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Mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： JoséM.Izquierdo centro de Biología Molecular Severo Ochoa(CBM) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

Identification of SUMO Targets by a Novel Proteomic Approach in Plants

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Journal of Integrative Plant Biology 2013年第1期55卷 96-107页

作者： Gema López-Torrejón Davide Guerra Rafael Catal Julio Salinas Juan C. del Pozo centro de biotecnología y genómica de Plantas (INIA-UPM) Campus de Montegancedo CRA-genomics Research Centre (GPG) centro de Investigaciones Biológicas (CSIC) Campus de la Ciudad Universitaria de Madrid

Post-translational modifications （PTMs） chemically and physically alter the properties of proteins, including their folding, subcellular localization, stability, activity, and consequently their function. In spite of their relevance, studies on PTMs in plants are still limited. Small Ubiquitin-like Modifier （SUMO） modification regulates several biological processes by affecting protein-protein interactions, or changing the subcellular Iocalizations of the target proteins. Here, we describe a novel proteomic approach to identify SUMO targets that combines 2-D liquid chromatography, immunodetection, and mass spectrometry （MS） analyses. We have applied this approach to identify nuclear SUMO targets in response to heat shock. Using a bacterial SUMOylation system, we validated that some of the targets identified here are, in fact, labeled with SUMO1. Interestingly, we found that GIGANTEA （GI）, a photoperiodic-pathway protein, is modified with SUMO in response to heat shock both in vitro and in vivo.

关键词： Mass spectrometry plants post-translational modification proteomics SUMO.

The cold-induced factor CBF3 mediates root stem cell activity,regeneration,and developmental responses to cold

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Plant Communications 2023年第6期4卷 197-211页

作者： Pablo Perez-Garcia Ornella Pucciariello Alvaro Sanchez-Corrionero Javier Cabrera Cristina del Barrio Juan Carlos del Pozo Mariano Perales Krzysztof Wabnik Miguel A.Moreno-Risueno centro de biotecnologíay genómica de Plantas(Universidad Politécnica de Madrid(UPM)–Instituto Nacional de Investigacióny Tecnología Agraria y Alimentaria–CSIC(INIA-CSIC)) MadridSpain

Plant growth and development involve the specification and regeneration of stem cell niches(SCNs).Although plants are exposed to disparate environmental conditions,how environmental cues affect developmental programs and stem cells is not well *** stem cells are accommodated in meristems in SCNs around the quiescent center(QC),which maintains their *** a combination of genetics and confocal microscopy to trace morphological defects and correlate them with changes in gene expression and protein levels,we show that the cold-induced transcription factor(TF)C-REPEAT BINDING FACTOR 3(CBF3),which has previously been associated with cold acclimation,regulates root development,stem cell activity,and ***3 is integrated into the SHORT-ROOT(SHR)regulatory network,forming a feedback loop that maintains SHR ***3 is primarily expressed in the root endodermis,whereas the CBF3 protein is localized to other meristematic tissues,including root *** of cbf3-1 using a wild-type CBF3 gene and a CBF3 fusion with reduced mobility show that CBF3 movement capacity is required for SCN patterning and regulates root ***,cold induces CBF3,affecting QC ***,exposure to moderate cold around 10℃–12℃promotes root regeneration and QC respecification in a CBF3-dependent manner during the recuperation *** contrast,CBF3 does not appear to regulate stem cell survival,which has been associated with recuperation from more acute cold(-4℃).We propose a role for CBF3 in mediating the molecular interrelationships among the cold response,stem cell activity,and development.

