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Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells:Potential implications for their clinical use

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World Journal of Stem Cells 2023年第5期15卷 400-420页

作者： Vitale Miceli Giovanni Zito Matteo Bulati Alessia Gallo Rosalia Busà Gioacchin Iannolo Pier Giulio Conaldi Department of Research IRCCS ISMETT(Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione)Palermo 90127Italy

Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative ***,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human *** fact,in many clinical trials it has been shown that MSCs have moderate or poor *** inefficacy appears to be ascribable primarily to the heterogeneity of ***,specific priming strategies have been used to improve the therapeutic properties of *** this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of *** found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological ***,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related *** shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory *** opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

关键词： Mesenchymal stromal/stem cells Mesenchymal stromal/stem cell therapeutic properties Mesenchymal stromal/stem cell paracrine effects Mesenchymal stromal/stem cell priming Pro-inflammatory priming Hypoxic priming,3D culture priming

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Dynamic contrast enhanced ultrasound in gastrointestinal diseases:A current trend or an indispensable tool?

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World Journal of Gastroenterology 2023年第25期29卷 4021-4035页

作者： Mattia Paratore Matteo Garcovich Maria Elena Ainora Laura Riccardi Antonio Gasbarrini Maria Assunta Zocco Medicina Interna e Gastroenterologia CEMAD Digestive Disease CenterFondazione Policlinico Universitario A.Gemelli IRCCSRome 00168Italy Medicina Interna e Gastroenterologia CEMAD Digestive Disease CenterUniversità Cattolica del Sacro CuoreFondazione Policlinico Universitario A.Gemelli IRCCSRome 00168Italy

Contrast enhanced ultrasound(CEUS)has been widely implemented in clinical practice because of the enormous quantity of information it provides,along with its low cost,reproducibility,minimal invasiveness,and safety of the secondgeneration ultrasound contrast *** overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour,quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent *** quantification of perfusion parameters[named as dynamic-CEUS(D-CEUS)]has several applications in gastrointestinal neoplastic and inflammatory ***,the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS,which potentially represents a valuable tool for clinical practice in management of gastrointestinal *** this article,we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases,with a special focus on liver,pancreas,and inflammatory bowel diseases.

关键词： Quantitative perfusion analysis Gastrointestinal diseases Time-intensity curve Multiparametric ultrasound

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Is Takotsubo cardiomyopathy still looking for its own nosological identity?

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World Journal of Cardiology 2022年第10期14卷 557-560页

作者： Riccardo Scagliola Gian Marco Rosa Cardiovascular Disease Unit IRCCS Ospedale Policlinico San MartinoGenoa 16132Italy

Despite several efforts to provide a proper nosological framework for Takotsubo cardiomyopathy(TCM),this remains an unresolved matter in clinical *** clinical,pathophysiologic and histologic findings support the conceivable hypothesis that TCM could be defined as a unique pathologic entity,rather than a distinct subset of myocardial infarction with non-obstructive coronary *** investigations are needed in order to define TCM with the most appropriate disease taxonomy.

关键词： Takotsubo cardiomyopathy Myocardial infarction with non-obstructive coronary arteries Disease classification

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Artificial intelligence and inflammatory bowel disease: Where are we going?

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World Journal of Gastroenterology 2023年第3期29卷 508-520页

作者： Leonardo Da Rio Marco Spadaccini Tommaso Lorenzo Parigi Roberto Gabbiadini Arianna Dal Buono Anita Busacca Roberta Maselli Alessandro Fugazza Matteo Colombo Silvia Carrara Gianluca Franchellucci Ludovico Alfarone Antonio Facciorusso Cesare Hassan Alessandro Repici Alessandro Armuzzi Department of Endoscopy Humanitas Research HospitalIRCCSRozzano 20089MilanoItaly Department of Biomedical Sciences Humanitas UniversityRozzano 20089MilanoItaly IBD Center Humanitas Research HospitalIRCCSRozzano 20089MilanoItaly Gastroenterology Unit Department of Medical SciencesUniversity of FoggiaFoggia 71122FoggiaItaly

