In 2012,the laboratories of Drs.Emmanuelle Charpentier and Jennifer Doudna reported the repurposing of a bacterial adaptive immune system,known as CRISPR,as a programmable,RNA guided DNA editing system in eukaryotic c...In 2012,the laboratories of Drs.Emmanuelle Charpentier and Jennifer Doudna reported the repurposing of a bacterial adaptive immune system,known as CRISPR,as a programmable,RNA guided DNA editing system in eukaryotic cells.Over the next 12 months,a tsunami of research papers emerged demonstrating the facile utilization of this newfound genome editing platform in a variety of cell types and animal models.Since 2013.展开更多
Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving resear...Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.展开更多
Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particu...Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particularly when those reports contribute to both the understanding and therapeutics of cancer.For many de-cades,natural products have been pivotal in drug discovery programs because they offer a diverse array of anticancer therapeutic possibilities.Recently,two manuscripts published in the World Journal of Gastrointestinal Oncology added new data to the already extensive body of anticancer preclinical evidence for resvera-trol and senegenin,two compounds widely present in herbal preparations used in traditional Chinese medicine.The first one,with comprehensive and recognized anticancer properties,and the second one,shows a compelling body of evidence supporting its neuroprotective effects,but with emerging anticancer activities.Natural products have become key elements in the expanding and dynamic field of anticancer drug discovery.However,urgent and collective efforts are still needed to bridge the gap between preclinical and clinical research and thus bring new anticancer therapeutic breakthroughs.展开更多
Periodontitis has emerged as one of the most critical oral diseases, and research on this condition holds great importance for the advancement of stomatology. As the most authoritative national scientific research fun...Periodontitis has emerged as one of the most critical oral diseases, and research on this condition holds great importance for the advancement of stomatology. As the most authoritative national scientific research funding institution in China, the National Natural Science Foundation of China (NSFC) has played a pivotal role in driving the progress of periodontal science by supporting research on periodontitis. This article provides a comprehensive review of the research and development progress related to periodontitis in China from 2014 to 2023, highlighting the significant contributions of the NSFC to this field. We have summarized the detailed funding information from the NSFC, including the number of applicant codes, funded programs and the distribution of funded scholars. These data illustrate the efforts of the NSFC in cultivating young scientists and building research groups to address key challenges in national scientific research. This study offers an overview of the current hot topics, recent breakthroughs and future research prospects related to periodontitis in China.展开更多
Th e perspective article by Yang et al.[1],“Build the virtual cell with artificial intelligence:a perspective for cancer research”,provides a compelling vision for the transformative potential of artificial intellig...Th e perspective article by Yang et al.[1],“Build the virtual cell with artificial intelligence:a perspective for cancer research”,provides a compelling vision for the transformative potential of artificial intelligence virtual cells(AIVCs)in oncology.The authors outline how AIVCs could revolutionize cancer research by enabling in silico experimentation,overcoming multiomics bottlenecks,and accelerating drug development.However,the article presents a comprehensive framework,yet several pivotal questions remain unresolved,which warrant further discussion to advance the fi eld.展开更多
Accurate genotyping and prognosis of glioma patients present significant clinical challenges,often dependent on subjective judgement and insufficient scientific evidence.This study aims to develop a robust,noninvasive...Accurate genotyping and prognosis of glioma patients present significant clinical challenges,often dependent on subjective judgement and insufficient scientific evidence.This study aims to develop a robust,noninvasive preoperative multi-modal MRIbased transformer learning model to predict IDH genotyping and glioma prognosis.This multi-centre study included 563 glioma patients to develop an interpretable classification model utilising various preoperative imaging sequences,including T1-weighted,T2-weighted,fluid-attenuated inversion recovery,contrast-enhanced T1-weighted,and diffusion-weighted imaging.The model employs a multi-task learning framework to extract and fuse radiomic,deep learning,and clinical features for IDH genotyping and glioma prognosis.Additionally,a multi-modal transformer strategy is integrated to analyse structural and functional MRI,thereby enhancing model performance.Experimental results indicate that the model demonstrates superior performance,surpassing previous research and other state-of-the-art methods.The model achieves an AUC of 91.40% in the IDH genotyping task and 93.37% in the glioma prognosis task.Group analysis reveals that the model exhibits higher sensitivity to IDH-mutant cases and more accurately identifies low-risk groups compared to medium-or high-risk groups.This study aims to achieve accurate IDH genotyping and glioma prognosis through effective classification method,offering valuable diagnostic insights for clinical practice and expediting treatment decisions.