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Axonal growth inhibitors and their receptors in spinal cord injury:from biology to clinical translation

Neural Regeneration Research 2023年第12期18卷 2573-2581页

作者： s.lvia sousa Chambel Célia Duarte Cruz Experimental Biology Unit Department of BiomedicineFaculty of Medicine of PortoUniversity of PortoPortoPortugal Translational NeuroUrology Instituto de Investigação e Inovação em Saúde-i3S and IBMCUniversidade do PortoPortoPortugal

Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory prot

关键词： chondroitin sulphate proteoglycans collapsin response mediator protein 2 inhibitory molecules leucine-rich repeat and ig domain containing 1 leucocyte common antigen related myelin-associated glycoprotein neurite outgrowth inhibitor A Nogo receptor 1 Nogo receptor 3 oligodendrocyte myelin glycoprotein p75 neurotrophin receptor Plexin A2 Ras homolog family member A/Rho-associated protein kinase receptor protein tyrosine phosphataseσ repulsive guidance molecule A spinal cord injury tumour necrosis factor receptor superfamily member 19

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MYC and KRAs cooperation:from historical challenges to therapeutic opportunities in cancer

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signal Transduction and Targeted Therapy 2024年第9期9卷 3840-3869页

作者： s.lvia Casacuberta-serra Íñigo González-Larreategui Daniel Capitán-Leo Laura soucek Peptomyc s.L. BarcelonaSpain Models of cancer therapies Laboratory Vall d’Hebron Institute of OncologyCellex CentreHospital University Vall d’Hebron CampusBarcelonaSpain institucióCatalana de Recerca i Estudis Avançats BarcelonaSpain Department of Biochemistry and Molecular Biology Universitat Autonoma de BarcelonaBellaterraSpain

RAs and MYC rank amongst the most commonly altered oncogenes in cancer,with RAs being the most frequently mutated and MYC the most *** cooperative interplay between RAs and MYC constitutes a complex and multifaceted phenomenon,profoundly influencing tumor *** and individually,these two oncogenes regulate most,if not all,hallmarks of cancer,including cell death escape,replicative immortality,tumor-associated angiogenesis,cell invasion and metastasis,metabolic adaptation,and immune *** to their frequent alteration and role in tumorigenesis,MYC and RAs emerge as highly appealing targets in cancer ***,due to their complex nature,both oncogenes have been long considered“undruggable”and,until recently,no drugs directly targeting them had reached the *** review aims to shed light on their complex partnership,with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in *** this review,we also present an update on the different inhibitors targeting RAs and MYC currently undergoing clinical trials,along with their clinical outcomes and the different combination strategies being explored to overcome drug *** recent clinical development suggests a paradigm shift in the long-standing belief of RAs and MYC“undruggability”,hinting at a new era in their therapeutic targeting.

关键词： therapeutic overcome Together

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Managing type 2 diabetes:targeting a microbial enzyme as a novel treatment option

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signal Transduction and Targeted Therapy 2024年第1期9卷 3-5页

作者： Anikó Keller-Pintér Tamás Korcsmáros Tibor Vellai Department of Biochemistry Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzeged6720Hungary Department of Metabolism Digestion and ReproductionImperial College LondonLondonW120NNUK Quadram institute Bioscience Norwich Research ParkNorwichNR47UQUK Department of Genetics Eötvös Loránd University(ELTE)Budapest1117Hungary Hungarian Research Network HUN-REN-ELTE Genetics Research Group Budapest1117Hungary

in a recent science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.

关键词： homeostasis stimulating clinical

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The versatility of mesenchymal stem cells:From regenerative medicine to COViD,what is next?

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BiOCELL 2022年第4期46卷 913-922页

作者： THAÍs CAsAGRANDE PAiM MÁRCiA rosÂNGELA WiNK Laboratório de Biologia Celular Universidade Federal de Ciências da Saúde de Porto Alegre(UFCSPA)Porto Alegre90050-170Brazil

Mesenchymal stem cells(MsCs)play key roles in regenerative medicine by promoting tissue *** can be isolated from different adult tissues and they are able to differentiate into several *** to their antiinflammatory,angiogenic and immune-modulatory properties,MsCs are suitable for tissue engineering applications and,when associated with biomaterials,their benefits can be ***,recently,MsCs have been studied for new clinical applications,such as in the treatment of patients with *** regenerative potential has been attributed to their secretome,which comprises extracellular matrix,soluble proteins and several elements,including the release of extracellular *** though,in order to explore all their therapeutic potential,it is still necessary to advance in the investigation of their basic cell biology characteristics.

