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blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés berardo Cristian R.bacaglio bárbara b.báez Rubén Sambuelli Kazim A.Sheikh Pablo H.H.lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba Departamento de Química biológica-Centro de Investigaciones en Química biológica de Córdoba(CIQUIbIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba Servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba Department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-barrèsyndrome,mostly related to halted axon ***-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon *** effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so *** aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated *** results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of *** with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous *** contrast,the same dose showed toxic effects on the regeneration of myelinated ***,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only ***,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal *** findings open the possibility of therapeutic pharmacological intervention targeting Rho A/R

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-barrésyndrome nerve repair ROCK Y-27632

beyond dentistry:could prevention and screening for neurodegenerative diseases start in the dental office?

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Neural Regeneration Research 2024年第1期19卷 156-157页

作者： francesca R.buccellato Daniela Galimberti Gianluca M.Tartaglia Department of biomedical Surgical and Dental SciencesUniversity of MilanMilanItalyFondazione IRCCS Ca’GrandaOspedale Maggiore PoliclinicoMilanItaly

The differential diagnosis of neurodegenerative diseases is complex and relies on clinical assessment,biomarker levels in cerebrospinal fluid,neuroimaging and neuropsychological *** efforts of the scientific community are focused on two aspects:a)the discovery of minimally invasive biomarkers;b)the discovery of early biomarkers that can predict the progression to clinical disease in the presymptomatic stage of a *** the impact of the number of patients affected by chronic neurodegenerative diseases on public health expenditures,early diagnosis seems to be a primary need of our society.

关键词： diagnosis diseases prevention

Risk of hepatitis b virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

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World Journal of Gastroenterology 2024年第9期30卷 1253-1256页

作者： francesca Colapietro Nicola Pugliese Antonio Voza Alessio Aghemo Stella De Nicola Department of biomedical Sciences Humanitas UniversityMilan 20072Italy Division of Internal Medicine and Hepatology Department of GastroenterologyHumanitas Research HospitalMilan 20089Italy Department of Emergency Humanitas Research HospitalMilan 20089Italy

Hepatitis b virus(HbV)reactivation(HbVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy *** assessment of HbVr traditionally considers factors such as HbV profile,including hepatitis b surface antigen(HbsAg)and antibody to hepatitis b core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.

关键词： Chronic hepatitis b Reactivation Nucleoside analogue Tyrosine kinase inhibitors Onco-hematology

Advancing immunosuppression in liver transplantation: A narrative review

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari francesca Laura Nava Ilaria Elena Zais Laurent Coubeau Mariano Ferraresso Evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of b-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

Left bundle branch area pacing:A new era of cardiac resynchronization therapy?

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World Journal of Cardiology 2024年第9期16卷 542-545页

作者： Carlo Alberto Caruzzo Elia Rigamonti francesca Romana Scopigni Department of Cardiology Istituto Cardiocentro del TicinoLugano 6900TISwitzerland

The recent systematic review and meta-analysis provided a comprehensive focus on the current state of cardiac resynchronization therapy(CRT).The authors determined the feasibility of physiological left bundle branch area pacing(LbbAP)in patients indicated for CRT through a careful analysis of *** found that LbbAP was associated with significant reductions in QRS duration,New York Heart Association functional class,b-type natriuretic peptide levels,and pacing thresholds as well as improvements in echocardiographic parameters compared to biventricular pacing.

关键词： Left bundle branch pacing biventricular pacing QRS duration Left ventricular ejection fraction Heart failure

Plant triterpenoid saponins function as susceptibility factors to promote the pathogenicity of botrytis cinerea

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Molecular Plant 2024年第7期17卷 1073-1089页

作者： Francisco J.Escaray Amelia Felipo-benavent Cristian J.Antonelli begona balaguer Maria Pilar lopez-Gresa Pablo Vera Instituto de biologia Molecular y Celular de Plantas Universidad Politecnica de Valencia-C.S.l.CCiudad Politecnica de la InnovacionEdificio 8Eacceso GIngeniero Fausto Elios/n46022ValenciaSpain

The gray mold fungus botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species,including high-value *** polyxenous nature and pathogenic success are due to its ability to perceive host signals in its *** this study,we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by *** to cause ***,poor-in-latex(pil)mutants,which lack laticifer cells,show full resistance to this pathogen,whereas lot-of-latex mutants,which produce more laticifer cells,are *** S factors are triterpenoid saponins,which are widely distributed natural products of vast structural *** downregulation of laticifer-specific oxydosqualene cyclase genes,which encode the first committed step enzymes for triterpene and,therefore,saponin biosynthesis,conferred disease resistance to ***,the Medicago truncatula Iha-1 mutant,compromised in triterpenoid saponin biosynthesis,showed enhanced ***,the application of different purified triterpenoid saponins pharmacologically complemented the diseaseresistant phenotype ofpil and hla-1 mutants and enhanced disease susceptibility in different plant *** found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in ***,leading to a change in its growth habit and infection strategy,culminating in the abundant formation of infection cushions,the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in *** together,these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote *** pathogenicity.