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerv...Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerve conduits have shown limited efficacy in protecting cells from posttraumatic inflammation.This study aims to develop a single-process PLGA-based nerve conduit loaded with melatonin to enhance the biological performance of pure PLGA materials by suppressing oxidative stress and inflammatory responses.Methods The PLGA conduit is prepared with dry-jet wet spinning methods.The melatonin is integrated into PLGA conduits directly with the single-step process.Scanning electrical microscope observation,FTIR test,degradation test and drug releasing test were performed to characterize the morphology and physical properties of the nerve conduits.Schwann cells were cultured to test the biocompatibility of the prepared nerve conduits.Oxidative stress was applied on Schwann cell using hydrogen peroxide.Then the protecting effects of the nerve conduits were tested on the hydrogen peroxide-treated cells.SD rat sciatic model was applied to test the conduit in vivo.Results The melatonin is successfully integrated into the nerve conduit with the dry-jet wet spinning method.Cell adhesion and proliferation test of the Schwann cell indicated that the nerve conduits exhibit excellent biocompatibility.While the mitochondrial morphology observation and JC-1 potential detection also showed protecting effects on Mitochondria.The q-PCR analysis showed nerve conduits reduced cellular oxidative stress and inflammatory responses while enhancing cellular proliferation.A marked enhancement on SD rat sciatic nerve regeneration was also observed on melatonin loaded conduits.Conclusions By integrating melatonin into PLGA using the dryjet wet-spinning technique,the conduit is endowed with multiple functional advantages,including antiinflammatory,antioxidant,and neuroprotective properties.This approach is expected to create a favorable microenvironment for nerve tissue regeneration and provide a new perspective for the treatment of peripheral nerve injuries.展开更多
Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low pe...Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.展开更多
Neurodegenerative disease is characterized by the presence of inclusion bodies containing abnormal toxic proteins in the central nervous system.Physiologicalα-synuclein exists in the form of a monomer or dimer at the...Neurodegenerative disease is characterized by the presence of inclusion bodies containing abnormal toxic proteins in the central nervous system.Physiologicalα-synuclein exists in the form of a monomer or dimer at the presynaptic nerve terminal.It serves as a key molecule to modulate endocytosis and exocytosis.However,under pathological conditions,α-synuclein adopts different conformations,being converted into toxic oligomers.The molecular weight ofα-synuclein oligomers ranges from 25 to 180 kDa,and they do not form filamentous aggregates ofα-synuclein.Subsequently,α-synuclein oligomers change to aggregates,including protofibrils and fibrils(Miki et al.,2022).This process has been implicated in the pathogenesis of neurodegenerative diseases collectively termed synucleinopathies,which include Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy(MSA).展开更多
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,para...Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).展开更多
Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the antica...Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives,P3C.1 and P3C.2,and to elucidate their mechanism of action in cancer cells.Methods:The cytotoxicity of the compounds was evaluated across 27 different cancer cell lines via a nuclear staining assay.Subsequent flow cytometric and biochemical analyses were performed to assess reactive oxygen species(ROS)generation,apoptosis induction,mitochondrial integrity,and cell cycle progression.Additional studies included transcriptome analyses and immunoassays to characterize the molecular mechanisms underlying drug activity.Results:Two novel pyrazole derivatives,P3C.1 and P3C.2,were identified with potent cytotoxicity on a variety of cancer cell lines.Among the adherent cell lines tested,the triple-negative breast cancer(TNBC)cell line MDA-MB-231 exhibited the highest sensitivity to both compounds and was therefore selected for further experimentation.In vitro assays demonstrated that both compounds induced ROS generation,mitochondrial