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Aggregation properties of a therapeutic peptide for rheumatoid arthritis:A spectroscopic and molecular dynamics study

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ChemPhysMater 2022年第1期1卷 62-70页

作者： Rita Cimino Marco Savioli Noemi Ferrante Carrante Ernesto Placidi Hilda Garay-Perez Matilde López-Abad Alexis Musacchio Lasa maria del carmen domínguez-horta Emanuela Gatto Francesca Cavalieri Gianfranco Bocchinfuso mariano Venanzi PEPSA-LAB Department of Chemical Sciences and TechnologyUniversity of Rome Tor VergataVia della Ricerca Scientifica 100133RomeItaly Department of Physics University of Rome‘Sapienza’P.le A.Moro 500185 RomeItaly Centre for Genetic Engineering and Biotechnology PO Box 616210600HavanaCuba School of Science RMIT UniversityMelbourneVIC 3001Australia

The biological properties of therapeutic peptides,such as their pharmacokinetics and pharmacodynamics,are correlated with their structure and aggregation ***,we studied the aggregation properties of a therapeutic peptide(CIGB-814),currently in phase 2 clinical trial,for the treatment of rheumatoid arthritis over a wide range of concentrations(μM-mM).We applied spectroscopic techniques(fluorescence,circular dichro-ism,resonance,and dynamic light scattering),atomic force microscopy,and molecular dynamics simulations to determine the aggregation mechanism of *** found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide ***,the peptide oligomers trigger the nucleation and growth of peptide nanostructures(cac=123μM),ultimately leading to the fibrillization of CIGB-814(cac’=508μM).These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.

关键词： Molecular dynamics of peptide oligomers Peptide aggregation Peptide fibrils Peptide nanostructures Therapeutic peptides Treatment of rheumatoid arthritis

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Surgical site infection following pancreaticoduodenectomy in a referral cancer center in Mexico

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 502-508页

作者： Rodrigo Villaseñor-Echavarri Javier Melchor-Ruan Mercedes Aranda-Audelo Gabriela Arredondo-Saldaña Patricia Volkow-Fernandez maria del carmen Manzano-Robleda Alejandro E Padilla-Rosciano Diana Vilar-Compte Department of Infectious Diseases Instituto Nacional de CancerologíaAv.San Fernando 22Belisario Domínguez Secc 16TlalpanMexico CityMexico School of Medicine Universidad PanamericanaAugusto Rodin No.498Insurgentes MixcoacBenito JuárezMexico CityMexico Department of Digestive Tube and Hepatopancreatobiliary Tumors Instituto Nacional de CancerologíaAv.San Fernando 22Belisario Domínguez Secc 16TlalpanMexico CityMexico Department of Infectious Diseases Hospital Manuel Gea GonzálezCalz.de Tlalpan 4800Belisario Domínguez Secc 16TlalpanMexico CityMexico Gastrointestinal and Endoscopy Department Instituto Nacional de CancerologíaAv.San Fernando 22Belisario Domínguez Secc 16TlalpanMexico CityMexico

Background: Pancreaticoduodenectomy is the standard treatment for resectable periampullary cancer. Surgical site infections(SSI) are common complications with increased morbidity. The study aimed to describe the prevalence, risk factors, microbiology, and outcomes of SSI among patients undergoing pancreaticoduodenectomy. Methods: We conducted a retrospective study in a referral cancer center between January 2015 and June 2021. We analyzed baseline patient characteristics and SSI occurrence. Culture results and susceptibility patterns were described. Multivariate logistic regression was used to determine risk factors, proportional hazards model to evaluate mortality, and Kaplan-Meier analysis to assess long-term survival. Results: A total of 219 patients were enrolled in the study;101(46%) developed SSI. Independent factors for SSI were diabetes mellitus, preoperative albumin level, biliary drainage, biliary prostheses, and clinically relevant postoperative pancreatic fistula. The main pathogens were Enterobacteria and Enterococci. Multidrug-resistance rate in SSI was high but not associated with increased mortality. Infected patients had higher odds of sepsis, longer hospital stay and intensive care unit stay, and readmission rate. Neither 30-day mortality nor long-term survival was significantly different between infected and non-infected patients. Conclusions: SSI prevalence among patients undergoing pancreaticoduodenectomy was high and largely caused by resistant microorganisms. Most risk factors were related to preoperative instrumentation of the biliary tree. SSI was associated with greater risk of unfavorable outcomes;however, survival was unaffected.

关键词： Surgical site infection Pancreaticoduodenectomy Pancreatic cancer Endoscopic biliary drainage Biliary prosthesis

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Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal Cancer

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Engineering 2021年第10期7卷 1393-1412页

作者： Ana Montero-Calle Itziar Aranguren-Abeigon María Garranzo-Asensio carmen Poves María Jesús Fernández-Aceñero Javier Martínez-Useros Rodrigo Sanz Jana Dziaková Javier Rodriguez-Cobos Guillermo Solís-Fernández Eloy Povedano maria Gamella Rebeca Magnolia Torrente-Rodríguez Miren Alonso-Navarro Vivian de los Ríos J.Ignacio Casal Gemma domínguez Ana Guzman-Aranguez Alberto Peláez-García JoséManuel Pingarrón Susana Campuzano Rodrigo Barderas Chronic Disease Program(UFIEC) Carlos III Health InstituteMadrid E-28220Spain Department of Biochemistry and Molecular Biology Faculty of Optics and OptometryComplutense University of MadridMadrid E-28040Spain Gastroenterology Unit San Carlos Clinical HospitalMadrid E-28040Spain Surgical Pathology Department San Carlos Clinical HospitalMadrid E-28040Spain Translational Oncology Division OncoHealth InstituteJimenez Diaz Foundation University HospitalMadrid E-28040Spain Department of Biochemistry Faculty of MedicineAlberto Sols Institute of Biomedical ResearchCSIC-UAMMadrid E-28029Spain Department of Analytical Chemistry Faculty of Chemical SciencesComplutense University of MadridMadrid E-28040Spain Center for Biological Research Spanish National Research Council(CSIC)MadridE-28040Spain Molecular Pathology and Therapeutic Targets Group La Paz University Hospital(IdiPAZ)Madrid E-28046Spain

Colorectal cancer(CRC)is the second leading cause of cancer-related death *** five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced *** against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early ***,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid *** that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to *** bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC *** validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC *** together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here

关键词： Autoantibodies Diagnosis Colorectal cancer Exosomes Tumor microenviroment Humoral immune response Point of care Biosensors

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