In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR)...In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR), University of Ghana. The ARL which hitherto was used for routine clinical research in viral, bacteria and immunological studies has since been the facility of choice for testing for all suspected cases of COVID-19 submitted from across Ghana and beyond. The success of testing at the ARL hinged on the availability of several laboratory spaces furnished with state-of-the-art diagnostic equipment and working aids. During the “peak season” where overwhelming numbers of clinical specimens were received, the ARL processed and got results for close to four thousand samples daily. After general disinfection and re-bagging into smaller numbers, at the entrance of the ARL, the samples are taken to a central receiving laboratory, where they are received and entered in a database with accompanying case investigation forms. All samples that are successfully sorted and matched are sent to general laboratories for nucleic acid extraction and then referred to the Instrumentation laboratory for real time reverse-transcription polymerase chain reaction (RT-PCR). When the RT-PCRs were completed, results were analysed and transmitted via email and/or local network to the data reporting office. The data managers then reported results to the investigators and the Ghana Health Service (GHS). Additionally, the ARL provided a next-generation Genome Sequencing platform in partnership with the West African Centre for Cell Biology of Infectious Pathogens at the University of Ghana, which was essential in reporting the genome data of the circulating variants of SARS-CoV-2 in Ghana. Conclusively, it is worth noting, that the NMIMR fulfilled its mandate of supporting the country with specialized diagnostics through the judicious use of the ARL for SARS-CoV-2 testing, from sample receipt to data reporting. The ARL facility and the research faculty have trained and continue to train budding laboratories on biosafety, biosecurity, best practices and testing protocols. It is obvious that the success story of SARS-CoV-2 testing in Ghana, cannot be complete without the mention of the ARL at NMIMR.展开更多
The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
Cancer remains a major global health concern,with escalating incidence and mortality rates underscoring the urgent need for novel diagnostic and therapeutic strategies.Increasing evidence has identified the oral micro...Cancer remains a major global health concern,with escalating incidence and mortality rates underscoring the urgent need for novel diagnostic and therapeutic strategies.Increasing evidence has identified the oral microbiota as a critical contributor to tumorigenesis,thereby expanding the understanding of cancer pathogenesis beyond conventional risk factors such as tobacco use and genetic predisposition.This review summarizes recent progress in elucidating the complex relationship between the oral microbiota and various malignancies,particularly oral squamous cell carcinoma,esophageal adenocarcinoma,and pancreatic ductal adenocarcinoma.Pathogenic bacteria,including Porphyromonas gingivalis and Fusobacterium nucleatum,have been implicated in promoting tumor progression through mechanisms involving chronic inflammation,the production of metabolic toxins,and immune evasion.The dysbiosis of the oral microbiota,often driven by lifestyle factors such as poor diet,tobacco use,and alcohol consumption,further exacerbates these carcinogenic processes.Emerging therapeutic approaches including probiotics,oral microbiota transplantation,and CRISPR-based bacterial editing are under investigation for their potential to restore microbial homeostasis and suppress pathogenic species.Additionally,saliva-based microbial biomarkers have shown promise for non-invasive cancer screening.The integration of multi-omics technologies and artificial intelligence-driven platforms is further advancing the development of precision oncology.This review aims to consolidate fragmented findings concerning the oral microbiota-cancer axis and address existing gaps in mechanistic understanding.The review’s significance lies in the translational potential of microbial research to clinical applications,offering opportunities to reduce the global cancer burden through early detection and microbiota-targeted therapies.展开更多
This paper is Taiji medicine based on the theory of traditional Chinese medicine and traditional medicine,and the core of Taiji medicine is“wave-particle duality of qi and field”,which is a life science based on cel...This paper is Taiji medicine based on the theory of traditional Chinese medicine and traditional medicine,and the core of Taiji medicine is“wave-particle duality of qi and field”,which is a life science based on cellular quantum medicine.this paper makes an important pioneering exploration and research on cellular quantum medicine.The cellular quantum agents corresponding to the disease frequency were obtained through specially prepared aqueous solution containing living cell quantum matrix and frequency modulation of herbal medicines with different frequencies.This study of cellular quantum pharmacy makes it a useful exploration to effectively treat AIDS,cancer,tumor,coronavirus and other difficult diseases.展开更多
Background:Three-dimensional(3D)printing has revolutionized craniofacial and craniomaxillofacial applications,leading to substantial advancements in patient-specific treatments.In this study,a bibliometric analysis wa...Background:Three-dimensional(3D)printing has revolutionized craniofacial and craniomaxillofacial applications,leading to substantial advancements in patient-specific treatments.In this study,a bibliometric analysis was performed to identify the key contributors,research trends,thematic developments,and collaboration networks in this evolving field.Methods:Two search strategies were employed to ensure a comprehensive analysis:(1)a broad search,in which selected keywords were searched in the title,abstract,and keyword fields to capture all relevant publications,and(2)a title-specific search,in which keywords were restricted to the title field to identify publications with a strong focus on 3D printing in craniofacial and craniomaxillofacial applications.The retrieved dataset was analyzed using VOSviewer and RStudio(bibliometrix package).Results:The broad search retrieved 3534 publications,whereas the title-specific search yielded 280 publications.The analysis of these 280 papers focused on identifying the top authors,universities,and countries,as well as their research dynamics and collaboration networks.A more detailed approach was adopted by examining the titles of these 280 papers.VOSviewer segmented the titles into approximately 800 words,which were then categorized into 18 distinct thematic groups to represent research trends.The focus areas of the ten most cited papers were also analyzed.Conclusion:This bibliometric study provides valuable insights into the progress in 3D printing for craniofacial and craniomaxillofacial applications.By highlighting the key contributors,thematic developments,and collaborative networks,this study offers a foundation for future research in this rapidly advancing field.展开更多