关键词： Mesenchymal stem cells Regenerative medicine secretome Biomaterials Extracellular vesicles

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Near-infrared leaf reflectance modeling of Annona emarginata seedlings for early detection of variations in nitrogen concentration

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Journal of Forestry Research 2023年第1期34卷 269-282页

作者： Rafaela Lancas Gomes Marília Caixeta sousa Felipe Girotto Campos Carmen s.lvia Fernandes Boaro José Raimundo de souza Passos Gisela Ferreira Bioestatistic Plant BiologyParasitology and Zoology DepartmentBioscience Institute(IBB)Universidade Estadual Paulista(UNESP)BotucatuSao PauloBrazil

Nitrogen(N)monitoring is essential in nurseries to ensure the production of high-quality *** spectroscopy(NiRs)is an instantaneous,nondestructive method to monitor *** data such as NiRs can also provide the basis for developing a new vegetation spectral index(Vsi).Here,we evaluated whether NiRs combined with statistical modeling can accurately detect early variations in N concentration in leaves of young plants of Annona emargiaata and developed a new Vsi for this *** were grown in a hydroponics system with 0,2.75,5.5or 11 mM N for 45 *** we measured gas exchange,chlorophylla fluorescence,and pigments in leaves;analyzed complete leaf nutrients,and recorded spectral data for leaves at 966 to 1685 nm using *** a statistical learning approach,the dimensionality of the spectral data was reduced,then models were generated using two classes(N deficiency,N)or four classes(0,2.75,5.5,11 mM N).The best combination of techniques for dimensionality reduction and classification,respectively,was stepwise regression(PROC sTEPDisC)and linear discriminant *** was possible to detect N deficiency in seedlings leaves with 100%precision,and the four N concentrations with93.55%accuracy before photosynthetic damage to the plant ***,NiRs combined with statistical modeling of multidimensional data is effective for detecting N variations in seedlings leaves of ***.

关键词： Mineral nutrition of plants Near-infrared spectroscopy spectral vegetation index Digital signature statistical learning Fluorescence of chlorophylla

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A proctolin-like peptide is regulated after baculovirus infection and mediates in caterpillar locomotion and digestion

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insect science 2022年第1期29卷 230-244页

作者： Angel Llopis-Giménez stefano Parenti Yue Han Vera i.D.ros salvador Herrero Department of Genetics and institut Universitari en Biotecnologia i Biomedicina(BiOTECMED) Universitat de ValenciaValenciaSpain Laboratory of Virology Wageningen University and ResearchWageningenthe Netherlands Current address.Department of Pathology University of CambridgeCambridgeUK

Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues, included the central nervous system (CNs). As a main component of the CNs, neuropeptides are small protein-like molecules functioning as neurohormones, neurotransmitters, or neuromodulators. These peptides are involved in regulating animal physiology and behavior and could be altered after baculovirus infection. in this study, we have investigated the effect of spodoptera exigua multiple nucleopolyhedrovirus (seMNPV) infection on expression of spodoptera exigua neuropeptides and neuropeptide-like genes. Expression of the gene encoding a polypeptide that resembles the well-known insect neuropeptide proctolin and named as proctolin-like peptide (PLP), was downregulated in the larval brain following infection and was chosen for further analysis. A recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) overexpressing the C-terminal part of the PLP was generated and used in bioassays using s. exigua larvae to study its influence on the viral infection and insect behavior. AcMNPV-PLP-infected larvae showed less locomotion activity and a reduction in growth compared to larvae infected with wild type AcMNPV or mock-infected larvae. These results are indicative of this new peptide as a neuromodulator that regulates visceral and skeletal muscle contractions and offers a novel effector involved in the behavioral changes during baculovirus infection.

关键词： beet armyworm behavior neuromodulator neuropeptide physiology seM-NPV

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Radiation and concomitant chemotherapy for patients with glioblastoma multiforme

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Chinese Journal of Cancer 2014年第1期33卷 25-31页

作者： salvador Villà Carme Balaà s.lvia Comas Radiation Oncology Catalan Institute of Oncology HU Germans TriasBadalona 08916 Catalonia Spain Medical Oncology Catalan Institute of Oncology HU Germans TriasBadalona 08916 Catalonia Spain

Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide(TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. in spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy(hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.

