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Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

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World journal of Gastrointestinal oncology 2024年第1期16卷 234-243页

作者： joão gra.a.a.isa.el gomes ferna.des Carolina Trabulo joana Gonçalves Rita Gameiro dos Santos Adriano Baptista Idília Pina Centro Hospitalar Barreiro Montijo Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal Medical oncology Unit Centro Hospitalar Barreiro MontijoSetúbalBarreiro 2830-003Portugal

BACKGRoUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational *** RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT *** the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR *** SUMMARY eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May *** the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and *** neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CoNCLUSIoN our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

关键词： Metastatic colorectal cancer Rat sarcoma virus mutational status Liquid biopsy Rat sarcoma virus wild-type Neo-rat sarcoma virus wild-type Anti-epidermal growth factor receptor therapy Case report

Dysregulated microRNAs in type 2 diabetes and breast cancer:Potential associated molecular mechanisms

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World journal of Diabetes 2024年第6期15卷 1187-1198页

作者： Alex Cleber Improta-Caria Filipe Ferrari joão Lucas Penteado gomes Paloma Brasilio Villalta Úrsula Paula RenóSoci Ricardo Stein Edilamar M oliveira Laboratory of Biochemistry and Molecular Biology of the Exercise Physical Education and Sport SchoolUniversity of São PauloSão Paulo 05508-030Brazil graduate Program in Cardiology and Cardiovascular Sciences Federal University of Rio Grande do SulHospital de Clínicas de Porto AlegrePorto Alegre 90035003Brazil Laboratory of Metabolic Disorders(Labdime) School of Applied SciencesUniversity of Campinas-UNICAMPCampinas 13484-350Brazil Departments of Internal Medicine Molecular Pharmacology and PhysiologyCenter for Regenerative MedicineUSF Health Heart InstituteMorsani College of MedicineUniversity of South FloridaTampaFL 33602United States

Type 2 diabetes(T2D)is a multifaceted and heterogeneous syndrome associated with complications such as hypertension,coronary artery disease,and notably,breast cancer(BC).The connection between T2D and BC is established through processes that involve insulin resistance,inflammation and other *** this comprehension the specific cellular and molecular mechanisms linking T2D to BC,especially through microRNAs(miRNAs),remain *** are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological ***,the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been *** review aims to identify dysregulated miRNAs in both T2D and BC,exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

关键词： Type 2 diabetes Breast cancer MicroRNAs Molecular mechanisms

Is magnesium deficiency the major cause of needle chlorosis of Pinus taeda in Brazil?

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journal of Forestry Research 2024年第2期35卷 209-221页

作者： Antônio Carlos Vargas Motta Shizuo Maeda Valdécio dos Santos dos Santos Rodrigues Tamires Maiara Ercole Stephen Arthur Prior Ana elisa Lyra Brumat Amanda Pacheco Cardoso Moura Julierme Zimmer Barbosa joão Bosco Vasconcellos gomes Department of Soil Sciences and Agriculture Engineering Federal University of ParanáR.dos Funcionários1540.CuritibaParanáCEP 80035‑050Brazil Brazilian Agricultural Research Company Embrapa FlorestasEstr.da Ribeira–Br‑476Km 111–Parque Monte Castelo.ColomboParanáCEP 83411‑000Brazil United States Department of Agriculture‑Agricultural Research Service USDA-ARS National Soil Dynamics Laboratory411 South Donahue DriveAuburnAL 36832USA Reforestation Remasa Rodovia PR 170–Km 522.BiturunaParanáCEP 84640‑000Brazil Federal Institute of Southeast of Minas Gerais R.Luz Interior360.Juiz de ForaMinas Gerais CEP 36030‑713Brazil

Needle chlorosis(NC)in Pinus taeda *** in Brazil becomes more frequent after second and third harvest rotation *** a study to identify factors contributing to yellowing needle chorosis(YNC),trees were grown in soils originating from contrasting parent materials,and soils and needles(whole,green and chlorotic portions)from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on *** were analyzed for various elements and *** soils had very low base levels(Ca^(2+),Mg^(2+)and K^(+))and P,suggesting a possible lack of multiple *** symptoms started at needle tips,then extended toward the needle base with *** flush needles had longer portions with YNC than second flush needles *** from the lower crown also had more symptoms along their length than those higher in the *** were similar to those reported for *** chlorotic portions,Mg and Ca concentrations were well below critical values;in particular,Mg levels were only one third of the critical value of 0.3 g kg^(-1).Collectively,results suggest that Mg deficiency is the primary reason for NC of *** in various parent soils in Brazil.

