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Mutational landscape of gastric adenocarcinoma in Latin America: A genetic approach for precision medicine

Genes & Diseases 2022年第4期9卷 928-940页

作者： dennis Cerrato-Izaguirre Yolanda I.Chirino Claudia M.García-Cuellar Miguel Santibáñez-Andrade Diddier Prada Angélica Hernández-Guerrero Octavio Alonso Larraga Javier Camacho Yesennia Sánchez-Pérez Subdirección de Investigación Básica Instituto Nacional de Cancerología(INCan)TlalpanCiudad de MéxicoCP 14080Mexico departamento de Farmacología Centro de Investigación y de Estudios Avanzados del I.P.N.(CINVESTAV)Ciudad de MéxicoCP 07360Mexico Unidad de Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoLos Reyes IztacalaTlalnepantla de BazEstado de MéxicoCP 54090Mexico departamento de Informática Biomédica Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoCoyoacánCiudad de MéxicoCP 04510Mexico department of Environmental Health Science Mailman School of Public HealthColumbia UniversityNew YorkNY 10027USA Servicio de Endoscopía Instituto Nacional de Cancerología(INCan)TlalpanCiudad de MéxicoCP 14080Mexico

Latin-America (LATAM) is the second region in gastric cancer incidence;gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian;IL-10 in Chilean;IL-10 in Colombian;EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.

关键词： Ethnicities Genome Latin America Mutati on Precisi on medicine Stomach neoplasms

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Role of microglial cells in photoreceptor degeneration

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Neural Regeneration Research 2019年第7期14卷 1186-1190页

作者： Johnny Di Pierdomenico Diego García-Ayuso Marta Agudo-Barriuso Manuel Vidal-Sanz María Paz Villegas-Pérez departamento de Oftalmología Facultad de MedicinaUniversidad de Murciaand Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca)

Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily cones.The mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of blindness.Understanding the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration process.Secondary cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a role.In this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor death.We also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial cells.The inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor degeneration.Furthermore,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.

关键词： Royal College of Surgeons RCS P23H-1 microglia minocycline photoreceptor retinal degeneration retinitis pigmentosa

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Evaluation of curcumin and copper acetate against Salmonella Typhimurium infection,intestinal permeability,and cecal microbiota composition in broiler chickens

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Journal of Animal Science and Biotechnology 2021年第3期12卷 1019-1030页

作者： Anaisa ALeyva-Diaz Daniel Hernandez-Patlan Bruno Solis-Cruz Bishnu Adhikari Young Min Kwon Juan D.Latorre Xochitl Hernandez-Velasco Benjamin Fuente-Martinez Billy M.Hargis Raquel Lopez-Arellano Guillermo Tellez-Isaias departamento de medicina y Zootecnia de Aves Facultad de Medicina Veterinaria y ZootecniaUNAM04510 Ciudad de MexicoMexico Laboratorio 5:LEdeFAR Unidad de Investigacion MultidisciplinariaFacultad de Estudios Superiores(FES)CuautitlanUniversidad Nacional Autonoma de Mexico(UNAM)54714 Cuautitlan IzcalliMexico department of Poultry Science Center of Excellence for Poultry ScienceUniversity of Arkansas1260 W.MaplePOSC 0-114FayettevilleAR 72704USA Centro de Ensenanza Investigacion y Extension en Produccion AvicolaFacultad de Medicina Veterinaria y ZootecniaUNAMCiudad de MexicoMexico

Background:Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance.One of the most studied groups are polyphenolic compounds,given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions.Therefore,the objective of the present study was to evaluate the impact of dietary supplementation of copper acetate(CA),curcumin(CR),and their combination(CA-CR)against Salmonella Typhimurium colonization,intestinal permeability,and cecal microbiota composition in broiler chickens through a laboratory Salmonella infection model.S.Typhimurium recovery was determined on day 10 post-challenge by isolating Salmonella in homogenates of the right cecal tonsil(12 chickens per group)on Xylose Lysine Tergitol-4(XLT-4)with novobiocin and nalidixic acid.Intestinal integrity was indirectly determined by the fluorometric measurement of fluorescein isothiocyanate dextran(FITC-d)in serum samples from blood obtained on d 10 post-S.Typhimurium challenge.Finally,microbiota analysis was performed using the content of the left caecal tonsil of 5 chickens per group by sequencing V4 region of 16S rRNA gene.Results:The results showed that in two independent studies,all experimental treatments were able to significantly reduce the S.Typhimurium colonization in cecal tonsils(CT,Pdependent studies.Furthermore,the serum fluorescein isothiocyanate dextran(FITC-d)concentration in chickens treated with CR was significantly lower when compared to PC(P=0.0084),which is related to a decrease in intestinal permeability and therefore intestinal integrity.The effect of dietary treatments in reducing Salmonella was further supported by the analysis of 16S rRNA gene sequences using Linear discriminant analysis effect size(LEfSe)sin