Inflammatory bowel diseases,namely ulcerative colitis and Crohn’s disease,are chronic and relapsing conditions that pose a growing burden on healthcare systems *** of their complex and partly unknown etiology and pathogenesis,the management of ulcerative colitis and Crohn’s disease can prove challenging not only from a clinical point of view but also for resource *** intelligence,an umbrella term that encompasses any cognitive function developed by machines for learning or problem solving,and its subsets machine learning and deep learning are becoming ever more essential tools with a plethora of applications in most medical *** this regard gastroenterology is no exception,and due to the importance of endoscopy and imaging numerous clinical studies have been gradually highlighting the relevant role that artificial intelligence has in inflammatory bowel diseases as *** aim of this review was to summarize the most recent evidence on the use of artificial intelligence in inflammatory bowel diseases in various contexts such as diagnosis,follow-up,treatment,prognosis,cancer surveillance,data collection,and ***,insights into the potential further developments in this field and their effects on future clinical practice were discussed.

关键词： Inflammatory bowel disease Artificial intelligence Machine learning Crohn’s disease Ulcerative colitis Computer-aided diagnosis

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Synaptic alterations as a common phase in neurological and neurodevelopmental diseases: JNK is a key mediator in synaptic changes

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Neural Regeneration Research 2023年第3期18卷 531-532页

作者： Clara Alice Musi Carlo Bonadonna Tiziana Borsello Department of Pharmacological and Biomolecular Sciences Universitàdegli Studi di MilanoMilanoItaly Mario Negri Insitute for Pharmacolgical Research-irccs MilanoItaly

Brain synapses play a key role in neuronal communication:this“conversation”is at the basis of all brain activities and synaptic dysfunction leads to brain *** study the modulators of this crucial synaptic function and we here present the evidence supporting the c-Jun N-terminal kinase(JNK)pathway as a pivotal actor in this scenario.

关键词： alterations diseases neurological

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Left abdominal mass with carcinosis:Unusual presentation of pancreatic acinar cell carcinoma

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Hepatobiliary & Pancreatic Diseases International 2023年第4期22卷 412-414页

作者： Davide Ciardiello Filomena Urbano Giuseppe Zamboni Nicola Palladino Francesca Bazzocchi Paola Parente Oncology Unit Fondazione IRCCS Ospedale Casa Sollievo della SofferenzaViale CappucciniSan Giovanni Rotondo 71013Italy Radiology Unit Fondazione IRCCS Ospedale Casa Sollievo della SofferenzaViale CappucciniSan Giovanni Rotondo 71013Italy Pathology Unit Ospedale Sacro Cuore Don Calabriavai SempreboniNegrar and University of VeronaNegrar 37024VRItaly Abdominal Surgical Unit Fondazione IRCCS Ospedale Casa Sollievo della SofferenzaViale CappucciniSan Giovanni Rotondo 71013Italy Pathology Unit Fondazione IRCCS Ospedale Casa Sollievo della SofferenzaViale CappucciniSan Giovanni Rotondo 71013Italy

Acinar cell carcinoma(ACC)is a rare malignant epithelial neoplasm accounting for 1%-2%of all pancreatic exocrine neoplasm,affecting more frequently man with an age between 50 and 70 *** patients present with nonspecific symptoms,which may give rise to difficulties in clinical diagnosis[1].ACC can manifest with diarrhea,weight loss,abdominal pain and,in up to 10%-15%,with lipase hypersecretion syndrome,characterized by elevated lipase production,diffuse subcutaneous fat necrosis and polyarthralgia[1,2].Biliary obstruction and jaundice are infre-quent clinical manifestations,unlike ductal adenocarcinoma,due to pushing rather than infiltrating growth of ACC.