Background: Peripheral nerve regeneration is a critical research area with significant implications for neurology,neurosurgery,and regenerative medicine.A bibliometric analysis was conducted to provide a structured ov...Background: Peripheral nerve regeneration is a critical research area with significant implications for neurology,neurosurgery,and regenerative medicine.A bibliometric analysis was conducted to provide a structured overview of research trends,intellectual impact,and evolving themes in peripheral nerve regeneration.This study aimed to identify the most influential research articles on peripheral nerve regeneration;analyze keyword trends,thematic evolution,and co-word structures;assess the contributions of top authors,universities,and countries;and examine collaboration networks and research dynamics.Methods: A systematic bibliometric approach was employed using two search strategies.The first strategy involved searching within the title,abstract,and keyword fields,yielding 15 317 papers,whereas the second strategy was restricted to searching titles only,retrieving 3 531 papers.From these,the 100 most cited papers were selected for analysis.A thematic analysis was conducted using co-word clustering.The leading contributors were ranked according to the number of publications,citations,h-index,g-index,and m-index.Results: The bibliometric analysis provided several key insights.Keyword analysis using bi-and tri-gram techniques revealed the dominant research themes within the field.The top contributors,including authors,universities,and countries,were ranked based on their productivity and citation impact.Collaboration networks were mapped at the author,institutional,and country levels,highlighting key partnerships and global research interactions.Thematic analysis classified research into seven major domains: neural regeneration and repair;cellular and molecular biology;biomaterials and tissue engineering;experimental studies and statistical analyses;functional and therapeutic aspects;neuropathic pain and peripheral nerve disorders;and Schwann cell and cellular responses.Additionally,the ten most influential papers were reviewed in detail to understand their contributions to the field.Conclusion: This study provides a comprehensive and structured overview of peripheral nerve regeneration research.These findings offer valuable insights into the intellectual foundation of the field by identifying key contributors,research trends,and collaboration patterns.The results serve as a guide for future research,helping researchers to navigate the evolving landscape of peripheral nerve regeneration.展开更多
Background: There is a notable scarcity of comprehensive bibliometric studies examining plastic surgery research across extended or recent timeframes and diverse regions in relevant journals. The major objective of th...Background: There is a notable scarcity of comprehensive bibliometric studies examining plastic surgery research across extended or recent timeframes and diverse regions in relevant journals. The major objective of this study was to comprehensively map historical trends and the global distribution of plastic surgery research efforts.Methods: We conducted a comprehensive bibliometric analysis(using the Scopus database) of 35 core plastic surgery journals identified in these studies. All the data were extracted from the Scopus database in June 2025.The timeframe was set from 1946 to June 2025, and only original research and review articles were included in the detailed analysis. Countries(Regions) were grouped into seven regions(Europe, Asia, Latin America, the Middle East,Africa, Australia, and New Zealand, and the United States as standalone categories) to examine regional publication trends.Results: From 1946 to June 2025, 208 381 documents were published in 35 journals, of which 162 014 were eligible for analysis. The annual publication output has grown steadily, peaking at 8 277 by 2024. The United States led with 66 174 publications, followed by Europe(46 688), and Asia(31 785). Citation analysis of the top100 regional papers revealed that the United States(70 530 citations) was the most impactful, followed by Europe(43 869), Asia(28 657), and Australia and New Zealand(23 409). The 100 most-cited papers globally accrued 78 833 citations, were dominated by United States-based contributions(71%), and were primarily published in Plastic and Reconstructive Surgery(57 papers). Chung KC, Mulliken JB, and Coleman SR emerged as the top authors(among the 100 most-cited global publications). Authors' performance is presented as the number of publications, citations, h-index, g-index, m-index, HG composite, and Q2 index.Conclusion: This study extends prior bibliometric investigations by offering a complete historical and geographical perspective on plastic surgery research. This inclusive, regionalized methodology provides a robust framework for future benchmarking and global equity assessments in surgical scholarship.展开更多
BACKGROUND Spinal tuberculosis(TB),also known as Pott’s spine,remains a significant global health issue,particularly in regions with a high TB burden.The disease presents complex challenges in diagnosis,management,an...BACKGROUND Spinal tuberculosis(TB),also known as Pott’s spine,remains a significant global health issue,particularly in regions with a high TB burden.The disease presents complex challenges in diagnosis,management,and treatment,prompting a growing interest in research over recent years.The advancements in imaging,diagnostics,and treatment strategies have driven an increased focus on publishing clinical outcomes,review articles,and case series related to spinal TB(STB).AIM To perform a bibliometric analysis of STB research published over the last 5 years(2019-2023)to identify trends in publication volume,contributions by country,and the nature of the research being conducted.METHODS A comprehensive bibliometric analysis was conducted using the PubMed database,focusing on research articles published between 2019 and 2023.Keywords such as“spine tuberculosis,”“spinal TB,”“TB spine,”and“Pott’s spine”were utilized to capture relevant publications.Articles were analyzed based on the type of research(e.g.,case reports,review articles,cohort studies,randomized controlled trials[RCTs]),number of citations,and country of