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Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling

signal Transduction and Targeted Therapy 2023年第11期8卷 5404-5416页

作者： Catarina macedo-silva Vera miranda-gonçalves Nuno Tiago Tavares Daniela Barros-silva Joana Lencart João Lobo Ângelo Oliveira margareta PCorreia Lucia Altucci Carmen Jerónimo Cancer Biology&Epigenetics Group Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Precision medicine University of Campania“Luigi Vanvitelli”80138NaplesItaly Department of Pathology and molecular Immunology ICBAS-School of Medicine&Biomedical SciencesUniversity of PortoR.Jorge de Viterbo Ferreira 2284050-313PortoPortugal medical Physics Radiobiology and Radiation Protection Group-Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of medical Physics Portuguese Oncology Institute of Porto4200-072PortoPortugal Department of Pathology Portuguese Oncology Institute of PortoPortoPortugal Department of Radiation Oncology Portuguese Oncology Institute of PortoPortoPortugal BIOGEm Molecular Biology and Genetics Research Institute83100AvellinoItaly IEOs Institute of Endocrinology and Oncology80100NaplesItaly

External beam radiotherapy(RT)is a leading first-line therapy for prostate cancer(PCa),and,in recent years,significant advances have been ***,RT resistance can arise and result in long-term recurrence or disease progression in the worst-case ***,making crucial the discovery of new targets for PCa ***,we generated a radioresistant PCa cell line,and found p53 to be highly expressed in radioresistant PCa cells,as well as in PCa patients with recurrent/disease progression submitted to *** dissection revealed that RT could promote p53 expression via epigenetic ***,a decrease of H3K27me3 occupancy at TP53 gene promoter,due to increased KDm6B activity,was observed in radioresistant PCa ***,p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated ***,KDm6B inhibition by GsK-J4 significantly decreased p53 expression,consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor ***,this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair,as well as the impact of epigenetic targeting for PCa radiosensitization.

关键词： TP53 damage cancer

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meningoencephalitis due to Listeria monocytogenes in a Young Immunocompetent Patient: Case Report with Literature Review

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Advances in Infectious Diseases 2024年第1期14卷 213-219页

作者： Janette Alejandra Gamiño Gutierrez Gustavo Adolfo Hernández Valdez Arleth Anahí montaño Gómez jorge morales Rojas Graciela Gaddy Robles martinez Anahi Herrera Ruelas Alin Kaori Ferreyra Gudiño Jocelin Celeste Jurado Cardona Jimena Jexabeth Ibáñez Núñez Anahí Fierros Ramos Departmento de Neurocirugia Hospital Civil de Guadalajara Fray Antonio Alcalde Guadalajara México Departamento de medicina Interna ISSSTE Tepic General Hospital APP Tepic México

meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompetent individuals. We present the case of a young adult patient without immunocompromise, who developed meningoencephalitis due to L. monocytogenes;This case is exceptional, since it occurred in an individual outside the classic age group, in addition to not having risk factors, which is why it should be considered an atypical causal agent.

关键词： meningitis Encephalitis Rhombencephalitis Listeria monocytogenes Immunocompetent

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Uremic Bleeding in 2 Patients with Dieulafoy’s Lesion: Case Report and Literature Review

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Open Journal of Gastroenterology 2024年第5期14卷 167-173页

作者： Gustavo Adolfo Hernández Valdez Diana Estefanía Ibarra García Juan Antonio Contreras Escamilla Janette Alejandra Gamiño Gutierrez Francisco manuel Tonatiuh Carrillo Beltran Ulises solis Gomez Jocelyn Nataly Quintero meléndez Ivan Alejandro medina Jimenez marco Antonio gonzález Villar jorge Rojas morales Department of Internal medicine ISSSTE APP General Hospital of Tepic Tepic Nayarit Mexico Hospital Civil de Guadalajara Fray Antonio Alcalde Guadalajara Jalisco M&#233xico

Dieulafoy’s lesions are rare vascular malformations of the gastrointestinal tract. A Dieulafoy’s lesion is an aberrant vessel that does not reduce in caliber when it extends from the submucosa to the mucosa. Damage to this artery can cause severe and intermittent arterial bleeding from small vascular stumps that are difficult to visualize. Furthermore, these catastrophic bleeding episodes frequently result in hemodynamic instability and the need for transfusion of multiple blood products. Recently, uremic syndrome has been identified as a risk factor for gastric mucosal lesions. We present two clinical cases of acute digestive bleeding due to Dielafoy lesion with chronic kidney disease as the main cause, where two different therapies were performed endoscopically. We concluded with the results of our patients that the best therapy was the application of the hemostatic hemoclip on the injury vs the injection with adrenaline on the wound site. Uremia is identified as a risk factor for upper gastrointestinal bleeding in patients with pre-existing Dieulafoy’s lesion, as well as a higher incidence of new bleeding.