关键词： abdominal clinical elevated

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Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

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Oncology Research 2024年第8期32卷 1309-1322页

作者： ANA S.CVETANOVIC MATTEO LAMBERTINI KEVIN PUNIE GORANA G.MATOVINA BRKO NIKOLA D.ZIVKOVIC MAJA J.POPOVIC MARIJANA M.MILOVIC KOVACEVIC LAZAR S.POPOVIC Department for Oncology Medical Faculty NisUniversity of NisNis18000Serbia Clinic of Oncology University Clinical Centre NisNis18000Serbia Department of Internal Medicine and Medical Sciences(DiMI) School of MedicineUniversity of GenovaGenova16100Italy Department of Medical Oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenova16100Italy Department of General Medical Oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuven3001Belgium Department of Medical Oncology Oncology Institute of VojvodinaSremska Kamenica21208Serbia Department for Pathology Medical Faculty NisUniversity of NisNis18000Serbia Center for Pathology University Clinical Centre NisNis18000Serbia Faculty of Medicine University of Novi SadNovi Sad21000Serbia Department of Medical Oncology Institute of Oncology and Radiology SerbiaBelgrade11000Serbia

Oncofertility is an extremely signiﬁcant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but signiﬁcantly contributes to preserving life *** effect of chemotherapy can range from minimal effects to complete ovarian *** data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and *** ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufﬁciency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian ***,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological ***,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor *** addition,studies on hematological malignancies have yielded negative results;nevertheless,theﬁndings must be interpreted with caution owing to numerous *** guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not *** this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisﬁeld

关键词： Gonadotropin-releasing hormone agonists(GnRHa) Fertility preservation Premature ovarian insufficiency(POI) Premenopausal patients

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Role of nutritional ketosis in the improvement of metabolic parameters following bariatric surgery

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World Journal of Diabetes 2022年第1期13卷 54-64页

作者： Fioralba Pindozzi Carlo Socci Massimiliano Bissolati Monica Marchi Elisabetta Devecchi Alessandro Saibene Caterina Conte Unitàdi Chirurgia Generale Provinciale Ospedale del DeltaLagosanto(FE)44023Italy Transplant and Metabolic/Bariatric Surgery Unit IRCCS Ospedale San RaffaeleMilan 20132Italy Department of General Medicine Diabetes and EndocrinologyIRCCS Ospedale San RaffaeleMilan 20132Italy Department of Human Sciences and Promotion of the Quality of Life San Raffaele Open UniversityRome 00166Italy Department of Endocrinology Nutrition and Metabolic DiseasesIRCCS MultiMedicaMilan 20099Italy

BACKGROUND Ketone bodies(KB)might act as potential metabolic modulators besides serving as energy *** metabolic surgery(BMS)offers a unique opportunity to study nutritional ketosis,as acute postoperative caloric restriction leads to increased lipolysis and circulating free fatty *** To characterize the relationship between KB production,weight loss(WL)and metabolic changes following *** For this retrospective study we enrolled male and female subjects aged 18-65 years who underwent BMS at a single *** on demographics,anthropometrics,body composition,laboratory values and urinary KB were *** Thirty-nine patients had data available for analyses[74.4%women,mean age 46.5±9.0 years,median body mass index 41.0(38.5;45.4)kg/m^(2),fat mass 45.2%±6.2%,23.1%had diabetes,43.6%arterial hypertension and 74.4%liver steatosis].At 46.0±13.6 d post-surgery,subjects had lost 12.0%±3.6%of pre-operative ***-nine percent developed *** with nutritional ketosis were significantly younger[42.9(37.6;50.7)years vs 51.9(48.3;59.9)years,P=0.018],and had significantly lower fasting glucose[89.5(82.5;96.3)mg/dL vs 96.0(91.0;105.3)mg/dL,P=0.025]and triglyceride levels[108.0(84.5;152.5)mg/dL vs 152.0(124.0;186.0)mg/dL,P=0.045]vs those with *** 6 mo,percent WL was greater in those with postoperative ketosis(-27.5%±5.1%vs 23.8%±4.3%,P=0.035).Urinary KBs correlated with percent WL at 6 and 12 *** metabolic changes were *** Our data support the hypothesis that subjects with worse metabolic status have reduced ketogenic capacity and,thereby,exhibit a lower WL following BMS.