关键词： Euphorbia lathyris laticifer cell latex appressorium infection cushion necrotrophic fungi

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

Evaluation of Human Impacts on bartlett Pond Ecosystem, Laredo, Southern Texas, USA, through Empirical Modeling

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Journal of Environmental Protection 2024年第4期15卷 497-526页

作者： Maya P. bhatt Amede Rubio Ganesh b. Malla Cristobal lopez Virginia Morales Erick Vazquez Cano David Marquez Orlando berumen Alvarez Alfred Addo-Mensah Department of biology and Chemistry Texas A&M International University Laredo USA Department of Mathematics Computer Geology and Physics University of Cincinnati-Clermont College Batavia USA

The trace elements chemistry of bartlett Pond, a small shallow wetland pond in Laredo, Southern Texas, was sampled to evaluate the dynamics of trace elements impacts on water quality and ecosystems ecology of the pond. Two types of fish (bass and tilapia) were also sampled to see the trace element accumulation in different parts of their body. The concentrations of trace elements in water samples were found in the following order: Fe ≫Sb > Pb > As ≫Co > Tl > Cr > Cd within bartlett Pond. Overall, the water quality of the pond is unacceptable for drinking and any other purposes as trace element concentrations (e.g. As, Cd, Co, Cr, Pb, Fe, Sb and Tl) are exceedingly higher (several fold) than the WHO and US EPA guidelines. Predictive and correlation analysis shows that most trace elements exhibit a strong positive correlation among them indicating the same anthropogenic sources and biogeochemical processes regulate these trace elements within the pond. Distributions of the trace elements in water exhibit different shapes mostly as positively skewed distribution for As, Cd, Co, Cr, and Tl, symmetrical distribution for Fe and almost symmetrical distribution for Pb and Sb. Concentrations of As, Co and Tl accumulated much higher in different parts of the bass than Tilapia fish. The concentrations of As, Tl, Co, and Sb appeared significantly higher in different parts of the body of both bass and Tilapia than the maximum SRM certified values. Accumulation of these contaminants in fish tissues pose increased health risks to humans who consume these contaminated fish although fishing is prohibited. Anthropogenic activities in the region primarily degrade the whole pond ecosystem ecology of the bartlett Pond and waters of this pond to be not recommended for any use. These findings may be useful for the scientific community and concerned authorities to improve understanding about these precious natural resources and conservation of the ecosystem ecology.

关键词： Trace Elements bartlett Pond Laredo Southern Texas Wetlands Ecosystem Ecology

A novel diagnostic gene region for distinguishing between two pest fruit flies:bactrocera tryoni(Froggatt)and bactrocera neohumeralis(Hardy)(Diptera:Tephritidae)

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Insect Science 2024年第4期31卷 1285-1295页

作者： Melissa L.Starkie Elizabeth V.Fowler Alexander M.Piper Xiaocheng Zhu Pauline Wyatt David Gopurenko Matt N.Krosch francesca Strutt Karen F.Armstrong Hamish Patrick Mark K.Schutze Mark J.blacket Department of Agriculture and Fisheries BiosecurityBrisbaneQueenslandAustralia Agriculture Victoria AgriBioBundooraVictoriaAustralia Department of Primary Industries Wagga Wagga Agricultural InstituteWagga WaggaNew South WalesAustralia Forensic Services Group Queensland Police ServiceBrisbaneQueenslandAustralia Department of Pest-management and Conservation Lincoln UniversityLincolnNew Zealand better border biosecurity(b3 B3nz.org.nz)LincolnNew Zealand

bactrocera tryoni and bactrocera neohumeralis are morphologically similar sibling pest fruit fly species that possess different biological attributes,geographic distributions,and host *** need to differentiate between the two species is critical for accurate pest status assessment,management,biosecurity,and maintenance of reference *** morphologically similar,adults may be separated based on subtle characters;however,some characters exhibit intraspecific variability,creating overlap between the two ***,there is currently no single molecular marker or rapid diagnostic assay that can reliably distinguish between *** and ***;therefore,ambiguous samples remain *** we report the first molecular marker that can consistently distinguish between *** and *** diagnostic region consists of two adjacent single nucleotide polymorphisms(SNPs)within the pangolin(pan)gene *** confirmed the genotypes of each species are consistent across their distributional range,then developed a tetra-primer amplification refractory mutation system(ARMS)PCR assay for rapid diagnosis of the *** assay utilizes four primers in multiplex,with two outer universal primers,and two internal primers:one designed to target two adjacent SNPs(AA)present in *** and the other targeting adjacent SNPs present in ***(GG).The assay accurately discriminates between the two species,but their SNP genotypes are shared with other nontarget tephritid fruit fly ***,this assay is most suited to adult diagnostics where species confirmation is necessary in determining ambiguous surveillance trap catches;maintaining pure colony lines;and in Sterile Insect Technique management responses.

关键词： ARMS-PCR colony molecular diagnostics pangolin tetra-primer