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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra marina Capece Luca Reggiani Bonetti Giovanni Nigita federica Calore Sydney Rentsch Paolo magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo m.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and molecular medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

Strong attenuation of SARS-CoV-2 Omicron BA.1 and increased replication of the BA.5 subvariant in human cardiomyocytes

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Signal Transduction and Targeted Therapy 2023年第1期8卷 10-12页

作者： Rayhane Nchioua federica Diofano Sabrina Noettger Pascal von maltitz Steffen Stenger Fabian Zech Jan münch Konstantin m.J.Sparrer Steffen Just Frank Kirchhoff Institute of molecular Virology Ulm University Medical CenterUlmGermany molecular Cardiology Department of Internal Medicine IIUlm UniversityUlmGermany Institute of medical microbiology and Hygiene Ulm University Medical CenterUlmGermany

Dear Editor,Since its first description in South Africa in November 2021,the SARS-CoV-2 Omicron variant rapidly outcompeted the previously dominating Delta *** is the fifth variant of concern(VOC).It contains an unusually high number of mutations compared to previous VOCs,especially in the viral Spike protein,and shows high transmissibility and efficient escape of neutralizing antibodies.

关键词： Strong neutral Omi

Deformation history and processes during accretion of seamounts in subduction zones:The example of the Durkan Complex(makran,SE Iran)

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Geoscience Frontiers 2023年第2期14卷 182-203页

作者： Edoardo Barbero maria Di Rosa Luca Pandolfi morteza Delavari Asghar Dolati federica Zaccarini Emilio Saccani michele marroni Dipartimento di Fisica e Scienze della Terra Universitàdi Ferrara44123 FerraraItaly Istituto di Geoscienze e Georisorse Consiglio Nazionale delle Ricerche(CNR)10125 TorinoItaly Dipartimento di Scienze della Terra Universitàdi Pisa56126 PisaItaly Istituto di Geoscienze e Georisorse Consiglio Nazionale delle Ricerche(CNR)56124 PisaItaly Faculty of Earth Sciences Kharazmi UniversityTehran 15719-19911Iran Department of Applied Geological Sciences and Geophysics University of Leoben8700 LeobenAustria

The Durkan Complex is a tectonic element of the makran Accretionary Prism(SE Iran)that includes fragments of Late Cretaceous *** this paper,the results of map-to micro-scale structural studies of the western Durkan Complex are presented with the aim to describe its structural and tectonometamorphic *** Durkan Complex consists of several tectonic units bordered by mainly NNW-striking *** main deformation phases(D_(1),D_(2),and D_(3))are distinguished and likely occurred from the Late Cretaceous to the miocene–Pliocene.D_(1) is characterized by sub-isoclinal to close and W-verging folds associated with an axial plane foliation and shear zone along the fold *** phase records the accretion of fragments of the seamount within the makran at blueschist facies metamorphic conditions(160–300℃ and 0.6–1.2 GPa).D_(2) is characterized by open to close folds with subhorizontal axial plane that likely developed during the exhumation of previously accreted seamount *** upper Paleocene–Eocene siliciclastic succession unconformably sealed the D_(1) and D_(2) structures and is,in turn,deformed by W-verging thrust faults typical of D_(3).The latter likely testifies for a miocene–Pliocene tectonic reworking of the accreted seamount fragments with the activation of out of sequence *** results shed light on the mechanism of accretion of seamount materials in the accretionary prisms,suggesting that seamount slope successions favour the localization and propagation of the basal dé*** study further confirms that the physiography of the subducting plates plays a significant role in the tectonic evolution of the subduction complexes.

关键词： Underplated seamount makran Accretionary Prism Tectono-sedimentary evolution Tectono-metamorphic evolution Cretaceous Iran

^(18)F-fluorodeoxyglucose positron emission tomography for intrahepatic cholangiocarcinoma N-and m-staging:should guidelines recommend it at last?

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Hepatobiliary Surgery and Nutrition 2022年第5期11卷 789-792页

作者： maurizio Zizzo magda Zanelli Francesca Sanguedolce Annibale Versari Pierpaolo Pattacini Andrea morini federica mereu Antonia Lavinia Zuliani Alessandro Giunta Surgical Oncology Unit Azienda UnitàSanitaria Locale-IRCCS di Reggio EmiliaArcispedale Santa Maria Nuova di Reggio EmiliaReggio EmiliaItaly Pathology Unit Azienda UnitàSanitaria Locale-IRCCS di Reggio EmiliaArcispedale Santa Maria Nuova di Reggio EmiliaReggio EmiliaItaly Pathology Unit Azienda Ospedaliero-UniversitariaOspedali Riuniti di FoggiaFoggiaItaly Nuclear medicine Unit Azienda UnitàSanitaria Locale-IRCCS di Reggio EmiliaArcispedale Santa Maria Nuova di Reggio EmiliaReggio EmiliaItaly Radiology Unit Azienda UnitàSanitaria Locale-IRCCS di Reggio EmiliaArcispedale Santa Maria Nuova di Reggio EmiliaReggio EmiliaItaly

We really appreciated Lin et al.’s“The influence of ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography on the N-and m-staging and subsequent clinical management of intrahepatic cholangiocarcinoma”in HepatoBiliary Surgery and Nutrition(1).A 291-patient population affected by intrahepatic cholangiocarcinoma(ICC)was retrospectively analyzed with the aim of assessing the accuracy of preoperative staging and treatment reallocation by ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)(1).