origin based on the corresponding author's details.Further subgroup analysis was performed according to the TB burden in various countries to assess research trends in high-burden regions.RESULTS A total of 528 articles met the inclusion criteria for this bibliometric analysis.The majority of articles were published between 2020 and 2023(440/528;83.3%),while the lowest number was published in 2019(88/528;16.7%).India led the global contributions with 25.8%of the total publications,followed by China(19.9%)and the United States(10.4%).Combined,African countries contributed 6.8%of the research on STB.Regarding the type of articles,case reports and case series dominated the literature(353/528;66.9%),followed by review articles(120/528;22.7%)and cohort studies(45/528;8.5%).Only 1.9%(10/528)of the studies were RCTs.Countries such as the United States,Germany,the United Kingdom,and Japan have pioneered the use of artificial intelligence(AI)in the diagnostic processes for STB,while India,China,South Africa,and other countries have been pivotal in conducting clinical trials and improving clinical management strategies.CONCLUSION This bibliometric analysis revealed a significant increase in STB research over the last 5 years,with India and China being the leading contributors.However,most publications are case reports or case series,with a limited number of RCTs.The results highlighted the need for more high-quality research,especially in terms of RCTs and innovations in diagnostic technologies.Additionally,the application of AI to STB diagnostics shows promise in developed countries,while high-burden countries are focusing on clinical trials and management strategies.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
Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxicological and neurological studies.Generating genet...Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxicological and neurological studies.Generating genetic tools to manipulate neurons in rats could benefit neurological research.Methods:Using the CRISPR/Cas9 system,we inserted a Cre cassette into endogenous Thy1 and NeuN loci.Thy1-Cre rats featured a downstream P2A-linked insertion,while NeuN-Cre was inserted at the transcriptional start site.The Cre activity was assessed by crossing with a Cre reporter(Rosa26 imCherry)rat and through analyzing mCherry expression patterns.The specificity of cell type was further confirmed by immunofluorescence with NeuN antibody.Phenotypic consequences were assessed by crossing with ND1^(LSL) rats to deplete ND1,followed by monitoring weight/survival and conducting motor function tests.Results:We generated two neuron-specific rats(Thy1-Cre and NeuN-Cre),which exhibited high neuron-specific Cre expression in brain and spinal cord with minor leakage in other tissues.Thy1-Cre showed minor leakage in spleen,lung and kidney while NeuN-Cre showed minor leakage in spleen and kidney.ND1^(Thy1-Cre) and ND1^(NeuN-Cre) rats both showed decreased body weights and survival times.The ND1^(NeuN-Cre) rats died within two weeks,while ND1^(Thy1-Cre) rats lived longer with impaired motor function.Conclusions:We successfully generated two neuron-specific NeuN-Cre and Thy1-Cre rats,and systemically analyzed their expression pattern.展开更多
Astrocytes have important neurosupportive functions in the brain that are altered in neurodegenerative diseases by unresolved mechanisms.We showed previously that astrocytes cultured from mice transgenic for human P30...Astrocytes have important neurosupportive functions in the brain that are altered in neurodegenerative diseases by unresolved mechanisms.We showed previously that astrocytes cultured from mice transgenic for human P301S-tau(P301S-mice)recapitulate the deficit in production and secretion of thrombospondin1 found in symptomatic P301S mouse brains,causing both reduced synapse formation and survival of cultured neurons.To further characterize how P301S-derived astrocytes differ from controls,we have compared the astrocyte-conditioned media of cultured astrocytes from postnatal day 7/8 P301S mice(P301S-astrocyte-conditioned media)versus controls(C57-astrocyte-conditioned media)using label-free liquid chromatography-mass spectrometry.We verified that thrombospondin1 secretion was significantly reduced in the P301S-astrocyte-conditioned media versus C57-astrocyte-conditioned media,demonstrating the robustness of the analysis.The most notable distinction was that~57%of the P301S-astrocyte-conditioned media-enriched proteins were cytoplasmic proteins linked to cellular metabolism that are not predicted to be secreted via classical or non-classical secretion pathways,whereas~88%of C57-astrocyte-conditioned media-enriched proteins comprised classically secreted proteins enriched in extracellular matrix components.These differences are associated with the finding that P301S-derived cultured astrocytes were smaller and in vivo appeared less mature in the cortex of P301S mice.The unconventional secretion pathway that P301S-astrocyte-conditioned media display shares similarities with several amyloid-β-exposed astrocyte-conditioned media,indicating that stimuli induced by tau and amyloid-βmay induce a common adverse response pathway.Altogether,members of this adverse pathway may serve as a potential set of biomarkers to aid the clinical diagnosis of Alzheimer’s disease and other tauopathies,while the list of reduced neurosupportive factors could indicate new approaches to enhance neuronal survival by factor supplementation in tauopathies.展开更多
Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance to...Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.展开更多
A lupuslike condition induced by intraperitoneal administration of pristane(2,6,10,14 tetramethylpentadecane)in mice is widely used as a model of systemic lupus erythematosus(SLE).Due to their phylogenetic distance fr...A lupuslike condition induced by intraperitoneal administration of pristane(2,6,10,14 tetramethylpentadecane)in mice is widely used as a model of systemic lupus erythematosus(SLE).Due to their phylogenetic distance from humans,murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE.In order to overcome speciesspecific limitations of murine models,this approach was tested in nonhuman primates-cynomolgus monkeys(Macaca fascicularis).Two intraperitoneal injections at a dose of 3.5 mL/kg,administered at weeks 1 and 23,recapitulated SLE features,including:production of antinuclear autoantibodies(ANA),membranoproliferative glomerulonephritis with immune complex(IC)deposition in the glomeruli.However,from week 27 five of eight pristanetreated monkeys developed progressive respiratory failure.Two of these died at week 28 and the remaining were euthanized at week 32.The histology of the monkey lungs suggested exogenous lipoid pneumonia.Thus,while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis,the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.展开更多
