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Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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World Journal of Gastroenterology 2024年第9期30卷 1132-1142页

作者： Antonietta Gerarda Gravina Iacopo Panarese Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico Hepatogastroenterology division Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Pathology division Department of Mental and Physical Health and Preventive MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Experimental medicine Division of PharmacologyUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Advanced Medical and Surgical Sciences(DAMSS) University of Campania Luigi VanvitelliNaples 80138Italy Department of Pharmacy University of Naples Federico IINaples 80131Italy

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin ***,data regarding their role in inflammatory bowel diseases(IBD)are currently *** This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic *** Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and *** sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal *** MC3R and MC5R are expressed in the colon of IBD ***,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

关键词： Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease

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A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jose Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vasquez Elman Rolando Gamarra-Osorio Juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez Luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru division of medicine Hospital de Apoyo ChepénChepenPeru division of Family medicine Hospital de Apoyo ChepénChepenPeru division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru division of Pediatrics Hospital de Apoyo ChepenChepenPeru division of Internal medicine Hospital de Apoyo ChepenChepenPeru division of Genetics Universidad Nacional de TrujilloTrujilloPeru division of Neonatology Hospital Belen de TrujilloTrujilloPeru division of Internal medicine Universidad Nacional de TrujilloTrujilloPeru Department of medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide *** causes account for 7%of the cases in children with extreme *** sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 *** search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case *** The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body ***,several important aspects of the pathophysiology of obesity remain *** causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this *** are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric *** Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

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Cholesterol business:lifeor death byrust

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1247-1248页

作者： Shubhangi Gavalil Francesca Maremonti Andreas Linkermann division of Nephrology Department of Internal Medicine 3University Hospital Carl Gustav Carus at the Technische Universitat DresdenDresdenGermany division of Nephrology Department of MedicineAlbert Einstein College of MedicineBronxNYUSA

In two recent manuscripts published in Nature,the cholesterol-synthesis pathway was identified as a master regulator of ferroptosis sensitivity and therefore as a novel therapeutic target.1,2 Ferroptosis does not only represent one way to eliminate cancer cells,but also contributes to acute organ damage in the kidney,heart,brain,and liver,and it kills tissues during the process of organ *** term“ferroptosis”should be defined as a cellular process of iron-catalyzed lipid peroxidation-mediated rupture of the plasma membrane.

关键词： rupture death damage

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Unveiling sinus venosus atrial septal defect and partial anomalous pulmonary venous return in an elderly patient

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Journal of Geriatric Cardiology 2024年第4期21卷 462-464页

作者： Cristina M Font Anamarys Blanco Fernandez Dinesh Kadariya Department of medicine Division of CardiologyUniversity of Florida College of MedicineJacksonvilleFloridaUSA

Sinus venosus defect(SVD) accounts for 4%–11% of all atrial septal defects(ASD) and may present with dyspnea, heart failure(HF), palpitations, or angina.^[1] The malformation typically involves an interatrial communication due to a deficiency in the common wall connecting the right pulmonary veins and the superior vena cava(SVC) and often accompanies anomalous pulmonary venous connection of some or all of the pulmonary veins.

关键词： atrial septal venous

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Engineering nanomedicines for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr division of Engineering in medicine and division of Renal medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicines for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicines Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response

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Genomic medicine and cancer clinical trial in Thailand

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Cancer Biology & medicine 2024年第1期21卷 10-15页

作者： Lucksamon Thamlikitkul Napa Parinyanitikul Virote Sriuranpong division of Medical Oncology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand division of Medical Oncology Department of MedicineFaculty of MedicineChulalongkorn University&The King Chulalongkorn Memorial HospitalBangkok 10330Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and *** the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic *** chemotherapy empirically affects all dividing cells,the targets are virtually *** this regard,toxic effects on normal tissue are essentially inevitable.

