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Protective effect of resveratrol against cadmium-induced toxicity on ovine oocyte in vitro maturation and fertilization

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Journal of Animal Science and Biotechnology 2023年第1期14卷 152-165页

作者： Anna Rita Piras federica ariu Alessio Maltana Giovanni Giuseppe Leoni Nicola Antonio Martino Antonella Mastrorocco Maria Elena Dell’Aquila Luisa Bogliolo Department of Veterinary Medicine University of Sassari07100 SassariSardiniaItaly. Department of Biosciences Biotechnologies&BiopharmaceuticsUniversity of Bari Aldo Moro70125 BariItaly.

Background:Heavy metal cadmium(Cd)is a widespread environmental contaminant with a potential toxicity that might negatively affect female reproduction and fertility.It has been reported that Cd exposure impaired the quality of oocytes and led to a defective maturation and fertilization,through oxidative stress induction.Resveratrol(Res)is a natural polyphenol with strong antioxidant properties that exhibited protective role in preventing oocyte redox homeostasis disruption and quality decline.Here,we explored whether the addition of Res to in vitro maturation(IVM)medium might act as a protection against Cd-induced toxicity on ovine oocyte maturation and fertilization.Firstly,we evaluated the effect of supplementing IVM medium with two different Res concentrations(1and 2μmol/L)on nuclear maturation and fertilization of oocytes matured under CdCl2(2μmol/L)exposure.Therefore,the concentration of 1μmol/L Res was selected to analyse the effects of this compound on intracellular ROS levels,mitochondrial(mt)distribution and activity,chromatin configuration,cytoskeleton morphology,cortical granules(CGs)distribution and mRNA expression of genes associated with cellular response to oxidative stress(i.e.SIRT1,SOD 1,GPX1,GSR,CAT)in Cd-exposed in vitro matured oocytes.Results:We found that 1μmol/L Res restored the reduced oocyte meiotic competence induced by Cd exposure as well as,Res sustained oocyte ability to be normally fertilized and decreased polyspermic fertilization at both tested concentrations.Moreover,we demonstrated that 1μmol/L Res mitigated Cd-induced alterations of oocyte cytoplasmic maturation by reducing reactive oxygen species(ROS)accumulation,preventing mt dysfunction,maintaining the correct meiotic spindle and cortical F-actin assembly and the normal cortical granule distribution as well as up-regulating SIRT1,SOD1 and GPX1 genes.Conclusions:Taken together,our findings highlighted the beneficial influence exerted by Res in preventing Cdinduced disturbance of nuclear and cytoplasmic maturation and subsequen

关键词： Cadmium In vitro maturation Oocyte Ovine Resveratrol

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Insights on ZEB1-AS1: emerging role from cancer to neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1187-1188页

作者： Stephana Carelli federica Rey Erika Maghraby Cristina Cereda Pediatric Research Center “Romeo ed Enrica Invernizzi” Department of Biomedical and Clinical Sciences University of Milan 2. Center of Functional Genomics and Rare Diseases Department of Pediatrics Buzzi Children's Hospital Department of Biology and Biotechnology “L.Spallanzani” University of Pavia

Implications for lncRNAs in the central nervous system: Transcriptional dysregulation is a key contributor to the pathogenesis of a wide range of diseases and long non-coding RNAs(lncRNAs) are highly expressed in the nervous system. Indeed, amongst the over 50,000 lncRNAs expressed in the human genome, more than 40% are specifically expressed in the brain where their roles in brain development, neuron functions, maintenance,

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Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis

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Neural Regeneration Research 2024年第8期19卷 1768-1771页

作者： federica Azzolini Ettore Dolcetti Antonio Bruno Valentina Rovella Diego Centonze Fabio Buttari Unit of Neurology IRCCS NeuromedPozzilliItaly Department of System Medicine University of Tor VergataRomeItaly Synaptic Immunopathology Lab Department of Systems MedicineTor Vergata UniversityRomeItaly

In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.