Parkinson’s disease(PD)is a progressive age-related neurodegenerative disorder clinically defined by motor symptoms and pathologically by the loss of dopaminergic(DA)neurons in the substantia nigra pars compacta.Thes...Parkinson’s disease(PD)is a progressive age-related neurodegenerative disorder clinically defined by motor symptoms and pathologically by the loss of dopaminergic(DA)neurons in the substantia nigra pars compacta.These neurons are characterized by the presence of the cytoplasmic pigment neuromelanin(NM),and their degeneration is closely associated with the accumulation ofα-synuclein(α-syn)into intraneuronal inclusions known as Lewy bodies(LBs),which represent a neuropathological hallmark of PD.展开更多
Perinatal exposure to infection/inflammation is highly associated with neural injury,and subsequent impaired cortical growth,disturbances in neuronal connectivity,and impaired neurodevelopment.However,our understandin...Perinatal exposure to infection/inflammation is highly associated with neural injury,and subsequent impaired cortical growth,disturbances in neuronal connectivity,and impaired neurodevelopment.However,our understanding of the pathophysiological substrate underpinning these changes in brain structure and function is limited.The objective of this review is to summarize the growing evidence from animal trials and human cohort studies that suggest exposure to infection/inflammation during the perinatal period promotes regional impairments in neuronal maturation and function,including loss of high-frequency electroencephalographic activity,and reduced growth and arborization of cortical dendrites and dendritic spines resulting in reduced cortical volume.These inflammation-induced disturbances to neuronal structure and function are likely to underpin subsequent disturbances to cortical development and connectivity in fetuses and/or newborns exposed to infection/inflammation during the perinatal period,leading,in the long term,to impaired neurodevelopment.The combined use of early electroencephalography monitoring with neuroimaging techniques that enable detailed evaluation of brain microstructure,and the use of therapeutics that successfully target systemic and central nervous system inflammation could provide an effective strategy for early detection and therapeutic intervention.展开更多
BACKGROUND Humeral shaft fractures are common and vary by age,with high-energy trauma observed in younger adults and low-impact injuries in older adults.Radial nerve palsy is a frequent complication.Treatment ranges f...BACKGROUND Humeral shaft fractures are common and vary by age,with high-energy trauma observed in younger adults and low-impact injuries in older adults.Radial nerve palsy is a frequent complication.Treatment ranges from nonoperative methods to surgical interventions such as intramedullary K-wires,which promote faster rehabilitation and improved elbow mobility.AIM To evaluate the outcomes of managing humeral shaft fractures using closed reduction and internal fixation with flexible intramedullary K-wires.METHODS This was a retrospective cohort study analyzing the medical records of patients with humeral shaft fractures managed with flexible intramedullary K-wires at King Abdulaziz Medical City,using non-random sampling and descriptive analysis for outcome evaluation.RESULTS This study assessed the clinical outcomes of 20 patients treated for humeral shaft fractures with intramedullary K-wires.Patients were predominantly male(n=16,80%),had an average age of 39.2 years,and a mean body mass index of 29.5 kg/m^(2).The fractures most frequently occurred in the middle third of the humerus(n=14,70%),with oblique fractures being the most common type(n=7,35%).All surgeries used general anesthesia and a posterior approach,with no intraoperative complications reported.Postoperatively,all patients achieved clinical and radiological union(n=20,100%),and the majority(n=13,65%)reached an elbow range of motion from 0 to 150 degrees.CONCLUSION These results suggest that intramedullary K-wire fixation may be an effective option for treating humeral shaft fractures,with favorable outcomes in range of motion recovery,fracture union,and a low rate of intraoperative complications.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provid...Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.展开更多
After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the o...After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.展开更多
Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
文摘In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR), University of Ghana. The ARL which hitherto was used for routine clinical research in viral, bacteria and immunological studies has since been the facility of choice for testing for all suspected cases of COVID-19 submitted from across Ghana and beyond. The success of testing at the ARL hinged on the availability of several laboratory spaces furnished with state-of-the-art diagnostic equipment and working aids. During the “peak season” where overwhelming numbers of clinical specimens were received, the ARL processed and got results for close to four thousand samples daily. After general disinfection and re-bagging into smaller numbers, at the entrance of the ARL, the samples are taken to a central receiving laboratory, where they are received and entered in a database with accompanying case investigation forms. All samples that are successfully sorted and matched are sent to general laboratories for nucleic acid extraction and then referred to the Instrumentation laboratory for real time reverse-transcription polymerase chain reaction (RT-PCR). When the RT-PCRs were completed, results were analysed and transmitted via email and/or local network to the data reporting office. The data managers then reported results to the investigators and the Ghana Health Service (GHS). Additionally, the ARL provided a next-generation Genome Sequencing platform in partnership with the West African Centre for Cell Biology of Infectious Pathogens at the University of Ghana, which was essential in reporting the genome data of the circulating variants of SARS-CoV-2 in Ghana. Conclusively, it is worth noting, that the NMIMR fulfilled its mandate of supporting the country with specialized diagnostics through the judicious use of the ARL for SARS-CoV-2 testing, from sample receipt to data reporting. The ARL facility and the research faculty have trained and continue to train budding laboratories on biosafety, biosecurity, best practices and testing protocols. It is obvious that the success story of SARS-CoV-2 testing in Ghana, cannot be complete without the mention of the ARL at NMIMR.
