Background: The incidence of intracranial metastases (ICMET) has been steadily rising, and its frequency with respect to primary brain tumours is relatively high. Objective: The objectives of this study were to elucid...Background: The incidence of intracranial metastases (ICMET) has been steadily rising, and its frequency with respect to primary brain tumours is relatively high. Objective: The objectives of this study were to elucidate the current epidemiology and describe the clinical, diagnostic and therapeutic features of ICMET in Yaounde. Method and findings: A descriptive cross-sectional study was done in the neurosurgery departments of the General and Central Hospitals of Yaounde during the period from January 2016 to December 2022. We included all medical booklets of patients admitted for a tumoral intracranial expansive process with our target population being patients with histological evidence of ICMET, and did a retrospective inclusion of data using a pre-established technical form aimed at collecting sociodemographic data, clinical data, paraclinical data, and the treatment procedures. Analysis was done using the SPSS statistical software. A total of 614 cases of intracranial tumors were included among whom 35 presented histological evidence of ICMET. This gives a frequency of 5.7%. The sex ratio was 0.94, the mean age was 55.68 +/- 14.4 years, extremes 28 and 86 years and the age range 50 - 59 was affected in 28.57% of cases. The clinical presentation included signs of raised intracranial pressure (headache, blurred vision, vomiting) in 26 cases (74.3%), motor deficit 48.6%, seizures 17.1%. The mode of onset was metachronous in 71.4% and synchronous in 28.6%. The imaging techniques were cerebral CT scan in 82.9%, cerebral MRI in 40%, TAP scan in 22.9%. The metastatic lesions were supratentorial in 94.3% and single in 62.9%. The primary cancers found were breast cancer (31.4%), lung cancer (25.7%), prostate cancer (17.1%), thyroid cancer (5.7%), colon cancer (2.9%), and melanoma (2.9%). The therapeutic modalities were total resection (68.6%), radiotherapy (37.1%). Conclusion: Intracranial metastases are relatively frequent. There is a female sex predominance and the age group 50 - 59 years is the most affected. Brain metastases mostly occur in patients with a history of known primary tumor. The clinical signs mainly include signs of raised intracranial pressure, motor deficit, seizures and mental confusion. Cerebral CT Scan is the main imaging technique used. Most of the lesions are single and supratentorially located. The primary cancers most represented include breast cancer, lung cancer and prostate cancer. Surgery is the main treatment procedure. The adjuvant treatment (radiotherapy, chemotherapy) was limited.展开更多
The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct facto...The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.展开更多
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen...Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.展开更多
Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell...Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.展开更多
Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrate...Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.展开更多
Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate trau...Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.展开更多
Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its appl...Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)...Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox...Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.展开更多
BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the exist...BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.展开更多
Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for ...Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.展开更多
After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune...After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.展开更多
Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the bloo...Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.展开更多
Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrate...Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.展开更多
BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,i...BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,ischemia,and hypoxia.The precision rehabilitation nursing model for chronic disease management is a continuous,fixed,orderly,and efficient nursing model aimed at standardizing the clinical nursing process,reducing the wastage of medical resources,and improving the quality of medical services.AIM To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction.METHODS Patients(n=124)admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects.The random number table method was used to divide them into a conventional nursing intervention group(n=61)and a model nursing intervention group(n=63).Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management.RESULTS Compared with the conventional intervention group,the model intervention group had a shorter time to clinical symptom relief(P<0.05),lower Hamilton Anxiety Scale and Hamilton Depression Scale scores,a lower incidence of total complications(P<0.05),a higher disease knowledge mastery rate,higher safety and quality,and a higher overall nursing satisfaction rate(P<0.05).CONCLUSION The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction,reducing the incidence of total complications and improving the clinical outcome of patients,and is worthy of application in clinical practice.展开更多
Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectiou...Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectious rate,a long incubation period and a variety of manifestations.In the absence of effective treatments for the virus,it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission.Hereby we focused on the surgical practice in Neurosurgery Department,Tongji Hospital,Wuhan,and drafted several recommendations based on the latest relevant guidelines and our experience.These recommendations have helped us until now to achieve'zero infection'of doctors and nurses in our department,we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.展开更多
BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizin...BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal...BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.展开更多
文摘Background: The incidence of intracranial metastases (ICMET) has been steadily rising, and its frequency with respect to primary brain tumours is relatively high. Objective: The objectives of this study were to elucidate the current epidemiology and describe the clinical, diagnostic and therapeutic features of ICMET in Yaounde. Method and findings: A descriptive cross-sectional study was done in the neurosurgery departments of the General and Central Hospitals of Yaounde during the period from January 2016 to December 2022. We included all medical booklets of patients admitted for a tumoral intracranial expansive process with our target population being patients with histological evidence of ICMET, and did a retrospective inclusion of data using a pre-established technical form aimed at collecting sociodemographic data, clinical data, paraclinical data, and the treatment procedures. Analysis was done using the SPSS statistical software. A total of 614 cases of intracranial tumors were included among whom 35 presented histological evidence of ICMET. This gives a frequency of 5.7%. The sex ratio was 0.94, the mean age was 55.68 +/- 14.4 years, extremes 28 and 86 years and the age range 50 - 59 was affected in 28.57% of cases. The clinical presentation included signs of raised intracranial pressure (headache, blurred vision, vomiting) in 26 cases (74.3%), motor deficit 48.6%, seizures 17.1%. The mode of onset was metachronous in 71.4% and synchronous in 28.6%. The imaging techniques were cerebral CT scan in 82.9%, cerebral MRI in 40%, TAP scan in 22.9%. The metastatic lesions were supratentorial in 94.3% and single in 62.9%. The primary cancers found were breast cancer (31.4%), lung cancer (25.7%), prostate cancer (17.1%), thyroid cancer (5.7%), colon cancer (2.9%), and melanoma (2.9%). The therapeutic modalities were total resection (68.6%), radiotherapy (37.1%). Conclusion: Intracranial metastases are relatively frequent. There is a female sex predominance and the age group 50 - 59 years is the most affected. Brain metastases mostly occur in patients with a history of known primary tumor. The clinical signs mainly include signs of raised intracranial pressure, motor deficit, seizures and mental confusion. Cerebral CT Scan is the main imaging technique used. Most of the lesions are single and supratentorially located. The primary cancers most represented include breast cancer, lung cancer and prostate cancer. Surgery is the main treatment procedure. The adjuvant treatment (radiotherapy, chemotherapy) was limited.
基金supported by the National Natural Science Foundation of China,Nos.82130037(to CH),81971122(to CH),82171323(to WL)the Natural Science Foundation of Jiangsu Province of China,No.BK20201113(to WL)。
文摘The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX)and 81671189(to RX)。
文摘Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.
基金supported by the National Natural Science Foundation of China,Nos.81974207(to JH),82001383(to DW)the Special Clinical Research Project of Health Profession of Shanghai Municipal Health Commission,No.20204Y0076(to DW)。
文摘Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.
基金supported by the Chongqing Science and Technology CommitteeNatural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0065 (to YL)。
文摘Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.
基金supported by the National Natural Science Foundation of China,No.81771355the Natural Science Foundation of Chongqing Science and Technology Bureau,Nos.CSTC2015jcyjA10096,cstc2021jcyj-msxmX0262(all to ZL)。
文摘Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.
基金supported by STI2030-Major Projects,No.2022ZD0207600 (to LZ)the National Natural Science Foundation of China,Nos.821 71446 (to JY),U22A20301 (to KFS),32070955 (to LZ)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.202381515040015 (to LZ)Science and Technology Program of Guangzhou of China,No.202007030012 (to KFS and LZ)
文摘Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
基金supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX)the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。
文摘Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
文摘Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.
基金approved by the medical ethics committee of the authors’institution(protocol number:56733164-203-E.5863).
