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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero Sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva Ana M.gomez-Lahoz Jorge Monserrat Mar Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain Department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

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Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury

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Liver Research 2024年第1期8卷 46-53页

作者： Joshua Hefler Rena Pawlick Braulio A.Marfil-Garza Aducio Thiesen Nerea Cuesta-gomez Sanaz Hatami Darren H.Freed Constantine Karvellas David L.Bigam A.M.James Shapiro Department of Surgery Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada Department of Medicine Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada CHRISTUS-LatAm Hub Excellence&Innovation Center MonterreyMexico Alberta Diabetes Institute University of AlbertaEdmontonABCanada Clinical Islet Transplant Program University of AlbertaEdmontonABCanada Department of Laboratory Medicine&Pathology Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada

Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control mice.Conclusions:Premedication with CsA or NIM-811 mitig

关键词： Cyclosporine(CsA) Cyclosporine analogue Liver surgery Ischemia-reperfusion injury(IRI) Animal model NIM-811

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Differential Expression of Genes Related to Fruit Development and Capsaicinoids Synthesis in Habanero Pepper Plants Grown in Contrasting Soil Types

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Phyton-International Journal of Experimental Botany 2024年第2期93卷 151-183页

作者： Eduardo Burgos-Valencia Federico García-Laynes Ileana Echevarría-Machado Fatima Medina-Lara Miriam Monforte-González JoséNarváez-Zapata manuel Martínez-Estévez Unidad de Bioquímica y Biología Molecular de Plantas Centro de Investigación Científica de YucatánCalle 43#130Chuburnáde HidalgoMéridaYucatán97205México Instituto Politécnico Nacional-Centro de Biotecnología Genómica Blvd Del Maestro esq.Elias PiñaReynosaTamaulipas88710México

Habanero pepper(Capsicum chinense Jacq.)is a crop of economic relevance in the Peninsula of Yucatan.Its fruits have a high level of capsaicinoids compared to peppers grown in other regions of the world,which gives them industrial importance.Soil is an important factor that affects pepper development,nutritional quality,and capsaicinoid content.However,the effect of soil type on fruit development and capsaicinoid metabolism has been little understood.This work aimed to compare the effect of soils with contrasting characteristics,black soil(BS)and red soil(RS),on the expression of genes related to the development of fruits,and capsaicinoid synthesis using a transcriptomic analysis of the habanero pepper fruits.Plants growing in RS had bigger fruits and higher expression of genes related to floral development,fruit abscission,and softening which suggests that RS stimulates fruit development from early stages until maturation stages.Fruits from plants growing in BS had enrichment in metabolic pathways related to growth,sugars,and photosynthesis.Besides,these fruits had higher capsaicinoid accumulation at 25 days post-anthesis,and higher expression of genes related to the branched-chain amino acids metabolism(ketol-acid reductisomerase KARI),pentose phosphate pathway and production of NADPH(glucose-6-phosphate-1-dehydrogenase G6PDH),and proteasome and vesicular traffic in cells(26S proteasome regulatory subunit T4 RPT4),which suggest that BS is better in the early stimulation of pathways related to the nutritional quality and capsaicinoid metabolism in the fruits.

关键词： Capsicum chinense jacq soil types plant growth environmental conditions fruit quality capsaicinoid metabolism transcriptome

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A Probabilistic Description of the Impact of Vaccine-Induced Immunity in the Dynamics of COVID-19 Transmission

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Open Journal of Modelling and Simulation 2024年第2期12卷 59-73页

作者： Javier Blecua Juan Fernández-Recio José manuel Gutiérrez Instituto de Ciencias de la Vid y del Vino (ICVV) CSIC-Universidad de La Rioja-Gobierno de La Rioja Logro&#241o Spain Departamento de Matemá ticas y Computaci&#243n Universidad de La Rioja Logro&#241o Spain

