Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Global mortality rates are greatly impacted by malignancies of the brain and nervous system.Although,Magnetic Resonance Imaging(MRI)plays a pivotal role in detecting brain tumors;however,manual assessment is time-cons...Global mortality rates are greatly impacted by malignancies of the brain and nervous system.Although,Magnetic Resonance Imaging(MRI)plays a pivotal role in detecting brain tumors;however,manual assessment is time-consuming and susceptible to human error.To address this,we introduce ICA2-SVM,an advanced computational framework integrating Independent Component Analysis Architecture-2(ICA2)and Support Vector Machine(SVM)for automated tumor segmentation and classification.ICA2 is utilized for image preprocessing and optimization,enhancing MRI consistency and contrast.The Fast-MarchingMethod(FMM)is employed to delineate tumor regions,followed by SVM for precise classification.Validation on the Contrast-Enhanced Magnetic Resonance Imaging(CEMRI)dataset demonstrates the superior performance of ICA2-SVM,achieving a Dice Similarity Coefficient(DSC)of 0.974,accuracy of 0.992,specificity of 0.99,and sensitivity of 0.99.Additionally,themodel surpasses existing approaches in computational efficiency,completing analysis within 0.41 s.By integrating state-of-the-art computational techniques,ICA2-SVM advances biomedical imaging,offering a highly accurate and efficient solution for brain tumor detection.Future research aims to incorporate multi-physics modeling and diverse classifiers to further enhance the adaptability and applicability of brain tumor diagnostic systems.展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indic...Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.展开更多
Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BC...Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the curr...Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain tumors.Its median survival time is typically less than a year after diagnosis.One of the major challenges in tr...Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain tumors.Its median survival time is typically less than a year after diagnosis.One of the major challenges in treating these cancers is the efficiency of the transport of drugs to the central nervous system.The blood-brain barrier is cooperating with advanced stages of malignancy.The blood-brain barrier poses a significant challenge to delivering systemic medications to brain tumors.Nanodrug delivery systems have emerged as promising tools for effectively crossing this barrier.Additionally,the development of smart nanoparticles brings new hope for cancer diagnosis and treatment.These nanoparticles improve drug delivery efficiency,allowing for the creation of targeted and stimuli-responsive delivery methods.This review highlights recent advancements in nanoparticle and smart nanoparticle technologies for brain cancer treatment,exploring the range of nanoparticles under development,their applications,targeting strategies,and the latest progress in enhancing transport across the blood-brain barrier.It also addresses the ongoing challenges and potential benefits of these innovative approaches.展开更多
Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels....Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.展开更多
Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GN...Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].展开更多
Lung cancer,particularly non-small cell lung cancer(NSCLC),remains a leading cause of cancer-related death globally,and a significant number of patients develop brain metastasis(BM)as the disease progresses.The presen...Lung cancer,particularly non-small cell lung cancer(NSCLC),remains a leading cause of cancer-related death globally,and a significant number of patients develop brain metastasis(BM)as the disease progresses.The presence of BM,which affects up to 60%of patients with NSCLC,is correlated with an unfavorable prognosis and markedly decreased quality of life.Standard treatment options for BMs,such as whole-brain radiation therapy and surgery,have displayed limited efficacy in controlling disease progression,and they can cause significant neurocognitive side effects.Stereotactic radiotherapy(SRT),including stereotactic radiosurgery,fractionated SRT,and stereotactic body radiotherapy,represents an advanced and precise approach for treating BM that minimizes damage to surrounding healthy tissues.This review highlights recent advances in the application of SRT for treating BM of NSCLC,focusing on its underlying biological principles and mechanisms of action as well as the quality standards necessary for effective SRT implementation.The ability of SRT to deliver substantial radiation doses in a precisely targeted manner has resulted in better local tumor management,fewer side effects,and increased patient survival rates.Future research is crucial to improve SRT procedures and successfully incorporate them into multimodal therapy plans for patients with NSCLC and BM.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Integration of artificial intelligence increases in all aspects of human life,particularly in healthcare systems.Traumatic brain injury is a significant cause of mortality and long-term disability,with an important im...Integration of artificial intelligence increases in all aspects of human life,particularly in healthcare systems.Traumatic brain injury is a significant cause of mortality and long-term disability,with an important impact on the socioeconomic system of healthcare.The role of artificial intelligence in imaging and outcome prediction for traumatic brain injury patients is reviewed with a particular emphasis to the characteristics of machine and deep learning methods.Evidence of potential improvement in the clinical practice in discussed.展开更多
Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairmen...Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.展开更多
Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire b...Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.展开更多
Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health chall...Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health challenges due to TBI,particularly in military settings,where combat-related injuries introduce unique considerations for prevalence and management[2].Despite notable advancements in acute care,our comprehension of the complex pathophysiological mechanisms underlying the long-term eff ects of TBI remains inadequate[3].Although the initial mechanical impact triggers the cascade of injury,it is often the subsequent neuroinfl ammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments[4,5].展开更多
Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,techno...Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM.Immunotherapies like immune checkpoint inhibitors,CAR-T targeting,oncolytic virus-based therapy,bispecific antibody treatment,and vaccination approaches,etc.,are emerging as promising avenues offering new hope in refining patient’s survival benefits.However,selective trafficking across the blood-brain barrier(BBB),immunosuppressive tumor microenvironment(TME),metabolic alteration,and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM.Furthermore,to address this concern,the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years.With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes,erythrocytes,platelets,glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition.These biomimetic nanotherapy offers advantages over conventional nanoparticles,focusing on greater target specificity,increased circulation stability,higher active loading capacity,BBB permeability(inherent inflammatory chemotaxis of neutrophils),decreased immunogenicity,efficient metabolism-based combinatorial effects,and prevention of tumor recurrence by induction of immunological memory,etc.provide new age of improved immunotherapies outcomes against HGGs and BM.In this review,we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat andmost lethal HGGs and BM.Moreover,the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.展开更多
Objective:Migrasomes,an emerging class of migration-facilitating membranous extracellular vesicles,remain largely uncharted in the intricate landscape of tumor metastasis.This study aimed to illuminate the roles and m...Objective:Migrasomes,an emerging class of migration-facilitating membranous extracellular vesicles,remain largely uncharted in the intricate landscape of tumor metastasis.This study aimed to illuminate the roles and mechanisms underlying cancer cell-derived migrasomes in breast cancer brain metastasis(BCBM).Methods:Migrasomes were isolated and purified from BCBM cells(231-BR)and non-specific organotropic parental counterparts(MDA-MB-231),specifically designated as Mig-BCBM and Mig-BC,respectively.The role of Mig-BCBM in BCBM was investigated using an in vitro endothelial cell layer permeability model and a BCBM mouse model.The regulatory mechanism underlying Mig-BCBM was assessed using RT-qPCR,western blotting,immunofluorescence,ex vivo fluorescence imaging,and a series of rescue experiments.Results:Mig-BCBM potently augmented the permeability of vascular endothelial layers,which facilitated the efficient migration of 231-BR cells across endothelial barriers in vitro.The administration of Mig-BCBM significantly disrupted the blood-brain barrier(BBB)and accelerated BCBM progression in vivo,as evidenced in mouse models,compared to the Mig-BC and control groups.Mechanistically,Mig-BCBM harbored ATF6,a critical transducer of endoplasmic reticulum(ER)stress.Upon internalization into hCMEC/D3 cells,ATF6 elicited robust ER stress responses,culminating in downregulation of ZO-1 and VE-cadherin.Digital PCR analysis disclosed significant upregulation of ATF6 in serum migrasomes derived from BCBM patients compared to migrasomes from breast cancer patients and healthy individuals.Conclusions:This study uncovered a pivotal role of cancer cell-derived in BCBM by harnessing ATF6-mediated ER stress to disrupt the BBB and promote metastasis,suggesting novel diagnostic and therapeutic strategies targeting migrasomes and migrasome cargo.展开更多
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by the Deanship of Graduate Studies and Scientific Research at Najran University through funding code NU/GP/MRC/13/771-1.
