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Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

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Neural Regeneration Research 2017年第8期12卷 1231-1240页

作者： Julia J.Segura-Uribe Rodolfo Pinto-Almazán Angélica Coyoy-Salgado Claudia E.fuentes-Venado Christian Guerra-Araiza Unidad de Investigacion Modica en Enfermedades Neurologicas Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico Seccion de Estudios de Posgrado e Investigacion Escuela Superior de Medicina Instituto Politecnico Nacional Mexico City Mexico Unidad de Investigacion Hospital Regional de Alta Especialidad Ixtapaluca Ixtapaluca Mexico Institute for the Developing Mind Children's Hospital Los Angeles Los Angeles CA USA Department of Pediatrics Keck School of Medicine University of Southern California Los Angeles CA USA Consejo Nacional de Ciencia y Tecnologia Mexico City Mexico Clinica de Trastornos del Sueno Universidad Autonoma Metropolitana-Iztapalapa Mexico City Mexico Servicio de Medicina Fisica y Rehabilitacion Hospital General de Zona No. 197 Texcoco Mexico Unidad de Investigacion Modica en Farmacologla Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

关键词： estrogen receptor modulators selective estrogen receptor modulators microtubules neurofilaments tibolone tamoxifen raloxifene

Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane

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Journal of Chinese Pharmaceutical Sciences 2016年第8期25卷 559-569页

作者： Francisco fuentes Yury Gomez Ximena Paredes-Gonzalez Avantika Barve Sujit Nair Siwang Yu Constance Lay Lay Saw Ah-Ng Tony Kong Facultad de Agronomia e Ingenieria Forestal Pontificia Universidad Cato1ica de Chile Casilla 306-22 Santiago Chile Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers The State University of New Jersey New Jersey 08854 USA Novartis Institutes for Biomedical Research East Hanover NJ-07470 USA Amrita cancer Discovery Biology Laboratory Amrita Vishwa Vidyapeetham University Amritapuri Clappana P.O. Kollam Kerala-690525 India School of Pharmaceutical Sciences Peking University Health Science Center Beo'ing 100191 China

The dietary phytochemicals curcumin （CUR） and sulforaphane （SFN） have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE （antioxidant response element） response in HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes-heme oxygenase-1 （HO-I） and UDP-glucuronosyltransferase-1A （UGT1A）-was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR （10 ~tM） and SFN （12.5 ~tM） significantly induced the expression of HO-1 and UGT 1 A1 proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in HepG2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.

关键词： Antioxidant response element, Curcumin, HepG2-C8 cell-s, HO-1, Nrf2, Sulforaphane, UGT 1A1

Targeting obesity-related inflammation in skin cancer： molecular and epigenetic insights for cancer chemoprevention by dietary phytochemicals

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Journal of Chinese Pharmaceutical Sciences 2016年第4期25卷 235-249页

作者： Ximena Paredes-Gonzalez Francisco fuentes Yaoping Lu 江亚伍 Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers The State University of New Jersey Facultad de Agronomía e Ingeniería Forestal Pontificia Universidad Católica de Chile Department of Chemical Biology Ernest Mario School of Pharmacy Rutgers The State University of New Jersey 美国Rutgers新泽西州立大学Ernest Mario药学院 Rutgers新泽西州立大学癌症预防研究中心

Non-melanoma skin cancer(NMSC) is one of the most common cancers in the US, although the role of obesity in skin cancer remains unclear. In vivo studies have consistently demonstrated that obese mice challenged with UVB radiation show increased skin tumorigenesis in comparison with leaner control mice. Growing evidence suggests that enhanced inflammation, oxidative stress and impaired apoptosis may play important roles in the development of skin cancer. Interventions such as voluntary exercise and the surgical removal of parametrial fat have been demonstrated to be effective in reducing adipose tissue that may influence the development of skin cancer; however, these interventions are not achievable in all obese patients. Therefore, the use of dietary natural phytochemicals that may modify and reverse the deregulated molecular and epigenetic events related to obesity and cancer development might represent a potential therapeutic modality due to their potential efficacy and low toxicity. In this review, we aim to provide the molecular and epigenetic basis of the NMSC-obesity relationship and to highlight the potential anti-cancer chemopreventive benefits of dietary phytochemicals such as sulforaphane and epigallocatechin-3-gallate.

