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Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?

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World Journal of Gastrointestinal Oncology 2023年第2期15卷 251-267页

作者： Jonadab E Olguin monica G mendoza-Rodriguez C Angel Sanchez-Barrera Luis I Terrazas Laboratorio nacional en Salud Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-degenerativasFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico Unidad de Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC. The conventional chemotherapeutic agent utilized throughout the last four decades is 5-fluorouracil, notwithstanding its low efficiency as a single therapy. In contrast, combining 5-fluorouracil therapy with leucovorin and oxaliplatin or irinotecan increases its efficiency. However, these treatments have limited and temporary solutions and aggressive side effects. Additionally, most patients treated with these regimens develop drug resistance, which leads to disease progression. The immune response is considered a hallmark of cancer;thus, the use of new strategies and methodologies involving immune molecules, cells, and transcription factors has been suggested for CRC patients diagnosed in stages Ⅲ and Ⅳ. despite the critical advances in immunotherapy, the development and impact of immune checkpoint inhibitors on CRC is still under investigation because less than 25% of CRC patients display an increased 5-year survival. The causes of CRC are diverse and include modifiable environmental factors(smoking, diet, obesity, and alcoholism), individual genetic mutations, and inflammation-associated bowel diseases. Due to these diverse causes, the solutions likely cannot be generalized. Interestingly, new strategies, such as single-cell multiomics, proteomics, genomics, flow cytometry, and massive sequencing for tumor microenvironment analysis, are beginning to clarify the way forward. Thus,the individual mechanisms involved in developing the CRC microenvironment, their causes, and their consequences need to be understood from a g

关键词： Colorectal cancer Immunotherapy checkpoint inhibitors Chemotherapy Immunotherapy Immune response

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mitochondrial phylogeography and molecular evolution of the rhodopsin visual pigment in troglobitic populations of Astyanax mexicanus(de Filippi,1853)

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Zoological Research 2023年第4期44卷 761-775页

作者： marco A.A.Garduño-Sánchez Vladimir de Jesus-Bonilla Silvia Perea Ramses miranda-Gamboa Andrea Herrera-García mauricio de la maza Benignos Claudia Patricia Ornelas-García Colección nacional de Peces Departamento de ZoologíaInstituto de BiologíaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoC.P.04510México Posgrado en Ciencias Biológicas Colección Nacional de PecesDepartamento de ZoologíaInstituto de BiologíaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoC.P.04510México Licenciatura en Ciencias Forenses Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoCiudad UniversitariaCoyoacánMéxico CityC.P.04510México Instituto de Energías Renovables Universidad Nacional Autónoma de MéxicoTemixcoMorelos C.P.62580Mexico Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo LeónCiudad UniversitariaSan Nicolás de los GarzaNuevo LeónC.P.66450México

Cave-adapted animals provide a unique opportunity to study the evolutionary mechanisms underlying phenotypic,metabolic,behavioral,and genetic evolution in response to cave environments.The mexican tetra(Astyanax mexicanus)is considered a unique model system as it shows both surface and cave-dwelling morphs.To date,at least 33 different cave populations have been identified,with phylogenetic studies suggesting an origin from at least two independent surface lineages,thereby providing a unique opportunity to study parallel evolution.In the present study,we carried out the most exhaustive phylogeographic study of A.mexicanus to date,including cave and surface localities,using two mitochondrial markers(cytochrome b(cyt b)and cytochrome c oxidase subunit I(COI))and nuclear rhodopsin visual pigment(rho).Additionally,we inferred the molecular evolution of rho within the two contrasting environments(cave and surface)and across three geographic regions(Sierra de El Abra,Sierra de Guatemala,and micos).In total,267 individuals were sequenced for the two mitochondrial fragments and 268 individuals were sequenced for the rho visual pigment from 22 cave and 46 surface populations.Phylogeographic results based on the mitochondrial data supported the two-lineage hypothesis,except for the Pachón and Chica caves,whose introgression has been largely documented.The Sierra de El Abra region depicted the largest genetic diversity,followed by the Sierra de Guatemala region.Regarding the phylogeographic patterns of rho,we recovered exclusive haplogroups for the Sierra de El Abra(Haplogroup I)and Sierra de Guatemala regions(Haplogroup IV).moreover,a 544 bp deletion in the rho gene was observed in the Escondido cave population from Sierra de Guatemala,reducing the protein from seven to three intramembrane domains.This change may produce a loss-of-function(LOF)but requires further investigation.Regarding nonsynonymous(dN)and synonymous(dS)substitution rates(omega valuesω),our results revealed the prevailing influence of purifying selection