关键词： Dieulafoy’s Lesion Gastrointestinal Bleeding Endoscopy Endoscopy Hemostatic Clips Kidney Disease Adrenaline Thermal Coagulation Dieulafoy

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Anchoring of 10-phenylphenothiazine to mesoporous silica materials:A water compatible organic photocatalyst for the degradation of pollutants

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Journal of materials science & Technology 2022年第8期103卷 134-143页

作者： Daniel gonzález-muñoz Almudena Gómez-Avilés Carmen B.molina jorge Bedia Carolina Belver Jose Alemán silvia Cabrera Organic Chemistry Department Science FacultyUniversidad Autónoma de Madrid28049 MadridSpain Chemical Engineering Department Science FacultyUniversidad Autónoma de Madrid28049 MadridSpain Institute for Advanced Research in Chemical sciences(IAdChem) Universidad Autónoma de Madrid28049 MadridSpain Inorganic Chemistry Department Science FacultyUniversidad Autónoma de Madrid28049 MadridSpain

The application of organic photocatalysts towards the oxidation of pollutants in water is hampered by different limitations such as their insolubility in the ***,we report that the grafting of a photoorganocatalyst into mesoporous silica materials is an ideal approach to obtain effective ***,the photocatalyst 10-phenylphenothiazine(PTH)was easily anchored into three different mesoporous silica-based materials(msN,msU-2 and sBA-15)with different particle sizes and pore sizes through an amide bond *** materials were characterized using IR analysis,solid-state X-ray diffraction,porosity and microscopy(sEm and TEm)techniques,showing that PTH is immobilized inside the pores of the materials and its optical properties are maintained after the *** homogeneous PTH was inactive in water media,the three photocatalytic materials were active for the degradation of ***-15-AP-PTH exhibited the highest catalytic performance towards the degradation of acetaminophen and diclofenac under solar irradiation,finding in this manner a new strategy for the decontamination of pollutants.

关键词： Organic semiconductors silica support solar photocatalysis Water treatment Pharmaceuticals

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Formation potential and analysis of 32 regulated and unregulated disinfection by-products: Two new simplified methods

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Journal of Environmental sciences 2022年第7期34卷 209-221页

作者： Jillian N.murakami Xu Zhang Joanne Ye Amy m.macDonald jorge Perez David W.Kinniburgh susana Y.Kimura Department of Chemistry University of CalgaryCalgaryAlbertaT2N 1N4Canada Alberta Centre for Toxicology University of CalgaryCalgaryAlbertaT2N 4N1Canada

Water disinfection is an essential process that provides safe water by inactivating pathogens that cause waterborne diseases. However, disinfectants react with organic matter naturally present in water, leading to the formation of disinfection by-products(DBPs). multi-analyte methods based on mass spectrometry(ms) are preferred to quantify multiple DBP classes at once however, most require extensive sample pre-treatment and significant resources. In this study, two analytical methods were developed for the quantification of 32 regulated and unregulated DBPs. A purge and trap(P&T) coupled with gas chromatography mass spectrometry(GC-ms) method was optimized that automated sample pre-treatment and analyzed volatile and semi-volatile compounds, including trihalomethanes(THms), iodinated trihalomethanes(I-THms), haloacetonitriles(HANs), haloketones(HKTs) and halonitromethanes(HNms). LOQs were between 0.02-0.4 μg/L for most DBPs except for 8 analytes that were in the low μg/L range. A second method with liquid chromatography(LC) tandem mass spectrometry(ms/ms) was developed for the quantification of 10 haloacetic acids(HAAs) with a simple clean-up and direct injection. The LC-ms/ms direct injection method has the lowest detection limits reported(0.2-0.5 μg/L). Both methods have a simple sample pre-treatment, which make it possible for routine analysis. Hyperchlorination and uniform formation conditions(UFC) formation potential tests with chlorine were evaluated with water samples containing high and low TOC. Hyperchlorination formation potential test maximized THms and HAAs while UFC maximized HANs. Ascorbic acid was found to be an appropriate quencher for both analytical methods. Disinfected drinking water from four water utilities in Alberta, Canada were also evaluated.