关键词：母细胞患者放疗胶质多形性 DNA甲基转移酶化疗放射治疗

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Characteristics of indirect laser-induced plasma from a thin film of oil on a metallic substrate

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Frontiers of physics 2015年第2期10卷 115-123页

作者：修俊山白雪石 Vincent Motto-ros 俞进 Department of sciences Shandong University of Technology Zibo 255049 China institut Lumiere Matiere UMR5306 Universite Lyon 1-CNRS Universite de Lyon 69622 Villeurbanne Cedex France

Optical emissions from the major and trace elements embodied in a transparent gel prepared from cooking oil were detected after the gel was spread in a thin film on a metallic substrate. such emissions are due to the indirect breakdown of the coating layer. The generated plasma, a mixture of substances from the substrate, the layer, and the ambient gas, was characterized using emission spectroscopy. The characteristics of the plasma formed on the metal with and without the coating layer were investigated. The results showed that A1 emission induced from the aluminum substrates coated with oil films extends away from the target surface to ablate the oil film. This finally formed a bifurcating circulation of aluminum vapor against a spherical confinement wall in the front of the plume, which differed from the evolution of the plasma induced from the uncoated aluminum target. The strongest emissions of elements from the oil films can be observed at 2 mm above the target after a detection delay of 1.0μs. A high temperature zone has been observed in the plasma after the delay of 1.0 μs for the plasma induced from the coated metal. This higher temperature determined in the plasma allows the consideration of the sensitive detection of trace elements in liquids, gels, biological samples, or thin films.

关键词： indirect laser-induced plasma thin layer aluminum substrate higher temperature

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Distal renal tubular acidosis:genetic causes and management

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World Journal of Pediatrics 2019年第5期15卷 422-431页

作者： s.lvia Bouissou Morais soares Luiz Alberto Wanderley de Menezes silva Flávia Cristina de Carvalho Mrad Ana Cristina simoes e silva interdisciplinary Laboratory of Medical investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Prof.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

Background Distal renal tubular acidosis(dRTA)is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine *** review aims to summarize the etiology,pathophysiology,clinical findings,diagnosis and therapeutic approach of dRTA,with emphasis on genetic causes of *** sources Literature reviews and original research articles from databases,including PubMed and Google *** searching was performed to identify additional studies about *** dRTA is characterized as the dysfunction of the distal urinary acidification,leading to metabolic *** pediatric patients,the most frequent etiology of dRTA is the genetic alteration of genes responsible for the codification of distal tubule channels,whereas,in adult patients,dRTA is more commonly secondary to autoimmune diseases,use of medications and *** with dRTA exhibit failure to thrive and important laboratory alterations,which are used to define the *** oral alkali and potassium supplementation can correct the biochemical defects,improve clinical manifestations and avoid nephrolithiasis and *** dRTA is a multifactorial disease leading to several clinical *** and laboratory alterations can be corrected by alkali replacement therapy.

关键词： Renal tubular acidosis Distal tubule physiology Metabolic acidosis Gene mutations Proton pump

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Parameter estimation in Manneville–Pomeau processes

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Probability, Uncertainty and Quantitative Risk 2023年第2期8卷 213-234页

作者： Barbara P.Olbermann s.lvia R.C.Lopes Artur O.Lopes Faculdade de Matemática-PUCRs 90650-002 Porto AlegreRSBrazil instituto de Matemática e Estatística-UFRGs 91500-900 Porto AlegreRSBrazil

in this paper,we study a class of stochastic processes{X_(t)}t∈N,where X_(t)=φ■T_(s)^(t)(X_(0))is obtained from the iterations of the transformation T_(s),invariant for an ergodic probabilityμ_(s)on[0,1]and a certain constant by partial functionφ:[0,1]→*** consider here the family of transformations T_(s):[0,1]→[0,1]indexed by a parameters>0,known as the Manneville–Pomeau family of *** autocorrelation function of the resulting process decays hyperbolically(or polynomially)and we obtain efficient methods to estimate the parameter s from a finite time *** a consequence,we also estimate the rate of convergence of the autocorrelation decay of these *** compare different estimation methods based on the periodogram function,the smoothed periodogram function,the variance of the partial sum,and the wavelet *** obtain our results we analyzed the properties of the spectral density function and the associated Fourier series.

关键词： Manneville–Pomeau maps Long and not so long dependence Estimation Autocorrelation decay spectral density function

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