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What do we know about the role of lncRNAs in multiple sclerosis?

Neural Regeneration Research 2021年第9期16卷 1715-1722页

作者： Viviana Nociti massimo santoro Institute of Neurology Fondazione Policlinico Universitario‘A.Gemelli’IRCCSUniversitàCattolica del Sacro CuoreRomeItaly IRCCS Fondazione Don Carlo Gnocchi FlorenceItaly

Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports an autoimmune pathogenesis. So far, the exact mechanisms leading to autoimmune diseases are still only partially understood. We know that genetic, epigenetic, molecular, and cellular factors resulting in pathogenic inflammatory responses are certainly involved. Long non-coding RNAs(lncRNAs) are non-protein coding transcripts longer than 200 nucleotides that play an important role in both innate and acquired immunity, so there is great interest in lncRNAs involved in autoimmune diseases. The research on multiple sclerosis has been enriched with many studies on the molecular role of lncRNAs in the pathogenesis of the disease and their potential application as diagnostic and prognostic biomarkers. In particular, many multiple sclerosis fields of research are based on the identification of lncRNAs as possible biomarkers able to predict the onset of the disease, its activity degree, its progression phase and the response to disease-modifying drugs. Last but not least, studies on lncRNAs can provide a new molecular target for new therapies, missing, so far, a cure for multiple sclerosis. While our knowledge on the role of lncRNA in multiple sclerosis has recently improved, further studies are required to better understand the specific role of lncRNAs in this neurological disease. In this review, we present the most recent studies on molecular characterization of lncRNAs in multiple sclerosis disorder discussing their clinical relevance as biomarkers for diagnosis and treatments.

关键词： antisense lncRNAs enhancer lncRNAs epigenetics immune system intergenic lncRNA intronic lncRNA multiple sclerosis sense lncRNAs single nucleotide polymorphisms

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Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

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Neural Regeneration Research 2020年第9期15卷 1757-1766页

作者： massimo santoro Roberto Piacentini Alessia Perna Eugenia Pisano Anna Severino Anna Modoni Claudio Grassi Gabriella Silvestri IRCCS Fondazione Don Carlo Gnocchi MilanItaly Department of Neuroscience Universita Cattolica del Sacro CuoreRomeItaly Department of Cardiovascular and Thoracic Sciences Universita Cattolica del Sacro CuoreRomeItaly Fondazione Policlinico Universitario A.Gemelli IRCCS RomeItaly

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

关键词： alternative splicing calcium homeostasis CUG-BP1 foci MBNL1 myotonic dystrophy type 1 myotubes resveratrol

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Treatment for isolated loco-regional recurrence of gastric adenocarcinoma: Does surgery play a role?

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World Journal of Gastroenterology 2005年第44期11卷 7014-7017页

作者： Fabio Carboni Pasquale Lepiane Roberto santoro Riccardo Lorusso Pietro Mancini massimo Carlini Eugenio santoro Department of Digestive Surgery and Liver Transplantation Division of General A.T.Surgery

AIM： To evaluate the role of surgical treatment for isolated Ioco-regional recurrences of operated gastric adenocarcinoma. METHODS： Among the 837 patients operated for gastric adenocarcinoma between December 1979 and April 2004, 713 （85%） underwent resection with curative intent. A retrospective review of a prospectively collected gastric cancer database was carried out. Overall recurrence rate was 44% （315 cases）, with 75% occurring within the first 2 years from the operation. Isolated L-R recurrences were observed in 38 （12%） patients. Symptomatic lesions were observed in 27 （71%）. RESULTS： Six （16%） patients were macroscopically resected with curative intent. The recurrence was located in the gastric stump after a STG in three patients, in the esophagojejunal anastomosis after a TG in two patients and in the gastric bed after a TG in one patient. Surgical procedures consisted of three secondary TG, two esophagojejunal resection and one excision of an extraluminal recurrence. Postoperative complications occurred in two patients （33%）, including one anastomotic leakage and one hemorrhage. The latter patient died of sepsis 35 d after the surgery （mortality rate 17%）. All patients died of recurrent gastric cancer： 2 within 1 year from surgery （8 and 11 mo, respectively）, 2 after 16 and 17 mo respectively and 1 after 28 mo from the second operation. CONCLUSION： Surgery plays a very limited role in the treatment for isolated Ioco-regional recurrence of gastric adenocarcinoma.