文摘Global mortality rates are greatly impacted by malignancies of the brain and nervous system.Although,Magnetic Resonance Imaging(MRI)plays a pivotal role in detecting brain tumors;however,manual assessment is time-consuming and susceptible to human error.To address this,we introduce ICA2-SVM,an advanced computational framework integrating Independent Component Analysis Architecture-2(ICA2)and Support Vector Machine(SVM)for automated tumor segmentation and classification.ICA2 is utilized for image preprocessing and optimization,enhancing MRI consistency and contrast.The Fast-MarchingMethod(FMM)is employed to delineate tumor regions,followed by SVM for precise classification.Validation on the Contrast-Enhanced Magnetic Resonance Imaging(CEMRI)dataset demonstrates the superior performance of ICA2-SVM,achieving a Dice Similarity Coefficient(DSC)of 0.974,accuracy of 0.992,specificity of 0.99,and sensitivity of 0.99.Additionally,themodel surpasses existing approaches in computational efficiency,completing analysis within 0.41 s.By integrating state-of-the-art computational techniques,ICA2-SVM advances biomedical imaging,offering a highly accurate and efficient solution for brain tumor detection.Future research aims to incorporate multi-physics modeling and diverse classifiers to further enhance the adaptability and applicability of brain tumor diagnostic systems.
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金financially supported by the Basic Science Center Program(T2288102)the Key Program of the National Natural Science Foundation of China(32230059)+3 种基金the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the Project supported by the Young Scientists Fund of the National Natural Science Foundation of China(32401128)Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251).
文摘Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.
基金supported by the National Key R&D Program of China(2021YFF1200602)the National Science Fund for Excellent Overseas Scholars(0401260011)+3 种基金the National Defense Science and Technology Innovation Fund of Chinese Academy of Sciences(c02022088)the Tianjin Science and Technology Program(20JCZDJC00810)the National Natural Science Foundation of China(82202798)the Shanghai Sailing Program(22YF1404200).
文摘Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
文摘Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain tumors.Its median survival time is typically less than a year after diagnosis.One of the major challenges in treating these cancers is the efficiency of the transport of drugs to the central nervous system.The blood-brain barrier is cooperating with advanced stages of malignancy.The blood-brain barrier poses a significant challenge to delivering systemic medications to brain tumors.Nanodrug delivery systems have emerged as promising tools for effectively crossing this barrier.Additionally,the development of smart nanoparticles brings new hope for cancer diagnosis and treatment.These nanoparticles improve drug delivery efficiency,allowing for the creation of targeted and stimuli-responsive delivery methods.This review highlights recent advancements in nanoparticle and smart nanoparticle technologies for brain cancer treatment,exploring the range of nanoparticles under development,their applications,targeting strategies,and the latest progress in enhancing transport across the blood-brain barrier.It also addresses the ongoing challenges and potential benefits of these innovative approaches.
文摘Uric acid(UA)is a naturally antioxidant that is strongly associated with the development and progression of Parkinson's disease(PD).The purine diet is an important exogenous pathway that modulates blood UA levels.Deep brain stimulation(DBS)is an important tool for PD treatment.This study aimed to explore the effects of preoperative purine diet on the prognosis of patients with PD after DBS.Sixty-four patients with PD who underwent DBS were included in this study,and their clinical data,blood UA levels,and daily purine intake.Patients were followed up for improvement 1 year after surgery.We found that patient higher purine intake was strongly associated with the rate of improvement after DBS and was a protective factor for patient prognosis.Daily purine intake from meat and seafood was significantly higher in the responsive patients than in the lessresponsive patients.Mediation analysis showed that UA mediated 78%of the effect of purine intake on motor symptom improvement after DBS.In summary,we observed that purine intake is strongly associated with the rate of improvement in motor symptoms after subthalamic nucleus-DBS in patients with PD.This study provides a reference for preoperative diet planning in patients with PD undergoing DBS.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010297)the National Natural Science Foundation of China(32100765)+1 种基金the Xiamen Medical Health Science and Technology Project(3502Z20194098)the Shenzhen-Hong Kong-Macao Science and Technology Innovation Project(SGDX2020110309280100).
