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Iron and Heart Failure: Current Concepts and Emerging Pharmacological Paradigms

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World Journal of Cardiovascular Diseases 2024年第4期14卷 195-216页

作者： maria rosaria de pascale maria Beatrice Rondinelli Flora Ascione Vincenzo Maffei Chiara Di Lorenzo Sarah Scagliarini Raffaella Faraonio Antonio Faiella Immunohematology and Transfusion Medicine Unit Cardarelli Hospital Naples Italy Immunohematology and Transfusion Medicine Unit San Camillo-Forlanini Hospital Rome Italy Health Management Office Cardarelli Hospital Naples Italy Anesthesiology Unit Cardarelli Hospital Naples Italy department of Medical and Translational Sciences University of Naples Federico II Naples Italy Oncology Unit Cardarelli Hospital Naples Italy department of Molecular Medicine and Medical Biotechnologies University of Naples Federico II Naples Italy

Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) and several trials have established that iron administration improves myocardial asset and clinical scenario in HF. Purpose: Recent acquisitions suggest that iron deficiency represents a concrete bias in the pathogenetic mechanism of chronic HF, so we have investigated the putative role of the hepcidin/ferroportin axis in the cardiovascular setting to advocate novel pharmacological and clinical approaches. Methods: Here, after an excursus on iron metabolism, we first reviewed the ongoing studies on novel iron targeted compounds. Then, we summarize large clinical interventional studies conducted on patient suffering from iron deficiency and HF which have tested the effects of drugging iron regard QoL, hospitalizations and cardiovascular death. Results: Novel compounds such as hepcidin agonist (PTG 300), synthetic human hepcidin (LJPC-401) and anti FPN (Vamifeport) are ongoing in iron overloaded patients, while the hepcidin blocker (PRS-080) is under investigation in anemic patients. Noteworthy, novel insights could arise from the results of a Phase IV interventional study regarding the modification of hepcidin pathway in a large cohort of HF patients (n = 1992) by sodium glucose cotransporter 2 inhibitors. To date, several studies highlight the beneficial effect of iron administration in cardiovascular setting and latest evidences consider hepcidin level as a novel biomarker of cardiac injury and atherosclerosis. Conclusions: We advocate that data from ongoing studies will suggest novel iron targeted therapies for diagnosis, prognosis and therapy transferable in selected heart failed patients.

关键词： Heart Failure Iron Anemia Iron deficiency Hepcidin

Potential application of the Kampo medicine goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy

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Journal of Integrative Medicine 2017年第2期15卷 77-87页

作者： Marco Cascella maria rosaria Muzio Division of Anesthesia Department of Anesthesia and Pain Medicine Istituto Nazionale Tumori "Fondazione G. Pascale"--IRCCS via Mariano Semmola Naples 80131 Italy Division of Infantile Neuropsychiatry UOMI-Maternal and Infant Health Asl NA 3 SUD Torre del Greco via Marconi Naples 80059 Italy

Chemotherapy-induced peripheral neuropathy （CIPN） is one of the most common and severe adverse effects related to cancer treatment. Unfortunately, although several agents and protocols have been proposed, no prophylactic strategies have yet to be proven useful. Therefore, new alternative therapies have been considered for CIPN prevention. Herbal medicine in Japan, called Kampo medicine, is derived from traditional Chinese medicine. Goshajinkigan （GJG） is a Kampo medicine, that is comprised of ten herbs. The aim of this work is to analyse the results of pre-clinical and clinical studies on the potential applications of GJG in CIPN prevention.

关键词： chemotherapy peripheral neuropathies herbal medicine alternative medicine natural products

Interaction of major genes predisposing to hepatocellular carcinoma with genes encoding signal transduction pathways influences tumor phenotype and prognosis

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World Journal of Gastroenterology 2008年第43期14卷 6601-6615页

作者： Francesco Feo Maddalena Frau Rosa maria pascale department of Biomedical Sciences Division of Experimental Pathology and OntologyUniversity of SassariSassari 07100Italy

Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma （HCC）. Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats and a G1-S block in lesions of resistant Brown norway （BN） rats. Unrestrained extracellular signal-regulated kinase （ERK） activity linked to proteasomal degradation of dual-specificity phosphatase 1 （DUSP1）, a specific ERK inhibitor, by the CKS1-SKP2 ubiquitin ligase complex occurs in more aggressive HCC of F344 rats and humans. This mechanism is less active in HCC of BN rats and human HCC with better prognosis. Upregulation of iNos cross-talk with IKK/NF-KB and RAS/ERK pathways occurs in rodent liver lesions at higher levels in the most aggressive models represented by HCC of F344 rats and c-Myc-TGF-α transgenic mice. iNOS, IKK/NF-κB, and RAS/ERK upregulation is highest in human HCC with a poorer prognosis and positively correlates with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Thus, cell cycle regulation and the activity of signal transduction pathways seem to be modulated by HCC modifier genes, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.

