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Current and emerging therapies for alcohol-associated hepatitis

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Liver Research 2023年第1期7卷 35-46页

作者： francisco Idalsoaga Gustavo Ayares Luis Antonio Díaz Jorge Arnold María Ayala-Valverde David Hudson Marco Arrese juan Pablo Arab Department of Gastroenterology School of MedicinePontificia Universidad Catolica de ChileSantiagoChile Internal Medicine Service Hospital El PinoCritical Patient UnitClinica DavilaSantiagoChile Division of Gastroenterology Department of MedicineSchulich School of MedicineWestern University&London Health Sciences CentreLondonOntarioCanada Department of Epidemiology and Biostatistics Schulich School of MedicineWestern UniversityLondonOntarioCanada Alimentiv LondonOntarioCanada

Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol *** includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated hepatitis(AH),the latter being the most severe acute form of the *** AH is associated with high mortality(reaching up to 30%e50%)at 90 *** cornerstone of ALD,and particularly AH,treatment continues to be abstinence,accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome(AWS).In severe AH with model for end-stage liver disease(MELD)score21,corticosteroids can be used,especially MELD score between 25 and 39,where the highest benefit is *** key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver *** development of new therapies based on the pathophysiology and mechanisms of liver injury are *** includes the modulation and management of the innate immune response,gut dysbiosis,bacterial translocation,and bacteria-derived products from the *** hold promise for the future of AH treatment.

关键词： Alcohol-associated hepatitis(AH) Alcohol-related liver disease(ALD) Alcohol use disorder(AUD) AUD treatment Nutritional therapy Steroids therapy Cirrhosis Fibrosis

SENP7 overexpression protects cancer cells from oxygen and glucose deprivation and associates with poor prognosis in colon cancer

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Genes & Diseases 2022年第6期9卷 1419-1422页

作者： francisco Gallardo-Chamizo Nieves Lara-Urena juan F.Correa-Vazquez Jose C.Reyes Benoit R.Gauthier Mario Garcia-Dominguez Cell Dynamics and Signaling Department CABIMERCSICUniversidad de Sevilla-Universidad Pablo de Olavide-Junta de AndaluciaSeville 41092Spain Genome Biology Department CABIMERCSIC-Universidad de Sevilla-Universidad Pablo de Olavide-Junta de AndaluciaSeville 41092Spain Cell Therapy and Regeneration Department CABIMERCSIC-Universidad de Sevilla-Universidad Pablo de Olavide-Junta de AndaluciaSeville 41092Spain Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabo´licas Asociadas(CIBERDEM) Madrid 28029Spain

To the Editor,Constricted oxygen and glucose supplies are common conditions that healthy cells following a stress such an ischemic insult as well as cancer cells within a solid tumor need to overcome in order to *** conditions are a serious challenge for cells,which accurately measure the impact to make a life or death *** cancer cells,aberrant gene expression and/or protein regulation,frequently linked to appearing mutations,may confer selective advantages to survive under these adverse *** the past years,cumulative evidence indicates that protein modification by covalent attachment of the Small Ubiquitin-like MOdifier(SUMO)plays a role in cell survival after oxygen and glucose deprivation(OGD).

关键词： cancer deprivation colon

Retrieval of Elastic Green’s Tensor near a Cylindrical Inhomogeneity from Vector Correlations

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Communications in Computational Physics 2008年第1期3卷 250-270页

作者： juan AP´erez-Ruiz francisco Luzon francisco J.Sanchez-Sesma Grupo de Geof´ısica Aplicada Departamento de F´ısica AplicadaUniversidad de Almer´ıaCa˜nada de San Urbano s/n04120-Almer´ıaSpain Departamento de Sismolog´ıa Instituto de IngenieriaUniversidad Nacional Aut´onoma de M´exicoCd.UniversitariaCircuito Escolar s/nCoyoac´an 04510M´exico D.F.Mexico.

