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Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis

World Journal of Gastroenterology 2014年第41期20卷 15190-15199页

作者： enrico Lupia luca Pigozzi Alberto Goffi emilio Hirsch Giuseppe Montrucchio Department of Medical Sciences University of Torino emergency Medicine Unit "Città della Salute e della Scienza" Hospital Interdepartmental Division of Critical Care Medicine University of Toronto Molecular Biotechnology Center Department of Molecular Biotechnology and Health SciencesUniversity of Torino

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis.

关键词： Phosphoinositide 3-kinase Cell signaling Inflammation Pathogenesis Acute pancreatitis

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Stem cells sources for intervertebral disc regeneration

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World Journal of Stem Cells 2016年第5期8卷 185-201页

作者： Gianluca Vadalà Fabrizio Russo luca Ambrosio Mattia Loppini Vincenzo Denaro Department of Orthopedic and Trauma Surgery University Campus Bio-Medico of Rome

Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible ***, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

关键词： Stem cells Intervertebral disc degeneration Spine Tissue engineering Cell therapy

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Optic nerve injury-induced regeneration in the adult zebrafish is accompanied by spatiotemporal changes in mitochondrial dynamics

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Neural Regeneration Research 2023年第1期18卷 219-225页

作者： An Beckers luca Masin Annelies Van Dyck Steven Bergmans Sophie Vanhunsel Anyi Zhang Tine Verreet Fabienne ePoulain Karl Farrow Lieve Moons Neural Circuit Development and Regeneration Research Group Animal Physiology and Neurobiology SectionDepartment of BiologyKatholieke Universiteit LeuvenLeuvenBelgium Poulain Lab Department of Biological SciencesUniversity of South CarolinaColumbiaSCUSA Neuro-electronics Research Flanders Vlaams Instituut voor Biotechnologie(VIB)LeuvenBelgium Leuven Brain Institute LeuvenBelgium Imec LeuvenBelgium

Axonal regeneration in the central nervous system is an energy-intensive *** contrast to mammals,adult zebrafish can functionally recover from neuronal *** raises the question of how zebrafish can cope with this high energy *** previously showed that in adult zebrafish,subjected to an optic nerve crush,an antagonistic axon-dendrite interplay exists wherein the retraction of retinal ganglion cell dendrites is a prerequisite for effective axonal *** postulate a‘dendrites for regeneration’paradigm that might be linked to intraneuronal mitochondrial reshuffling,as ganglion cells likely have insufficient resources to maintain dendrites and restore axons ***,we characterized both mitochondrial distribution and mitochondrial dynamics within the different ganglion cell compartments(dendrites,somas,and axons)during the regenerative *** nerve crush resulted in a reduction of mitochondria in the dendrites during dendritic retraction,whereafter enlarged mitochondria appeared in the optic nerve/tract during axonal *** dendritic regrowth in the retina,mitochondrial density inside the retinal dendrites returned to baseline ***,a transient increase in mitochondrial fission and biogenesis was observed in retinal ganglion cell somas after optic nerve *** together,these findings suggest that during optic nerve injury-induced regeneration,mitochondria shift from the dendrites to the axons and back again and that temporary changes in mitochondrial dynamics support axonal and dendritic regrowth after optic nerve crush.

关键词： axonal regeneration central nervous system dendrite remodeling energy metabolism fission mitochondria mitochondrial trafficking optic nerve crush retina zebrafish

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Towards hydrometeorological thresholds of reservoir-induced landslide from subsurface strain observations

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Science China(Technological Sciences) 2024年第6期67卷 1907-1922页

作者： Ye Xiao ZHU HongHu WANG Jia ZHeNG WanJi ZHANG Wei SCHeNATO luca PASUTO Alessandro CATANI Filippo School of earth Sciences and engineering Nanjing UniversityNanjing210023China Department of Geosciences University of PadovaPadova35131Italy School of Geosciences and Info-Physics Central South UniversityChangsha410083China Department of Information engineering University of PadovaPadova35131Italy National Research Council-Research Institute for Geo-Hydrological Protection(CNR-IRPI) Padova35127Italy

Synergistic multi-factor early warning of large-scale landslides is a crucial component of geohazard prevention and mitigation efforts in reservoir *** forecasting and early warning based on surface displacements have been widely ***,the lack of direct subsurface real-time observations limits our ability to predict critical hydrometeorological conditions that trigger landslide *** this paper,we leverage subsurface strain data measured by high-resolution fiber optic sensing nerves that were installed in a giant reservoir landslide in the Three Gorges Reservoir(TGR)region,China,spanning a whole hydrologic year since February *** spatiotemporal strain profile has preliminarily identified the slip zones and potential drivers,indicating that high-intensity short-duration rainstorms controlled the landslide kinematics from an observation *** the time lag effect,we reexamined and quantified potential controls of accelerated movements using a data-driven approach,which reveals immediate response of landslide deformation to extreme rainfall with a zero-day *** identify critical hydrometeorological rules in accelerated movements,accounting for the dual effect of rainfall and reservoir water level variations,we thus construct a landslide prediction model that relies upon the boosting decision tree(BDT)algorithm using a dataset comprising daily rainfall,rainfall intensity,reservoir water level,water level fluctuations,and slip zone strain time *** results indicate that landslide acceleration is most likely to occur under the conditions of mid-low water levels(i.e.,e-amount and high-intensity rainfalls(i.e.,daily rainfall>57.9 mm and rainfall intensity>24.4 mm/h).Moreover,this prediction model allows us to update hydrometeorological thresholds by incorporating the latest monitoring *** on the shoulder of this landslide case,our study informs a practical and reliable path