文摘Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].
基金Supported by the National Key Research and Development Program of China,No.2022YFE0110200Project of Science and Technology Department of Jilin Province,No.20240501002GH and No.YDZJ202102CXJD020+3 种基金Jilin University Norman Bethune Medical Department“Medicine+X”Project,No.2022JBGS04Project of Development and Reform Commission of Jilin Province,No.2021C023Department of Human Resources and Social Security Project of Jilin Province20th Batch of Innovation and Entrepreneurship Talent Funding Project of Jilin Province.
文摘Lung cancer,particularly non-small cell lung cancer(NSCLC),remains a leading cause of cancer-related death globally,and a significant number of patients develop brain metastasis(BM)as the disease progresses.The presence of BM,which affects up to 60%of patients with NSCLC,is correlated with an unfavorable prognosis and markedly decreased quality of life.Standard treatment options for BMs,such as whole-brain radiation therapy and surgery,have displayed limited efficacy in controlling disease progression,and they can cause significant neurocognitive side effects.Stereotactic radiotherapy(SRT),including stereotactic radiosurgery,fractionated SRT,and stereotactic body radiotherapy,represents an advanced and precise approach for treating BM that minimizes damage to surrounding healthy tissues.This review highlights recent advances in the application of SRT for treating BM of NSCLC,focusing on its underlying biological principles and mechanisms of action as well as the quality standards necessary for effective SRT implementation.The ability of SRT to deliver substantial radiation doses in a precisely targeted manner has resulted in better local tumor management,fewer side effects,and increased patient survival rates.Future research is crucial to improve SRT procedures and successfully incorporate them into multimodal therapy plans for patients with NSCLC and BM.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
文摘Integration of artificial intelligence increases in all aspects of human life,particularly in healthcare systems.Traumatic brain injury is a significant cause of mortality and long-term disability,with an important impact on the socioeconomic system of healthcare.The role of artificial intelligence in imaging and outcome prediction for traumatic brain injury patients is reviewed with a particular emphasis to the characteristics of machine and deep learning methods.Evidence of potential improvement in the clinical practice in discussed.
基金supported by the University of Macao(MYRG2022-00054-FHS and MYRGGRG2023-00038-FHS-UMDF)the Macao Science and Technology Development Fund(FDCT0048/2021/AGJ and FDCT0020/2019/AMJ)Natural Science Foundation of Guangdong Province(EF017/FHS-YZ/2021/GDSTC).
文摘Acquired brain injury(ABI)is an injury that affects the brain structure and function.Traditional ABI treatment strategies,including medications and rehabilitation therapy,exhibit their ability to improve its impairments in cognition,emotion,and physical activity.Recently,near-infrared(NIR)photobiomodulation(PBM)has emerged as a promising physical intervention method for ABI,demonstrating that low-level light therapy can modulate cellular metabolic processes,reduce the in flammation and reactive oxygen species of ABI microenvironments,and promote neural repair and regeneration.Preclinical studies using ABI models have been carried out,revealing the potential of PBM in promoting brain injury recovery although its clinical application is still in its early stages.In this review,we first inspected the possible physical and biological mechanisms of NIR-PBM,and then reported the pathophysiology and physiology of ABI underlying NIR-PBM intervention.Therefore,the potential of NIR-PBM as a therapeutic intervention in ABI was demonstrated and it is also expected that further work can facilitate its clinical applications.
基金supported by the STI 2030-Major Project(2021ZD0204400,2022ZD0205203,2021ZD0200104,2022ZD0211900)the Shenzhen Science and Technology Program(RCYX20210706092100003,RCBS20221008093311027)+3 种基金the Shenzhen Medical Research Funds(A2303005)the Youth Innovation Promotion Association CAS(2022367)the National Natural Science Foundation of China(32100896)NSFC-Guangdong Joint Fund(U20A6005).