关键词： Nutritional deficiency Forest management Soil depletion Pine foliar analysis Needle chlorosis

Development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano joão Ezequiel oliveira Carlos Roberto jorge Soares Ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura fernanda Garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael gomes da Silva Luiza Mascarenhas Balieiro joel Mendes elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-grade Generators Metastatic Prostate Cancer PET Imaging

Deep Morphea in an Immunosuppressed Patient With Anti-U1RNP Myositis:A Case Report

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International journal of Dermatology and Venereology 2024年第2期7卷 111-114页

作者： Ahmad Berjawi Laure L.Irani Jinane R.el Khoury Department of Dermatology Gilbert and Rose Marie Chagoury School of MedicineLebanese American UniversityBeirut 1100Lebanon Department of Rheumatology Division of Internal MedicineGilbert and Rose Marie Chagoury School of MedicineLebanese American University Medical CenterBeirut 1100Lebanon

Introduction:Morphea is an inflammatory skin disease characterized by skin thickening due to increased collagen deposition in the dermis or subcutaneous ***-U1RNP myositis is a newly described entity characterized by myositis,arthritis,interstitial lung disease,and Raynaud *** present a case of a unique combination of deep morphea in a patient with anti-U1RNP *** presentation:A 64-year-old male with 5-year history of proximal muscle weakness,polyarthritis,Raynaud phenomenon,and dyspnea on multiple immunosuppressives presented with localized infiltrated,tight,and hyperpigmented plaques over the posterior thighs and mid-to-lower back developing over the last 2 years and limiting his *** workup revealed a positive ANA,anti-U1RNP antibody,anti-jo1 antibody,and anti-Ro52 *** workup showed restrictive lung disease,kidney disease,and *** was diagnosed with anti-U1RNP *** biopsy of the back lesion showed deep ***:Association of deep morphea with anti-U1RNP myositis is not described prior in the *** of morphea is challenging since the patient is already on immunosuppressive *** patient failed methotrexate prior and is currently on Mycophenolate mofetil and Deflazacort which are reported as potential treatment for ***,physical therapy plus topical Tacrolimus were suggested as an initial measure to preserve the range of motion of his posterior thighs and *** is a case of progressive deep morphea developing in a patient with a unique autoimmune profile on immunosuppressive ***:Anti-U1RNP myositis is a challenging diagnosis and should be always thought of in patients with positive anti-U1RNP,myositis,interstitial lung disease,arthritis,kidney disease,and Raynaud ***,deep morphea treatment in immunosuppressed patients is challenging and different measures should be considered.

关键词： deep morphea immunosuppression anti-U1RNP myositis case report

The role of surface functionalization of silica nanoparticles for bioimaging

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journal of Innovative optical Health Sciences 2016年第4期9卷 11-26页

作者： Maria C.gomes Angela Cunha Tito Trindade joão P.C.Tome QoPNA University of Aveiro 3810-193 AveiroPortugal CICECo and Department of Chemistry University of Aveiro 3810-193 AveiroPortugal CESAM and Department of Biology University of Aveiro 3810-193 AveiroPortugal Centro de Quimica Estrutural Instituto Superior Tecnico Universidade de LisboaAv.Rovisco Pais1049-001 LisboaPortugal Department of organic and Macromolecular Chemistry Ghent University B-9000 Gent Belgium

Among the several types of inorganic nanoparticles available,silica nanoparticles(SNP)have earned their relevance in biological applications namely,as bioimaging *** fact,uorescent SNP(FSNP)have been explored in this-eld as protective nanocarriers,overcoming some limitations presented by conventional organic dyes such as high photobleaching rates.A crucial aspect on the use of uorescent SNP relates to their surface properties,since it determines the extent of interaction between nanoparticles and biological systems,namely in terms of colloidal stability in water,cellular recognition and internalization,tracking,biodistribution and speci-city,among ***,it is imperative to understand the mechanisms underlying the interaction between biosystems and the SNP surfaces,making surface functionalization a relevant step in order to take full advantage of particle *** versatility of the surface chemistry on silica platforms,together with the intrinsic hydrophilicity and biocompatibility,make these systems suitable for bioimaging applications,such as those mentioned in this review.

关键词： Fluorescent silica nanoparticles bioimaging surface functionalization nanoparticlecell interactions.

Is magnesium deficiency the major cause of needle chlorosis of Pinus taeda in Brazil?