关键词： Visual pigments Selection Cavefish Vision loss Loss of function

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Plumbing System of Hunga Tonga Hunga Ha'apai Volcano

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Journal of Earth Science 2023年第3期34卷 706-716页

作者： Román Alvarez miguel Camacho Instituto de Investigaciones en matemáticas Aplicadas y en Sistemas(IImAS) Universidad Nacional Autónoma de MéxicoCoyoacán CDMX 04510Mexico Posgrado en Ciencias de la Tierra Universidad Nacional Autónoma de MéxicoCoyoacán CDMX 04510Mexico

The Hunga Tonga Hunga Ha’apai submarine volcano has experienced repeated eruptions in the latest decades.The recent one,in January 2022,released an enormous amount of energy inducing global perturbations,as tsunamis and atmospheric waves.The structure of the volcano is poorly understood,especially its internal structure.deep-seated magmatic connections are difficult to define or visualize.We use a high-resolution gravity data set obtained via satellite to calculate the Bouguer anomaly over its structure,to perform a preliminary exploration of its interior.Executing 3D gravity inversions,we find a complex plumbing system with various exhaust trajectories and multiple surface pockets of low-density material within the volcanic edifice;some appear to be associated with ring fractures.This is in line with the report of the 2009 eruption,described as beginning from multiple vents.We found no signs of a magma chamber within 6 km depth,although several volcanic conduits are identified from such depth to the surface.density variations occur within a plumbing conduit or may vary from one conduit to another in the same volcano.These models yield quantitative estimates for areas of magma-water interaction,constituting a baseline to compare with structural changes to be induced in future eruptions.

关键词： Hunga Tonga Hunga Ha'apai satellite gravity data 3D inversions volcano Tofua Island

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Comparative analysis of two nonlethal methods for the study of the gut bacterial communities in wild lizards

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Integrative Zoology 2023年第6期18卷 1056-1071页

作者： mauricio HERNÁNdeZ Sergio ANCONA Stephanie HEREIRA-PACHECO Aníbal HDÍAZ de LA VEGA-PÉREZ yendi E.NAVARRO-NOyA Doctorado en Ciencias Biológicas Centro de Tlaxcala de Biología de la ConductaUniversidad Autónoma de TlaxcalaTlaxcalaMexico departamento de Ecología Evolutiva Instituto de EcologíaUniversidad Nacional Autónoma de MéxicoMexico CityMexico Estación Científica la malinche Centro de Tlaxcala de Biología de la ConductaUniversidad Autónoma de TlaxcalaTlaxcalaMexico Consejo nacional de Ciencia y Tecnología—Centro Tlaxcala de Biología de la Conducta Universidad Autónoma de TlaxcalaTlaxcalaMexico Laboratorio de Interacciones Bióticas Centro de Investigación en Ciencias BiológicasUniversidad Autónoma de TlaxcalaTlaxcalaMexico

