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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

The role of clinical diagnosis criteria on the frequency of accommodative insufficiency

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 647-653页

作者： María García-Montero Beatriz Antona Ana Rosa Barrio Carmen Nieto-Zayas Irene Martínez-Alberquilla José luis hernández-Verdejo Department of Optometry and Vision Faculty of Optics and Optometry Complutense University of Madrid Department of Statistics and Operations Research Ⅲ Faculty of Statistical Studies Complutense University of Madrid

AIM: To estimate and compare the frequency of accommodative insufficiency(AI) within the same clinical population sample depending on the type of clinical criteria used for diagnosis. Comparing the frequency within the same population would help to minimize bias due to sampling or methodological variability. METHODS: Retrospective study of 205 medical records of symptomatic subjects free of any organic cause and symptoms persisting despite optical compensation evaluated. Based on the most commonly clinical diagnostics criteria found in the literature, four diagnostics criteria were established for AI(Ⅰ, Ⅱ, Ⅲ and Ⅳ) based on subjective accommodative tests: monocular accommodative amplitude two or more diopters below Hofstetter's minimum value [15-(0.25×age)](Ⅰ, Ⅱ, Ⅲ, Ⅳ); failing monocular accommodative facility with minus lens, establishing the cut-off in 0 cycles per minute(cpm)(Ⅰ) and in 6 cpm(Ⅱ, Ⅲ); failing binocular accommodative facility with minus lens, establishing the cut-off in 0 cpm(Ⅰ) and in 3 cpm(Ⅱ).RESULTS: The proportion of AI(95%CⅠ) for criteria Ⅰ, Ⅱ, Ⅲ and Ⅳ were 1.95%(0.04%-3.86%), 2.93%(0.31%-4.57%), 6.34%(1.90%-7.85%) and 41.95%(35.14%-48.76%) respectively, with a statistically significant difference shown between these values(χ2=226.7, P<0.001). A pairwise multiple comparison revealed that the proportion of AI detected for criterion Ⅳ was significantly greater than the proportion for the rest of the criteria(P-adjusted<0.05 in all cases).CONCLUSION: The prevalence of cases of AI within the same clinical population varies with the clinical diagnostic criteria selected. The variation is statistically significant when considering the monocular accommodative amplitude as the only clinical diagnostic sign.

关键词： epidemiology amplitude of accommodation accommodative facility

Antifeedant Activity of Caesalpinia coriaria Essential Oil Against Incisitermes marginipennis (Latreille)

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Phyton-International Journal of Experimental Botany 2021年第3期90卷 907-920页

作者： Cesar B.Ramírez-López Rita Beltrán-Sánchez Alistair hernández-Izquierdo Joséluis Salvador-hernández Eduardo Salcedo-Pérez Rosa E.del Río Mauro M.Martínez Pacheco Instituto de Investigaciones Químico Biológicas Universidad Michoacana de San Nicolás de HidalgoMorelia58030Mexico Departamento de Botánica y Zoología CUCBA Universidad de GuadalajaraNextipac45200Mexico

This study scrutinized the possibility of finding toxicant or deterrent plant metabolites against the dry wood termite Incisitermes marginipennis(Latreille).Plant deterrent agents act as repellents or antifeedants to prevent wood decay and increase its useful *** potential of the tree Caesalpinia coriaria(Fabaceae)as a biological source of molecules with deterrent effects against the dry wood termite was assessed by a phytochemical fractionation guided by repellence and antifeedant *** gas chromatography-mass spectrometry analysis of the leaf essential oil showed geraniol to be one of the major components and its repellent and antifeedant effects were *** had only an antifeedant effect without affecting the body weight or survival of the dry wood *** the leaf essential oil,geraniol did not exhibit a repellency *** in-silico approach of the activity of acetylcholinesterase in interaction with geraniol resulted in an affinity energy of−7.5 Kcal/*** interacted with the amino acid tyrosine 324 located in the enzyme’s active site while citronellol(negative control)interacted with tryptophan 83 located adjacent to the active *** deterring terpenes have not been implemented for the preservation and restoration of wood products exposed to the attack of the dry wood ***,they are an important natural control alternative.