membrane depolarization,cell cycle arrest and apoptosis.Whole-transcriptome sequencing of P3C.1 and P3C.2-treated MDA-MB-231 and two lymphoblastic leukemia cell lines revealed four genes in common associated with cell signaling and membrane dynamics.Connectivity Map(CMAP)database comparisons of shared genes for each cancer subtype revealed a strong similarity between the two compounds with tubulin inhibitors,and subsequent assays confirmed that these compounds act as microtubule-disrupting agents.Moreover,protein phosphorylation analysis indicated that both compounds induced hyperphosphorylation of JNK,and ERK1/2,along with hypophosphorylation of p38 kinases.Conclusions:P3C.1 and P3C.2 emerged as promising anti-breast cancer agents with dual mechanisms of action involving microtubule disruption and altered kinase signaling,leading to induction of apoptosis.展开更多
Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is cha...Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical...The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.展开更多
Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxa...Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.展开更多
G protein-coupled receptor 37(GPR37)is an orphan receptor predominantly expressed in the brain,particularly in oligodendrocytes and certain types of neurons.Notably,it has been shown that the N-terminal domain of GPR3...G protein-coupled receptor 37(GPR37)is an orphan receptor predominantly expressed in the brain,particularly in oligodendrocytes and certain types of neurons.Notably,it has been shown that the N-terminal domain of GPR37 undergoes proteolysis under normal physiological conditions,resulting in the formation of cleaved receptor forms and the release of its ectodomain(ecto-GPR37)into the extracellular milieu(Mattila et al.,2021).Importantly,ecto-GPR37 density is increased in cerebrospinal fluid(CSF)of patients suffering from sporadic Parkinson’s disease(PD),together with an abnormal GPR37 processing in post-mortem PD substantia nigra(Moratóet al.,2021;Figure 1A).展开更多
Mitochondria are the central organelles that allow eukaryotic cells to efficiently convert nutrients into energy for cellular functions such as anabolic reactions,movement,and regulation.A reduction in the number of m...Mitochondria are the central organelles that allow eukaryotic cells to efficiently convert nutrients into energy for cellular functions such as anabolic reactions,movement,and regulation.A reduction in the number of mitochondria or the occurrence of dysfunctional mitochondria leads to serious diseases such as the Leigh syndrome.However,such changes have also been connected to Alzheimer’s disease(AD)and many more diseases of different organ systems and occur during the aging process.Mitochondria are,therefore.展开更多
GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,i...GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).展开更多
文摘In 2012,the laboratories of Drs.Emmanuelle Charpentier and Jennifer Doudna reported the repurposing of a bacterial adaptive immune system,known as CRISPR,as a programmable,RNA guided DNA editing system in eukaryotic cells.Over the next 12 months,a tsunami of research papers emerged demonstrating the facile utilization of this newfound genome editing platform in a variety of cell types and animal models.Since 2013.
基金supported by Key Research and Development Plan of Hunan Province(2024DK2006)the Fundamental Research Funds for the Central Universities of Central South University(1053320221769)+2 种基金Hunan Provincial Respiratory Disease Rehabilitation and Nursing Engineering Research Center Innovation Capacity Building Project(No.202012)the Zhangjiajie Science and Technology Development Key Special Project(No.202304)the National Key Clinical Specialty Major Scientific Research Project(No.20230382).
文摘Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.
文摘Any new report on the anticancer properties of natural products always awakens new satisfaction and hope about the role of the international scientific community in its continuous contributions to human health,particularly when those reports contribute to both the understanding and therapeutics of cancer.For many de-cades,natural products have been pivotal in drug discovery programs because they offer a diverse array of anticancer therapeutic possibilities.Recently,two manuscripts published in the World Journal of Gastrointestinal Oncology added new data to the already extensive body of anticancer preclinical evidence for resvera-trol and senegenin,two compounds widely present in herbal preparations used in traditional Chinese medicine.The first one,with comprehensive and recognized anticancer properties,and the second one,shows a compelling body of evidence supporting its neuroprotective effects,but with emerging anticancer activities.Natural products have become key elements in the expanding and dynamic field of anticancer drug discovery.However,urgent and collective efforts are still needed to bridge the gap between preclinical and clinical research and thus bring new anticancer therapeutic breakthroughs.
