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Allicin neuroprotective effect during oxidative/inflammatory injury involves AT1-Hsp70-iNOS counterbalance axis

BIOCELL 2020年第4期44卷 671-681页

作者： LUCIANA MAZZEI MARÍA BELÉN RUIZ-ROSO natalia de las heras SANDRA BALLESTEROS CAROLINA TORRESPALAZZOLO LEÓN FERdeR ALEJANDRA BEATRIZ CAMARGO WALTER MANUCHA Instituto de Medicina y Biología Experimental de Cuyo(IMBECU) Consejo Nacional de Investigaciones Científicas y Tecnológicas(CONICET)Mendoza5500Argentina Área de Farmacología Departamento de PatologíaFacultad de Ciencias MédicasUniversidad Nacional de Cuyo Centro UniversitarioMendoza5500Argentina departamento de Fisiología Facultad de MedicinaUniversidad ComplutenseMadrid34523España IBAM Universidad Nacional de CuyoCONICETFacultad de Ciencias AgrariasMendozaM5528AHBArgentina department of Pediatrics Nephrology DivisionMiller School of MedicineUniversity of MiamiMiami33012USA

The ancestral cultures have described many therapeutic properties of garlic,therefore,it is of central interest to elucidate the molecular basis explaining this millenary empirical knowledge.Indeed,it has been demonstrated a neuroprotective effect of allicin–a phytochemical present in garlic-linked to oxidative-inflammatory modulation.Allicin improved neuronal injury by heat shock protein 70(Hsp70)and inducible nitric oxide synthase(iNOS)regulation.Also,allicin exerts renal protection involving a possible angiotensin type 1 receptor(AT1)interaction.In connection,AT1 overexpression has been recognized as a central deleterious factor in many brain diseases.However,there are no studies that evaluate AT1-Hsp70-iNOS interaction as a mechanism linked to neuroinflammation.Thus,our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-iNOS counterbalance axis.For this study,a murine microglial cell line(BV-2)was injured with lipopolysaccharides and treated or not with allicin.Then,it was evaluated cell viability,proinflammatory cytokine levels,cellular oxidative stress,iNOS,Hsp70,and AT1 protein expression(cellular and mitochondrial fractions),nitrite levels,and protein-protein interactions.The results demonstrated that allicin could prevent neuronal injury due to a reduction in oxidative stress and inflammatory status mediated by an AT1-Hsp70-iNOS counterbalance axis linked to direct protein-protein interaction.

关键词： Allicin neuroinflammation BV-2 cells AT1 receptors iNOS Hsp70

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Splanchnic-aortic inflammatory axis in experimental portal hypertension

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World Journal of Gastroenterology 2013年第44期19卷 7992-7999页

作者： Maria-Angeles Aller natalia de las heras Maria-Paz Nava Javier Regadera Jaime Arias Vicente Lahera Surgery department School of Medicine Complutense University of Madrid 28040 MadridSpain department of Physiology School of Medicine Complutense University of Madrid28040 Madrid Spain Animal Physiology II School of BiologyComplutense University of Madrid 28040 Madrid Spain department of Histology and Neuroscience School of Medicine Universidad Autonoma Madrid 28046Spain

Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension.This experimental model causes minimal alternations in the liver,thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension.Low-grade splanchnic inflammation after longterm triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy.In fact,we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans.Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension.Among the systemic impairments,aortopathy characterized by oxidative stress,increased levels of proinflammatory cytokines and profibrogenic mediators stand out.In this experimental model of long-term triple portal vein ligated-rats,the abdominal aortic proinflammatory response could be attributed to oxidative stress.Thus,the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate[NAD(P)H]oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation.Also,oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis.The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension.