关键词： slow-moving landslide fiber-optic monitoring subsurface strain hydrometeorological threshold extreme weather

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Schwann cell development,maturation and regeneration：a focus on classic and emerging intracellular signaling pathways

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Neural Regeneration Research 2017年第7期12卷 1013-1023页

作者： luca Franco Castelnovo Veronica Bonalume Simona Melfi Marinella Ballabio Deborah Colleoni Valerio Magnaghi Dipartimento di Scienze Farmacologiche e Biomolecolari Universita degli Studi di Milano Milan Italy

The development,maturation and regeneration of Schwann cells（SCs）,the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracellular *** regulatory molecules consist of integrins,neuregulins,growth factors,hormones,neurotransmitters,as well as entire intracellular pathways including protein-kinase A,C,Akt,erk/MAPK,Hippo,mTOR,*** instance,Hippo pathway is overall involved in proliferation,apoptosis,regeneration and organ size control,being crucial in cancer proliferation *** SCs,Hippo is linked to merlin and YAP/TAZ signaling and it seems to respond to mechanic/physical ***,among factors regulating SCs,also the signaling intermediates Src tyrosine kinase and focal adhesion kinase（FAK）proved relevant for SC fate,participating in the regulation of adhesion,motility,migration and in vitro *** SCs,the factors Src and FAK are regulated by the neuroactive steroid allopregnanolone,thus corroborating the importance of this steroid in the control of SC *** this review,we illustrate some old and novel signaling pathways modulating SC biology and functions during the different developmental,mature and regenerative states

关键词： myelin neuroactive steroids electromagnetic field peripheral nervous system

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Standardization issues in botanicals:A metabolomic and in silico approach to Monascus purpureus food supplements

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Food Bioscience 2022年第6期50卷 1064-1073页

作者： Laura Righetti luca Dellafiora enrico Rolli Chiara Dall’Asta Renato Bruni Dipartimento di Scienze degli Alimenti e del Farmaco University of ParmaParco Area delle Scienze27a43124ParmaItaly Dipartimento di Scienze Chimiche della Vita e della Sostenibilità AmbientaleUniversity of ParmaParco Area delle Scienze11a43124ParmaItaly

A metabolomic strategy was explored to profile 33 Monascus purpureus botanicals,revealing low standardization levels in terms of monacolins and Monascus pigments.A fast and highly accurate screening method was applied by means of UHPLC-TWIMS-QTOF,enabling the monitoring of 36 monacolins and 8 *** confirmed that very different fermentation processes are used for red yeast rice production,resulting in erratic profiles and large variability among ***,minor monacolins represented on average a 37%(range 8–54%)of the sum of monacolins and *** and dihydromonacolins were spanning from 7 to 43%with as many as 26 products containing a relative percentage exceeding 20%.Total pigments average ranged between traces and 65%,with a percentage exceeding 20%in 12 *** silico docking results showed that monacolins other than Monacolin K had lower but not negligeable inhibitory potential for 3-hydroxy-3-methylglutaryl coenzyme A reductase for precise structural *** results confirms that standardization of Monascus purpureus botanicals is dubious and strict quality control must be *** the same time,they reinforce the opportunity to take advantage of new metabolomic tools to properly describe raw materials or food supplements used in investigations and clinical trials,suggesting extensive phytochemical analysis beyond the mere quantification of Monacolin K.

关键词： Food supplements Metabolomics Monacus pigments Monacolins Ion mobility Standardization

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Percutaneous transarterial embolization of extrahepatic arteroportal fistula

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World Journal of Gastroenterology 2006年第34期12卷 5562-5564页

作者： Gianluca Marrone Settimo Caruso Roberto Miraglia Ilaria Tarantino Riccardo Volpes Angelo luca Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IsMeTT) Palermo Italy

Arteroportal fistula is a rare cause of prehepatic portal hypertension. A 44-year-old male with hepatitis virus C infection was admitted for acute variceal bleeding. endoscopy showed the presence of large esophageal varices. The ultrasound revealed a mass near the head of pancreas, which was characterized at the color- Doppler by a turbulent flow, and arterialization of portal vein flow. CT scan of abdomen showed a large aneurysm of the gastroduodenal artery communicating into the superior mesenteric vein. The sinusoidal portal pressure measured as hepatic vein pressure gradient was normal, confirming the pre-hepatic origin of portal hypertension. The diagnosis of extrahepatic portal hypertension secondary to arteroportal fistula was established, and the percutaneous embolization was performed. Three months later, the endoscopy showed absence of esophageal varices and ascites. At the moment, the patient is in good clinical condition, without signs of portal hypertension.