关键词： disease-modifying behaviour endocannabinoid system long-term potentiation multiple sclerosis neuroplasticity neuroprotection physical exercise synaptopathy

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Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

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Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi federica Cherchi Alasdair J.Gibb Department of Neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly Department of Neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

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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 straw.Ovine 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"E.Vit",composed by a 0.25-m L straw with a 50-μm pore polycarbonate grid at one end.Embryos at each stage(EBs and FEBs)were vitrified by either Two-step(TS)or Multi-step(MS;6 different concentrations of vitrification solutions)protocol.Non-vitrified embryos(n=102)were maintained in in vitro culture as a control.Warming consisted of placing the straws directly into 1.5 m L tubes containing a TCM-199 solution with three decreasing concentrations of sucrose.Blastocyst re-expansion,embryo survival and hatching rate were evaluated at2,24 and 48 h post warming.The number of apoptotic cells was determined by TUNEL assay.Results:Blastocyst re-expansion(2 h)after warming was higher(P<0.05)in FEBs group,vitrified with the MS 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(P<0.001)in both methods(MS and TS)than vitrified EBs(MS:56.25%;TS:42.42%)and was higher(P<0.05)in the MS 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 FEBs.The number of apoptotic cells in FEBs vitrified with MS was comparable to the control.Conclusions:A high survival rate of IVP embryos can be achieved by the new"E.Vit"device with hatching rates in vitro comparable with control fresh embryos.This 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

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Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis

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Asian Journal of Andrology 2024年第2期26卷 144-154页

作者： Rossella Cannarella Carmelo Gusmano Claudia Leanza Vincenzo Garofalo Andrea Crafa federica Barbagallo Rosita A Condorelli Sandro La Vignera Aldo E Calogero Department of Clinical and Experimental Medicine University of CataniaCatania 95123Italy Glickman Urological&Kidney Institute Cleveland Clinic FoundationClevelandOH44195USA

To evaluate the relationship between testosterone replacement therapy(TRT)and arterial and/or venous thrombosis in patients with pre-treatment total testosterone(TT)<12 nmol I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome model.Population:men with TT<12 nmol I^(-1) or clear mention of hypogonadism in the inclusion criteria of patients;intervention:TRT;comparison:placebo or no therapy;outcomes:arterial thrombotic events(stroke,myocardial infarction[MI],upper limbs,and lower limbs),VTE(deep vein thrombosis[DVT],portal vein thrombosis,splenic thrombosis,and pulmonary embolism),and mortality.A total of 2423 abstracts were assessed for eligibility.Twenty-four studies,including 14 randomized controlled trials(RCTs),were finally included,with a total of 4027 and 310288 hypotestosteronemic male patients,from RCTs and from observational studies,respectively.Based on RCT-derived data,TRT did not influence the risk of arterial thrombosis(odds ratio[OR]=1.27,95%confidence interval[CI]:0.47-3.43,P=0.64),stroke(OR=1.34,95%CI:0.09-18.97,P=0.83),MI(OR=0.51,95%CI:0.11-2.31,P=0.39),VTE(OR=1.42,95%CI:0.22-9.03,P=0.71),pulmonary embolism(OR=1.38,95%CI:0.27-7.04,P=0.70),and mortality(OR=0.70,95%CI:0.20-2.38,P=0.56).Meanwhile,when only observational studies are considered,a significant reduction in the risk of developing arterial thrombotic events,Ml,venous thromboembolism,and mortality was observed.The risk for DVT remains uncertain,due to the paucity of RCT-based data.TRT in men with TT<12 nmol I^(-1) is safe from the risk of adverse cardiovascular events.Further studies specifically assessing the risk of DVT in men on TRT are needed.

关键词： hypogonadism testosterone testosterone replacement therapy thromboembolism thrombosis TRT

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Stochastic Maximum Principle for Optimal Advertising Models with Delay and Non-Convex Control Spaces

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Advances in Pure Mathematics 2024年第6期14卷 442-450页

作者： Giuseppina Guatteri federica Masiero Dipartimento di Matematica Politecnico di Milano via Bonardi Milano Italia Dipartimento di Matematica e Applicazioni Universit di Milano-Bicocca via Cozzi Milano Italia

In this paper we study optimal advertising problems that model the introduction of a new product into the market in the presence of carryover effects of the advertisement and with memory effects in the level of goodwill. In particular, we let the dynamics of the product goodwill to depend on the past, and also on past advertising efforts. We treat the problem by means of the stochastic Pontryagin maximum principle, that here is considered for a class of problems where in the state equation either the state or the control depend on the past. Moreover the control acts on the martingale term and the space of controls U can be chosen to be non-convex but now the space of controls U can be chosen to be non-convex. The maximum principle is thus formulated using a first-order adjoint Backward Stochastic Differential Equations (BSDEs), which can be explicitly computed due to the specific characteristics of the model, and a second-order adjoint relation.

