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The challenge of drug resistance in pancreatic ductal adenocarcinoma:a current overview

Cancer Biology & Medicine 2019年第4期16卷 688-699页

作者： Francisco Quinonero cristina Mesas Kevin Doello Laura Cabeza Gloria Perazzoli cristina jimenez-luna Ana Rosa Rama Consolación Melguizo Jose Prados Institute of Biopathology and Regenerative Medicine(IBIMER) Center of Biomedical Research(CIBM)University of Gran adaz Gran ada 18100Spain Department of An atomy and Embryology Faculty of Medici neUn iversity of Gran adaGranada 18071Spain Instituto Biosanitario de Granada(ibs.GRANADA) Granada 18014Spain Medical Oncology Service Virgen de las Nieves HospitalGranada 1812Spain Department of Oncology Ludwig Institute for Cancer ResearchUniversity of LausanneEpalinges 1066Switzerland Department of Health Scienee University of JaenJa6n 23071Spain

Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer *** delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and ***,these strategies are insufficient to improve its poor *** the advances made in chemotherapy(***-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug ***,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and ***,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(***-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and ***,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage *** the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.

关键词： Pancreatic ductal adenocarcinoma chemotherapy drug resistance cancer stem cells therapeutic strategies

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Liquid biopsy approach to pancreatic cancer

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1263-1287页

作者： Sonia Perales Carolina Torres cristina jimenez-luna Jose Prados Joaquina Martinez-Galan Jose Manuel Sanchez-Manas Octavio Caba Department of Biochemistry and Molecular Biology I Faculty of SciencesUniversity of GranadaGranada 18071Spain Department of Biochemistry and Molecular Biology III and Immunology Faculty of SciencesUniversity of GranadaGranada 18071Spain Institute of Biopathology and Regenerative Medicine(IBIMER) Center of Biomedical Research(CIBM)University of GranadaGranada 18100Spain Department of Medical Oncology Hospital Universitario Virgen de las NievesGranada 18011Spain School for International Postgraduate Studies University of GranadaGranada 18071Spain

Pancreatic cancer(PC)continues to pose a major clinical *** has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by *** dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available *** patients are diagnosed when the disease has already metastasized and cannot be *** interception is vital,actively intervening in the malignization process before the development of a full-blown advanced *** early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early *** is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored *** aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.

关键词： Pancreatic cancer Biomarkers Liquid biopsy Clinical management Cancer interception Cancer monitoring

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Patient and physician factors contributing to delays in inflammatory bowel diseases:Enhancing timely diagnosis

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World Journal of Gastroenterology 2025年第6期31卷 115-120页

作者： Horia Minea Ana-Maria Singeap Laura Huiban cristina Maria Muzica Carol Stanciu Anca Trifan Department of Gastroenterology Faculty of Medicine“Grigore T.Popa”University of Medicine and PharmacyIasi 700115Romania Institute of Gastroenterology and Hepatology “St.Spiridon”University HospitalIasi 700111Romania

In this article,we comment on the article by Blüthner et *** article provides a comprehensive analysis of the factors contributing to the late detection of Crohn’s disease and ulcerative colitis within a German *** highlights the conse-quences on patient outcomes,particularly disease progression and the increased risk of developing *** study identifies specific predictors asso-ciated with both patient-related and physician-related delays,offering a detailed exploration of the initial ***,the article delves into the distinct patterns observed in the German population,stressing the unique aspects of diagnostic delays that may differ from those reported in other *** detailed examination offers valuable insights into the specific challenges faced within the German healthcare system and underscores the necessity of targeted interventions to facilitate early *** importance of improved screening tools,patient education,and better healthcare infrastructure is emphasized as crucial steps toward improving patient care in inflammatory bowel disease.