The recent outbreak of COVID-19 has caused millions of deaths worldwide and a huge societal and economic impact in virtually all countries. A large variety of mathematical models to describe the dynamics of COVID-19 transmission have been reported. Among them, Bayesian probabilistic models of COVID-19 transmission dynamics have been very efficient in the interpretation of early data from the beginning of the pandemic, helping to estimate the impact of non-pharmacological measures in each country, and forecasting the evolution of the pandemic in different potential scenarios. These models use probability distribution curves to describe key dynamic aspects of the transmission, like the probability for every infected person of infecting other individuals, dying or recovering, with parameters obtained from experimental epidemiological data. However, the impact of vaccine-induced immunity, which has been key for controlling the public health emergency caused by the pandemic, has been more challenging to describe in these models, due to the complexity of experimental data. Here we report different probability distribution curves to model the acquisition and decay of immunity after vaccination. We discuss the mathematical background and how these models can be integrated in existing Bayesian probabilistic models to provide a good estimation of the dynamics of COVID-19 transmission during the entire pandemic period.

关键词： COVID-19 Transmission Dynamics Probabilistic Model Bayesian Analysis Markov Chain Monte Carlo

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Assessing the impact of concurrent high-fructose and highsaturated fat diets on pediatric metabolic syndrome:A review

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World Journal of Clinical Pediatrics 2024年第2期13卷 62-79页

作者： manuel Alejandro Vargas-Vargas Marcela González-Montoya Olin Torres-Isidro Claudia Isabel García-Berumen Omar Ortiz-Avila Elizabeth Calderón-Cortés Christian Cortés-Rojo Instituto de Investigaciones Químico–Biológicas Universidad Michoacana de San Nicolás de HidalgoMorelia 58030MichoacánMexico Facultad de Enfermería Universidad Michoacana de San Nicolás de HidalgoMorelia 58020MichoacánMexico

High-saturated fat(HF)or high-fructose(HFr)consumption in children predispose them to metabolic syndrome(MetS).In rodent models of MetS,diets containing individually HF or HFr lead to a variable degree of MetS.Nevertheless,simultaneous intake of HF plus HFr have synergistic effects,worsening MetS outcomes.In children,the effects of HF or HFr intake usually have been addressed individually.Therefore,we have reviewed the outcomes of HF or HFr diets in children,and we compare them with the effects reported in rodents.In humans,HFr intake causes increased lipogenesis,hypertriglyceridemia,obesity and insulin resistance.On the other hand,HF diets promote low grade-inflammation,obesity,insulin resistance.Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents,there is little information about the combined effects of HF plus HFr intake in children.The aim of this review is to warn about this issue,as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population.We consider that this is an alarming issue that needs to be assessed,as the simultaneous intake of HF plus HFr is common on fast food menus.

关键词： Fructose Saturated fat Metabolic syndrome Insulin resistance Type 2 diabetes Ultra processed foods Children Obesity Dyslipidemia Non-alcoholic fatty liver disease

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Phenazines:Natural products for microbial growth control

hLife

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hLife 2024年第3期2卷 100-112页

作者： Cátia A Sousa Marta Ribeiro Francisca Vale manuel Simões ISEP/P.PORTO School of EngineeringPolytechnic of PortoPortoPortugal LEPABE-Laboratory for Process Engineering EnvironmentBiotechnology and EnergyFaculty of EngineeringUniversity of PortoPortoPortugal ALiCE-Associate Laboratory in Chemical Engineering Faculty of EngineeringUniversity of PortoPortoPortugal

The unprecedented problem of antibiotic resistance has become a major challenge for public health,which has contributed to an increase in infections caused by such bacteria.These microbial infections,typically biofilm-related,are alsocoupled to an increase in human mortality and morbidity.However,the demand for new antimicrobial agents hasincreased along with the evolution of microbial resistance mechanisms.Natural products produced by bacteria,such as phenazines,have been recognized as an important source for the development of new antimicrobial agents,through the exploitation of their capacity to increase oxidative stress in other organisms.Phenazines are a large groupof nitrogen-containing heterocyclic compounds and are essential for several cellular processes including iron acquisition,signaling events,enzymatic processes,and biofilm formation.Phenazine-inspired antibiotics(i.e.,2-bromo-1-hydroxyphenazine,2,4-dibromo-1-hydroxyphenazine,bromophenazine-21,phenazine-13,and phenazine-14)are veryactive against a wide range of gram-positive and gram-negative bacteria,including those associated with severe infections.In this study,mechanisms of phenazine-inspired antibiotics in the cellular processes of planktonic and sessilebacteria are reviewed.Moreover,the application of phenazine-inspired antibiotics for the eradication of multidrugresistant planktonic and biofilm bacterial infections is also reviewed.