关键词： Chemoprevention Epigenetics Obesity Non-melanoma skin cancer

Preclinical models of idiosyncratic drug-induced liver injury(iDILI):Moving towards prediction

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3685-3726页

作者： Antonio Segovia-Zafra Daniel E.Di Zeo-Sanchez carlos Lopez-Gomez Zeus Perez-Valdes Eduardo Garcıa-fuentes Raul J.Andrade M.Isabel Lucena Marina Villanueva-Paz Unidad de Gestio´n Clı´nica de Gastroenterologı´a Servicio de Farmacologıa ClınicaInstituto de Investigacio´n Biomedica de Malaga-IBIMAHospital Universitario Virgen de la VictoriaUniversidad de MalagaMalaga 29071Spain Centro de Investigacion Biomedica en Red en el Area Tematica de Enfermedades Hepaticas y Digestivas(CIBERehd) Madrid 28029Spain Platform ISCIII de Ensayos Clınicos UICEC-IBIMAMalaga 29071Spain Unidad de Gestion Clınica de Aparato Digestivo Instituto de Investigacion Biomedica de Malaga(IBIMA)Hospital Universitario Virgen de la VictoriaMalaga 29010Spai

Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the *** remains a major public health problem and a major cause of drug *** the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is *** of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant ***,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI ***,there are many gaps for explaining all the complexity of iDILI susceptibility and ***,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug ***,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI *** also comment about in silico approaches and the increasing relevance of patient-derived cellular models.

关键词： Drug-induced liver injury Preclinical models Mechanisms Oxidative stress Mitochondrial damage Immune response Personalized medicine

Flexible computational photodetectors for self-powered activity sensing

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npj Flexible Electronics 2022年第1期6卷 45-52页

作者： Dingtian Zhang canek fuentes-Hernandez Raaghesh Vijayan Yang Zhang Yunzhi Li Jung Wook Park Yiyang Wang Yuhui Zhao Nivedita Arora Ali Mirzazadeh Youngwook Do Tingyu Cheng Saiganesh Swaminathan Thad Starner Trisha L.Andrew Gregory D.Abowd School of Interactive Computing Georgia Institute of TechnologyAtlantaGAUSA School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGAUSA Department of Electrical and Computer Engineering Northeastern UniversityBostonMAUSA Department of Chemistry University of Massachusetts AmherstAmherstMAUSA Department of Electrical and Computer Engineering University of CaliforniaLos AngelesCAUSA Human-Computer Interaction Institute Carnegie Mellon UniversityPittsburghPAUSA Departments of Chemistry and Chemical Engineering University of Massachusetts AmherstAmherstMAUSA

Conventional vision-based systems,such as cameras,have demonstrated their enormous versatility in sensing human activities and developing interactive ***,these systems have long been criticized for incurring privacy,power,and latency issues due to their underlying structure of pixel-wise analog signal acquisition,computation,and *** this research,we overcome these limitations by introducing in-sensor analog computation through the distribution of interconnected photodetectors in space,having a weighted responsivity,to create what we call a computational *** photodetectors can be used to extract mid-level vision features as a single continuous analog signal measured via a two-pin *** develop computational photodetectors using thin and flexible low-noise organic photodiode arrays coupled with a self-powered wireless system to demonstrate a set of designs that capture position,orientation,direction,speed,and identification information,in a range of applications from explicit interactions on everyday surfaces to implicit activity detection.

关键词： everyday overcome photodetector

Synthesis of Pt and Pt-Fe nanoparticles supported on MWCNTs used as electrocatalysts in the methanol oxidation reaction

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Journal of Energy Chemistry 2014年第4期23卷 483-490页

作者： J.R.Rodriguez R.M.Félix E.A.Reynoso Y.Gochi-Ponce Y.Verde Gómez S.fuentes Moyado G.Alonso-Núez Universidad Nacional Autónoma de Mxico Centro de Nanociencias y Nanotecnología Ensenada B.C. C.P.22860 Mexico Instituto Tecnológico de Tijuana Centro de Graduados e Investigación Tijuana B.C. C.P.22000 Mexico Instituto Tecnológico de Oaxaca Departamento de Ingeniería Química y Bioquímica Oaxaca Oax. C.P.68030 Mexico Instituto Tecnológico de cancún Av.Kabah Km.3 Cancún Q.R. C.P.77500 Mexico