关键词： Inflammatory bowel disease Diagnostic delay Disease awareness Healthcare system Screening tools

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Assessing bioaccessibility and bioavailability in vitro of phenolic compounds from freeze-dried apple pomace by LC-Q-TOF-MS

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Food Bioscience 2022年第4期48卷 733-740页

作者： luna Pollini Ana Juan-García Francesca Blasi Jordi Manes Lina Cossignani cristina Juan Department of Pharmaceutical Sciences Food Science and Nutrition SectionUniversity of PerugiaItaly Laboratory of Food Chemistry and Toxicology Faculty of PharmacyUniversity of ValenciaSpain

Apple pomace is one of the most abundant by-product in fruit processing *** this work,fresh and freeze-dried apple pomace variety‘Red Delicious’apples“*** de Girona”was used to evaluate the potential amount of phenolic compounds available from the food matrix by in vitro bioaccessibility *** the simulated digestion of freeze-dried apple pomace,an in vitro bioavailability test by using differentiated Caco-2 cells simulating the intestinal barried were assayed for 1 h,2 h,3 h and,4 ***-Q-TOF-MS has permitted to perform a monitoring of phloridzin,chlorogenic and gallic acids in apple pomace in apical and basal *** obtained with LC-Q-TOF-MS demonstrated that chlorogenic acid had greater percentage of bioaccesibility(44%),than phloridzin(17%)and gallic acid(7%),with similar values for fresh and freeze-dried ***,only chlorogenic acid reported higher bioavailability in basal compartments after 3 h and 4 h,in particular about 56%of chlorogenic acid passed the transepithelial *** is the first work about the evaluation of bioavailability of polyphenols from digested freeze-dried apple pomace ***,this interesting by-product rich in polyphenol,with a great bioavailability,should be a promising ingredient to develop new functional foods.

关键词： Apple pomace Bioaccessibility Bioavailability Chlorogenic acid Phloridzin Caco-2 cells

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Prehospital critical care drug-therapy and 30-day mortality in patients with acute respiratory disease

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World Journal of Emergency Medicine 2025年第1期16卷 43-50页

作者： Jesús Jurado-Palomo JoséLuis Martín-Conty Begoña Polonio-López cristina Rivera Picón Raúl López-Izquierdo Carlos del Pozo Vegas Pedro Ángel de Santos Castro Ancor Sanz-García Francisco Martín-Rodríguez Technological Innovation Applied to Health Research Group(ITAS) Faculty of Health SciencesCastilla-La Mancha UniversityTalavera de la Reina 45600Spain Nuestra Señora del Prado General Hospital Talavera de la Reina 45600Spain Emergency Department Rio Hortega University HospitalValladolid 47012Spain CIBER of Respiratory Diseases(CIBERES) Institute of Health Carlos ⅢMadrid 28029Spain Faculty of Medicine University of ValladolidValladolid 470003Spain Emergency Department University Clinical HospitalValladolid 47003Spain Prehospital Emergency Medical Services(SACYL) Valladolid 47007Spain

BACKGROUND: Prehospital medication is a reality, and the role of these therapies must be explored to assess their validity, especially for acute respiratory diseases, which are usually associated with increased morbidity. The aim of this study was to examine the association of prehospital medication use with mortality in patients with acute respiratory ***: A prospective, multicenter, emergency medical service(EMS) delivery cohort study was carried out in adults with unselected respiratory diseases managed by EMS who were transferred to the emergency department. From January 1, 2019, to October 31, 2023, six advanced life support units, thirty-eight basic life support units, and four hospitals in Spain participated in the study. Demographic data, vital signs, use of mechanical ventilation, prehospital respiratory diagnosis, and prehospital medication were collected. The primary outcome was 30-day in-hospital ***: A total of 961 patients were included, with a mortality rate of 17.5%(168 patients). Age, an increasing number of comorbidities, the use of invasive mechanical ventilation(IMV), the use of major analgesics, hypnotics, and bicarbonate were risk factors. In contrast, elevated systolic blood pressure and Glasgow Coma Scale scores were found to be protective factors against mortality. The predictive capacity of the model reached an area under the curve(AUC) of 0.857(95% confidence interval [95% CI] 0.827–0.888).CONCLUSION: Our data revealed that IMV, major analgesics, hypnotics and bicarbonate administration were associated with elevated mortality. Adding prehospital drug therapy information to demographic variables and vital signs could improve EMS decision-making, allowing a better characterization of patients at risk of clinical worsening.