关键词： Portal hypertension Inflammation Aortopathy Hepatic steatosis

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CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer

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World Journal of Gastroenterology 2018年第42期24卷 4738-4749页

作者： Sara Cabrero-de las heras Eva Martínez-Balibrea Program Against Cancer Therapeutic Resistance Catalan Institute of OncologyGermans Trias i Pujol health research institute Program of Predictive and Personalized Cancer Medicine Germans Trias i Pujol health research institute

Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates.In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines(CXCL1 to 17) are small(8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors(CXCR) 1 to 8.Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively.In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore,the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer.These pathways have been studied in tumor tissues(using immunohistochemistry or measuring mRNA levels)or serum [using enzyme-linked immuno sorbent assay(ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes themost recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.

关键词： Biomarkers Treatment Chemotherapy Oxaliplatin Irinotecan Immunotherapy Colorectal cancer CXC chemokines Immune system Bevacizumab

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Clinicopathological differences,risk factors and prognostic scores for western patients with intestinal and diffuse-type gastric cancer

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World Journal of Gastrointestinal Oncology 2022年第6期14卷 1162-1174页

作者： Cristina Díaz del Arco Lourdes Estrada Muñoz Luis Ortega Medina Elena Molina Roldán MÁngeles Cerón Nieto Soledad García Gómez de las heras M Jesús Fernández Aceñero department of Surgical Pathology Hospital Clínico San CarlosMadrid 28040Spain department of Legal Medicine Psychiatry and PathologyComplutense University of MadridMadrid 28040Spain department of Surgical Pathology Hospital Rey Juan CarlosMadrid 28933Spain department of Basic Medical Sciences Rey Juan Carlos UniversityMadrid 28933Spain

BACKGROUND In the molecular era,the Laurén system is still a cost-effective and widely implemented classification for gastric cancer(GC)and it has been recently associated with clinical,histological and molecular features of these tumors.despite recent advances in the understanding of the molecular biology of GC,there is a need to develop new prognostic tools for patient stratification in clinical practice.Thus,the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in GC.AIM To identify clinicopathological differences,risk factors,and to develop costeffective prognostic scores for patients with intestinal and diffuse-type GC.METHODS Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019.286 cases met inclusion criteria(intestinal:190,diffuse:96).Clinical data and gross findings were collected.All specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was followed.Five tissue microarrays(TMAs)were constructed and sections of the TMA block were immunostained for HERCEPTEST,MSH2,MSH6,MLH1 and PMS2.Statistical analyses were performed and prognostic scores were developed based on hazard ratios.RESULTS Intestinal and diffuse-type GC showed different epidemiological,clinicopathological and prognostic features.Diffuse tumors were significantly associated with younger age,less symptomatology,flat morphology,deeper invasion,perineural infiltration,advanced stage at diagnosis,administration of adjuvant therapy and poorer prognosis.Intestinal lesions were fungoid or polypoid,showed necrosis,desmoplasia,microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier stages.Tumor depth,desmoplasia,macroscopic type and lymph node involvement were independently related to the Laurén subtype.Furthermore,intestinal and diffuse GC were associated with different risk factors for progressi

关键词： Gastric cancer Clinicopathological Score Prognosis Laurén Molecular

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The extractable hydrokinetic power from an oscillating membrane-based harvester

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Theoretical & Applied Mechanics Letters 2019年第2期9卷 66-70页

作者： Francisco J.Arias Salvador de las heras department of Fluid Mechanics University of Catalonia

The extractable hydrokinetic power from an oscillating membrane in standing motion and induced by a water flow and its possible significance with regard energy harvesting is discussed.The main attractiveness of such an energy harvester lies in the possibility of an inexpensive technology able to be used in those water flows which either because limitation of space(narrow channels) or a limited differential pressure drop with the surrounding but yet with a non negligible velocity are not well suited to be turbined. Utilizing a simplified geometrical model, an estimate of the extractable output density power per area of membrane was derived. Preliminary experiments were performed using a rectangular thin rubber membrane and for a typical domestic water intake as source. The experimental data quantitatively agree very well with the theoretical prediction where it was found that for water flows around 2 m/s the output power density from the membrane may be around 30 mW/cm^2 of membrane. Additional research and development is required in order to arrive at a reliable practical and commercial design.