关键词： antimicrobial agents biofilms multidrug-resistant natural products phenazines

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Loggerhead Sea Turtles Hand-Reared in Captivity: Isotopic Insights into Their Inherent Dietary Variation

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Open Journal of Ecology 2024年第5期14卷 435-454页

作者： Brenda Natasha Mejía-Guarnizo Carlos Julio Polo-Silva Guiomar Aminta Jauregui-romero Antonio Delgado-Huertas Centro de Investigaciones en Ciencias Marinas (CICIMAR-IPN) La Paz M&#233xico Marine Biology Program Faculty of Natural Sciences and Engineering Jorge Tadeo Lozano University Santa Marta Colombia Sharky Management and Consulting Oldsmar FL USA Programa de Conservació n de Tortugas y Mam&#237feros Marinos (ProCTMM) Santa Marta Colombia Instituto Andaluz de Ciencias de la Tierra (CSIC-UGR) Armilla Spain

Stable isotope analysis is a widely used method for gathering ecological insights into the diet and feeding habitats of various species. While captive studies often limit lethal sampling and differ from wild conditions, they offer valuable insights into inherent isotopic variations among individuals, which are often assumed to reflect differences between natural populations. In the Sea Turtle Conservation Program, loggerhead turtle hatchlings from different nests were fed. Necropsies were conducted on turtles that died during this period, obtaining bone fragments for analysis. We evaluated the isotopic variation of carbon (δ13C) and nitrogen (δ15N) in bone tissue across six turtle nests (n = 66 samples) and assessed differences in Straight Carapace Length (SCL, n = 71 samples). Using SIBER and nicheROVER in R, we calculated niche width and overlap, while the simmr package determined primary prey assimilation. Despite feeding the hatchlings the same prey, we observed variations in nitrogen isotope assimilation between nests. Nests 4 and 6 had a niche width >1.8‰, indicating consistent consumption frequencies across all prey and >70% niche overlap with other nests. In contrast, nests 1 and 2 showed a narrower niche width (Mugil sp. constituted the primary diet component (>40%) across all groups. This study demonstrates how factors like competition or prey preference can influence the assimilation of diet, even when the source remains constant (inherent variation).

关键词： Stable Isotopes Caretta caretta Head-Starting Nests Straight Carapace Length

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Uremic Bleeding in 2 Patients with Dieulafoy’s Lesion: Case Report and Literature Review

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Open Journal of Gastroenterology 2024年第5期14卷 167-173页

作者： Gustavo Adolfo Hernández Valdez Diana Estefanía Ibarra García Juan Antonio Contreras Escamilla Janette Alejandra Gamiño Gutierrez Francisco manuel Tonatiuh Carrillo Beltran Ulises Solis gomez Jocelyn Nataly Quintero Meléndez Ivan Alejandro Medina Jimenez Marco Antonio González Villar Jorge Rojas Morales Department of Internal Medicine ISSSTE APP General Hospital of Tepic Tepic Nayarit Mexico Hospital Civil de Guadalajara Fray Antonio Alcalde Guadalajara Jalisco M&#233xico

Dieulafoy’s lesions are rare vascular malformations of the gastrointestinal tract. A Dieulafoy’s lesion is an aberrant vessel that does not reduce in caliber when it extends from the submucosa to the mucosa. Damage to this artery can cause severe and intermittent arterial bleeding from small vascular stumps that are difficult to visualize. Furthermore, these catastrophic bleeding episodes frequently result in hemodynamic instability and the need for transfusion of multiple blood products. Recently, uremic syndrome has been identified as a risk factor for gastric mucosal lesions. We present two clinical cases of acute digestive bleeding due to Dielafoy lesion with chronic kidney disease as the main cause, where two different therapies were performed endoscopically. We concluded with the results of our patients that the best therapy was the application of the hemostatic hemoclip on the injury vs the injection with adrenaline on the wound site. Uremia is identified as a risk factor for upper gastrointestinal bleeding in patients with pre-existing Dieulafoy’s lesion, as well as a higher incidence of new bleeding.