关键词： Drug-therapy Medication Prehospital Mortality Emergency medical services

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Occasional Tillage in a Field Established under Conservation Agriculture for Tomato Cropping

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Agricultural Sciences 2025年第1期16卷 31-47页

作者： Roberto Botelho Ferraz Branco Bruno Cesar Ananias Andréia cristina Silva Hirata Humberto Sampaio de Araújo Jane Maria de Carvalho Silveira Agronomic Institute So Paulo Agency of Agribusiness Technology (IAC/APTA) Centre of Horticulture Ribeiro Preto Brazil Syngenta Crop Protection So Paulo Brazil So Paulo Agency of Agribusiness Technology (APTA) Presidente Prudente Brazil So Paulo Agency of Agribusiness Technology (APTA) Andradina Brazil Agronomic Institute So Paulo Agency of Agribusiness Technology (IAC/APTA) Centre of Agricultural Biosystems and Post Harvest Campinas Brazil

The Conservation Agriculture (CA) is a current concept drives to save natural resources for agricultural production based on the minimum soil disturbance or no-tillage, crop rotation and permanent maintenance of straw on soil surface. The increasing in soil density is a problem to achieve great copping yield under CA, so occasional one-time tillage is considered as an alternative to continuous no-tillage. In this way, this experiment was carried out to compare occasional tillage and no-tillage interacting with cover crops in a field established under conservation agriculture. Thus, the experimental treatments were set up by two tillage methods, conventional tillage and no-tillage and two cover crops, white lupin and millet setting in a randomized blocks with split plot design with four replications. The traits evaluated in the research were soil fertility, soil resistance to penetration, soil moisture and tomato agronomic performance. No-tillage was more efficient to preserve soil moisture;however soil fertility, soil resistance to penetration and tomato yield were favored by conventional tillage. Regarding to cover crops white lupin increased the soil K concentration and enhanced the tomato growth. Although occasional tillage had better performance to the soil fertility and tomato yield, we highlighted that CA is the better way to increase soil health and soil and water conservation along the time leading to so desired regenerative agriculture.

关键词： No Tillage Crop Rotation Cover Crops Solanum lycopersicum L.

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Atypical Presentation of Crohn’s Disease: Diagnostic Challenges in a Clinical Case

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Case Reports in Clinical Medicine 2025年第1期14卷 10-14页

作者： Catarina Pinto Silva Rita Sevivas Flávia Ramos Dany Cruz cristina Marques Beatriz Rosa Márcia Ribeiro Carlos S. Oliveira Santa Maria Maior Hospital Barcelos Portugal

Introduction: Crohn’s Disease (CD) is a chronic inflammatory disorder with a heterogeneous presentation. While diarrhea, abdominal pain, and weight loss are hallmarks, atypical manifestations can obscure the diagnosis. This report highlights an unusual presentation of CD to emphasize the need for comprehensive diagnostic strategies. Case Report: A 25-year-old male presented with peripheral edema, anorexia, and abdominal distension but lacked classic gastrointestinal (GI) symptoms. Laboratory findings included microcytic anemia and hypoalbuminemia, while imaging revealed ascites and bowel wall thickening. Elevated fecal calprotectin and positive Anti-Saccharomyces cerevisiae antibodies (ASCA) supported the diagnosis. Endoscopy confirmed ileocolic Crohn’s Disease (L3 + L4). Infliximab therapy resulted in marked clinical improvement. Discussion: This case underscores the complexity of atypical CD presentations. Early use of serological markers, imaging, and endoscopy guided the diagnosis. Recognition of CD’s diverse manifestations is critical for timely intervention. Conclusion: Atypical CD presentations require heightened clinical suspicion and a multidisciplinary approach to reduce diagnostic delays and improve patient outcomes.

关键词： Crohn’s Disease Atypical Presentation Diagnostic Challenges Inflammatory Markers Infliximab Imaging

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Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis

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Translational Neurodegeneration 2023年第1期12卷 722-744页

作者： cristina de Dios Xenia Abadin Vicente Roca-Agujetas Marina jimenez-Martinez Albert Morales Ramon Trullas Montserrat Mari Anna Colell Department of Cell Death and Proliferation Institut d’Investigacions Biomèdiques de BarcelonaConsejo Superior de Investigaciones Científicas(CSIC)Institut d’Investigacions Biomèdiques August Pi I Sunyer(IDIBAPS)BarcelonaSpain Centro de Investigación Biomédica en Red Sobre Enferme-dades Neurodegenerativas(CIBERNED) MadridSpain Department of Biomedicine Faculty of MedicineUniversitat de BarcelonaBarcelonaSpain Present Address:Department of Biochemistry and Molecular Biology Faculty of PharmacyUniversidad de Sevilla.Instituto de Biomedicina de Sevilla(IBiS)-Hospital Universitario Virgen del Rocío/CSICSevilleSpain Present Address:Department of Clinical Immunology and Rheumatology Amsterdam UMCAmsterdamNetherlands