Fecal samples or cloacal swabs are preferred over lethal dissections to study vertebrate gut microbiota for ethical reasons,but it remains unclear which nonlethal methods provide more accurate information about gut microbiota.We compared the bacterial communities of three gastrointestinal tract(GIT)segments,that is,stomach,small intestine(midgut),and rectum(hindgut)with the bacterial communities of the cloaca and feces in the mesquite lizard Sceloporus grammicus.The hindgut had the highest taxonomic and functional alpha diversity,followed by midgut and feces,whereas the stomach and cloaca showed the lowest diversities.The taxonomic assemblages of the GIT segments at the phylum level were strongly correlated with those retrieved from feces and cloacal swabs(rs>0.84 in all cases).The turnover ratio of Amplicon Sequence Variants(ASVs)between midgut and hindgut and the feces was lower than the ratio between these segments and the cloaca.more than half of the core-ASVs in the midgut(24 of 32)and hindgut(58 of 97)were also found in feces,while less than 5 were found in the cloaca.At the ASVs level,however,the structure of the bacterial communities of the midgut and hindgut were similar to those detected in feces and cloaca.Our findings suggest that fecal samples and cloacal swabs of spiny lizards provide a good approximation of the taxonomic assemblages and beta diversity of midgut and hindgut microbiota,while feces better represent the bacterial communities of the intestinal segments at a single nucleotide variation level than cloacal swabs.

关键词： animal microbiome cloacal swabs fecal samples intestinal tract reptile gut microbiome

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Thinking outside the black box:are the brain endothelial cells the new main target in Alzheimer's disease?

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Neural Regeneration Research 2023年第12期18卷 2592-2598页

作者： Enrique Estudillo Adolfo López-Ornelas Alejandro Rodríguez-Oviedo Neptali Gutiérrez de la Cruz marco Antonio Vargas-Hernández Adriana Jiménez Laboratorio de Reprogramación Celular Instituto Nacional de Neurología y Neurocirugía Manuel Velasco SuárezMexico CityMexico División de Investigación Hospital Juárez de MéxicoMexico CityMexico Hospital nacional Homeopático Hospitales Federales de ReferenciaMexico CityMexico Facultad de Ciencias Universidad Nacional Autónoma de MéxicoMexico CityMexico Laboratorio de morfología Escuela Militar de Graduados de SanidadSecretaría de la Defensa NacionalBatalla de CelayaLomas de SoteloMiguel HidalgoMexico CityMexico escuela militar de Graduados de Sanidad Secretaría de la Defensa NacionalBatalla de CelayaLomas de SoteloMiguel HidalgoMexico CityMexico

The blood-brain barrier is the interface through which the brain interacts with the milieu and consists mainly of a sophisticated network of brain endothelial cells that forms blood vessels and selectively moves molecules inside and outside the brain through multiple mechanisms of transport.Although brain endothelial cell function is crucial for brain homeostasis,their role in neurodegenerative diseases has historically not been considered with the same importance as other brain cells such as microglia,astroglia,neurons,or even molecules such as amyloid beta,Tau,or alpha-synuclein.Alzheimer's disease is the most common neurodegenerative disease,and brain endothelial cell dysfunction has been reported by several groups.However,its impairment has barely been considered as a potential therapeutic target.Here we review the most recent advances in the relationship between Alzheimer's disease and brain endothelial cells commitment and analyze the possible mechanisms through which their alterations contribute to this neurodegenerative disease,highlighting their inflammatory phenotype and the possibility of an impaired secretory pattern of brain endothelial cells that could contribute to the progression of this ailment.Finally,we discuss why shall brain endothelial cells be appreciated as a therapeutic target instead of solely an obstacle for delivering treatments to the injured brain in Alzheimer's disease.

关键词： dementia endothelial cells neurodegeneration neuroinflammation neuronal death paracellular transport transcellular transport

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Commitment of human mesenchymal stromal cells to skeletal lineages is independent of their morphogenetic capacity

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World Journal of Stem Cells 2023年第7期15卷 701-712页

作者： Jessica Cristina marín-Llera Damián García-García Estefania Garay-Pacheco Victor Adrian Cortes-morales Juan Jose montesinos-montesinos Jesus Chimal-monroy medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCoyoacan 04510Mexico Laboratorio de Células Troncales mesenquimales Unidad de Investigación Médica en Enfermedades OncológicasHospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico departamento de medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCoyoacan 04510Mexico