关键词： Dieulafoy’s Lesion Gastrointestinal Bleeding Endoscopy Endoscopy Hemostatic Clips Kidney Disease Adrenaline Thermal Coagulation Dieulafoy

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Multi-omic study to unmask genes involved in prostate cancer development in amulti-case family

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Cancer Communications 2024年第3期44卷 443-447页

作者： Lucia Chica-Redecillas Sergio Cuenca-Lopez Eduardo Andres-Leon Laura Carmen Terron-Camero Blanca Cano-Gutierrez Jose manuel Cozar Jose Antonio Lorente Fernando Vazquez-Alonso Luis Javier Martinez-Gonzalez Maria Jesus Alvarez-Cubero GENYO Centre for Genomics and Oncological ResearchPfizerUniversity of GranadaAndalusian Regional GovernmentPTS GranadaGranadaGranadaSpain Department of Biochemistry Molecular Biology III and ImmunologyFaculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Bioinformatics Unit Institute of Parasitology and Biomedicine“López-Neyra”Spanish National Research CouncilGranadaGranadaSpain Nursery Service.University Hospital Clínico San Cecilio GranadaGranadaSpain Urology Department University Hospital Virgen de las NievesGranadaGranadaSpain Legal Medicine and Toxicology Department Faculty of MedicineUniversity of GranadaPTS GranadaGranadaGranadaSpain Ibs Biosanitary Research InstituteGranadaGranadaSpain

Dear Editor,Hereditary prostate cancer(PC)comprises 5%-10%of all PC cases.The increased risk of PC in menwith a family his-tory of the disease is well known and is commonly caused by germline mutations,leading to clinical guidelines men-tioning various genes for identifying high-risk individuals.However,the complex inheritance patterns involvingmul-tiple single nucleotide polymorphisms(SNPs)make it a genetically heterogeneous disease,with genetic testing still in its early stages.

关键词： cancer clinical cases

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Expanding the Boundaries of the Chemical Space of DNA Methyltransferase 1 Modulators

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Computational Molecular Bioscience 2024年第1期14卷 1-16页

作者： Massyel S. Martínez-Cortés Diana L. Prado-romero José L. Medina-Franco DIFACQUIM Research Group Department of Pharmacy School of Chemistry Universidad Nacional Autónoma de México Avenida Universidad 3000 Mexico City México

DNA methyltransferase 1 (DNMT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecule DNMT1 modulators are attractive for biochemical epigenetic studies and have the potential to become drugs. So far, more than five hundred small molecules have been reported as DNMT1 inhibitors. However, only a limited number of DNMT1 activators have been disclosed because, at least in part, DNMT1 activators are typically regarded as negative data in virtual screening campaigns or optimization projects. This manuscript aims to report the chemical structures and biological activity of small molecules that increase the enzymatic activity of DNMT1. Results of the biochemical experimental assays are discussed. It was found that small molecule activators have a large variety of chemical scaffolds but share pharmacophore features. Visual analysis of the chemical space and multiverse based on molecular fingertips supported that activators are structurally diverse. This is the first report of eight small molecules that increase the enzymatic activity of DNMT1 by more than 400% in an enzymatic-based assay. The outcome warrants further investigation of the epigenetic activity of the compounds in a counter-screen assay, e.g., cell-based and in vivo context.

关键词： Chemical Multiverse Chemoinformatics Epigenetics Pharmacophore Hypothesis Small Molecules

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