文摘Periodontitis has emerged as one of the most critical oral diseases, and research on this condition holds great importance for the advancement of stomatology. As the most authoritative national scientific research funding institution in China, the National Natural Science Foundation of China (NSFC) has played a pivotal role in driving the progress of periodontal science by supporting research on periodontitis. This article provides a comprehensive review of the research and development progress related to periodontitis in China from 2014 to 2023, highlighting the significant contributions of the NSFC to this field. We have summarized the detailed funding information from the NSFC, including the number of applicant codes, funded programs and the distribution of funded scholars. These data illustrate the efforts of the NSFC in cultivating young scientists and building research groups to address key challenges in national scientific research. This study offers an overview of the current hot topics, recent breakthroughs and future research prospects related to periodontitis in China.
文摘Th e perspective article by Yang et al.[1],“Build the virtual cell with artificial intelligence:a perspective for cancer research”,provides a compelling vision for the transformative potential of artificial intelligence virtual cells(AIVCs)in oncology.The authors outline how AIVCs could revolutionize cancer research by enabling in silico experimentation,overcoming multiomics bottlenecks,and accelerating drug development.However,the article presents a comprehensive framework,yet several pivotal questions remain unresolved,which warrant further discussion to advance the fi eld.
基金supported by the National Natural Science Foundation of China(Grants 82441022,82371934)Medical Science and Technology Research Project of Henan Province(SBGJ202101002)+1 种基金Joint Fund of Henan Province Science and Technology R&D Programme(225200810062)Henan Provincial Medical Science and Technology Research Joint Construction Project(LHGJ20240053,LHGJ20240036).
文摘Accurate genotyping and prognosis of glioma patients present significant clinical challenges,often dependent on subjective judgement and insufficient scientific evidence.This study aims to develop a robust,noninvasive preoperative multi-modal MRIbased transformer learning model to predict IDH genotyping and glioma prognosis.This multi-centre study included 563 glioma patients to develop an interpretable classification model utilising various preoperative imaging sequences,including T1-weighted,T2-weighted,fluid-attenuated inversion recovery,contrast-enhanced T1-weighted,and diffusion-weighted imaging.The model employs a multi-task learning framework to extract and fuse radiomic,deep learning,and clinical features for IDH genotyping and glioma prognosis.Additionally,a multi-modal transformer strategy is integrated to analyse structural and functional MRI,thereby enhancing model performance.Experimental results indicate that the model demonstrates superior performance,surpassing previous research and other state-of-the-art methods.The model achieves an AUC of 91.40% in the IDH genotyping task and 93.37% in the glioma prognosis task.Group analysis reveals that the model exhibits higher sensitivity to IDH-mutant cases and more accurately identifies low-risk groups compared to medium-or high-risk groups.This study aims to achieve accurate IDH genotyping and glioma prognosis through effective classification method,offering valuable diagnostic insights for clinical practice and expediting treatment decisions.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
文摘Objective Peripheral nerve injury leads to various degrees of functional defects.Nerve guidance conduits are considered as a new promising scaffold for peripheral nerve repair.However,conventional single-material nerve conduits have shown limited efficacy in protecting cells from posttraumatic inflammation.This study aims to develop a single-process PLGA-based nerve conduit loaded with melatonin to enhance the biological performance of pure PLGA materials by suppressing oxidative stress and inflammatory responses.Methods The PLGA conduit is prepared with dry-jet wet spinning methods.The melatonin is integrated into PLGA conduits directly with the single-step process.Scanning electrical microscope observation,FTIR test,degradation test and drug releasing test were performed to characterize the morphology and physical properties of the nerve conduits.Schwann cells were cultured to test the biocompatibility of the prepared nerve conduits.Oxidative stress was applied on Schwann cell using hydrogen peroxide.Then the protecting effects of the nerve conduits were tested on the hydrogen peroxide-treated cells.SD rat sciatic model was applied to test the conduit in vivo.Results The melatonin is successfully integrated into the nerve conduit with the dry-jet wet spinning method.Cell adhesion and proliferation test of the Schwann cell indicated that the nerve conduits exhibit excellent biocompatibility.While the mitochondrial morphology observation and JC-1 potential detection also showed protecting effects on Mitochondria.The q-PCR analysis showed nerve conduits reduced cellular oxidative stress and inflammatory responses while enhancing cellular proliferation.A marked enhancement on SD rat sciatic nerve regeneration was also observed on melatonin loaded conduits.Conclusions By integrating melatonin into PLGA using the dryjet wet-spinning technique,the conduit is endowed with multiple functional advantages,including antiinflammatory,antioxidant,and neuroprotective properties.This approach is expected to create a favorable microenvironment for nerve tissue regeneration and provide a new perspective for the treatment of peripheral nerve injuries.