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
基金Supported by Key Science and Technology Research and Development Program Project of Guangxi,No.GuikeAB22035017,and No.GuikeAB25069071.
文摘Cancer remains a major global health concern,with escalating incidence and mortality rates underscoring the urgent need for novel diagnostic and therapeutic strategies.Increasing evidence has identified the oral microbiota as a critical contributor to tumorigenesis,thereby expanding the understanding of cancer pathogenesis beyond conventional risk factors such as tobacco use and genetic predisposition.This review summarizes recent progress in elucidating the complex relationship between the oral microbiota and various malignancies,particularly oral squamous cell carcinoma,esophageal adenocarcinoma,and pancreatic ductal adenocarcinoma.Pathogenic bacteria,including Porphyromonas gingivalis and Fusobacterium nucleatum,have been implicated in promoting tumor progression through mechanisms involving chronic inflammation,the production of metabolic toxins,and immune evasion.The dysbiosis of the oral microbiota,often driven by lifestyle factors such as poor diet,tobacco use,and alcohol consumption,further exacerbates these carcinogenic processes.Emerging therapeutic approaches including probiotics,oral microbiota transplantation,and CRISPR-based bacterial editing are under investigation for their potential to restore microbial homeostasis and suppress pathogenic species.Additionally,saliva-based microbial biomarkers have shown promise for non-invasive cancer screening.The integration of multi-omics technologies and artificial intelligence-driven platforms is further advancing the development of precision oncology.This review aims to consolidate fragmented findings concerning the oral microbiota-cancer axis and address existing gaps in mechanistic understanding.The review’s significance lies in the translational potential of microbial research to clinical applications,offering opportunities to reduce the global cancer burden through early detection and microbiota-targeted therapies.
文摘This paper is Taiji medicine based on the theory of traditional Chinese medicine and traditional medicine,and the core of Taiji medicine is“wave-particle duality of qi and field”,which is a life science based on cellular quantum medicine.this paper makes an important pioneering exploration and research on cellular quantum medicine.The cellular quantum agents corresponding to the disease frequency were obtained through specially prepared aqueous solution containing living cell quantum matrix and frequency modulation of herbal medicines with different frequencies.This study of cellular quantum pharmacy makes it a useful exploration to effectively treat AIDS,cancer,tumor,coronavirus and other difficult diseases.
文摘Background:Three-dimensional(3D)printing has revolutionized craniofacial and craniomaxillofacial applications,leading to substantial advancements in patient-specific treatments.In this study,a bibliometric analysis was performed to identify the key contributors,research trends,thematic developments,and collaboration networks in this evolving field.Methods:Two search strategies were employed to ensure a comprehensive analysis:(1)a broad search,in which selected keywords were searched in the title,abstract,and keyword fields to capture all relevant publications,and(2)a title-specific search,in which keywords were restricted to the title field to identify publications with a strong focus on 3D printing in craniofacial and craniomaxillofacial applications.The retrieved dataset was analyzed using VOSviewer and RStudio(bibliometrix package).Results:The broad search retrieved 3534 publications,whereas the title-specific search yielded 280 publications.The analysis of these 280 papers focused on identifying the top authors,universities,and countries,as well as their research dynamics and collaboration networks.A more detailed approach was adopted by examining the titles of these 280 papers.VOSviewer segmented the titles into approximately 800 words,which were then categorized into 18 distinct thematic groups to represent research trends.The focus areas of the ten most cited papers were also analyzed.Conclusion:This bibliometric study provides valuable insights into the progress in 3D printing for craniofacial and craniomaxillofacial applications.By highlighting the key contributors,thematic developments,and collaborative networks,this study offers a foundation for future research in this rapidly advancing field.
文摘Background: Peripheral nerve regeneration is a critical research area with significant implications for neurology,neurosurgery,and regenerative medicine.A bibliometric analysis was conducted to provide a structured overview of research trends,intellectual impact,and evolving themes in peripheral nerve regeneration.This study aimed to identify the most influential research articles on peripheral nerve regeneration;analyze keyword trends,thematic evolution,and co-word structures;assess the contributions of top authors,universities,and countries;and examine collaboration networks and research dynamics.Methods: A systematic bibliometric approach was employed using two search strategies.The first strategy involved searching within the title,abstract,and keyword fields,yielding 15 317 papers,whereas the second strategy was restricted to searching titles only,retrieving 3 531 papers.From these,the 100 most cited papers were selected for analysis.A thematic analysis was conducted using co-word clustering.The leading contributors were ranked according to the number of publications,citations,h-index,g-index,and m-index.Results: The bibliometric analysis provided several key insights.Keyword analysis using bi-and tri-gram techniques revealed the dominant research themes within the field.The top contributors,including authors,universities,and countries,were ranked based on their productivity and citation impact.Collaboration networks were mapped at the author,institutional,and country levels,highlighting key partnerships and global research interactions.Thematic analysis classified research into seven major domains: neural regeneration and repair;cellular and molecular biology;biomaterials and tissue engineering;experimental studies and statistical analyses;functional and therapeutic aspects;neuropathic pain and peripheral nerve disorders;and Schwann cell and cellular responses.Additionally,the ten most influential papers were reviewed in detail to understand their contributions to the field.Conclusion: This study provides a comprehensive and structured overview of peripheral nerve regeneration research.These findings offer valuable insights into the intellectual foundation of the field by identifying key contributors,research trends,and collaboration patterns.The results serve as a guide for future research,helping researchers to navigate the evolving landscape of peripheral nerve regeneration.