关键词： Hepatocarcinogenesis Genetic predisposition Polygenic disease, Redifferentiation Signal transduction pathways Cell cycle Cell proliferation Apoptosis Proteasomal degradation

Transjugular portosystemic shunt for early-onset refractory ascites after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2021年第1期20卷 90-93页

作者： Giuseppe Bianco Marco maria pascale Francesco Frongillo Erida Nure Salvatore Agnes Gabriele Spoletini General Surgery and Liver Transplant Unit Fondazione IRCCS-Policlinico Universitario“A.Gemelli”Rome 00168Italy

Liver transplantation(LT)is the most effective treatment for end-stage liver disease and complications of portal hypertension(PHT).However,PHT can relapse as a consequence of viral,alcoholic or metabolic chronic liver disease(CLD)recurrence,rejection,vascular abnormalities,small-for-size syndrome and technical complications(e.g.,portal or hepatic veins stenosis and/or thrombosis)[1].LT recipients with PHT may suffer from com plications similarly to non-transplanted cirrhotic patients(e.g.,refractory ascites,variceal hemorrhages and hydrothorax)although with higher morbidity and mortality due to their postoperative status and concomitant immunosuppressive therapy[2].

关键词： ascites liver mortality

Towards a better understanding of anesthesia emergence mechanisms: Research and clinical implications

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World Journal of Methodology 2018年第2期8卷 9-16页

作者： Marco Cascella Sabrina Bimonte maria rosaria Muzio Division of Anesthesia and Pain Management Department of Supportive CareIstituto Nazionale Tumori "Fondazione G.Pascale"-IRCSS Division of Infantile Neuropsychiatry UOMI-Maternal and Infant HealthASL NA3 SUD Torre del Greco

Emergence from anesthesia(AE) is the ending stage of anesthesia featuring the transition from unconsciousness to complete wakefulness and recovery of consciousness(RoC). A wide range of undesirable complications, including coughing, respiratory/cardiovascular events, and mental status changes such as emergence delirium, and delayed RoC, may occur during this critical phase. In general anesthesia processes, induction and AE represent a neurobiological example of "hysteresis". Indeed, AE mechanisms should not be simply considered as reverse events of those occurring in the induction phase. Anesthesia-induced loss of consciousness(LoC) and AE until RoC are quite distinct phenomena with, in part, a distinct neurobiology. Althoughanaesthetics produce LoC mostly by affecting cortical connectivity, arousal processes at the end of anesthesia are triggered by structures deep in the brain, rather than being induced within the neocortex. This work aimed to provide an overview on AE processes research, in terms of mechanisms, and EEG findings. Because most of the research in this field concerns preclinical investigations, translational suggestions and research perspectives are proposed. However, little is known about the relationship between AE neurobiology, and potential complications occurring during the emergence, and after the RoC. Thus, another scope of this review is to underline why a better understanding of AE mechanisms could have significant clinical implications, such as improving the patients' quality of recovery, and avoiding early and late postoperative complications.

关键词： delirium Anesthesia Isoflurane Propofol Consciousness Awareness Electroencephalography

On the Jebsen-Birkhoff Theorem in a Born-Infeld Type Theory of Gravity

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Journal of High Energy Physics, Gravitation and Cosmology 2019年第4期5卷 1051-1056页

作者： Tiago de Oliveira Rosa maria Emilia Xavier Guimar&atilde es Rocco pascale Neto Joaquim Lopes Neto Instituto Federal Goiano Campus Urutaí Rodovia Geraldo Silva Nascimento Urutaí Brazil Instituto de Física Universidade Federal Fluminense Niterói Brazil Instituto de Física Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil

In this paper we work with a special theory of gravity|the Novello-Di Lorenci-Luciane (hereby called NDL theory) which extends the Feynman-deser standard theoretical-fi eld approach to General Relativity. In the so-called NDL theory, matter interacts universally with gravity in accordance with the Weak Equivalence Principle, while gravitons have a nonlinear self-interaction. Our main aim in this work is to show that, though the NDL theory does not admit a Schwarzschild solution, the Jebsen-Birkhoff theorem is still valid in this framework.

关键词： Electrostatic Trapping Bootstrap Current Mitigation Peeling-Ballooning Mode

Acute anemia after dental extraction:A case report

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Open Journal of Stomatology 2014年第2期4卷 67-72页

作者： Stephane Aiche maria Pia Gandolfini pascale Gaussem Alp Alantar Oral Surgery Unit Charles Foix HospitalIvry-sur-SeineFrance Cardiology Unit Max Fourestier HospitalNanterreFrance Paris descartes University Sorbonne Paris CiteParisFrance AP-HP Hopital Europeen Georges PompidouHematology DepartmentParisFrance InsermUMR-S765 Faculte de PharmacieParisFrance Oral Surgery Unit Max Fourestier HospitalNanterreFrance

A patient treated with a vitamin K antagonist (VKA) since the implantation of two mechanical heart valves developed acute anemia after the extraction of a tooth. This case report and data in the literature indicate a need for specific measures before, during, and after oral surgery in patients taking anticoagulant therapy: 1) the bleeding risk should be evaluated before the procedure. The INR should be measured routinely, 2) the procedure should be scheduled early in the week to allow an evaluation at the fibrinolysis peak, i.e., 48 to 72 hours after surgery, which is the time of greatest risk of delayed bleeding, 3) the surgical procedure should be appropriate for the elevated bleeding risk, 4) postoperative monitoring is of the most importance, as bleeding is usually delayed in patients on VKA therapy, 5) when poor treatment adherence is expected, day-hospital admission is useful to ensure that the postoperative protocol is implemented properly and to detect early bleeding. The treatment of post-extraction acute anemia includes local hemostasis protocol with the revision of the socket followed by red-blood-cell pack transfusion. A daily fluindione dosage control, and a normal hemoglobin level will allow the patient to leave the hospital.