Multiple scattering of elastic waves in realistic media makes that averagefield intensities or energy densities follow diffusive processes. In such regime the successiveP to S energy conversions by distributed random inhomogeneities give rise toequipartition which means that in the phase space the available elastic energy is distributedin averagewith equal amounts among the possible states of P and S waves. Insuch diffusive regime the P to S energy ratio equilibrates in an universal way independentof the particular details of the scattering. It has been demonstrated that averagingthe cross correlations at any two points of an elastic medium subjected to diffuse elasticwavefields leads to the emergence of the Green function, which is the wave fieldthat would be observed at one position if an impulsive load is applied at the other. Inthis work we study the problem of the retrieval of the 2D tensor elastodynamic Greenfunction in an infinite elastic space containing a circular cylinder inclusion. We illuminateisotropically the elastic spacewith plane waves. We assume the spectra for both Pand S waves uniform but such that the energy ratio ES/EP=(a/b)2, which is the onepredicted by equipartition theory in two-dimensions. We then show that the Fouriertransform of azimuthal average of the cross-correlation of motion between two pointswithin an elastic medium is proportional to the imaginary part of the exact Green tensorfunction between these points. The numerical results presented here point out thepossibility of detection and imaging of diffractors and resonant diffractors by crosscorrelation even in presence of attenuation exists.

关键词： Multiple scattering elastic waves elastic Green’s tensor

非正式学习环境中的STEM教育:美国博物馆学习服务案例研究

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世界教育信息 2024年第6期37卷 44-52页

作者：杨娟欧阳媛中国农业大学高等教育研究中心北京100091 首都师范大学教育学院北京100089

非正式学习环境为STEM教育提供了独特的机会和资源。作为非正式学习环境的典型代表,美国博物馆以知识共享为使命,通过策划丰富多样的教育活动,为各年龄段学生提供有针对性的STEM教育资源。研究聚焦于美国国家自然历史博物馆、旧金山探... 详细信息

非正式学习环境为STEM教育提供了独特的机会和资源。作为非正式学习环境的典型代表,美国博物馆以知识共享为使命,通过策划丰富多样的教育活动,为各年龄段学生提供有针对性的STEM教育资源。研究聚焦于美国国家自然历史博物馆、旧金山探索博物馆和西雅图飞行博物馆在STEM教育领域的实践探索,归纳总结了美国博物馆在提供STEM学习资源,与学校STEM教育有效衔接,支持STEM教师专业发展,吸引家庭参与STEM教育,促进STEM教育公平等方面的经验,这些经验为我国发展非正式学习环境中的STEM教育,丰富STEM教育资源提供了良好的借鉴。

关键词：非正式学习环境 STEM教育博物馆学习服务

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2-Cys Peroxiredoxins Participate in the Oxidation of Chloroplast Enzymes in the Dark

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Molecular Plant 2018年第11期11卷 1377-1388页

作者： Valle Ojeda juan Manuel Perez-Ruiz francisco Javier Cejudo Instituto de Bioquimica Vegetaly Fotosintesis Universidad de Sevilla and Consejo Superior de lnvestigaciones CientificasAvenida Americo Vespucio 4941092SevillaSpain

Most redox-regulated chloroplast enzymes are reduced during the day and oxidized during the *** the reduction mechanism of light-dependent enzymes is well known,the mechanism mediating their oxidation in the dark remains *** thiol-dependent peroxidases,2-Cys peroxiredoxins (Prxs),play a key role in light-dependent reduction of chloroplast *** transfer reducing equivalents of thiols to hydrogen peroxide,suggesting the participation of these peroxidases in enzyme oxidation in the ***,we have addressed this issue by analyzing the redox state of well-known redox-regulated chloroplast enzymes in response to darkness in Arabidopsis thaliana mutants deficient in chloroplastlocalized Prxs (2-Cys Prxs A and B,Prx ⅡE,and Prx Q).Mutant plants lacking 2-Cys Prxs A and B,and plants overexpressing NADPH-dependent thioredoxin (Trx) reductase C showed delayed oxidation of chloroplast enzymes in the *** contrast,the deficiencies of Prx ⅡE or Prx Q exerted no *** vitro assays allowed the reconstitution of the pathway of reducing equivalents from reduced fructose 1,6-bisphosphatase to hydrogen peroxide mediated by Trxs and 2-Cys *** together,these results suggest that 2-Cys Prxs participate in the short-term oxidation of chloroplast enzymes in the dark.