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High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico

journal of Forestry Research 2024年第2期 213-225页

作者： Ant?nio Carlos Vargas Motta Shizuo Maeda Valdécio dos Santos dos Santos Rodrigues Tamires Maiara Ercole Stephen Arthur Prior Ana elisa Lyra Brumat Amanda Pacheco Cardoso Moura Julierme Zimmer Barbosa jo?o Bosco Vasconcellos gomes Department of Soil Sciences and Agriculture Engineering Federal University of Paraná Brazilian Agricultural Research Company Embrapa Florestas 3. United States Department of Agriculture-Agricultural Research Service USDA-ARS National Soil Dynamics Laboratory 4. Reforestation Remasa 5. Federal Institute of Southeast of Minas Gerais

Needle chlorosis(NC) in Pinus taeda L. systems in Brazil becomes more frequent after second and third harvest rotation cycles. In a study to identify factors contributing to yellowing needle chorosis(YNC), trees were grown in soils originating from contrasting parent materials, and soils and needles(whole, green and chlorotic portions) from 1-and 2-year-old branches and the first and second needle flush release at four sites with YNC on P. taeda were analyzed for various elements and properties. All soils had very low base levels(Ca2+, Mg2+and K+) and P, suggesting a possible lack of multiple elements. YNC symptoms started at needle tips, then extended toward the needle base with time. First flush needles had longer portions with YNC than second flush needles did. Needles from the lower crown also had more symptoms along their length than those higher in the canopy. Symptoms were similar to those reported for Mg. In chlorotic portions, Mg and Ca concentrations were well below critical values; in particular, Mg levels were only one third of the critical value of 0.3 g kg-1. Collectively, results suggest that Mg deficiency is the primary reason for NC of P. taeda in various parent soils in Brazil.

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journal of Clinical and Translational Hepatology 2023年第5期11卷 1023-1034页

作者： Alexis jose-Abrego Sonia Roman joão Renato Rebello Pinho Michele Soares gomes-Gouvêa Arturo Panduro Department of Genomic Medicine in Hepatology Civil Hospital of Guadalajara“Fray Antonio Alcalde”GuadalajaraJaliscoMexico Health Sciences Center University of GuadalajaraGuadalajaraJaliscoMexico LIM07 Department of GastroenterologyUniversity of São PauloSão PauloBrazil Hospital Israelita Albert Einstein São PauloBrazil

Background and Aims:Lamivudine(3TC),telbivudine(LdT),entecavir(ETV),adefovir(ADF),and tenofovir(TFV)are drugs used to treat hepatitis B virus(HBV)infection,but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape *** mutations have not been thoroughly investigated in *** study aimed to estimate the prevalence of HBV antiviral resistance and escape ***:This cross-sectional study analyzed 158 *** DNA was extracted,amplified,and sequenced in serum samples using the spin column method,PCR assay,and Sanger’s sequencing,*** genotypes were determined,and HBV mutations were tested using the Geno2pheno ***:overall,68.4%(108/158)of HBV patients were infected with genotype H,followed by G(11.4%,18/158),A2(10.8%,17/158),F1b(6.9.0%,11/158),D(1.9%,3/158),and E(0.6%,1/158),and 5.1%(8/158)had evidence of *** prevalence of resistance mutations was 8.2%(13/158)and the most common combined mutation was rt180M+***,we found the combinations rt180M+rt204V+rt173L(n=2)and rt180M+rt204V+rt202G(n=1)that confer multidrug resistance to 3TC,LdT,and *** mutations were found in genotypes A2(11.8%,2/17),and H(10.2%,11/108),and escape mutations were detected in HBV genotypes A2(11.8%,2/17),H(10.2%,11/108),F1b(9.1%,1/11)and G(5.6%,1/18).Conclusions:The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and *** earliest cases of HBV multidrug resistance were detected in Mexico.

关键词： Hepatitis B virus Drug resistance mutations Multidrug resistance strain Immune escape

Scalable fabrication,compartmentalization and applications of living microtissues

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Bioactive Materials 2023年第1期19卷 392-405页

作者： Maik Schot Nuno Araújo-gomes Bas van Loo Tom Kamperman Jeroen Leijten Department of Developmental Bioengineering Faculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522NBEnschedethe Netherlands

Living microtissues are used in a multitude of applications as they more closely resemble native tissue physiology,as compared to 2D *** are typically composed of a combination of cells and materials in varying combinations,which are dictated by the applications’design *** applications range wide,from fundamental biological research such as differentiation studies to industrial applications such as cruelty-free meat ***,their translation to industrial and clinical settings has been hindered due to the lack of scalability of microtissue production *** microfluidic processes provide an opportunity to overcome this limitation as they offer higher throughput production rates as compared to traditional batch techniques,while maintaining reproducible control over microtissue composition and *** this review,we provide a comprehensive overview of the current approaches to engineer microtissues with a focus on the advantages of,and need for,the use of continuous processes to produce microtissues in large ***,an outlook is provided that outlines the required developments to enable large-scale microtissue fabrication using continuous processes.

关键词： Tissue engineering Micromaterials Microfluidics Upscaling Clinical translation Industrial translation