTS)University of QuebecMontreal H3C 1K3Canada Civil Engineering Department Universidad Isaac NewtonSan José10108Costa Rica

The primary aim of this study is to correlate the impact of aggregates,if any,on the viscoelastic behavior of rejuvenated asphalt mixtures containing very high amounts of reclaimed asphalt pavement(RAP)(>50%).First,gradation of 100%RAP was rectified,using a modified Bailey method by adding virgin aggregates to achieve two coarse dense-graded and one fine dense-graded *** modulus test was then performed from−35 to+35℃and 0.01–10 *** addition to performance grade(PG)testing,extracted and recovered binders from different asphalt mixtures underwent shear complex modulus test within−8℃to high temperature PG and frequencies from 0.001 to 30 ***−Cole,Black space,complex modulus and phase angle master curves were constructed and ShiftHomothety-Shift in time-Shift(SHStS)transformation was used to compare the linear viscoelastic behavior of asphalt binders and *** influence of aggregates on the viscoelastic behavior of asphalt mixtures depends on temperature and/or *** role of asphalt binders in the behavior of asphalt mixtures is more pronounced at high temperatures and the effect of the aggregate structure increases as the temperature *** maximum difference(60%to 70%)in the viscoelastic behavior of the binder and mixture based on SHStS transformed Cole−Cole curves is within the phase angle of 15°–20°.

关键词： RAP complex modulus SHStS transformation rejuvenation behavior of asphalt binder and mixture

The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis： perspectives for remyelination therapeutic strategies

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Neural Regeneration Research 2017年第12期12卷 1939-1944页

作者： adriana Octaviana Dulamea Department of Neurology Fundeni Clinical Institute University of Medicine and Pharmacy "Carol Davila" Bucharest Romania

Oligodencrocytes（OLs） are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis（MS）, there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells（OPCs） and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.

关键词： multiple sclerosis oligodencrocytes oligodendrocyte progenitor cells demyelination remyelination semaphorin basic helix-loop-helix transcription factor oligodendrocyte transcription factor 2 leucin-rich repeatand immunoglobulin-like-domain-containing nogo receptor-interacting protein I canonical Notch signaling endocrine receptors

INFLUENCE OF RARE EARTH DOPING ON MECHANICAL PROPERTY AND MICRO-STRUCTURE OF CHROMIA OXIDE FILM

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Chinese Journal of Mechanical Engineering 2008年第3期21卷 16-19页

作者： JIN Huiming FELIX adriana College of Mechanical Engineering Yangzhou University Yangzhou 225005 China College of Materials Engineenng National University of Antiuquia Medellin 23715 Colombia

The isothermal oxidizing kinetics of Co-40Cr alloy and its yttrium ion-implanted samples are studied at 1 000 ℃ in air by thermal-gravity analysis （TGA）. Scanning electronic microscopy （SEM） is used to examine the Cr2O3 oxide film＇s morphology after oxidation. Acoustic emission （AE） method is used in situ for monitoring the cracking and spalling of oxide films formed on both samples during oxidizing and subsequent air-cooling stages. Theoretical model is proposed relating to the film fracture process and is used for analyzing the acoustic emission spectrum both on time domain and on AE-event number domain. It is found that yttrium implantation remarkably reduces the isothermal oxidizing rate of Co-40Cr and improves the anti-cracking and anti-spalling properties of Cr2O3 oxide film. The reasons for the improvement are mainly that the implanted yttrium reduced the grain size of Cr2O3 oxide, increased the high temperature plasticity of oxide film, and remarkably reduced the number and size of Cr2O3/Co-40Cr inteffacial defects.

关键词： Stress Acoustic emission Interface Yttrium Oxidation