基金supported by the NIH RF1 grant NS119477 jointly funded by NINDS and NIA(to RM).
文摘Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.
基金supported by Hirosaki University Priority Research Grant for Future Innovation(to YM),JSPS KAKENHI Grant Numbers 24K10654(to YM)and 23K24209(to KW)the Collaborative Research Project of the Brain Research Institute,Niigata University(to YM).
文摘Neurodegenerative disease is characterized by the presence of inclusion bodies containing abnormal toxic proteins in the central nervous system.Physiologicalα-synuclein exists in the form of a monomer or dimer at the presynaptic nerve terminal.It serves as a key molecule to modulate endocytosis and exocytosis.However,under pathological conditions,α-synuclein adopts different conformations,being converted into toxic oligomers.The molecular weight ofα-synuclein oligomers ranges from 25 to 180 kDa,and they do not form filamentous aggregates ofα-synuclein.Subsequently,α-synuclein oligomers change to aggregates,including protofibrils and fibrils(Miki et al.,2022).This process has been implicated in the pathogenesis of neurodegenerative diseases collectively termed synucleinopathies,which include Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy(MSA).
文摘Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).
基金supported by NIH grant 1R16GM149379 to Renato J.Aguilerasupported by the core facilities of the BBRC,funded by the Research Centers in Minority Institutions grant 5U54MD007592 from the National Institute on Minority Health and Health Disparities to Robert A.Kirkensupported Denisse A.Gutierrez,Ana P.Betancourt,Elisa Robles-Escajeda and Armando Varela-Ramirez。
文摘Objectives:Drug resistance is the major determinant of chemotherapy failure,leading to relapse and tumor progression,demonstrating the urgent need for novel antineoplastic drugs.This study aimed to evaluate the anticancer potential of two novel pyrazole derivatives,P3C.1 and P3C.2,and to elucidate their mechanism of action in cancer cells.Methods:The cytotoxicity of the compounds was evaluated across 27 different cancer cell lines via a nuclear staining assay.Subsequent flow cytometric and biochemical analyses were performed to assess reactive oxygen species(ROS)generation,apoptosis induction,mitochondrial integrity,and cell cycle progression.Additional studies included transcriptome analyses and immunoassays to characterize the molecular mechanisms underlying drug activity.Results:Two novel pyrazole derivatives,P3C.1 and P3C.2,were identified with potent cytotoxicity on a variety of cancer cell lines.Among the adherent cell lines tested,the triple-negative breast cancer(TNBC)cell line MDA-MB-231 exhibited the highest sensitivity to both compounds and was therefore selected for further experimentation.In vitro assays demonstrated that both compounds induced ROS generation,mitochondrial membrane depolarization,cell cycle arrest and apoptosis.Whole-transcriptome sequencing of P3C.1 and P3C.2-treated MDA-MB-231 and two lymphoblastic leukemia cell lines revealed four genes in common associated with cell signaling and membrane dynamics.Connectivity Map(CMAP)database comparisons of shared genes for each cancer subtype revealed a strong similarity between the two compounds with tubulin inhibitors,and subsequent assays confirmed that these compounds act as microtubule-disrupting agents.Moreover,protein phosphorylation analysis indicated that both compounds induced hyperphosphorylation of JNK,and ERK1/2,along with hypophosphorylation of p38 kinases.Conclusions:P3C.1 and P3C.2 emerged as promising anti-breast cancer agents with dual mechanisms of action involving microtubule disruption and altered kinase signaling,leading to induction of apoptosis.