关键词： positron deoxy

Seamless integration of bioelectronic interface in an animal model via in vivo polymerization of conjugated oligomers

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Bioactive materials 2022年第4期7卷 107-116页

作者： Giuseppina Tommasini Gwennael Dufil federica Fardella Xenofon Strakosas Eugenio Fergola Tobias Abrahamsson David Bliman Roger Olsson magnus Berggren Angela Tino Eleni Stavrinidou Claudia Tortiglione Istituto di Scienze Applicate e Sistemi Intelligenti“E.Caianiello” Consiglio Nazionale delle RicercheVia Campi Flegrei 3480078PozzuoliItaly Laboratory of Organic Electronics Department of Science and TechnologyLinkoping UniversitySE-60174NorrkopingSweden Department of Chemistry and molecular Biology University of GothenburgSE-40530GothenburgSweden Chemical Biology&Therapeutics Department of Experimental Medical ScienceLund UniversitySE-22184LundSweden

Leveraging the biocatalytic machinery of living organisms for fabricating functional bioelectronic interfaces,in vivo,defines a new class of micro-biohybrids enabling the seamless integration of technology with living biological ***,we have demonstrated the in vivo polymerization of conjugated oligomers forming conductors within the structures of ***,we expand this concept by reporting that Hydra,an invertebrate animal,polymerizes the conjugated oligomer ETE-S both within cells that expresses peroxidase activity and within the adhesive material that is secreted to promote underwater surface *** resulting conjugated polymer forms electronically conducting and electrochemically activeμm-sized domains,which are inter-connected resulting in percolative conduction pathways extending beyond 100μm,that are fully integrated within the Hydra tissue and the secreted ***,the introduction and in vivo polymerization of ETE-S can be used as a biochemical marker to follow the dynamics of Hydra budding(reproduction)and *** work paves the way for well-defined self-organized electronics in animal tissue to modulate biological functions and in vivo biofabrication of hybrid functional materials and devices.

关键词： In vivo polymerization Bioelectronics interfaces Conjugated oligomers model organism

High in vitro survival rate of sheep in vitro produced blastocysts vitrified with a new method and device

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Journal of Animal Science and Biotechnology 2020年第1期11卷 71-80页

作者： Sergio Ledda Jen m.Kelly Stefano Nieddu Daniela Bebbere federica Ariu Luisa Bogliolo Dity Natan Amir Arav Department of Veterinary medicine University of SassariSassariItaly South Australian Research and Development Institute Turretfield Research Centre129 Holland RoadRosedaleSA 5350Australia FertilSafe Ltd 11 Haharash st7403118 Ness ZionaIsrael.

Background:To advance the use of embryo vitrification in veterinary practice,we developed a system in which embryo vitrification,warming and dilution can be performed within a *** in vitro produced embryos(IVEP)were vitrified at either early(EBs:n=74)or fully expanded blastocyst stage(FEBs:n=195),using a new device named"***",composed by a 0.25-m L straw with a 50-μm pore polycarbonate grid at one *** at each stage(EBs and FEBs)were vitrified by either Two-step(TS)or multi-step(mS;6 different concentrations of vitrification solutions)***-vitrified embryos(n=102)were maintained in in vitro culture as a *** consisted of placing the straws directly into 1.5 m L tubes containing a TCm-199 solution with three decreasing concentrations of *** re-expansion,embryo survival and hatching rate were evaluated at2,24 and 48 h post *** number of apoptotic cells was determined by TUNEL ***:Blastocyst re-expansion(2 h)after warming was higher(PmS and TS methods(77.90%and 71.25%,respectively)compared with the EBs group(mS:59.38%and TS:48.50%,respectively).Survival rates of vitrified FEBs after 24 h IVC were higher(Pmethods(mS and TS)than vitrified EBs(mS:56.25%;TS:42.42%)and was higher(PmS method(94.19%)compared with those in TS(83.75%).After 48 h of culture the hatching rate for FEBs vitrified in mS system(91.86%)was similar to control(91.89%),but higher than FEB TS(77.5%)and EBs vitrified in mS(37.5%)and TS(33.33%).Number of apoptotic cells were higher in EBs,irrespective of the system used,compared to *** number of apoptotic cells in FEBs vitrified with mS was comparable to the ***:A high survival rate of IVP embryos can be achieved by the new"***"device with hatching rates in vitro comparable with control fresh *** method has the potential for use in direct embryo transfer in field conditions.