关键词： Obesity Ketone bodies Bariatric surgery Weight loss Glucose metabolism Lipid metabolism

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Immortalized hippocampal astrocytes from 3xTg-AD mice,a new model to study disease-related astrocytic dysfunction:a comparative review

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Neural Regeneration Research 2023年第8期18卷 1672-1678页

作者： Laura Tapella Giulia Dematteis Armando A Genazzani Massimiliano De Paola Dmitry Lim Department of Pharmaceutical Sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly Department of Neuroscience Mario Negri Institute for Pharmacological Research IRCCSMilanoItaly

Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific ***,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific ***,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including *** models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and ***-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in ***,no stable cell lines were available from genetic mouse AD ***,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary *** groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier *** we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived *** conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

关键词： Alzheimer's disease astrocytes immortalization astroglial Alzheimers's disease model blood-brain barrier calcium signaling central nervous system homeostasis disproteostasis endoplasmic reticulum-mitochondria contacts induced pluripotent stem cell-derived astrocytes protein synthesis

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Left atrium veno-arterial extra corporeal membrane oxygenation as temporary mechanical support for cardiogenic shock:A case report

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世界临床病例杂志 2023年第27期11卷 6531-6536页

作者： Rossana Lamastra David Michael Abbott Antonella Degani Carlo Pellegrini Roberto Veronesi Stefano Pelenghi Chiara Dezza Giulia Gazzaniga Mirko Belliato Department of Surgical Pediatric and Diagnostic SciencesUniversity of PaviaPavia 27100PVItaly Department of Cardiothoracic Surgery Fondazione IRCCS Policlinico San MatteoPavia 27100PVItaly Clinical SurgicalDiagnostic and Pediatric Sciences DepartmentUniversity of PaviaItaly-Department of Cardiac SurgeryFondazione IRCCS Policlinico San Matteo FoundationPavia 27100PVItaly SC-AR2 Anestesia e Terapia Intensiva Cardiotoracica Fondazione irccs Policlinico San Matteo Pavia 27100PVItaly Department of Cardiac Surgery 1 IRCCS University Hospital Foundation"San Matteo"Pavia 27100Italy

BACKGROUND Veno-arterial extra corporeal membrane oxygenation(VA-ECMO)support is commonly complicated with left ventricle(LV)distension in patients with cardiogenic *** resolved this problem by transeptally converting VAECMO to left atrium veno-arterial(LAVA)-ECMO that functioned as a temporary paracorporeal left ventricular assist device to resolve LV *** our case LAVA-ECMO was also functioning as a bridge-to-transplant device,a technique that has been scarcely reported in the *** SUMMARY A 65 year-old man suffered from acute myocardial injury that required percutaneous *** than two weeks later,noncompliance to antiplatelet therapy led to stent thrombosis,cardiogenic shock,and cardiac *** VA-ECMO support was started,and the patient underwent a second coronary angiography with re-stenting and intra-aortic balloon pump *** VA-ECMO support was complicated by left ventricular distension which we resolved via ***,episodes of bleeding and sepsis complicated the clinical picture and the patient passed away 27 d after initiating *** This clinical case demonstrates that LAVA-ECMO is a viable strategy to unload the LV without another invasive percutaneous or surgical *** also demonstrate that LAVA-ECMO can also be weaned to a left ventricular assist device system.A benefit of this technique is that the procedure is potentially reversible,should the patient require VA-ECMO support again.A transeptal LV venting approach like LAVA-ECMO may be indicated over ImpellaTM in cases where less LV unloading is required and where a restrictive myocardium could cause LV *** ventricular over-distention is a well-known complication of peripheral VA-ECMO in cardiogenic shock and LAVA ECMO through transeptal cannulation offers a novel and safe approach for treating LV overloading,without the need of an additional percutaneous access.

关键词： Left atrium venoarterial extra corporeal membrane oxygenation Shock Case report

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