关键词： Energy harvesting Residual waters Waste waters

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Necrotic enteritis challenge regulates peroxisome proliferator-1 activated receptors signaling and β-oxidation pathways in broiler chickens

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Animal Nutrition 2021年第1期7卷 239-251页

作者： Kosar Gharib-Naseri Sara de las heras-Saldana Sarbast Kheravii Lihong Qin Jingxue Wang Shu-Biao Wu School of Environment and Rural Science University of New EnglandArmidaleNSW2351Australia Animal Science and Husbandary Branch Jilin Academy of Agricultural SciencesGongzhulingJilin136100China College of Life Sciences Shanxi UniversityTaiyuanShanxi030006China

Necrotic enteritis(NE)is an important enteric disease in poultry and has become a major concern in poultry production in the post-antibiotic era.The infection with NE can damage the intestinal mucosa of the birds leading to impaired health and,thus,productivity.To gain a better understanding of how NE impacts the gut function of infected broilers,global mRNA sequencing(RNA-seq)was performed in the jejunum tissue of NE challenged and non-challenged broilers to identify the pathways and genes affected by this disease.Briefly,to induce NE,birds in the challenge group were inoculated with 1 mL of Eimeria species on day 9 followed by 1 mL of approximately 108 CFU/mL of a NetB producing Clostridium per-fringens on days 14 and 15.On day 16,2 birds in each treatment were randomly selected and euthanized and the whole intestinal tract was evaluated for lesion scores.Duodenum tissue samples from one of the euthanized birds of each replicate(n=4)was used for histology,and the jejunum tissue for RNA extraction.RNA-seq analysis was performed with an Illumina RNA HiSeq 2000 sequencer.The differ-entially expressed genes(deG)were identified and functional analysis was performed in DAVID to find protein-protein interactions(PPI).At a false discovery rate thresholddeG(207 upregulated and 170 downregulated)deG were identified.Pathway enrichment analysis revealed that deG were considerably enriched in peroxisome proliferator-activated receptors(PPAR)signaling(PdeG were mostly related to fatty acid metabolism and degradation(cluster of differentiation 36[CD36],acyl-CoA synthetase bubblegum family member-1[ACSBG1],fatty acid-binding protein-1 and-2[FABP1]and[FABP2];and acyl-coenzyme A synthetase-1[ACSL1]),bile acid production and transportation(acyl-CoA oxidase-2[ACOX2],apical sodium-bile acid transporter[ASBT])and essential genes in the immune system(interferon-,[IFN-γ],LCK proto-oncogene,Src family tyrosine kinase[LCK],zeta chain of T cell receptor associated protein kin

关键词： Necrotic enteritis Clostridium perfringens Transcriptome Fatty acid metabolism Broiler Challenge

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Geochemistry of a Tidal Transgressive Heterolithic Succession: The Ituzaingó Formation (Middle Miocene), Argentina

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Chinese Journal Of Geochemistry 2000年第1期19卷 52-57页

作者： ROBERTO TORRA (Centro de Geociencias Aplicadas, Universidad Nacional del Nordeste. Avda. las heras 727, 3500, RESISTENCIA, Chaco, Argentina) Centro de Geociencias Aplicadas Universidad National del Nordeste. Avda Resistencia Argentina

Geochemical analysis by means of XRF and ICP\|AES was carried out on 35 selected samples. Major and trace elements were determined. They were: CaCO\-3, P\-2O\-5, Fe\-2O\-3, TiO\-2, SiO\-2, Al\-2O\-3, CaO, K\-2O, MnO, Rb, Cs, Ga, Zr, Ta, Nb, Sr, Ba, Cr, Ni, Zn, Pb, Cu, V and B. The country rocks studied were of sandy\|muddy lithofacies, belonging to a typical tide marine transgressive heterolithic succession of Middle Miocene age. They are called the Ituzaingó Formation. The formation outcrops in northeastern Argentina on the left of the Paraná River Valley. The depositional setting largely depends on the outstanding internal structures and textures (i.e., herringbone cross stratification, tidal bundles, reactivation surfaces). In the study area, loessial friable sediment was used as geochemical background because it overlies shallow marine sediments. The results show significant differences. Boron is absent in loessial sediments. On the other hand, several trace elements such as vanadium and chromium are concentrated in the shallow marine sediments. These results may be useful to discern uncertain beds in the area studied.