文摘Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
基金supported by the I+D+i(PID2022-142418OB-C21)grant funded by MICIU/AEI/10.13039/501100011033 and by ERDF/UE.
文摘The ErbB signaling network has recently emerged as a key modulator of central nervous system responses to injury.This review provides a comprehensive overview of ErbB receptors and their ligands,highlighting canonical and non-canonical signaling mechanisms relevant to brain damage.We explore how ErbB signaling is dynamically regulated following injury and how it orchestrates processes such as neuroinflammation,gliosis,and neural repair.Special attention is given to its interplay with other critical pathways,including Notch signaling,and its roles within adult neurogenic niches,where it modulates neural stem cell behavior in response to damage.Based on accumulating preclinical evidence,we propose two therapeutic strategies for targeting ErbB signaling in brain injury:(1)dampening neuroinflammation through ErbB inhibition and(2)promoting neuroprotection and neurogenesis via neuregulin-1-mediated activation.The first strategy is supported by studies,which demonstrate that inhibition of ErbB1 limits neuroinflammation and supports neural repair in preclinical models.The latter strategy is supported by emerging studies demonstrating the significant potential of novel protein kinase C activating diterpenes in modulating ErbB signaling pathways through the regulation of neuregulin-1 release.Diterpenes,by influencing the ErbB pathway,may uniquely bridge the gap between neuroprotection and regeneration.Their potential to modulate inflammation and promote pro-regenerative cellular environments positions them as promising tools in the development of targeted therapies.By dissecting these mechanisms,we aim to shed light on the translational potential of ErbB-targeted therapies and their capacity to enhance endogenous repair processes in the injured brain.
基金funding from the European Union -NextGenerationEU through the Italian Ministry of University and Research under PRIN PNRR REG D.R.1718-2022– Project number PRJ-1575 INDICA。
文摘Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.
基金FEDER/Ministerio de Ciencia,Innovacióny Universidades-Agencia Estatal de Investigación(PID2023-147425OB-I00 to FC)Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)-Generalitat de Catalunya(2021 SGR 00698 to FC).
文摘G protein-coupled receptor 37(GPR37)is an orphan receptor predominantly expressed in the brain,particularly in oligodendrocytes and certain types of neurons.Notably,it has been shown that the N-terminal domain of GPR37 undergoes proteolysis under normal physiological conditions,resulting in the formation of cleaved receptor forms and the release of its ectodomain(ecto-GPR37)into the extracellular milieu(Mattila et al.,2021).Importantly,ecto-GPR37 density is increased in cerebrospinal fluid(CSF)of patients suffering from sporadic Parkinson’s disease(PD),together with an abnormal GPR37 processing in post-mortem PD substantia nigra(Moratóet al.,2021;Figure 1A).
文摘Mitochondria are the central organelles that allow eukaryotic cells to efficiently convert nutrients into energy for cellular functions such as anabolic reactions,movement,and regulation.A reduction in the number of mitochondria or the occurrence of dysfunctional mitochondria leads to serious diseases such as the Leigh syndrome.However,such changes have also been connected to Alzheimer’s disease(AD)and many more diseases of different organ systems and occur during the aging process.Mitochondria are,therefore.
文摘GNAO1-associated disorder is a rare disease and an example of developmental and epileptic encephalopathies.Caused by ca.150 different dominant missense mutations in the gene encoding the major neuronal G protein Gao,it spans a wide range of neurological clinical manifestations,that may include epileptic seizures,motor dysfunctions,developmental and intellectual delay,and other symptoms(Sáez González et al.,2023).