关键词： Gastric adenocarcinoma Recurrence Diagnosis Surgery

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Music therapy and pediatric palliative care:songwriting with children in the end-of-life

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World Journal of Pediatrics 2022年第10期18卷 695-699页

作者： Filippo Giordano Chiara Rutigliano Mariagrazia Baroni massimo Grassi Paola Muggeo Nicola santoro Department of Emergency and Organ Transplants University of Bari Aldo MoroPiazza G.Cesare 1170124BariItaly Section of Pediatric Hematology-Oncology University Hospital of BariBariItaly Hospice Madonna Dell’Uliveto AlbineaREItaly

Children's needs in pediatric palliative care(PPC)are complex and are determined by age,the course of the disease,family structure,and cultural background[1].The child's family system also has multiple needs which mus... 详细信息

关键词： pediatric assessed palliative

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Management and treatment of lactose malabsorption

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World Journal of Gastroenterology 2006年第2期12卷 187-191页

作者： massimo Montalto Valentina Curigliano Luca santoro Monica Vastola Giovanni Cammarota Raffaele Manna Antonio Gasbarrini Giovanni Gasbarrini Department of Internal Medicine Catholic UniversityRomeItaly

Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world＇s population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous β-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.

关键词： Lactose Malabsorption Intolerance Therapy

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Can chronic gastritis cause an increase in fecal calprotectin concentrations?

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World Journal of Gastroenterology 2010年第27期16卷 3406-3410页

作者： massimo Montalto Antonella Gallo Gianluca Ianiro Luca santoro Ferruccio D Onofrio Riccardo Ricci Giovanni Cammarota Marcello Covino Monica Vastola Antonio Gasbarrini Giovanni Gasbarrini Ricca rdo Ricci Institute of Internal Medicine Catholic University Institute of Pathology Institute of Pa thology Catholic University00168RomeItaly

AIM:To evaluate fecal calprotectin concentrations(FCCs) in subjects with chronic gastritis and the correlation between FCCs and gastritis activity ***:FCCs were measured in 61 patients with histological diagnosis of gastritis and in 74 healthy *** grading of gastritis was performed according to the updated Sydney gastritis *** were subdivided into 2 groups according to the presence/absence of an active *** with chronic active gastritis were divided into 3 subgroups on the basis of the activity score(mild,moderate,marked).FFCs in relation to Helicobacter pylori(***) infection and proton pump inhibitor(PPI) use were also ***:FCCs in patients with chronic active gastritis were not significantly different to FCCs either in subjects with non active gastritis or in healthy *** patients with chronic active gastritis(even marked),FCCs did not significantly differ according to activity *** significant differences in FCCs were found when considering ***,as well as when considering PPI chronic ***:FCCs were not significantly increased in subjects with chronic gastritis,even in those patients with a marked neutrophil infiltration.

关键词： Chronic gastritis Fecal calprotectin Intestinal inflammation Neutrophils

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Music therapy in children affected by brain tumors

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World Journal of Pediatric Surgery 2021年第3期4卷 44-45页

作者： Filippo Giordano Raffaella Messina Anna Riefolo Chiara Rutigliano Teresa Perillo massimo Grassi Nicola santoro Francesco Signorelli School of Medicine University of BariBariItaly Department of Basic Medical Sciences Neurosciences and Sense OrgansDivision of NeurosurgeryUniversity of BariBariPugliaItaly Anesthesia and Intensive Care Unit Azienda Ospedaliero-Universitaria Consorziale Policlinico di BariBariPugliaItaly Pediatric Hemathology-Oncology Policlinico di Bari Ospedale Giovanni XXIIIBariPugliaItaly

Children affected by brain tumors experi-ence significant levels of anxiety,nervousness,and fear regarding surgery,especially in the preoperative *** operating room can be an intimidating environment for them,and preoperative anxiety can adversely affect postoperative pain.1 Interest is growing in finding non-pharmacological means that may be used to reduce these symptoms.

关键词： tumors surgery dating

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Transcranial Doppler ultrasonography: From methodology to major clinical applications

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World Journal of Cardiology 2016年第7期8卷 383-400页

作者： Antonello D'Andrea Marianna Conte massimo Cavallaro Raffaella Scarafile Lucia Riegler Rosangela Cocchia Enrica Pezzullo Andreina Carbone Francesco Natale Giuseppe santoro Pio Caso Maria Giovanna Russo Eduardo Bossone Raffaele Calabrò Integrated Diagnostic Cardiology Second University of NaplesAORN "dei Colli"Monaldi Hospital Department of Cardiology and Cardiac Surgery University Hospital

Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler(TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency(≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage(caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.

关键词： Transcranial Doppler ultrasonography Lindegaard ratio Paradoxical embolism Microembolic signals Middle cerebral artery Patent foramen ovale Cryptogenic STroke Vasospasm Acute subarachnoid hemorrhage Ischemic stroke

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