文摘Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.
基金supported by the National Natural Science Foundation of China(82102645)the Guangdong Basic and Applied Basic Research Foundation(2021A1515011042)the China Postdoctoral Science Foundation(2019M662995).
文摘Traumatic brain injury(TBI)remains a prominent global cause of mortality and disability,accounting for an estimated 69 million new cases annually[1].Both civilian and military populations face substantial health challenges due to TBI,particularly in military settings,where combat-related injuries introduce unique considerations for prevalence and management[2].Despite notable advancements in acute care,our comprehension of the complex pathophysiological mechanisms underlying the long-term eff ects of TBI remains inadequate[3].Although the initial mechanical impact triggers the cascade of injury,it is often the subsequent neuroinfl ammatory processes that propel progressive neuronal damage and lead to long-term neurological impairments[4,5].
文摘Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM.Immunotherapies like immune checkpoint inhibitors,CAR-T targeting,oncolytic virus-based therapy,bispecific antibody treatment,and vaccination approaches,etc.,are emerging as promising avenues offering new hope in refining patient’s survival benefits.However,selective trafficking across the blood-brain barrier(BBB),immunosuppressive tumor microenvironment(TME),metabolic alteration,and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM.Furthermore,to address this concern,the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years.With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes,erythrocytes,platelets,glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition.These biomimetic nanotherapy offers advantages over conventional nanoparticles,focusing on greater target specificity,increased circulation stability,higher active loading capacity,BBB permeability(inherent inflammatory chemotaxis of neutrophils),decreased immunogenicity,efficient metabolism-based combinatorial effects,and prevention of tumor recurrence by induction of immunological memory,etc.provide new age of improved immunotherapies outcomes against HGGs and BM.In this review,we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat andmost lethal HGGs and BM.Moreover,the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.
基金supported by the National Natural Science Foundation of China(Grant No.81702884)Natural Science Foundation of Shandong Province(Grant Nos.ZR2022MH272,ZR2020QH216,and ZR2023QH115)Medicine and Health Science and Technology Foundation of Shandong Province(Grant Nos.202402060623 and 202202080721).
文摘Objective:Migrasomes,an emerging class of migration-facilitating membranous extracellular vesicles,remain largely uncharted in the intricate landscape of tumor metastasis.This study aimed to illuminate the roles and mechanisms underlying cancer cell-derived migrasomes in breast cancer brain metastasis(BCBM).Methods:Migrasomes were isolated and purified from BCBM cells(231-BR)and non-specific organotropic parental counterparts(MDA-MB-231),specifically designated as Mig-BCBM and Mig-BC,respectively.The role of Mig-BCBM in BCBM was investigated using an in vitro endothelial cell layer permeability model and a BCBM mouse model.The regulatory mechanism underlying Mig-BCBM was assessed using RT-qPCR,western blotting,immunofluorescence,ex vivo fluorescence imaging,and a series of rescue experiments.Results:Mig-BCBM potently augmented the permeability of vascular endothelial layers,which facilitated the efficient migration of 231-BR cells across endothelial barriers in vitro.The administration of Mig-BCBM significantly disrupted the blood-brain barrier(BBB)and accelerated BCBM progression in vivo,as evidenced in mouse models,compared to the Mig-BC and control groups.Mechanistically,Mig-BCBM harbored ATF6,a critical transducer of endoplasmic reticulum(ER)stress.Upon internalization into hCMEC/D3 cells,ATF6 elicited robust ER stress responses,culminating in downregulation of ZO-1 and VE-cadherin.Digital PCR analysis disclosed significant upregulation of ATF6 in serum migrasomes derived from BCBM patients compared to migrasomes from breast cancer patients and healthy individuals.Conclusions:This study uncovered a pivotal role of cancer cell-derived in BCBM by harnessing ATF6-mediated ER stress to disrupt the BBB and promote metastasis,suggesting novel diagnostic and therapeutic strategies targeting migrasomes and migrasome cargo.