关键词： chemotherapy cancer Cancer

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Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 845-856页

作者： Naweed Mohammad Regina Oshins Tongjun Gu Virginia Clark Jorge Lascano Naziheh Assarzadegan George Marek Mark Brantly Nazli Khodayari division of Pulmonary Critical Care and Sleep MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Interdisciplinary Center for Biotechnology Research Bioinformatics CoreUniversity of FloridaGainesvilleFLUSA division of Gastroenterology Hepatology and NutritionCollege of MedicineUniversity of FloridaGainesvilleFLUSA division of Pathology Immunologyand Laboratory MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue *** results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the *** goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene ***:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional *** used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver *** observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those ***:A total of 339 genes were differentially *** pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with *** analysis also revealed higher levels of fibrosis and hepatocellular damage in these ***:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is *** believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

关键词： Alpha-1 antitrypsin deficiency Chronic obstructive pulmonary disease Liver fibrosis Liver biopsy Liver histology Transcriptomics

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Hepatocellular Carcinoma with Gastric Metastasis Mimicking a 4 cm Gastrointestinal Stromal Tumor After a 3-year Disease-free Interval

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 218-221页

作者： Wei-Ting Chen Shiu-Feng Kathy Huang Ming-Ling Chang Yun-Fan Liaw division of Hepatology Department of Gastroenterology and HepatologyChang Gung Memorial HospitalTaoyuan Department of medicine College of MedicineChang Gung UniversityTaoyuan division of Molecular and Genomic medicine National Health Research InstitutesMiaoli

Hepatocellular carcinoma(HCC)is an aggressive tumor that usually occurs in patients with chronic liver disease and *** resection is an optimal treatment for HCC,but the 5-year recurrence rates are significantly *** majority of recurrent HCCs occur through intrahepatic metastasis with local tumor progression,and less than 20%of recurrences are extrahepatic *** with gastric metastasis is extremely rare,and it is easily misdiagnosed as primary gastric cancer with liver *** 80-yearold male chronic hepatitis B virus carrier had received lamivudine and entecavir for years and was regularly followed up in the *** had a 3.5 cm solitary HCC with microvascular invasion and received curative surgical resection in *** 2013,he developed a 1.3 cm solitary HCC again and was treated with combination therapy with radiofrequency ablation and pure ethanol ***,he was followed every 3–6 months and was *** years later,in 2016,endoscopy for intermittent epigastralgia showed a solitary 4 cm intraluminal gastric subepithelial tumor without mucosal ulcers or erosions over the gastric *** imaging studies,including computed tomography,favored the diagnosis of gastrointestinal stromal tumor(GIST),but the pathology of the tumor proved to be *** patient did not receive any systemic anticancer therapy but only wedge resection of the stomach and remained tumor-and HCC-free until his latest clinic visit in *** current case is unique and indicates the possibility of HCC with late solitary gastric metastasis mimicking *** gastric tumor resection ensured an extremely good outcome for the patient,which is different from the devastating prognosis of most cases of HCC with gastric metastasis.

关键词： Hepatocellular carcinoma Hepatitis B virus Gastric Gastrointestinal stromal tumor

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Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo Luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro Federico Department of Precision medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Precision medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic *** on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),*** Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these ***,due to its invasiveness and costs,CSPH is almost never evaluated in clinical ***,recognizing noninvasively predicting tools still have more appeal across healthcare *** red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been *** In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD *** Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 *** baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were *** FUP,DEs(timing and modaities)were *** was assessed at the baseline and on DE occurrence according to the available Clinical Practice *** Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve a

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational medicine Prognostic biomarker

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Is medical management useful in Moyamoya disease?

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World Journal of Clinical Cases 2024年第3期12卷 466-473页

作者： Sombat Muengtaweepongsa Vatcharasorn Panpattanakul Center of Excellence in Stroke Division of NeurologyDepartment of MedicineFaculty of MedicineThammasat UniversityRangsit CampusKlonglaung 12120Pathum ThaniThailand division of Neurology Department of Internal MedicineSchool of MedicineUniversity of PhayaoPhayao 56000Thailand

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral *** antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic *** doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic ***,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension ***,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains ***-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and *** protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

关键词： Moyamoya disease Cerebral infarction Antithrombotic management Transcranial doppler Revascularization Intracerebral hemorrhage Antihypertensive intervention Lipid-lowering therapies

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