This work reports a feasible synthesis of highly-dispersed Pt and Pt-Fe nanoparticles supported on multiwall carbon nanotubes （MWCNTs） without Fe and multiwall carbon nanotubes with iron （MWCNTs-Fe） which applied as electrocatalysts for methanol electrooxidation. A Pt coordination complex salt was synthesized in an aqueous solution and it was used as precursor to prepare Pt/MWCNTs, Pt/MWCNTs-Fe, and Pt-Fe/MWCNTs using FeC12.4H20 as iron source which were named S 1, S2 and S3, respectively. The coordination complex of platinum （TOA）2PtC16 was obtained by the chemical reaction between （NH4）2PtC16 with tetraoctylammonium bromide （TOAB） and it was characterized by FT-IR and TGA. The materials were characterized by Raman spectroscopy, SEM, EDS, XRD, TEM and TGA. The electrocatalytic activity of Pt-based supported on MWCNTs in the methanol oxidation was investigated by cyclic voltammetry （CV） and chronoamperometry （ca）. Pt-Fe/MWCNTs electrocatalysts showed the highest electrocatalytic activity and stability among the tested electrocatalysts due to that the addition of ＂Fe＂ promotes the OH species adsorption on the electrocatalyst surface at low potentials, thus, enhancing the activity toward the methanol oxidation reaction （MOR）.

关键词： coordination complex salt MWCNTs nanoparticles catalysts electrooxidation

A biomarker study in Peruvian males with breast cancer

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World Journal of Clinical Oncology 2021年第10期12卷 926-934页

作者： carlos A castaneda Miluska castillo Luis A Bernabe Joselyn Sanchez Ebert Torres Nancy Suarez Katherine Tello Hugo fuentes Jorge Dunstan Miguel De La Cruz Jose Manuel Cotrina Julio Abugattas Henry Guerra Henry L Gomez Faculty of Health Sciences Universidad Cientifica del SurLima 15067Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Breast cancer Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru

BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female *** cancer clinical and pathological features differ by race in *** infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3ca gene mutations are predictive biomarkers of response to biological therapy in female *** is limited information about clinical and pathological features as well as predictive biomarkers in males of non-caucasian races with *** To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian *** This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June *** pathological features,TIL levels,MMR proteins,AR immunohistochemistry staining,and PIK3ca gene mutations were prospectively evaluated in cases with available paraffin *** of AR and estrogen receptor(ER)positive cells was additionally calculated by software after slide *** analyses included association tests,intraclass correlation test and Kaplan Meier overall survival *** The median age was 63 years and most cases were ER-positive(85.7%),HER2 negative(87.2%),Luminal-A phenotype(60%)and clinical stage II(41.5%)among our male breast *** TIL was 10%and higher levels tended to be associated with Luminal-B phenotype and higher ***-positive was found in 85.3%and was correlated with ER(intraclass index of 0.835,Pca mutation(H1047R)in 14.3%(belonged to the Luminal-A phenotype).Loss of MMR proteins was associated with AR-negative(P=0.018)but not with ER(P=0.43)or TIL(P=0.84).Early stages(Pca mutation was not associated

关键词： Male breast neoplasm Androgen receptor Tumor-infiltrating lymphocyte Mismatch repair protein PIK3ca mutation

Nanoengineered Shear-Thinning Hydrogel Barrier for Preventing Postoperative Abdominal Adhesions

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Nano-Micro Letters 2021年第12期13卷 452-467页

作者： Guillermo U.Ruiz-Esparza Xichi Wang Xingcai Zhang Sofia Jimenez-Vazquez Liliana Diaz-Gomez Anne-Marie Lavoie Samson Afewerki Andres Afuentes-Baldemar Roberto Parra-Saldivar Nan Jiang Nasim Annabi Bahram Saleh Ali K.Yetisen Amir Sheikhi Thomas H.Jozefiak Su Ryon Shin Nianguo Dong Ali Khademhosseini Biomaterials Innovation Research Center Division of Engineering in MedicineDepartment of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMA 02139USA Division of Health Sciences and Technology Harvard University-Massachusetts Institute of TechnologyCambridgeMA 02139USA Department of cardiovascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022People’s Republic of China School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA School of Engineering and Science Tecnologico de MonterreyCampus MonterreyMonterreyNuevo Leon 64849Mexico School of Medicine and Health Science Campus GuadalajaraZapopanJalisco 45201Mexico West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu 610041China Department of Chemical and Biomolecular Engineering University of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA Department of Chemical Engineering Imperial College LondonLondon SW72AZUK Department of Chemical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Terasaki Institute for Biomedical Innovation 11570 W Olympic BlvdLos AngelesCA 90024USA

More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive *** solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable *** also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in *** STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative *** two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion *** and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB *** technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.

关键词： Postoperative adhesions Shear-thinning hydrogel Silicate nanoplatelets Nanotechnology Nanomedicine