关键词： Stochastic Optimal Control Delay Equations Advertisement Models Stochastic Maximum Principle

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Characterization of the molecular dysfunctions occurring in Aicardi-Goutieres syndrome patients with mutations in ADAR1

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Genes & Diseases 2024年第3期11卷 116-119页

作者： Sofan Al wardat Loredana Frasinlli Elisa Orecchini federica Rey Silvia Anna Ciafre Silvia Galardi Jessica Garau Stella Gagliardi Simona Orcesi Davide Tonduti Stephana Carelli Cristina Cereda Ernesto Picardi Alessandro Michienzi Department of Biomedicine and Prevention University of Rome Tor VergataRome 00133Italy Pediatric Clinical Research Center"Romeo ed Enrica Invernizzi" Department of Biomedical and Clinical SciencesUniversity of MilanoMilano 20157Italy Center of Functional Genomics and Rare Diseases Department of PediatricsBuzzi Children's HospitalMilano20154Italy Department of Child Neurology and Psychiatry IRccs Mondino FoundationPavia 27100Italy Unit of Pediatric Neurology C.O.A.L.A(Center for Diagnosis and Treatment of Leukodystrophies)Buzzi Children's HospitalMilano 20154Italy Department of Biosciences Biotechnologies and EnvironmentUniversityof Bari"AldoMoro"Bari 70125Italy Institute of Biomembranes Bioenergetics and Molecular Biotechnologies(IBIOM)National Research Council(CNR)Bari 70126Italy Biostructures and Biosystems National Institute(INBB) Rome00136Italy Institute of Biochemistry and Cell Biology IBBC-CNRCampus Adriano Buzzati TraversoRome 00015Italy

Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).

关键词： ADAR1 interferon res

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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 supplies.PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment.Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC.Here,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient deprivation.We 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 patients.Mechanistically,we discovered that miR-15a repressed IGF1R expression via Fra-2 targeting.In miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient deprivation.In a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet restriction.Consistently,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent manner.Overall,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

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From strength to precision: A systematic review exploring the clinical utility of 7-Tesla magnetic resonance imaging in abdominal imaging

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World Journal of Radiology 2024年第1期16卷 20-31页

作者： Arosh S Perera Molligoda Arachchige Ana Claudia Teixeira de Castro Gonçalves Ortega federica Catapano Letterio S Politi Michael N Hoff Faculty of Medicine Humanitas UniversityPieve Emanuele 20072MilanItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20072MilanItaly IRCCS Humanitas Research Hospital Rozzano 20089MilanItaly Department of Neuroradiology IRCCS Humanitas Research HospitalRozzano 20089MilanItaly Department of Radiology and Biomedical Imaging University of CaliforniaSan FranciscoCA 94143United States

BACKGROUND After approval for clinical use in 2017 early investigations of ultra-high-field abdominal magnetic resonance imaging(MRI)have demonstrated the feasibility as well as diagnostic capabilities of liver,kidney,and prostate MRI at 7-Tesla.However,the elevation of the field strength to 7-Tesla not only brought advantages to abdominal MRI but also presented considerable challenges and drawbacks,primarily stemming from heightened artifacts and limitations in Specific Absorption Rate,etc.Furthermore,evidence in the literature is relatively scarce concerning human studies in comparison to phantom/animal studies which necessitates an investigation into the evidence so far in humans and summarizing all relevant evidence.AIM To offer a comprehensive overview of current literature on clinical abdominal 7T MRI that emphasizes current trends,details relevant challenges,and provides a concise set of potential solutions.METHODS This systematic review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.A PubMed search,utilizing Medical Subject Headings terms such as"7-Tesla"and organ-specific terms,was conducted for articles published between January 1,1985,and July 25,2023.Eligibility criteria included studies exploring 7T MRI for imaging human abdominal organs,encompassing various study types(in-vivo/ex-vivo,method development,reviews/meta-analyses).Exclusion criteria involved animal studies and those lacking extractable data.Study selection involved initial identification via title/abstract,followed by a full-text review by two researchers,with discrepancies resolved through discussion.Data extraction covered publication details,study design,population,sample size,7T MRI protocol,image characteristics,endpoints,and conclusions.RESULTS The systematic review included a total of 21 studies.The distribution of clinical 7T abdominal imaging studies revealed a predominant focus on the prostate(n=8),followed by the kidney(n=6)and the hepatobiliary system(n=5).Studies on these organs,and

关键词： 7-Tesla magnetic resonance imaging Abdominal Prostate Kidney Renal Pancreas Hepatobiliary Liver Small bowel

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