关键词： Portal hypertension Arteroportal fistula Portal shunt esophageal varices bleeding embolization Interventional radiology Psudoaneurysm

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Dehydration of plant cells shoves nuclei rotation allowing for 3D phase-contrast tomography

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Light(Science & Applications) 2021年第10期10卷 1889-1904页

作者： Zhe Wang Vittorio Bianco Daniele Pirone Pasquale Memmolo Massimiliano Maria Villone Pier luca Maffettone Pietro Ferraro Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale Universitàdegli Studi di Napoli“Federico II”Piazzale Tecchio 8080125 NapoliItaly NeAPoLIS Numerical and Experimental Advanced Program on Liquids and Interface SystemsJoint Research Center CNR-Universitàdegli Studi di Napoli“Federico II”NapoliItaly CNR-ISASI Institute of Applied Sciences and Intelligent Systems“E.Caianiello”Via Campi Flegrei 3480078 PozzuoliNapoliItaly Dipartimento di Ingegneria elettrica e delle Tecnologie dell’Informazione Universitàdegli Studi di Napoli“Federico II”via Claudio 2180125 NapoliItaly

Single-cell phase-contrast tomography promises to become decisive for studying 3D intracellular structures in *** involves probing cells with light at wide angles,which unfortunately requires complex *** we show an intriguing concept based on an inherent natural process for plants biology,i.e.,dehydration,allowing us to easily obtain 3D-tomography of onion-epidermal cells’*** fact,the loss of water reduces the turgor pressure and we recognize it induces significant rotation of cells’*** to the holographic focusing flexibility and an ad-hoc angles’tracking algorithm,we combine different phase-contrast views of the nuclei to retrieve their 3D refractive index *** identification capability and a strategy for measuring morphology,dry mass,biovolume,and refractive index statistics are reported and *** new concept could revolutionize the investigation in plant biology by enabling dynamic 3D quantitative and label-free analysis at sub-nuclear level using a conventional holographic setup.

关键词： rotation holographic phase

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Complete pancreatic heterotopia of gallbladder with hypertrophic duct simulating an adenomyoma

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World Journal of Gastroenterology 2006年第11期12卷 1786-1787页

作者： luca Pilloni Alessandro Cois Alessandro Uccheddu Rossano Ambu Pierpaolo Coni Gavino Faa Istituto di Anatomia Patologica Dipartimento di Citomorfologia Universita degli Studi di CagliariItaly Semeiotica Chirurgica Dipartimento Chirurgico Materno Infantile e di Scienze delle Immagini Università degli Studi di CagliariItaly Istituto di Anatomia Patologica Dipartimento di Citomorfologia Università degli Studi di CagliariItaly

The gallbladder is an unusual location of pancreatic heterotopia, defined as the presence of pancreatic tissue lacking anatomical and vascular continuity with the main body of the gland. A 28-year-old man presented with anorexia, nausea and pain in the right upper abdomen. On physical examination, the abdomen was tender to palpation and Murphy sign was positive. The patient underwent a cholecystecomy. This case, in our opinion, is very interesting since it permits to consider a controversial issue in the pathology of the gallbladder. The histological appearance of ductal structure in pancreatic heterotopia resembles the histological picture of both Aschoff-Rokitansky （AR） sinuses and adenomyomas. This finding suggests that these lesions are linked by a common histogenetic origin. We suggest that the finding of an adenomyoma in the gallbladder should prompt an extensive sampling of the organ in order to verify the coexistence of pancreatic rests.

关键词： Pancreatic heterotopia Gallbladder Hypertrophic duct Adenomyoma Aschoff-Rokitansky sinuses

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Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies

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Neural Regeneration Research 2020年第5期15卷 802-816页

作者： Giulia Costa Maria Antonietta De luca Gessica Piras Jacopo Marongiu Liana Fattore Nicola Simola Department of Biomedical Sciences University of CagliariCagliariItaly National Institute of Neuroscience (INN) University of CagliariCagliariItaly National Research Council of Italy Institute of NeuroscienceCagliariItaly

Preclinical and clinical studies indicate that synthetic psychoactive substances,in addition to having abuse potential,may elicit toxic effects of varying severity at the peripheral and central ***,toxicity induced by synthetic psychoactive substances poses a serious harm for health,since recreational use of these substances is on the rise among young and adult *** present review summarizes recent findings on the peripheral and central toxicity elicited by “old” and “new” synthetic psychoactive substances in humans and experimental animals,focusing on amphetamine derivatives,hallucinogen and dissociative drugs and synthetic cannabinoids.

关键词： cannabinoids dissociatives hallucinogens ketamine MDMA methamphetamine methoxetamine neuroinflammation neurotoxicity NPS

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