文摘Background: There is a notable scarcity of comprehensive bibliometric studies examining plastic surgery research across extended or recent timeframes and diverse regions in relevant journals. The major objective of this study was to comprehensively map historical trends and the global distribution of plastic surgery research efforts.Methods: We conducted a comprehensive bibliometric analysis(using the Scopus database) of 35 core plastic surgery journals identified in these studies. All the data were extracted from the Scopus database in June 2025.The timeframe was set from 1946 to June 2025, and only original research and review articles were included in the detailed analysis. Countries(Regions) were grouped into seven regions(Europe, Asia, Latin America, the Middle East,Africa, Australia, and New Zealand, and the United States as standalone categories) to examine regional publication trends.Results: From 1946 to June 2025, 208 381 documents were published in 35 journals, of which 162 014 were eligible for analysis. The annual publication output has grown steadily, peaking at 8 277 by 2024. The United States led with 66 174 publications, followed by Europe(46 688), and Asia(31 785). Citation analysis of the top100 regional papers revealed that the United States(70 530 citations) was the most impactful, followed by Europe(43 869), Asia(28 657), and Australia and New Zealand(23 409). The 100 most-cited papers globally accrued 78 833 citations, were dominated by United States-based contributions(71%), and were primarily published in Plastic and Reconstructive Surgery(57 papers). Chung KC, Mulliken JB, and Coleman SR emerged as the top authors(among the 100 most-cited global publications). Authors' performance is presented as the number of publications, citations, h-index, g-index, m-index, HG composite, and Q2 index.Conclusion: This study extends prior bibliometric investigations by offering a complete historical and geographical perspective on plastic surgery research. This inclusive, regionalized methodology provides a robust framework for future benchmarking and global equity assessments in surgical scholarship.
文摘BACKGROUND Spinal tuberculosis(TB),also known as Pott’s spine,remains a significant global health issue,particularly in regions with a high TB burden.The disease presents complex challenges in diagnosis,management,and treatment,prompting a growing interest in research over recent years.The advancements in imaging,diagnostics,and treatment strategies have driven an increased focus on publishing clinical outcomes,review articles,and case series related to spinal TB(STB).AIM To perform a bibliometric analysis of STB research published over the last 5 years(2019-2023)to identify trends in publication volume,contributions by country,and the nature of the research being conducted.METHODS A comprehensive bibliometric analysis was conducted using the PubMed database,focusing on research articles published between 2019 and 2023.Keywords such as“spine tuberculosis,”“spinal TB,”“TB spine,”and“Pott’s spine”were utilized to capture relevant publications.Articles were analyzed based on the type of research(e.g.,case reports,review articles,cohort studies,randomized controlled trials[RCTs]),number of citations,and country of origin based on the corresponding author's details.Further subgroup analysis was performed according to the TB burden in various countries to assess research trends in high-burden regions.RESULTS A total of 528 articles met the inclusion criteria for this bibliometric analysis.The majority of articles were published between 2020 and 2023(440/528;83.3%),while the lowest number was published in 2019(88/528;16.7%).India led the global contributions with 25.8%of the total publications,followed by China(19.9%)and the United States(10.4%).Combined,African countries contributed 6.8%of the research on STB.Regarding the type of articles,case reports and case series dominated the literature(353/528;66.9%),followed by review articles(120/528;22.7%)and cohort studies(45/528;8.5%).Only 1.9%(10/528)of the studies were RCTs.Countries such as the United States,Germany,the United Kingdom,and Japan have pioneered the use of artificial intelligence(AI)in the diagnostic processes for STB,while India,China,South Africa,and other countries have been pivotal in conducting clinical trials and improving clinical management strategies.CONCLUSION This bibliometric analysis revealed a significant increase in STB research over the last 5 years,with India and China being the leading contributors.However,most publications are case reports or case series,with a limited number of RCTs.The results highlighted the need for more high-quality research,especially in terms of RCTs and innovations in diagnostic technologies.Additionally,the application of AI to STB diagnostics shows promise in developed countries,while high-burden countries are focusing on clinical trials and management strategies.
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Research Project of China Baoyuan Investment Co.,Ltd,Grant/Award Number:Program CBYI202102Haihe Laboratory of Cell Ecosystem Innovation Fund,Grant/Award Number:HH24KYZX0007+4 种基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-024,2021-I2M-1-034 and 2023-I2M-2-001Fundamental Research Funds for the Central Universities,Grant/Award Number:3332022040 and 3332023164Open Research Project in State Key Laboratory of Vascular Homeostasis and Remodeling,Peking University,Grant/Award Number:202411State Key Laboratory Special Fund,Grant/Award Number:2060204the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01.