关键词： chloroplast enzyme oxidation peroxiredoxin thioredoxin hydrogen peroxide darkness

Characteristics and in-hospital mortality of elderly patients with heart failure in Spanish hospitals

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Journal of Geriatric Cardiology 2023年第4期20卷 247-255页

作者： Alberto Esteban-Fernández Manuel Anguita-Sánchez juan Luis Bonilla-Palomas María Anguita-Gámez María García JoséLuis Bernal Náyade Del Prado Cristina Fernández-Pérez Julián Pérez-Villacastin juan JoséGómez-Doblas francisco Javier Elola Cardiology Department Hospital Universitario Severo OchoaMadridSpain Cardiology Department Hospital Universitario Reina SofíaCórdobaSpain Cardiology Department Hospital San Juan de la CruzÚbedaSpain Cardiology Department Hospital Clínico San CarlosMadridSpain Fundación Instituto para la Mejora de la Asistencia Sanitaria MadridSpain Management Control Department Hospital Universitario 12 de OctubreMadridSpain Department of Preventive Medicine Área Sanitaria de Santiago de Compostela y BarbanzaInstituto de Investigación de SantiagoSantiago de CompostelaSpain Cardiology Department Hospital Universitario Virgen de la VictoriaMálagaSpain

BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older ***,there are little data on in-hospital mortality in patients with HF≥75 years in *** A retrospective analysis of the Spanish Minimum Basic Data Set was performed,including all HF episodes discharged from public hospitals in Spain between 2016 and *** was performed using the International Classification of Diseases,10th ***≥75 years with HF as the principal diagnosis were *** calculated:(1)the crude in-hospital mortality rate and its distribution according to age and sex;(2)the risk-standardized in-hospital mortality ratio;and(3)the association between in-hospital mortality and the availability of an intensive cardiac care unit(ICCU)in the *** We included 354,792 HF episodes of patients over 75 *** mean age was 85.2±5.5 years,and 59.2%of patients were *** most frequent comorbidities were renal failure(46.1%),diabetes mellitus(35.5%),valvular disease(33.9%),cardiorespiratory failure(29.8%),and hypertension(26.9%).In-hospital mortality was 12.7%,and increased with age[odds ratio(OR)=1.07,95%CI:1.07–1.07,P<0.001]and was lower in women(OR=0.96,95%CI:0.92–0.97,P<0.001).The main predictors of mortality were the presence of cardiogenic shock(OR=19.5,95%CI:16.8–22.7,P<0.001),stroke(OR=3.5,95%CI:3.0–4.0,P<0.001)and advanced cancer(OR=2.6,95%CI:2.5–2.8,P<0.001).In hospitals with ICCU,the in-hospital risk-adjusted mortality tended to be lower(OR=0.85,95%CI:0.72–1.00,P=0.053).CONCLUSIONS In-hospital mortality in patients with HF≥75 years between 2016 and 2019 was 12.7%,higher in males and elderly *** main predictors of mortality were cardiogenic shock,stroke,and advanced *** was a trend toward lower mortality in centers with an ICCU.

关键词： patients mortality diagnosis

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Virtual screening of flavonoids from Jatropha gossypiifolia *** potential drugs for diabetic complications

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Traditional Medicine Research 2022年第2期7卷 34-42页

作者： Yudith Cañizares-Carmenate Roberto Díaz-Amador Mirtha Mayra Gonzalez-Bedia Tan Tran Quang Nhat francisco Torrens juan Alberto Castillo-Garit Unit of Computer-Aided Molecular“Biosilico”Discovery and Bioinformatic Research Departamento de FarmaciaFacultad de Química-FarmaciaUniversidad Central“Marta Abreu”de Las VillasSanta Clara 54830Villa ClaraCuba Departamento de Ciencias de la Computación Facultad de MatemáticaFísica y ComputaciónUniversidad CelaraCuntral“Marta Abreu”de Las VillasSanta Clara 54830Villa ClaraCuba Institut Universitari de Ciència Molecular Universitat de ValènciaEdifici d’Instituts de PaternaP.O.Box 22085ValènciaSpain. Unidad de Toxicología Experimental Universidad de Ciencias Médicas de Villa ClaraSanta Clara 50200Villa ClaraCuba.