关键词： Broiler chickens Copper acetate Curcumin Intestinal permeability Microbiota composition Salmonella Typhimurium

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Role of copper nanoparticles in wound healing for chronic wounds:literature review

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Burns & Trauma 2022年第1期10卷 805-813页

作者： Jessica Salvo Cristian Sandoval Escuela de Enfermería Facultad de CienciasUniversidad MayorChile Programa de Doctorado en Ciencias Morfológicas Facultad de MedicinaUniversidad de la FronteraAv.Francisco Salazar 011454811230TemucoChile Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásLos Carreras 7535310431OsornoChile departamento de Ciencias Preclínicas Facultad de MedicinaUniversidad de la FronteraAv.Francisco Salazar 011454811230TemucoChile

Chronic wounds are defined as wounds that fail to proceed through the normal phases of wound healing in an orderly and timely manner.The most common and inevitable impairment to wound healing is the installation of an infection,usually in the case of chronic wounds.Therefore,the objective of the present review was to identify the importance of copper nanoparticles in dressings for wound healing.Nanoparticles such as silver,gold and copper combat infectious processes through the inhibition of protein synthesis,peroxidation of the cell membrane and destroying the nucleic acids of bacteria and viruses.Among bioactive nanoparticles,copper plays a complex role in various cells,it modulates several cytokines and growth factor mechanisms of action and is essentially involved in all stages of the wound healing process.More importantly,copper plays a key role in skin regeneration and angiogenesis and accelerates the healing process through induction of vascular endothelial growth factor(VEGF)and angiogenesis by hypoxia-induced factor-1-alpha(HIF-1α)action where copper enhances HIF-1αexpression and HIF-1αbinding to the critical motifs in the promoter and putative enhancer regions of HIF-1-regulated genes.

关键词： Angiogenesis Antimicrobial Nanoparticles Regeneration Wound healing Chronic wound VEGF HIF-1α

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Activation of Wnt/β-catenin signaling in abdominal aortic aneurysm:A potential therapeutic opportunity?

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Genes & Diseases 2023年第3期10卷 639-642页

作者： Lídia Puertas-Umbert Saray Varona Carme Ballester-Servera Judith Alonso Silvia Aguiló Mar Orriols Ernesto Martínez-Martínez Antonio Rodríguez-Sinovas JoséMartínez-González Cristina Rodríguez Institut de Recerca Hospital de la Santa Creu i Sant Pau(IRHSCSP) Barcelona 08025Spain Instituto de Investigación Biomédica Sant Pau Barcelona 08036Spain CIBER de Enfermedades Cardiovasculares ISCIIIMadrid 28029Spain Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas(IIBB-CSIC) Barcelona 08036Spain facultad de medicina Universidad Complutense de MadridInstituto de Investigación Sanitaria Gregorio MarañónMadrid 28040Spain Cardiovascular Diseases Research Group Vall d’Hebron Institut de RecercaVall d’Hebron Hospital UniversitariVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain

Abdominal aortic aneurysm (AAA) is a common degenerative vascular disease with a prevalence up to 8% in males over 60 years of age.1 This is a complex disorder characterized by permanent and focal dilation of abdominal aorta that exceeds at least 50% of the normal diameter. In these patients, the aortic diameter progressively expands boosted by smoking and aging as major risk factors. Unfortunately, aneurysm growth increases the risk of aortic rupture, a life-threatening emergency that carries a mortality rate of 80%. despite the increasing effort of the scientific community to identify therapeutic strategies for AAA, there are currently no pharmacological tools that ameliorate aneurysm expansion, while the underlying mechanisms involved in this disease are not completely understood.