文摘Background:The Cre/loxP system is most popular in mice,but its application in rats has largely lagged far behind.The rat is vital laboratory animal,especially in toxicological and neurological studies.Generating genetic tools to manipulate neurons in rats could benefit neurological research.Methods:Using the CRISPR/Cas9 system,we inserted a Cre cassette into endogenous Thy1 and NeuN loci.Thy1-Cre rats featured a downstream P2A-linked insertion,while NeuN-Cre was inserted at the transcriptional start site.The Cre activity was assessed by crossing with a Cre reporter(Rosa26 imCherry)rat and through analyzing mCherry expression patterns.The specificity of cell type was further confirmed by immunofluorescence with NeuN antibody.Phenotypic consequences were assessed by crossing with ND1^(LSL) rats to deplete ND1,followed by monitoring weight/survival and conducting motor function tests.Results:We generated two neuron-specific rats(Thy1-Cre and NeuN-Cre),which exhibited high neuron-specific Cre expression in brain and spinal cord with minor leakage in other tissues.Thy1-Cre showed minor leakage in spleen,lung and kidney while NeuN-Cre showed minor leakage in spleen and kidney.ND1^(Thy1-Cre) and ND1^(NeuN-Cre) rats both showed decreased body weights and survival times.The ND1^(NeuN-Cre) rats died within two weeks,while ND1^(Thy1-Cre) rats lived longer with impaired motor function.Conclusions:We successfully generated two neuron-specific NeuN-Cre and Thy1-Cre rats,and systemically analyzed their expression pattern.
基金MGS from the Alzheimer Society(#384,AS-PG-17-026,Alzheimer’s Research UK(ART-PG2011-20 and ARUK-EXT2015B-2)the BBSRC(BB/T509085/1)+1 种基金The Fondation Recherche Alzheimer(G112606)the Scholl Foundation,and to MGS and AMT from the National Center for the Replacement,Refinement,&Reduction of Animals in Research(NC3R)(#NC/L000741/1).
文摘Astrocytes have important neurosupportive functions in the brain that are altered in neurodegenerative diseases by unresolved mechanisms.We showed previously that astrocytes cultured from mice transgenic for human P301S-tau(P301S-mice)recapitulate the deficit in production and secretion of thrombospondin1 found in symptomatic P301S mouse brains,causing both reduced synapse formation and survival of cultured neurons.To further characterize how P301S-derived astrocytes differ from controls,we have compared the astrocyte-conditioned media of cultured astrocytes from postnatal day 7/8 P301S mice(P301S-astrocyte-conditioned media)versus controls(C57-astrocyte-conditioned media)using label-free liquid chromatography-mass spectrometry.We verified that thrombospondin1 secretion was significantly reduced in the P301S-astrocyte-conditioned media versus C57-astrocyte-conditioned media,demonstrating the robustness of the analysis.The most notable distinction was that~57%of the P301S-astrocyte-conditioned media-enriched proteins were cytoplasmic proteins linked to cellular metabolism that are not predicted to be secreted via classical or non-classical secretion pathways,whereas~88%of C57-astrocyte-conditioned media-enriched proteins comprised classically secreted proteins enriched in extracellular matrix components.These differences are associated with the finding that P301S-derived cultured astrocytes were smaller and in vivo appeared less mature in the cortex of P301S mice.The unconventional secretion pathway that P301S-astrocyte-conditioned media display shares similarities with several amyloid-β-exposed astrocyte-conditioned media,indicating that stimuli induced by tau and amyloid-βmay induce a common adverse response pathway.Altogether,members of this adverse pathway may serve as a potential set of biomarkers to aid the clinical diagnosis of Alzheimer’s disease and other tauopathies,while the list of reduced neurosupportive factors could indicate new approaches to enhance neuronal survival by factor supplementation in tauopathies.
基金supported by the Fundamental Research Funds for the Central Universities,Nos.G2021KY05107,G2021KY05101the National Natural Science Foundation of China,Nos.32071316,32211530049+1 种基金the Natural Science Foundation of Shaanxi Province,No.2022-JM482the Education and Teaching Reform Funds for the Central Universities,No.23GZ230102(all to LL and HH).
文摘Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.
文摘A lupuslike condition induced by intraperitoneal administration of pristane(2,6,10,14 tetramethylpentadecane)in mice is widely used as a model of systemic lupus erythematosus(SLE).Due to their phylogenetic distance from humans,murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE.In order to overcome speciesspecific limitations of murine models,this approach was tested in nonhuman primates-cynomolgus monkeys(Macaca fascicularis).Two intraperitoneal injections at a dose of 3.5 mL/kg,administered at weeks 1 and 23,recapitulated SLE features,including:production of antinuclear autoantibodies(ANA),membranoproliferative glomerulonephritis with immune complex(IC)deposition in the glomeruli.However,from week 27 five of eight pristanetreated monkeys developed progressive respiratory failure.Two of these died at week 28 and the remaining were euthanized at week 32.The histology of the monkey lungs suggested exogenous lipoid pneumonia.Thus,while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis,the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.
文摘Parkinson’s disease(PD)is a progressive age-related neurodegenerative disorder clinically defined by motor symptoms and pathologically by the loss of dopaminergic(DA)neurons in the substantia nigra pars compacta.These neurons are characterized by the presence of the cytoplasmic pigment neuromelanin(NM),and their degeneration is closely associated with the accumulation ofα-synuclein(α-syn)into intraneuronal inclusions known as Lewy bodies(LBs),which represent a neuropathological hallmark of PD.