关键词：地球化学潮汐 X射线荧光分析中新世阿根廷示踪元素

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Comparison between type-2 and type-1 myocardial infarction：clinical features, treatment strategies and outcomes

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Journal of Geriatric Cardiology 2016年第1期13卷 15-22页

作者： Angel Lopez-Cuenca Miriam Gomez-Molina Pedro J Flores-Blanco Marianela Sanchez-Martinez Andrea Garcia-Narbon Ignacio de las heras-Gomez Maria J Sainchez-Galian Esther Guerrero-Perez Mariano Valdes Sergio Manzano-Femandez department of Internal Medicine Hospital de la Vega Lorenzo Guirao Cieza Spain Division of Cardiology University Hospital Virgen de la Arrixaca School of Medicine IMIB Murcia Spain department of Biochemistry University Hospital Virgen de la Arrixaca School of Medicine IMIB Murcia Spain department of lnternal Medicine University of Murcia Murcia Spain

ObjectiveTo 与尖锐心肌的梗塞(AMI ).MethodsWe 包括了的 type-2 对 type-1 在病人在发生，临床的特征，当前的治疗策略和结果估计差别有 type-1 或 type-2 AMI 的诊断的 824 个连续病人。在索引住院期间，临床的特征和治疗策略详细被... 详细信息

ObjectiveTo 与尖锐心肌的梗塞(AMI ).MethodsWe 包括了的 type-2 对 type-1 在病人在发生，临床的特征，当前的治疗策略和结果估计差别有 type-1 或 type-2 AMI 的诊断的 824 个连续病人。在索引住院期间，临床的特征和治疗策略详细被收集。在 1 年的后续，死亡，击，流血的非致命的心肌的梗塞和专业是 recorded.ResultsType-1 AMI 在 707 是在场的(86%) 盒子当(14%) 117 作为 type-2 被分类时。有 type-2 AMI 的病人更经常是象糖尿病那样的女、有的更高的合作病态，以前的非圣片断举起急性冠的症候群，损害肾的功能，贫血症， atrial 纤维性颤动和恶意。然而，保存了左室的喷射部分，正常冠的动脉是经常看见的更多，侵略治疗是不太普通的，并且反血小板药， statins 和 beta-blockers 是在有 type-2 AMI 的病人规定的更少。在 1 年的后续， type-2 AMI 与更高粗略的死亡风险被联系(HR：1.75， 95% CI：1.14-2.68；P = 0.001 ) ，但是这个协会没在 multivariable 调整以后仍然保持重要(P = 0.785 ) 。而且，我们没发现 type-2 AMI 与另外的临床的 outcomes.ConclusionsIn 被联系这张真实人口与 type-1 相比， type-2 AMI 是主要女人们并且有更多的合作病态。侵略治疗策略和 cardioprotective 药是在 type-2 使用的更少，当 1 年的临床的结果是类似的时。

关键词：冠的容器后续学习心肌的梗塞

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EFFECT OF FOSSIL DIATOMS ON THE GROWTH OF TWO SYNGENEIC MURINE LEUKEMIAS

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Chinese Journal of Oceanology and Limnology 1984年第2期2卷 161-167页

作者： Oscar D. Bustuoabad and Alejandro M. S. Mayer(PLEX-CONICET, Institute de Investigaciones Hematoldgicas, Academia Nacional de Medicina, las heras 3092, 1425 Buenos Aires, Argentina) Plex-Conicet Instituto de Investigaciones Hematológicas Academia Nacional de Medicina Buenos Aires Argentina