关键词： aneurysm aortic therapeutic

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Beyond reproduction：the role of progesterone in neuropathic pain after spinal cord injury

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Neural Regeneration Research 2016年第8期11卷 1238-1240页

作者： Susana Laura González María Florencia Coronel Universidad de Buenos Aires Facultad de Medicina Departamento de Bioquimica Humana Buenos Aires Argentina Laboratorio de Nocicepcion y Dolor Neuropatico Instituto de Biologia y Medicina Experimental CONICET Buenos Aires Argentina

Neuropathic pain,a type of pain arising after direct damage or disease of the nervous system,is often intractable and challenges the search of effective therapeutic strategies.In particular,neuropathic pain is a very ... 详细信息

关键词： progesterone intractable Beyond contributor reproduction neuronal NMDAR glial synaptic targeting

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Cell death Mechanisms Induced by Cytotoxic Lymphocytes

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Cellular & Molecular Immunology 2009年第1期6卷 15-25页

作者： Chávez-Galán L Arenas-del Angel MC Zenteno E Chávez R Lascurain R departamento de Bioquímica Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" departamento de Bioquímica Facultad de MedicinaUniversidad Nacional Autónoma de México

One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer （NK） cells and CD8^＋T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor （TNF） and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis. Cellular ＆ Molecular Immunology.

关键词： apoptosis cytotoxic cell granule-dependent exocytosis FasL TNF

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Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration

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Neural Regeneration Research 2022年第4期17卷 854-866页

作者： Manuel A.Fernandez-Parrilla David Reyes-Corona Yazmin M.Flores-Martinez Rasajna Nadella Michael J.Bannon Lourdes Escobedo Minerva Maldonado-Berny Jaime Santoyo-Salazar Luis O.Soto-Rojas Claudia Luna-Herrera Jose Ayala-Davila Juan A.Gonzalez-Barrios Gonzalo Flores Maria E.Gutierrez-Castillo Armando JEspadas-Alvarez Irma A.Martínez-Dávila Porfirio Nava Daniel Martinez-Fong departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa Institucional de Biomedicina Molecular Escuela Nacional de Medicina y HomeopatíaInstituto Politécnico NacionalCiudad de MéxicoMéxico department of Biosciences IIIT-SrikakulamRajiv Gandhi University of Knowledge Technologies(RGUKT)Andhra PradeshIndia department of Pharmacology Wayne State University School of MedicineDetroitMIUSA departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de MéxicoTlalnepantla de BazEdo.de MéxicoMéxico departamento de Fisiología Escuela Nacional de Ciencias BiológicasCiudad de MéxicoMéxico Laboratorio de medicina Genómica Hospital Regional“1°de Octubre”ISSSTECiudad de MéxicoMéxico Laboratorio de Neuropsiquiatría Instituto de FisiologíaBenemérita Universidad Autónoma de PueblaPueblaPueblaMéxico departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Programa de Nanociencias y nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system,a hallmark in Parkinson's disease.The human cerebral dopamine neurotrophic factor(h CDNF)has recently emerged as a strong candidate for Parkinson's disease therapy.This study shows that h CDNF expression in dopamine neurons using the neurotensinpolyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological,biochemical,and behavioral alterations.Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the h CDNF gene,ranging in size from 20 to 150 nm,enabled the expression of a secretable h CDNF in vitro.Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable h CDNF in dopamine neurons,whose levels remained constant throughout the study in the substantia nigra compacta and striatum.Compared with the lesioned group,tyrosine hydroxylase-positive(TH^(+))nigral cell population and TH+fiber density rose in the substantia nigra compacta and striatum after h CDNF transfection.An increase inβIII-tubulin and growth-associated protein 43 phospho-S41(GAP43 p)followed TH^(+)cell recovery,as well as dopamine and its catabolite levels.Partial reversal(80%)of drugactivated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved.Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects.These findings support the potential of nanoparticle-mediated h CDNF gene delivery to develop a disease-modifying treatment against Parkinson's disease.The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use(authorization No.162-15)on June 9,2019.

关键词： axonal growth brain-derived neurotrophic factor gene delivery nanoparticles neuritogenesis neuronal cytoskeleton neuroregeneration neurorestoration neurotrophic therapy Parkinson's disease reinnervation substantia nigra

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Facial nerve monitoring in parotid gland surgery:design and feasibility assessment of a potential standardized technique

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第4期9卷 280-287页

作者： Carlos S.Duque Andrés F.Londoño Ana M.Duque Jhon J.Zuleta Marcela Marulanda Lina M.Otálvaro Miguel Agudelo Juan P.Dueñas María F.Palacio Gianlorenzo Dionigi Hospital Pablo Tobón Uribe Departmento deCancerologíaMedellinColombia Clínica de Otorrinolaringología de Antioquia“Orlant” MedellínColombia Sección Otorrinolaringología Departamentode CirugíaFacultad de MedicinaUniversidadde AntioquiaMedellínColombia Hospital Pablo Tobón Uribe DirecciónCientíficaMedellinColombia Sección Cirugia de Cabeza y Cuello Departamento de CirugíaFacultad deMedicinaUniversidad de AntioquiaMedellinColombia department of Internal Medicine IsraelMedical CenterNewarkNew JerseyUSA departamento de Cirugía Clínica El RosarioEl TesoroMedellínColombia Sección Cabeza y Cuello Instituto deCancerologíaClínica Las Américas–AunaMedellínColombia Chirurgia Generale Capitanio AuxiologicoMilanItaly