Background:Diabetes mellitus is a chronic metabolic disease that is a risk factor for epidemic *** hyperglycemic conditions,the enzyme aldose reductase catalyzes the formation of sorbitol in the metabolism of glucose via polyols,leading to the development of diabetic ***,inhibitors of this enzyme are therapeutic targets for the prophylaxis and treatment of these ***:In this study,a generalized linear regression model was developed to analyze flavonoids-obtained from a database-that have been tested as inhibitors of aldose *** this sense,the molecular descriptors implemented in DRAGON and MATLAB software were used to determine the correlation between the chemical structure of the inhibitors and their pharmacological *** model was validated according to the Organisation for Economic Co-operation and Development Standards and subsequently used for the virtual screening of the flavonoids identified in Jatropha gossypiifolia ***:The proposed model showed a good fit for its statistical parameters(R2=0.95).In addition,it showed good predictive power(R2 ext=0.94)and robustness(Q2 LOO=0.92).The experimental chemical space wherein the predictions were reliable(domain of application)was also ***,the model was used to identify 10 flavonoids from Jatropha gossypiifolia *** candidates for natural *** with a low probability of oral absorption were identified,among which the elagic acid biflavonoid showed the greatest promise(pIC50 predicted=9.75).Conclusion:The Jatropha gossypiifolia *** harbors flavonoids with high potential as inhibitors of the aldose reductase enzyme,in which the biflavonoid ellagic acid was shown to be the most promising inhibitor of the aldose reductase enzyme,suggesting its possible use in the treatment of the late complications of diabetes mellitus.

关键词： Jatropha gossypiifolia L. aldose reductase generalized linear regression model diabetic complications

Endothelial progenitor cells as a therapeutic option in intracerebral hemorrhage

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Neural Regeneration Research 2017年第4期12卷 558-561页

作者： juan Pías-Peleteiro francisco Campos José Castillo Tomás Sobrino Clinical Neurosciences Research Laboratory Department of NeurologyStroke UnitUniversity Clinical HospitalUniversidade de Santiago de CompostelaHealth Research Institute of Santiago de Compostela (IDIS)

Intracerebral hemorrhage （ICH） is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells （EPCs） have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.

关键词： cellular therapy endothelial progenitor cells growth factors intracerebral hemorrhage neurorepair outcome

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Comorbidity negatively influences prognosis in patients with extrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2009年第42期15卷 5279-5286页

作者： Mario Fernández-Ruiz juan-Manuel Guerra-Vales francisco Colina-Ruizdelgado Department of Internal Medicine University Hospital "12 de Octubre"Avenue Córdobas/nUniversidad ComplutenseMadrid 28041Spain Hospital Tumor Registry University Hospital "12 de Octubre"Avenue Córdobas/nUniversidad ComplutenseMadrid 28041Spain

AIM:To study the outcome and prognostic factors in a series of patients with extrahepatic cholangiocarcinoma and determine the impact of comorbidity on ***:A retrospective analysis of 68 patients with extrahepatic cholangiocarcinoma(perihilar,n = 37;distal,n = 31) seen at a single tertiary-care institution during the period 1999-2003 was *** on presentation,management,and outcome were assessed by chart *** confirmation was obtained in 37 cases(54.4%) .Comorbidity was evaluated by using the Charlson comorbidity index(CCI) .RESULTS:Mean age at diagnosis was 73.4 ± 11.5 *** was the most common symptom presented(86.8%) .Median CCI score was 1(range,0 to 4) .Nineteen patients(27.9%) underwent tumor *** biliary drainage was performed in 39 patients(57.4%) ,and 6 patients(8.8%) received only best supportive ***-free margin status(R0) was achieved in 15 cases(78.9% of resection group) .Baseline serum carbohydrate antigen 19-9(CA 19-9) level was revealed to be an independent predictor of surgical treatment(P = 0.026) .Overall median survival was 3.1 ± 0.9 mo,with 1-and 2-year survival rates of 21% and 7%,*** the univariate analysis,tumor resection,CCI score,and serum CA 19-9 levels correlated significantly with *** the multivariate analysis,only resection(HR 0.10;95% CI,0.02-0.51,P = 0.005) and a CCI score ≥ 2(HR 3.36;95% CI,1.0-10.9,P = 0.045) were found to independently predict ***:Tumor resection and comorbidity emerged as significant prognostic variables in extrahepatic *** evaluation instruments should be applied in the clinical management of such patients.

关键词：预后患者胆管癌