关键词： Disinfection byproducts Purge and trap LC-ms/ms Drinking water DBP formation potential HAAs HANs

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Distal nucleotides affect the rate of stop codon read-through

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Quantitative Biology 2023年第1期11卷 44-58页

作者： Luciana I.Escobar Andres m.Alonso jorge R.Ronderos Luis Diambra CREG Universidad Nacional de La Plata-CONICETLa Plata CP 1900Argentina INTechUniversidad Nacional de San MartinChascomus CP 7130Argentina FCNyMUniversidad Nacional de La PlataLa Plata CP 1900Argentina

Background:A key step in gene expression is the recognition of the stop codon to terminate translation at the correct ***,it has been observed that ribosomes can misinterpret the stop codon and continue the translation in the 3′UTR *** phenomenon is called stop codon read-through(sCR).It has been suggested that these events would occur on a programmed basis,but the underlying mechanisms are still not well ***:Here,we present a strategy for the comprehensive identification of sCR events in the Drosophila melanogaster transcriptome by evaluating the ribosomal density *** associated ribosomal leak rate was estimated for every event identified.A statistical characterization of the frequency of nucleotide use in the proximal region to the stop codon in the sequences associated to sCR events was ***:The results show that the nucleotide usage pattern in transcripts with the UGA codon is different from the pattern for those transcripts ending in the UAA codon,suggesting the existence of at least two mechanisms that could alter the translational termination ***,a linear regression models for each of the three stop codons was developed,and we show that the models using the nucleotides at informative positions outperforms those models that consider the entire sequence context to the stop ***:We report that distal nucleotides can affect the sCR rate in a stop-codon dependent manner.

关键词： translational readthrough stop codons translational termination ribosomal density profiles nucleotide usage frequency

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Computational solution of an acid-mediated tumor-growth radial model under logistic growth regimes for normal and cancer cells

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International Journal of Biomathematics 2023年第3期16卷 45-62页

作者： Farhan Khan mudassar Abbas jorge E.macias-Diaz muhammad Bilal Khan safar m.Alghamdi Department of mathematics and Computer sciences University of Palermo 90133 PalermoItaly Department of mathematics and Applications “R.Caccioppoli”University of Naples Federico iiVia Cintia 80126NaplesItaly Department of mathematics School of Digital Technologies Tallinn University10120 TallinnEstonia Departamento de Matematicas y Fisica Universidad Autonoma de Aguascalientes AguascalientesAgs.20131Merico Department of mathematics COmsATs University Islamabad Islambad44000 Pakistan Department of mathematics and statistics College of science Taif University Taif 21944Saudi Arabia

Tumor invasion follows a complex mechanism which involves cell migration and *** study the processes in which primary and secondary metastases invade and damage the normal cells,mathematical models are often extremely *** this paper,we present a mathematical model of acid-mediated tumor growth consisting of radially symmetric reaction-diffusion *** assumption on the radial symmetry of the solutions is imposed here in view that tumors present spherical symmetry at the microscopic ***,we consider various empirical mechanisms which describe the propagation of tumors by considering cancer cells,normal cells,and the concentration of H+*** other assumptions,we suppose that these components follow logistictype growth ***,this is an important difference with respect to various other mathematical models for tumor growth available in the ***,we also add competition terms of normal and tumor cells *** carry out a balancing study of the equations of the model,and a numerical model is proposed to produce *** practical remarks derived from our assumptions are provided in the discussion of our simulations.

关键词： Cancer growth model radially symmetric system acid-mediated tumor growth computer simulations

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Curupira V1.0: Joint Inversion of VEs and TEm for Environmental and mass movements studies

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International Journal of Geosciences 2023年第11期14卷 1160-1176页

作者： Cassiano Antonio Bortolozo jorge Luís Porsani Tristan Pryer jorge Luis Abril Benjumea Fernando Acácio monteiro dos santos marco Antonio Couto Jr. Luana Albertani Pampuch Tatiana sussel gonçalves mendes Daniel metodiev marcio Augusto Ernesto de moraes Rodolfo moreda mendes marcio Roberto magalhães de Andrade CEmADEN—National Center for monitoring and Early Warning of Natural Disasters General Coordination of Research and Development S&#227o José dos Campos Brazil Geophysics Department Institute of Astronomy Geophysics and Atmospheric Sciences (IAG) University of S&#227o Paulo (USP) S&#227o Paulo Brazil Department of mathematical sciences University of Bath Bath UK Colombian Geological service (sGC) Bogotá Colombia Don Luiz Institute (IDL) University of Lisboa Lisboa Portugal CPRm—Brazilian Geological survey SUREG-BH Belo Horizonte Brazil Institute of science and Technology S&#227o Paulo State University (Unesp) S&#227o José dos Campos Brazil

An innovative inversion code, named “Curupira v1.0”, has been developed using matlab to determine the vertical distribution of resistivity beneath the subsoil. The program integrates Vertical Electrical sounding (VEs), successful in shallow subsurface exploration and Time Domain Electromagnetic (TEm) techniques, better suited for deeper exploration, both of which are widely employed in geophysical exploration. These methodologies involve calculating subsurface resistivity through appropriate inversion processes. To address the ill-posed nature of inverse problems in geophysics, a joint inversion scheme combining VEs and TEm data has been incorporated into Curupira v1.0. The software has been tested on both synthetic and real-world data, the latter of which was acquired from the Parana sedimentary basin which we summarise here. The results indicate that the joint inversion of VEs and TEm techniques offers improved recovery of simulated models and demonstrates significant potential for hydrogeological studies.