关键词： Case Study Oral Hemorrhage Acute Anemia Anti Coagulant Treatment Extraction Hemostasis

Non-invasive prenatal testing can detect silent cancers in expecting mothers

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Genes & Diseases 2024年第2期11卷 585-588页

作者： Alessandro Ottaiano Monica Ianniello Nadia Petrillo mariachiara Santorsola Luigia de Falco Salvatore Giovanni Castaldi maria Antonietta Castaldi Valentina Giudice Carmine Selleri Giovanni Savarese Unit of Innovative Therapies for Abdominal Metastases Istituto Nazionale Tumori di NapoliIRCCS “G.Pascale”Via Mariano SemmolaNapoli 80131Italy AMES Centro Polidiagnostico Strumentale SRLVia Padre Carmine Fico 24Casalnuovo Di Napoli 80013Italy Specialization School of Clinical Pathology Università degli Studi di SalernoVia Giovanni Paolo II 132Fisciano 84084Italy Unit of High-Risk Pregnancy and Prenatal Diagnosis University Hospital “San Giovanni di Dio e Ruggi d'Aragona”Via San LeonardoSalerno 84125Italy Hematology and Transplant Center University Hospital “San Giovanni di Dio e Ruggi d'Aragona”Via San LeonardoSalerno 84125Italy department of Medicine Surgery and Dentistry“Scuola Medica Salernitana”Via Salvador Allende 43Baronissi 84081Italy

Pregnancy is a unique physiological state in which several changes *** of the most important aspects is the maternal immune system,which sets to tolerate the presence of thedeveloping fetus(a semi-allogeneic organism),while at the same time providing protection against pathogens.1 Pregnancy has long been known to affect the risk of certain cancers including breast cancer in the short term,gestational trophoblastic disease(GTD),cervical cancer,and melanoma.2,3 The reasons for the increased risk of these cancers during pregnancy are not fully understood,but several hypotheses have been proposed as the hormonal and immune system changes.

关键词： mother cancers fetus

Precision medicine in gastric cancer

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World Journal of Gastrointestinal Oncology 2019年第10期11卷 804-829页

作者： Patrizia Bonelli Antonella Borrelli Franca maria Tuccillo Lucrezia Silvestro Raffaele Palaia Franco maria Buonaguro Molecular Biology and Viral Oncology Istituto Nazionale Tumori-IRCCS-Fondazione G PascaleNapoli 80131Italy Abdominal Medical Oncology Istituto Nazionale Tumori-IRCCS-Fondazione G PascaleNapoli 80131Italy Gastro-pancreatic Surgery Division Istituto Nazionale Tumori-IRCCS-Fondazione G PascaleNapoli 80131Italy

Gastric cancer(GC)is a complex disease linked to a series of environmental factors and unhealthy lifestyle habits,and especially to genetic *** represents the second leading cause of cancer-related deaths *** onset is subtle,and the majority of patients are diagnosed once the cancer is already *** recent years,there have been innovations in the management of advanced GC including the introduction of new classifications based on its molecular *** to new technologies such as next-generation sequencing and microarray,the Cancer Genome Atlas and Asian Cancer Research Group classifications have also paved the way for precision medicine in GC,making it possible to integrate diagnostic and therapeutic *** the objectives of the subdivision of GC into subtypes is to select patients in whom molecular targeted drugs can achieve the best results;many lines of research have been initiated to this *** phase III clinical trials,trastuzumab,anti-Erb-B2 receptor tyrosine kinase 2(commonly known as ERBB2)and ramucirumab,anti-vascular endothelial growth factor receptor 2(commonly known as VEGFR2)monoclonal antibodies,were approved and introduced into first-and second-line therapies for patients with advanced/metastatic ***,the heterogeneity of this neoplasia makes the practical application of such approaches ***,scientific progress has not been matched by progress in clinical practice in terms of significant improvements in *** continues to be low in contrast to the reduction in deaths from many common cancers such as colorectal,lung,breast,and prostate *** several target molecules have been identified on which targeted drugs can act and novel products have been introduced into experimental therapeutic protocols,the overall approach to treating advanced stage GC has not substantially ***,surgical resection with adjuvant or neoadjuvant radiotherapy and ch

关键词： Gastric cancer Molecular characterization Biomarkers Precision medicine Targeted therapy