Background Persistent inflammatory response in the brain can lead to tissue damage and *** Alzheimer’s disease(AD),there is an aberrant activation of inflammasomes,molecular platforms that drive inflammation through caspase-1-mediated proteolytic cleavage of proinflammatory cytokines and gasdermin D(GSDMD),the executor of ***,the mechanisms underlying the sustained activation of inflammasomes in AD are largely *** have previously shown that high brain cholesterol levels promote amyloid-β(Aβ)accumulation and oxidative ***,we investigate whether these cholesterol-mediated changes may regulate the inflam-masome *** SIM-A9 microglia and SH-SY5Y neuroblastoma cells were cholesterol-enriched using a water-soluble cholesterol *** exposure to lipopolysaccharide(LPS)plus muramyl dipeptide or Aβ,activation of the inflammasome pathway was analyzed by immunofluorescence,ELISA and immunoblotting ***-labeled Aβwas employed to monitor changes in microglia *** medium was used to study how microglia-neuron interrelationship modulates the inflammasome-mediated *** In activated microglia,cholesterol enrichment promoted the release of encapsulated IL-1βaccompanied by a switch to a more neuroprotective phenotype,with increased phagocytic capacity and release of neurotrophic *** contrast,in SH-SY5Y cells,high cholesterol levels stimulated inflammasome assembly triggered by both bacterial toxins and Aβpeptides,resulting in GSDMD-mediated ***(GSH)ethyl ester treatment,which recovered the cholesterol-mediated depletion of mitochondrial GSH levels,significantly reduced the Aβ-induced oxidative stress in the neuronal cells,resulting in lower inflammasome activation and cell ***,using conditioned media,we showed that neuronal pyroptosis affects the function of the cholesterol-enriched microglia,lowering its phagocytic activity and,the

关键词： Neuroinflammation Mitochondrial oxidative stress Phagocytosis Alzheimer’s disease DAM signature NLRP3

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Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2023年第2期15卷 268-275页

作者： Octavio Caba Carmelo Diéguez-Castillo Joaquina Martínez-Galán Irene González-Cebrián cristina Jiménez-luna Institute of Biopathology and Regenerative Medicine(IBIMER) University of GranadaGranada 18016Spain Biosanitary Institute of Granada(ibs.GRANADA) 18014 GranadaSpain Department of Gastroenterology San Cecilio University HospitalGranada 18016Spain Department of Medical Oncology Virgen de las Nieves University HospitalGranada 18014Spain.Biosanitary Institute of Granada(ibs.GRANADA)18014 GranadaSpain Department of Digestive Cancer San Cecilio University HospitalGranada 18016Spain

Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these *** this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are ***,this approach has some ***,IgG4 antibody concentrations are also elevated in sera from some patients with *** review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and *** proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in *** addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.

关键词： Autoimmune pancreatitis Pancreatic ductal adenocarcinoma Serum Biomarkers Differentiation

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Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

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Cellular & Molecular Immunology 2021年第4期18卷 905-918页

作者： cristina Tecchio Marco Antonio Cassatella Department of Medicine Section of Hem atology and Bone Marrow Transplant UnitUniversity of VeronaVeronaItaly Department of Medicine Section of General PathologyUniversity of VeronaVeronaItaly

Allogeneic hematopoietic stem cell transplantation(alloHSCT)is a life-saving procedure used for the treatment of selected hematological malignancies,inborn errors of metabolism,and bone marrow *** role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against ***,recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered ***,neutrophils are emerging as highly versatile cells that are able to acquire different,often opposite,functional capacities depending on the microenvironment and their differentiation ***,we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT,from the hematopoietic stem cell(HSC)mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC *** also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versushost disease(GVHD)***,the potential involvement of neutrophils in alloHSCT-related complications,such as transplant-associated thrombotic microangiopathy(TA-TMA),acute and chronic GVHD,and cytomegalovirus(CMV)reactivation,is also *** on the data reviewed herein,the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial ***,much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.

关键词： neutrophils allogeneic hematopoietic stem cell transplantation(alloHSCT) alloHSCT-associated complications lowdensity neutrophils(LDNs) normal-density neutrophils(NDNs)

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