BACKGROUND mesenchymal stromal cells(mSCs)are multipotent cell populations obtained from fetal and adult tissues.They share some characteristics with limb bud mesodermal cells such as differentiation potential into osteogenic,chondrogenic,and tenogenic lineages and an embryonic mesodermal origin.Although mSCs differentiate into skeletal-related lineages in vitro,they have not been shown to selforganize into complex skeletal structures or connective tissues,as in the limb.In this work,we demonstrate that the expression of molecular markers to commit mSCs to skeletal lineages is not sufficient to generate skeletal elements in vivo.AIm To evaluate the potential of mSCs to differentiate into skeletal lineages and generate complex skeletal structures using the recombinant limb(RL)system.mETHODS We used the experimental system of RLs from dissociated-reaggregated human placenta(PL)and umbilical cord blood(UCB)mSCs.After being harvested and reaggregated in a pellet,cultured cells were introduced into an ectodermal cover obtained from an early chicken limb bud.Next,this filled ectoderm was grafted into the back of a donor chick embryo.Under these conditions,the cells received and responded to the ectoderm’s embryonic signals in a spatiotemporal manner to differentiate and pattern into skeletal elements.Their response to differentiation and morphogenetic signals was evaluated by quantitative poly-merase chain reaction,histology,immunofluorescence,scanning electron microscopy,and in situ hybridization.RESULTS We found that human PL-mSCs and UCB-mSCs constituting the RLs expressed chondrogenic,osteogenic,and tenogenic molecular markers while differentially committing into limb lineages but could not generate complex structures in vivo.mSCs-RL from PL or UCB were committed early to chondrogenic lineage.Nevertheless,the UCB-RL osteogenic commitment was favored,although preferentially to a tenogenic cell fate.These findings suggest that the commitment of mSCs to differentiate into skeletal lineages differs according to the sou

关键词： Human mesenchymal stromal cells Recombinant limbs mesenchymal stromal cell morphogene-sis mesenchymal stromal cell in vivo differentiation Skeletal tissues

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Control of tendon cell fate in the embryonic limb: A molecular perspective

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BIOCELL 2023年第3期47卷 465-471页

作者： JESSICA CRISTINA mARÍN-LLERA CARLOS AmAURy JImÉNEZ-CÁRdeNAS JESÚS CHImAL-mONROy departamento de medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de México Ciudad UniversitariaApartado Postal 70228MéxicoDF 04510México

The molecular cascade underlying tendon formation starts when progenitor cells begin to express the Scleraxis(Scx)gene.Scx knockout mice develop some but not all tendons,suggesting that additional factors are necessary for tendon commitment,maintenance,and differentiation.Other transcription factors,such as mohawk(mkx)or early growth response(Egr),maintain Scx expression and extracellular matrix formation during fibrillogenesis.The inhibition of wingless and int-related protein signaling is necessary and sufficient to induce the expression of Scx.Once the commitment of tenogenic lineage occurs,transforming growth factor-beta(TGFβ)induces the Scx gene expression,becoming involved in the maintenance of tendon cell fate.From this point of view,we discussed two phases of the tenogenic process during limb development:dependent and independent of mechanical forces.Finally,we highlight the importance of understanding embryonic tendon development to improve therapeutic strategies in regenerative medicines for tendons.

关键词： Tendon differentiation Tenocyte Scleraxis mohawk Early growth response Tendon development WNT TGFβ

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Glacial reconstruction and periglacial dynamics at the end of Late Pleistocene on the surface of Cofre de Perote volcano,méxico:a climatological retrospective

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Journal of mountain Science 2023年第9期20卷 2453-2467页