关键词： VEs TEm Joint Inversion CRs—Controlled Random search Paraná sedimentary Basin Brazil

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Analysis of antisym metric cross-ply laminates using high-order shear deformation theories:a meshless approach

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Acta mechanica sinica 2020年第5期36卷 1078-1098,I0003页

作者： D.E.s.Rodrigues J.Belinha L.m.J.s.Dinis R.m.Natal jorge Institute of science and Innovation in mechanical and Industrial Engineering 4200-465 PortoPortugal Department of mechanical Engineering School of EngineeringPolytechnic of Porto(ISEP)4200-072 PortoPortugal Department of mechanical Engineering Faculty of EngineeringUniversity of Porto(FEUP)4200-465 PortoPortugal

For many years finite element method(FEm)was the chosen numerical method for the analysis of composite ***,in the last 20 years,the scientific community has witnessed the birth and development of several meshless methods,which are more flexible and equally accurate numerical *** meshless method used in this work is the natural neighbour radial point interpolation method(NNRPIm).In order to discretize the problem domain,the NNRPIm only requires an unstructured nodal ***,using the Voronoi mathematical concept,it enforces the nodal connectivity and constructs the background integration *** NNRPIm shape functions are constructed using the radial point interpolation *** this work,the displacement field of composite laminated plates is defined by high-order shear deformation *** the end,several antisymmetric cross-ply laminates were analysed and the NNRPIm solutions were compared with the *** obtained results show the efficiency and accuracy of the NNRPIm formulation.

关键词： Antisymmetric cross-ply laminates High-order shear deformation theories meshless methods Naturalneighbour radial point interpolation method(NNRPIm)

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N-terminally truncated Aβ4-x proteoforms and their relevance for Alzheimer’s pathophysiology

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Translational Neurodegeneration 2022年第1期11卷 496-513页

作者： Agueda Rostagno Erwin Cabrera Tammaryn Lashley jorge Ghiso Departments of Pathology New York University School of MedicineNew YorkNY 10016USA The Queen square Brain Bank for Neurological Disorders Department of Clinical and Movement NeurosciencesUCL Queen Square Institute of NeurologyLondon WC1N 3BGUK Department of Neurodegenerative Disease UCL Queen Square Institute of NeurologyLondon WC1N 3BGUK Departments of Psychiatry New York University School of Medicine550 First AvenueNew YorkNY 10016USA Current affiliation:Farmingdale state College State University of New YorkFarmingdaleNY 11735USA.

Background:The molecular heterogeneity of Alzheimer’s amyloid-β(Aβ)deposits extends well beyond the clas-sic Aβ1-40/Aβ1-42 dichotomy,substantially expanded by multiple post-translational modifications that increase the proteome *** truncated fragments consistently populate the brain Aβpeptidome,and their homeo-static regulation and potential contribution to disease pathogenesis are largely unknown.Aβ4-x peptides have been reported as major components of plaque cores and the limited studies available indicate their relative abundance in Alzheimer’s disease(AD).methods:Immunohistochemistry was used to assess the topographic distribution of Aβ4-x species in well-char-acterized AD cases using custom-generated monoclonal antibody 18H6-specific for Aβ4-x species and blind for full-length Aβ1-40/Aβ1-42-in conjunction with thioflavin-s and antibodies recognizing Aβx-40 and Aβx-42 *** dichroism,thioflavin-T binding,and electron microscopy evaluated the biophysical and aggregation/oligomerization properties of full-length and truncated synthetic homologues,whereas stereotaxic intracerebral injections of monomeric and oligomeric radiolabeled homologues in wild-type mice were used to evaluate their brain clearance ***:All types of amyloid deposits contained the probed Aβepitopes,albeit expressed in different proportions.Aβ4-x species showed preferential localization within thioflavin-s-positive cerebral amyloid angiopathy and cored plaques,strongly suggesting poor clearance characteristics and consistent with the reduced solubility and enhanced oligomerization of their synthetic *** vivo clearance studies demonstrated a fast brain efflux of N-termi-nally truncated and full-length monomeric forms whereas their oligomeric counterparts-particularly of Aβ4-40 and Aβ4-42-consistently exhibited enhanced brain ***:The persistence of aggregation-prone Aβ4-x proteoforms likely contributes to the process of

关键词： Alzheimer’s disease Amyloid-βtruncated species Peptide oligomerization Brain clearance Brain efflux stereotaxic intracerebral injection

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