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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 *** 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 *** 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, *** 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 *** 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

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 *** infection with NE can damage the intestinal mucosa of the birds leading to impaired health and,thus,*** 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 ***,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 *** day 16,2 birds in each treatment were randomly selected and euthanized and the whole intestinal tract was evaluated for lesion *** tissue samples from one of the euthanized birds of each replicate(n=4)was used for histology,and the jejunum tissue for RNA ***-seq analysis was performed with an Illumina RNA HiSeq 2000 *** 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 *** 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

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

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 *** experimental model causes minimal alternations in the liver,thus making a more selective study possible for the pathological changes characteristic of prehepatic portal ***-grade splanchnic inflammation after longterm triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal *** 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 *** 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 *** the systemic impairments,aortopathy characterized by oxidative stress,increased levels of proinflammatory cytokines and profibrogenic mediators stand *** this experimental model of long-term triple portal vein ligated-rats,the abdominal aortic proinflammatory response could be attributed to oxidative ***,the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate[NAD(P)H]oxidase activity could be associated with reactive oxygen species production and promote aortic ***,oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and *** 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

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

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

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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 ***,it has been demonstrated a neuroprotective effect of allicin–a phytochemical present in garlic-linked to oxidative-inflammatory *** improved neuronal injury by heat shock protein 70(Hsp70)and inducible nitric oxide synthase(iNOS)***,allicin exerts renal protection involving a possible angiotensin type 1 receptor(AT1)*** connection,AT1 overexpression has been recognized as a central deleterious factor in many brain ***,there are no studies that evaluate AT1-Hsp70-iNOS interaction as a mechanism linked to ***,our central aim is to evaluate if the allicin protective effect is associated with an AT1-Hsp70-iNOS counterbalance *** this study,a murine microglial cell line(BV-2)was injured with lipopolysaccharides and treated or not with ***,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 *** 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

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

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 *** 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 ***,the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in *** To identify clinicopathological differences,risk factors,and to develop costeffective prognostic scores for patients with intestinal and diffuse-type *** 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 *** specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was *** tissue microarrays(TMAs)were constructed and sections of the TMA block were immunostained for HERCEPTEST,MSH2,MSH6,MLH1 and *** analyses were performed and prognostic scores were developed based on hazard *** Intestinal and diffuse-type GC showed different epidemiological,clinicopathological and prognostic *** 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 *** lesions were fungoid or polypoid,showed necrosis,desmoplasia,microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier *** depth,desmoplasia,macroscopic type and lymph node involvement were independently related to the Laurén ***,intestinal and diffuse GC were asso

关键词： Gastric cancer Clinicopathological Score Prognosis Laurén Molecular

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

Objective To assess the differences in incidence, clinical features, current treatment strategies and outcome in patients with type-2vs. type-1 acute myocardial infarction （AMI）.Methods We included 824 consecutive patients with a diagnosis of type-1 or type-2 AMI. Dur-ing index hospitalization, clinical features and treatment strategies were collected in detail. At 1-year follow-up, mortality, stroke, non-fatal myocardial infarction and major bleeding were ***-1 AMI was present in 707 （86%） of the cases while 117 （14%） were classified as type-2. Patients with type-2 AMI were more frequently female and had higher co-morbidities such as diabetes, previous non-ST segment elevation acute coronary syndromes, impaired renal function, anaemia, atrial fibrillation and malignancy. However, preserved left ventricular ejection fraction and normal coronary arteries were more frequently seen, an invasive treatment was less common, and anti-platelet medications, statins and beta-blockers were less prescribed in patients with type-2 AMI. At 1-year follow-up, type-2 AMI was associated with a higher crude mortality risk （HR： 1.75, 95% CI： 1.14-2.68;P = 0.001）, but this association did not remain significant after multivariable adjustment （P = 0.785）. Furthermore, we did not find type-2 AMI to be associated with other clinical *** In this real-life population, compared with type-1, type-2 AMI were predominantly women and had more co-morbidities. Invasive treatment strategies and cardioprotective medications were less used in type-2, while the 1-year clinical outcomes were similar.

关键词： Coronary vessels Follow-up studies Myocardial infarction

复发缓解型多发性硬化与人类疱疹病毒6型活动性感染

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世界核心医学期刊文摘（神经病学分册） 2005年第3期1卷 10-11页

作者： lvarez Lafuente R. de las heras V. BartoloméM. 黄卫东 Lab.de Invest.Ta Norte Hospital Clnico San Carlos C/ Profesor Martn Lagos s/n 28040 Madrid Spain Dr.

Background: Recent studies have focused on the relationship between human herp esvirus 6 (HHV 6) and multiple sclerosis (MS). Objective: To analyze HHV 6 mes senger RNA expression in patients with relapsing remitting (RR) MS vs healthy b lood donors (HBDs). design: One hunred fiftyfour subjects were enrolled in the study: 105 patients with [Dr. R. Alvar ez Lafuente, Lab. de Invest. 7a Norte, Hospi RRMS (32 in relapse) and 49 HBDs. Total DNA and messenger RNA were extracted from serum and blood samples, respec tively, and analyzed by quantitative real time reverse transcription polymeras e chain reaction for the detection of 3 HHV 6 immediate early genes (U16/U17, U89/U90, and U94) and both HHV 6 variants (HHV 6A and HHV 6B). Results: Activ e HHV 6 infection was detected in 16%of patients with RRMS vs 0%of HBDs (P=.0 03). Seven patients with RRMS with exacerbation had HHV 6 active replication, a nd the virus remained latent in only 1 of them. We did not find any statisticall y significant difference between HHV 6 active or latent infection for patients in remission (P = .12). Among patients with RRMS with HHV 6 active replication, viral load was higher when they experienced an acute attack than when in remiss ion (P = .04). In those patients with RRMS who had an active infection only, HHV 6A was found. Cell free HHV 6 DNA detected in serum samples confirmed the re sults. Conclusions: The results show that a subset of patients with RRMS experie nce HHV 6 active infection, and there likely is an association between the vira l active replication and relapses; therefore, HHV 6 active infection may imply a greater risk of exacerbations in a subgroup of patients with RRMS.

关键词：人类疱疹病毒活动性感染多发性硬化健康献血者即刻早期基因全血标本潜伏性感染缓解期患者病毒量受试对象