关键词： stem cells regeneration organ patterning protein movement cell fate low temperature

Potential seed germination-enhancing plant growth-promoting rhizobacteria for restoration of Pinus chiapensis ecosystems

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Journal of Forestry Research 2021年第5期32卷 2143-2153页

作者： Cristina Domínguez-Castillo Julia María Alatorre-Cruz Dolores Castañeda-Antonio Jose Antonio Munive Xianwu Guo Jesús Francisco López-Olguín Luis Ernesto Fuentes-Ramírez Ricardo Carreño-López centro de Investigaciones en Ciencias Microbiológicas Instituto de CienciasBenemérita Universidad Autónoma de PueblaPueblaMéxico Universidad Autónoma de Querétaro QuerétaroMéxico centro de biotecnología genómica Instituto Politécnico NacionalReynosaTamaulipasMéxico

Rhizosphere soil samples of three Pinus chiapensis sites were analyzed for their physicochemical properties,soil bacteria isolated and screened in vitro for growthpromoting *** isolates that showed promise were identified to five genera Dyella,Luteimonas,Euterobacter,Paraburkholderia and Bacillus based on the sequences of16 S rRNA *** the strains were isolated from nondisturbed *** bacteria significantly decreased germination time and increased sprout *** acetic acid and gibberellin production and phosphate solubilisation were *** indicate that these biochemicals could be essential for *** distribution and suggest the possibility that PGPR inoculation on *** seeds prior to planting could improve germination and possibly seedling development.

关键词： Pinus chiapensis Plant growth-promoting rhizobacteria Dyella Luteimonas Enterobacter

How to make the end of a gene,the simple way

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BIOCELL 2022年第6期46卷 1453-1457页

作者： KAREL H.M.VAN WELY centro Nacional de biotecnología/CSIC Madrid28049Spain

Transcription termination of nearly all protein-coding genes in mammals requires 3’end processing by a multiprotein complex that will cleave and polyadenylate the messenger RNA *** a variety of enzyme complexes intervene,3’end processing was thought to be fundamentally complex and subject to a multitude of regulatory *** possibility to select just one out of several polyadenylation sites,in particular,has caused much questioning and *** appear to be separate mechanisms however can be combined into a defined set of rules,allowing for a relatively simple interpretation of 3’end ***,readiness of the terminal exon splice site determines when a transcript reaches the maturity to select a nearby polyadenylation *** pausing then acts in concert,extending the timeframe during which the transcription complex is close to polyadenylation *** RNA polymerase pausing is governed by the same type of sequences in bacteria and metazoans,mammalian transcription termination resembles its prokaryote counterpart more than generally thought.

关键词： RNA transcription RNA polymerase II pausing Splicing Termination Polyadenylation

Misfolded amyloid-beta conformational variants(strains)as drivers of Alzheimer's disease neuropathology

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Neural Regeneration Research 2025年第11期20卷 3219-3220页

作者： Salvatore Saieva Rodrigo Morales department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Pathological and clinical variability in Alzheimer's disease(AD):AD is clinically cha racterized by progressive memory loss and cognitive *** a pathological point of view,the main features of AD are the deposition of amyloid plaques(composed of amyloid-beta,Aβ)and neurofibrillary tangles containing hyperphosphorylated Tau in the brain,accompanied by neu ronal and synaptic loss,neuroinflammation and brain atrophy(Jellinger,2022).Regardless of these common traits,growing evidence shows increased heterogen eity in the brain of AD patients considering both clinical manifestations and pathological features.

关键词： amyloid Alzheimer clinical

Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

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Neural Regeneration Research 2025年第4期20卷 1087-1089页

作者： Nazaret Gamez Rodrigo Morales department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)***,Aβdeposits have been identified in peripheral ***,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well *** presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated *** latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of *** this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

关键词： therapeutic amyloid latter

degradation of duloxetine: Identification of transformation products by UHPLC-ESI(+)-HRMS/MS,in silico toxicity and wastewater analysis

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Journal of Environmental Sciences 2019年第8期31卷 113-123页

作者： Rodrigo A.Osawa Ana P.Carvalho Olinda C.Monteiro M.Conceicao Oliveira M.Helena Florêncio centro de Química e Bioquímica Faculdade de Ciências Universidade de Lisboa Laboratório de FTICR e Espectrometria de Massa Estrutural Faculdade de Ciências Universidade de Lisboa centro de Química Estrutural Instituto Superior Técnico Universidade de Lisboa

Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.

关键词： High resolution mass spectrometry Duloxetine degradation processes Transformation products Wastewater analysis In silico toxicity