作者： Victor SOTO Hugo deLGADO-GRANADOS Carlos m.WELSH Kenji yOSHIKAWA Centro de Ciencias de la Tierra Universidad VeracruzanaXalapaVeracruz 91090México Instituto de Geofísica Universidad Nacional Autónoma de MéxicoCiudad de México 04150México Water and Environmental Research Center University of Alaska FairbanksFairbanksAlaska 99775USA

despite being within the intertropical region of the planet,the mexican territory still has glacier-covered mountains.In recent decades,important advances have been made in studies on glaciology and periglacial environment in mexico both for current and past conditions.However,in spite of Cofre de Perote volcano(4200 m a.s.l.)being a strategically located mountain,it has not yet been studied in regards to the glacial and periglacial processes;in fact,those dynamics have modified the mountain massifs in the past.To complement the series of studies on glacial history in the high mountain environment of méxico,this study reconstructs the glacial cover and the periglacial environment of the volcano surface during the final stage of the Late Pleistocene based on climatic retrospective and through the identification of geomorphological features.The findings indicate the existence of a large glacier(ice cap)that covered the northern,western,and southern slopes of the mountain;while in the eastern sector there were two small glaciers,one being of cirque type,and the other of valley type.The current temperature conditions prevent the occurrence of permanent ice bodies;at the same time,it was found that the periglacial blockfields of the slopes is a legacy of the climatic conditions that prevailed at the end of Late Pleistocene.

关键词： Cofre de Perote Glacial cover Periglacial environment Climatic retrospective Palaeoclimatic modelling

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

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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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Conifer establishment after the eruption of the Paricutin volcano in central mexico

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Forest Ecosystems 2022年第1期9卷 71-82页

作者： Jesús Eduardo Sáenz-Ceja Blanca Lizeth Sáenz-Ceja J.Trinidad Sáenz-Reyes Diego Rafael Pérez-Salicrup Instituto de Investigaciones en Ecosistemas y Sustentabilidad Universidad Nacional Autéonoma de MéxicoAntigua Carretera a Patzcuaro 8701 Col.Ex hacienda San Joséde la Huerta58190MoreliaMexico escuela nacional de Estudios Superiores Unidad morelia Universidad Nacional Autónoma de MéxicoAntigua Carretera a Patzcuaro 8701 Col.Ex hacienda San Joséde la Huerta58190MoreliaMexico Instituto nacional de Investigaciones Forestales Agrícolas y PecuariasCampo Experimental UruapanAv.Latinoamericana 1101Col.Revolución60500UruapanMexico

Background:Volcanic eruptions have large effects on forest ecosystems and create new substrates,triggering primary succession processes.The Paricutín volcano,born in central-western mexico,erupted between 1943 and 1952.After the cessation of the eruptive activity,plant colonization began on the lava flows and tephra deposits,including the conifer species that dominate the surrounding mature forests.This study aims to reconstruct the history of the establishment of conifer trees on the substrates created by the Paricutín eruption.methods:16 sampling plots were established along three transects with northern,southern,and south-western aspects,located every 250 m from the preserved forest to the volcanic cone.Increment cores from 400 conifer trees were extracted and their age was determined by cross-dating annual tree rings.The order of the species colonization and the tree establishment,abundance,and dominance patterns were characterized.Also,the influence of the distance from the mature forests and the inter-annual climatic conditions on the temporal tree establishment pattern was evaluated.Results:Eight pine and one fir species have been established since 1970,only 18 years after the end of the eruptive period.However,tree establishment increased by 12.9%annually after 1995,with the youngest tree in our sample getting established in 2015.We did not find a well-defined temporal and spatial pattern of species arrival,which suggests that colonization occurred randomly,although the four pine species that were established early became the most abundant and dominant.Tree establishment was not influenced by the distance from the mature forest,and wet inter-annual conditions did not enhance pulses of tree recruitment,exhibiting a continuous tree establishment pattern.Conclusions:Conifer species have shown a great capacity for colonizing volcanic substrates created by the Paricutín eruption,which suggests that tropical montane conifers can regenerate rapidly under high-magnitude disturbances.These findings support the use

关键词： Age structure dendrochronology Lava flow Primary succession Tropical montane forest

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