基金supported by National Health and Medical Research Council of Australia(APP1090890 and APP1164954)Cerebral Palsy Alliance(ERG02123)the Victorian Government’s Operational Infrastructure Support Program。
文摘Perinatal exposure to infection/inflammation is highly associated with neural injury,and subsequent impaired cortical growth,disturbances in neuronal connectivity,and impaired neurodevelopment.However,our understanding of the pathophysiological substrate underpinning these changes in brain structure and function is limited.The objective of this review is to summarize the growing evidence from animal trials and human cohort studies that suggest exposure to infection/inflammation during the perinatal period promotes regional impairments in neuronal maturation and function,including loss of high-frequency electroencephalographic activity,and reduced growth and arborization of cortical dendrites and dendritic spines resulting in reduced cortical volume.These inflammation-induced disturbances to neuronal structure and function are likely to underpin subsequent disturbances to cortical development and connectivity in fetuses and/or newborns exposed to infection/inflammation during the perinatal period,leading,in the long term,to impaired neurodevelopment.The combined use of early electroencephalography monitoring with neuroimaging techniques that enable detailed evaluation of brain microstructure,and the use of therapeutics that successfully target systemic and central nervous system inflammation could provide an effective strategy for early detection and therapeutic intervention.
基金approved by King Abdullah International Medical Research Center Ethics Committee(approval No.0000074524).
文摘BACKGROUND Humeral shaft fractures are common and vary by age,with high-energy trauma observed in younger adults and low-impact injuries in older adults.Radial nerve palsy is a frequent complication.Treatment ranges from nonoperative methods to surgical interventions such as intramedullary K-wires,which promote faster rehabilitation and improved elbow mobility.AIM To evaluate the outcomes of managing humeral shaft fractures using closed reduction and internal fixation with flexible intramedullary K-wires.METHODS This was a retrospective cohort study analyzing the medical records of patients with humeral shaft fractures managed with flexible intramedullary K-wires at King Abdulaziz Medical City,using non-random sampling and descriptive analysis for outcome evaluation.RESULTS This study assessed the clinical outcomes of 20 patients treated for humeral shaft fractures with intramedullary K-wires.Patients were predominantly male(n=16,80%),had an average age of 39.2 years,and a mean body mass index of 29.5 kg/m^(2).The fractures most frequently occurred in the middle third of the humerus(n=14,70%),with oblique fractures being the most common type(n=7,35%).All surgeries used general anesthesia and a posterior approach,with no intraoperative complications reported.Postoperatively,all patients achieved clinical and radiological union(n=20,100%),and the majority(n=13,65%)reached an elbow range of motion from 0 to 150 degrees.CONCLUSION These results suggest that intramedullary K-wire fixation may be an effective option for treating humeral shaft fractures,with favorable outcomes in range of motion recovery,fracture union,and a low rate of intraoperative complications.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
基金supported by grants from Guangdong Basic and Applied Basic Research Foundation,No.2021A1515110801(to SW)the National Natural Science Foundation of China,No.82301511(to SW)+1 种基金“Double First-Class”Construction Project of NPU,Nos.0515023GH0202320(to JC),0515023SH0201320(to JC)973 Program,No.2011CB504100(to JC).
文摘Myelination,the continuous ensheathment of neuronal axons,is a lifelong process in the nervous system that is essential for the precise,temporospatial conduction of action potentials between neurons.Myelin also provides intercellular metabolic support to axons.Even minor disruptions in the integrity of myelin can impair neural performance and increase susceptibility to neurological diseases.In fact,myelin degeneration is a well-known neuropathological condition that is associated with normal aging and several neurodegenerative diseases,including multiple sclerosis and Alzheimer’s disease.In the central nervous system,compact myelin sheaths are formed by fully mature oligodendrocytes.However,the entire oligodendrocyte lineage is susceptible to changes in the biological microenvironment and other risk factors that arise as the brain ages.In addition to their well-known role in action potential propagation,oligodendrocytes also provide intercellular metabolic support to axons by transferring energy metabolites and delivering exosomes.Therefore,myelin degeneration in the aging central nervous system is a significant contributor to the development of neurodegenerative diseases.Interventions that mitigate age-related myelin degeneration can improve neurological function in aging individuals.In this review,we investigate the changes in myelin that are associated with aging and their underlying mechanisms.We also discuss recent advances in understanding how myelin degeneration in the aging brain contributes to neurodegenerative diseases and explore the factors that can prevent,slow down,or even reverse age-related myelin degeneration.Future research will enhance our understanding of how reducing age-related myelin degeneration can be used as a therapeutic target for delaying or preventing neurodegenerative diseases.
文摘After injury,bone tissue initiates a reparative response to restore its structure and function.The failure to initiate or delay this response could result in fracture nonunion.The molecular mechanisms underlying the occurrence of fracture nonunion are not yet established.We propose that hypoxia-triggered signaling pathways,mediated by reactive oxygen species(ROS)homeostasis,control Bmp2 expression and fracture healing initiation.The excessive ROS leads to oxidative stress and,ultimately,fracture nonunion.In this study,we silenced Apex1,the final ROS signaling transducer that mediates the activation of key transcription factors by their cysteines oxidoreduction,evaluating its role during endochondral ossification and fracture repair.Silencing Apex1 in limb bud mesenchyme results in transient metaphyseal dysplasia derived from impaired chondrocyte differentiation.During bone regeneration,Apex1 silencing induces a fracture nonunion phenotype,characterized by delayed fracture repair initiation,impaired periosteal response,and reduced chondrocyte and osteoblast differentiation.This compromised chondrocyte differentiation hampers callus vascularization and healing progression.Our findings highlight a critical mechanism where hypoxia-driven ROS signaling in mesenchymal progenitors through APEX1 is essential for fracture healing initiation.
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