Background:Even though the use of nerve monitoring during parotid gland surgery is not the gold standard to prevent damage to the nerve,it surely offers some advantages over the traditional approach.Different from thyroid surgery,where a series of steps in intraoperative nerve monitoring have been described to confirm not only the integrity but—most importantly—the function of the recurrent laryngeal nerve,in parotid gland surgery,a formal guideline to follow while dissecting the facial nerve has yet to be described.Methods:A five‐year retrospective study was done reviewing the intraoperative records of patients who underwent parotid gland surgery under neural monitoring.The operative findings regarding the neuromonitoring process,particularly in regard to the amplitude of two main branches,were revised.A literature search was done to search for guidelines to follow when a facial nerve loss of signal is encountered.Results:Fifty‐five patients were operated on using the Nim 3 Nerve Monitoring System(Medtronic);31 were female patients,and 47 patients had benign lesions.Minimum changes were observed in the amplitude records after a comparison was made between the first and the last stimulation.There were only three articles discussing the term loss of signal during parotid gland surgery.Conclusion:Today,no sufficient attention has been given to the facial nerve monitoring process during parotidectomy.This study proposes a formal guideline to follow during this procedure as well as an instruction to consider when a loss of signal is observed to develop a uniform technique of facial nerve stimulation.

关键词： amplitude facial nerve intraoperative neural monitoring latency loss of signal nerve monitoring parotid gland

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Type 1 diabetes loci display a variety of native American and African ancestries in diseased individuals from Northwest Colombia

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World Journal of Diabetes 2019年第11期10卷 534-545页

作者： Natalia Gomez-Lopera Juan M Alfaro Suzanne M Leal Nicolas Pineda-Trujillo departamento de Pediatría Facultad de MedicinaUniversidad de AntioquiaMedellín 050010470Colombia Sección de Endocrinología Pediátrica Departamento de PediatríaFacultad de MedicinaUniversidad de AntioquiaMedellín 050010470Colombia Center for Statistical Genetics Columbia UniversityNew YorkNY 10032United States

BACKGROUND Type 1 diabetes(T1D)is a complex disease with a higher incidence in Europeans than other populations.The Colombians Living in Medellin(CLM)is admixed with ancestry contributions from Europeans,Native Americans(NAT)and Africans(AFR).AIM Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease.METHODS Seventy-four ancestry informative markers(AIMs),which tagged 41 T1D candidate loci/genes,were tested by studying a cohort of 200 Northwest Colombia diseased individuals.T1D status was classified by testing for glutamic acid decarboxylase(GAD-65 kDa)and protein tyrosine-like antigen-2 autoantibodies in serum samples.Candidate loci/genes included HLA,INS,PTPN22,CTLA4,IL2RA,SUMO4,CLEC16A,IFIH1,EFR3B,IL7R,NRP1 and RNASEH1,amongst others.The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM.As the data did not comply with a normal distribution,medians were compared between groups using the Mann-Whitney U-test.RESULTS Both T1D patients and individuals from CLM displayed mainly European ancestry(61.58 vs 62.06)followed by Native American(27.34 vs 27.46)and to a lesser extent the AFR ancestry(10.28 vs 10.65)components.However,compared to CLM,ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B(24.30 vs 37.10)and an increase at genes IFIH1(32.07 vs 14.99)and IL7R(52.18 vs 39.18).Also,for gene NRP1(36.67 vs 0.003),we observed a non-AFR contribution(attributed to NAT).Autoimmune patients(positive for any of two auto-antibodies)displayed lower NAT ancestry than idiopathic patients at the MHC region(20.36 vs 31.88).Also,late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R(19.96 vs 6.17).An association analysis showed that,even after adjusting for admixture,an association exists for at least seven such AIMs,with the strongest findings on chromosomes 5 and 10(gene IL7R,P=5.56×10-6 and gene NRP1,P=8.70×10-19,respectively).CONCLUSION Although Colom

关键词： Type 1 diabetes Genetic admixture Native American Idiopathic Colombia

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