The effect of micronized frustules. of fossil diatoms (DS) on tumor growth and survival of mice receiving an ip inoculations of either a spontaneous lymphoblastic leukemia (LB) or P-388 lymphocyt-ic leukemia (P-388) was investigated. A multi-dose study was designed, mice receiving 1000,100,10 arid 1 μg of a suspension of DS, either ip or sc on day 1, 4 and 9 after tumor inoculation. With LB the best results were observed when DS were inoculated by the ip route, no effect being observed with the sc route. The best therapeutic effect resulted with 1 μg DS: 33 % of the mice were alive 24 days after tumor inoculation, when all the controls had died. With P-388, only a temporary effect with the 10 μg DS dose was. observed. In no case was it possible to prolong survival. It is concluded that at low doses of DS therapeutic effect is greatest, while toxicity due to SiO2 is greatly reduced.

关键词： EFFECT OF FOSSIL DIATOMS ON THE GROWTH OF TWO SYNGENEIC MURINE LEUKEMIAS DS

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Petrography and tectonic provenance of the Permian Tunas Formation:Implications on the paleotectonic setting during the ClaromecóForeland Basin evolution,southwestern Gondwana margin,Argentina

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Journal of Palaeogeography 2022年第3期11卷 427-447页

作者： María Belén Febbo Renata N.Tomezzoli Nora N.Cesaretti Giselle Choque natalia B.Fortunatti Guadalupe Arzadún Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET) Argentina Dpto.de Geología Universidad Nacional del SurAvenida Alem 1253B8000ICPBahía BlancaArgentina Centro de Geología Aplicada y Medio Ambiente(CGAMA CIC–UNS)Dpto.de GeologíaUniversidad Nacional del SurBahía BlancaArgentina Laboratorio de Paleomagnetismo“Daniel A.Valencio” Instituto de Geociencias BásicasAplicadas y Ambientales de Buenos Aires(IGEBA)Departamento de Ciencias GeológicasFacultad de Ciencias Exactas y Naturales(FCEyN)Universidad de Buenos Aires(UBA)Pabellón II(1428)CABAArgentina Laboratorio de Termocronología(La.Te Andes–CONICET) Las Moreras 310A4401XBAVaquerosSaltaArgentina

The Claromec o Basin is located at the south-western sector of the Buenos Aires province,Argentina.This basin is considered a foreland basin closely related to the evolution of the southwestern Gondwana margin.This contribution focuses on the provenance analysis of the Tunas Formation(Permian,Pillahuinc o Group),which represents the last filling stage for the Claromec o Foreland Basin.Petrographic and tectonic provenance analyses were performed in sandstones recovered from subsurface(PANG 0001 and PANG0003 exploration wells)and outcrops located close to the basin center(Gonzales Chaves locality).In the subsurface,the analyzed succession is composed of medium-to fine-grained sandstones interbedded with tuffs,mudrocks,carbonaceous mudrocks and coal beds.In outcrops,the succession is dominated by mediumto fine-grained sandstones interbedded with siltstones.Modal composition patterns are distributed into the recycled orogen and transitionally recycled to mixed fields.Petrographic analyses,in addition to provenance and sedimentological studies,confirm that sedimentary material was derived from a mixed source,which largely comes from the Sierras Australes fold and thrust belt,located towards the W-SW,where the sedimentary succession is interbedded with volcanic material.The Tunas Formation shows clear differences in its modal composition,paleocurrent direction and paleoenvironmental conditions with respect to the underlying units of the Pillahuinc o Group(Sauce Grande,Piedra Azul and Bonete formations).Source areas changed from cratonic to mixed fold belt/arc-derived material,suggesting variations in the Claromec o Basin configuration during the Late Paleozoic.Changes in the paleotectonic scenario during the deposition of the Tunas Formation have been interpreted as a consequence of a compressive post-collisional deformation event,the product of adjustment,accommodation and translation of terrains towards the equator during the Permian-Triassic to form Pangea.

关键词： Provenance area Petrography Tunas Formation ClaromecóForeland Basin Southwestern Gondwana margin Permian Upper Paleozoic

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