关键词： Termite geraniol repellent antifeedant deterrent

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

C3G contributes to platelet activation and aggregation by regulating major signaling pathways

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2103-2117页

作者： Sara Gutiérrez-Herrero Cristina Fernández-Infante luis hernández-Cano Sara Ortiz-Rivero Carlos Guijas Víctor Martín-Granado JoséRamón González-Porras Jesús Balsinde Almudena Porras Carmen Guerrero Instituto de Biología Molecular y Celular del Cáncer(IMBCC) University of Salamanca-CSICSalamancaSpain Instituto de Investigación Biomédica de Salamanca(IBSAL) SalamancaSpain Instituto de Biología y Genética Molecular(IBGM) Consejo Superior de Investigaciones Científicas(CSIC)University of ValladolidValladolidSpain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas(CIBERDEM) MadridSpain Departamento de Hematologiá Hospital Universitario de Salamanca(HUS)SalamancaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaComplutense University of Madrid.Instituto de Investigación Sanitaria del Hospital Clínico San Carlos(IdISSC)MadridSpain Departamento de Medicina University of SalamancaSalamancaSpain

C3G is a GEF(guanine nucleotide exchange factor)for Rap GTPases,among which the isoform Rap1b is an essential protein in platelet *** transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat,we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKCRap1b pathway.C3G also plays important roles in angiogenesis,tumor growth,and metastasis through its regulation of the platelet *** addition,C3G contributes to megakaryopoiesis and ***,we used a platelet-specific C3G-KO mouse model to further support the role of C3G in hemostasis.C3G-KO platelets showed a significant delay in platelet activation and aggregation as a consequence of the defective activation of Rap1,which resulted in decreased thrombus formation in ***,we explored the contribution of C3G-Rap1b to platelet signaling pathways triggered by thrombin,PMA or ADP,in the referenced transgenic mouse model,through the use of a battery of specific *** found that platelet C3G is phosphorylated at Tyr504 by a mechanism involving *** phosphorylation was shown to be positively regulated by ERKs through their inhibition of the tyrosine phosphatase ***,C3G participates in the ADP-P2Y12-PI3K-Rap1b pathway and is a mediator of thrombin-TXA2 ***,it inhibits the synthesis of TXA2 through cPLA2 *** together,our data reveal the critical role of C3G in the main pathways leading to platelet activation and aggregation through the regulation of Rap1b.

关键词： C3G platelet activation

Effect of Antimony Additions on Corrosion and Mechanical Properties of Sn-Bi Eutectic Lead-Free Solder Alloy

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Materials Sciences and Applications 2012年第6期3卷 355-362页

作者： Alberto Torres luis hernández Octavio Domínguez Instituto de Metalurgia-UASLP San Luis Potosí México

The goal of the present work is to investigate the effects of the addition of Sb (0, 3 and 6 wt%) on structure, melting, corrosion and mechanical properties of Sn-Bi eutectic solder alloys. The mechanical properties of the bulk Sn-Bi-Sb solders were higher as the amount of antimony increases, making compressive strength augment from 65 MPa to 100 MPa when 6 wt% Sb was incorporated to the Sn-Bi eutectic alloy. The three alloys presented a melting temperature that is smaller to the one exhibited by the eutectic alloy Sn-38Pb (Tm = 183°C). According to the electrochemical results, the addition of higher contents of Sb to the Sn-Bi eutectic alloy had a positive effect: it ennobled the Ecorr values.

关键词： Lead Free Solder Alloys Sn-Bi-Sb Mechanical Properties Corrosion Properties

Comparison of the impact of nesofilcon A hydrogel contact lens on the ocular surface and the comfort of presbyopic and non-presbyopic wearers

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 640-646页

作者： Amalia Lorente-Velázquez María García-Montero Francisco Javier Gómez-Sanz Laura Rico del Viejo José luis hernández-Verdejo David Madrid-Costa Department of Optometry and Vision Faculty of Optics and Optometry Complutense University of Madrid

AIM: To assess and compare the impact of a daily disposable contact lens(CL) with high water content on the ocular surface and comfort of the presbyopic and nonpresbyopic population after one day of use. METHODS: Totally 20 presbyopes and 30 non-presbyopes non-contact wearers were fitted with nesofilcon A CLs. CL thickness was measured to assess material stability during daily wear, and ocular surface parameters were also assessed. Optical quality was analyzed for all cases. In addition, CL comfort was ***: No significant differences were found in CL thickness, tear film osmolarity, average tear break-up time, bulbar redness, central corneal thickness, corneal volume, root-mean-square of higher-order aberrations(RMS of HOAs) and vertical and horizontal coma, either as a function of the group or time of use. A significant decrease in tear meniscus height and first break-up of the tear film was found in the presbyopic group(P=0.038; P=0.007 respectively). A decrease in spherical aberration coefficient was found after CL insertion(P=0.031 monofocal CL; P=0.023 low addition multifocal CL; P=0.016 high addition multifocal CL). Multifocal CL were thicker than monofocal CL(P=0.045). Comparison between groups showed more discomfort in presbyopes than non-presbyopes(P=0.003).CONCLUSION: This study evidence that the behavior of the daily disposable CL with high water content seems to be stable during the day of use. Ocular parameters measured during wear show that CL behavior is the same for presbyopes and non-presbyopes, being more uncomfortable for presbyopes.