关键词： Blastocysts High survival In-straw In vitro embryo produced Ovine

Tumor-associated myeloid cells:diversity and therapeutic targeting

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Cellular & molecular Immunology 2021年第3期18卷 566-578页

作者： Alberto mantovani federica marchesi Sebastien Jaillon Cecilia Garlanda Paola Allavena Department of Immunology and Inflammation Humanitas Clinical and Research Center-IRCCSRozzanoItaly Department of Biomedical Science Humanitas UniversityRozzanoItaly The William Harvey Research Institute Queen Mary University of LondonLondonUK Department of Biotechnology and Translational medicine University of MilanMilanItaly

myeloid cells in tumor tissues constitute a dynamic immune population characterized by a non-uniform phenotype and diverse functional *** tumor-associated macrophages(TAms),which are more abundantly represented,and tumor-associated neutrophils(TANs)are known to sustain tumor cell growth and invasion,support neoangiogenesis and suppress anticancer adaptive immune *** recent decades,several therapeutic approaches have been implemented in preclinical cancer models to neutralize the tumor-promoting roles of both TAms and *** of the most successful strategies have now reached the clinic and are being investigated in clinical *** this review,we provide an overview of the recent literature on the evergrowing complexity of the biology of TAms and TANs and the development of the most promising approaches to target these populations therapeutically in cancer patients.

关键词： tumor-associated macrophages tumor microenvironment macrophage targeting

IKKβ binds NLRP3 providing a shortcut to inflammasome activation for rapid immune responses

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4022-4024页

作者： Yaw Asare margarita Shnipova LukaŽivković Christina Schlegl federica Tosato Arailym Aronova markus Brandhofer Laura Strohm Nathalie Beaufort Rainer malik Christian Weber Jürgen Bernhagen martin Dichgans Institute for Stroke and Dementia Research(ISD) University HospitalLudwig-Maximilians-University(LMU)MunichGermany munich Cluster for Systems Neurology(SyNergy) MunichGermany Institute for Cardiovascular Prevention(IPEK) LMUMunichGermany

Dear Editor,A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring *** response is largely mediated by the concerted action of pattern recognition receptors(PRRs).Such cooperativity has been described for Toll-like receptors(TLRs)and NACHT,LRR,and pyrin domain-containing protein 3(NLRP3),but the underlying molecular mechanisms remain incompletely *** are multi-protein complexes defined by a cytosolic innate immune sensor,usually a PRR,which recruits the adaptor molecule apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)to activate the effector caspase-1 leading to the release of matured IL-1βand *** caspase-1 further cleaves gasdermin D(GSDmD)allowing the N-terminal domain of GSDmD(GSDmD-N)to form pores in the plasma membrane,thus facilitating the release of matured IL-1βand ***-forming GSDmD-N further induces pyroptosis,an inflammatory form of cell death.

关键词： NLRP3 release activation

The Group A Streptococcus Interleukin-8 Protease SpyCEP Promotes Bacterial Intracellular Survival by Evasion of Autophagy

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Infectious microbes & Diseases 2022年第3期4卷 116-123页

作者： RenéBergmann Giuseppe Gulotta federica Andreoni Tomoko Sumitomo Shigetada Kawabata Annelies S.Zinkernagel Gursharan S.Chhatwal Victor Nizet manfred Rohde Satoshi Uchiyama Central Unit for microscopy(ZEIm) Helmholtz Centre for Infection ResearchBraunschweigGermany Division of Infectious Diseases and Hospital Epidemiology University Hospital ZurichZurichSwitzerland Department of Oral and molecular microbiology Osaka University Graduate School of DentistrySuita-OsakaJapan Division of Host-microbe Systems and Therapeutics Department of PediatricsUniversity of CaliforniaSan DiegoLa JollaCalifornia

Autophagy serves an innate immune function in defending the host against invading bacteria,including group A Streptococcus(GAS).Autophagy is regulated by numerous host proteins,including the endogenous negative regulator calpain,a cytosolic *** disseminated serotypem1T1 GAS strains associated with high invasive disease potential express numerous virulence factors and resist autophagic *** in vitro infection of human epithelial cell lines with representative wild-type GAS m1T1 strain 5448(m1.5448),we observed increased calpain activation linked to a specific GAS virulence factor,the interleukin-8 protease *** activation inhibited autophagy and decreased capture of cytosolic GAS in *** contrast,the serotype m6 GAS strain JRS4(***4),which is highly susceptible to host autophagy-mediated killing,expresses low levels of SpyCEP and does not activate *** of SpyCEP in ***4 stimulated calpain activation,inhibited autophagy,and significantly decreased bacterial capture in *** paired loss-and gain-of-function studies reveal a novel role for the bacterial protease SpyCEP in enabling GAS m1 evasion of autophagy and host innate immune clearance.

关键词： group A Streptococcus SpyCEP virulence factor epithelial cells intracellular survival autophagy xenophagy calpain