关键词： nesofilcon A hydrogel material ocular surface parameters presbyopia multifocal daily contact lenses

Evaluation of Ocimum basilicum *** Different Concentrations of K^(+)as an Inhibitor of Pathogenic Bacterial Strains

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Phyton-International Journal of Experimental Botany 2021年第2期90卷 533-541页

作者： Mercedes Georgina Ramírez-Aragón Victoria Jared Borroel-García Ramón Valenzuela-Soto Ricardo David Valdez-Cepeda Francisco Javier Wong-Corral Joséluis García-hernández Universidad Politécnica de Gómez Palacio Gómez Palacio35120México Universidad Autónoma Chapingo Centro Regional Universitario Centro-NorteZacatecasZac.Universidad Autónoma de ZacatecasFacultad de MatemáticasZacatecas98053México Departamento de Investigación y Posgrado en Alimentos Universidad de SonoraHermosillo83000México Facultad de Agricultura y Zootecnia Universidad Juárez del Estado de DurangoGómez Palacio34000México

The extraction of bioactive compounds has become one of the most interesting areas of modern *** therapeutic reasons,it´s important to obtain antimicrobial agents from natural *** objective of the present study was to determine the inhibitory effect of ethanolic extract of basil(Ocimum basilicum *** Rubin)subjected to different concentrations of potassium(K^(+))on the activity of three bacterial strains that are pathogens in *** was evaluated by inhibition surface and these results were compared to two antibiotics:Gentamicin(GE)and Ciprofloxacin(CPF)for their efficacy against each bacterial *** variables presented significant difference(p≤0.05).According to the results,basil extract evaluated showed positive antibacterial activity against the three strains of Pseudomonas aeruginosa,Listeria monocytogenes and Staphylococcus aureus on Mueller Hinton *** was observed highest inhibition areas of different diameters(15.3 mm,21.3 mm and 21.6 mm respectively)when the extract used was obtained from the plants with the highest concentration of potassium(13 mmol L-1).These values were even superior to the highest values showed on the treatments with the antibiotic gentamicin.

关键词： Basil inhibition potassium secondary metabolites antibiotics

Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions

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World Journal of Clinical Cases 2018年第15期6卷 922-930页

作者： Nahum Méndez-Sánchez Felipe Zamarripa-Dorsey Arturo Panduro Emma Purón-González Edgar Ulises Coronado-Alejandro Carlos Alejandro Cortez-hernández Fátima Higuera de la Tijera José luis Pérez-hernández Eira Cerda-Reyes Heriberto Rodríguez-hernández Vania César Cruz-Ramón Oscar Lenin Ramírez-Pérez Nancy Edith Aguilar-Olivos Olga Fabiola Rodríguez-Martínez Samantha Cabrera-Palma Guillermo Cabrera-álvarez Liver Research Unit Medica Sur Clinic and Foundation Department of Gastroenterology Hospital "Juárez" of México Department of Molecular Biology in Me-dicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" Department of Internal Medicine "Christus Muguerza "Super Specialty" Hospital" Monterrey Department of Gas-troenterology "University Hospital "Jose Eleuterio González" Monterrey Department of Gastroenterology "General Hospital of Mexico "Dr.Eduardo Liceaga" Department of Gastroenterology "Central Military Hospital" Faculty of Medicine and Nutrition Juárez University of the State of Durango Liver Clinic Regional General Hospital IMSS 1

AIM To investigate the main current etiologies of cirrhosis in *** We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period(January 2012-December 2017). RESULTS A total of 1210 patients were included. The mean age was 62.5 years(SD = 12.1), and the percentages of men and women were similar(52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus(HCV)(36.2%), alcoholic liver disease(ALD)(31.2%), and nonalcoholic steatohepatitis(23.2%), and the least frequent were hepatitis B virus(1.1%), autoimmune disorders(7.3%), and other conditions(1.0%).CONCLUSION HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease(NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.

关键词： Alcoholic liver disease Hepatitis C virus Nonalcoholic steatohepatitis Liver cirrhosis