文摘BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain prognoses.Currently,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve injuries.AIM To examine the impact of exosomes on the process of functional recovery following a complete radial nerve damage.METHODS A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife assault.The cut is located on the left arm,specifically below the elbow.The neurological examination and electrodiagnostic testing reveal evidence of left radial nerve damage.The sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion microvesicles.This exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural pathway.The patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic testing.RESULTS The duration of the patient’s follow-up period was 180 d.An increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve grafting.Upon the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the nerve.This assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon scale.The results indicated that the level of improvement in motor function was classified as M5,denoting an excellent outcome.Additionally,the level of improvement in sensory function was classified as S3+,indicating a good outcome.It is noteworthy that these assessments were conducted in the absence of physical therapy.At the 10th wk post-injury,despite the persistence of substantial axonal damage,the nerve exhibited indications of nerve re-innervation as evidenced by control electromyography(EMG).In contrast to the preceding.EMG analysis revealed a significant electrophysiological enhancement in the EMG conducted at the 6th-mo follow-up,indicating ongoing regeneration.CONCLUSION Enhanced comprehension of the neurobiological ramifications associated with peripheral nerve damage,as well as the experimental and therapy approaches delineated in this investigation,holds the potential to catalyze future clinical progress.
基金supported by the National Natural Science Foundation of China,No.31970906(to WLei)the Natural Science Foundation of Guangdong Province,No.2020A1515011079(to WLei)+4 种基金Key Technologies R&D Program of Guangdong Province,No.2018B030332001(to GC)Science and Technology Projects of Guangzhou,No.202206060002(to GC)the Youth Science Program of the National Natural Science Foundation of China,No.32100793(to ZX)the Pearl River Innovation and Entrepreneurship Team,No.2021ZT09 Y552Yi-Liang Liu Endowment Fund from Jinan University Education Development Foundation。
文摘Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.
基金supported by the National Institutes of HealthNo.R56 NS117935(to ASH and WLM)+1 种基金funded by Institutional Clinical and Translational Science AwardNo.UL1 TR002373。
文摘After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.
基金supported by the Ningbo Public Welfare Science and Technology Program,No.2022S023(to JY)Ningbo Natural Science Foundation,No.2022J211(to JS)+2 种基金Ningbo Medical and Health Brand Discipline,No.PPXK2018-04(to XG)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.
基金supported by the National Natural Science Foundation of China(Grant No.:32070740)Zhejiang Provincial Natural Science Foundation(Grant No.:LZ23H160005)+1 种基金Natural Science Foundation of Jiangsu Province(Grant No.:BK20201197)Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program,Zhejiang Provincial Qianjiang Talents Program to Jianbin Zhang.
文摘Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8^(+)GZMB^(+)T cells and the decrease of CD8^(+)PD-1^(+)T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.
文摘BACKGROUND Cerebral infarction,previously referred to as cerebral infarction or ischemic stroke,refers to the localized brain tissue experiencing ischemic necrosis or softening due to disorders in brain blood supply,ischemia,and hypoxia.The precision rehabilitation nursing model for chronic disease management is a continuous,fixed,orderly,and efficient nursing model aimed at standardizing the clinical nursing process,reducing the wastage of medical resources,and improving the quality of medical services.AIM To analyze the value of a precise rehabilitation nursing model for chronic disease management in patients with cerebral infarction.METHODS Patients(n=124)admitted to our hospital with cerebral infarction between November 2019 and November 2021 were enrolled as the study subjects.The random number table method was used to divide them into a conventional nursing intervention group(n=61)and a model nursing intervention group(n=63).Changes in the nursing index for the two groups were compared after conventional nursing intervention and precise rehabilitation intervention nursing for chronic disease management.RESULTS Compared with the conventional intervention group,the model intervention group had a shorter time to clinical symptom relief(P<0.05),lower Hamilton Anxiety Scale and Hamilton Depression Scale scores,a lower incidence of total complications(P<0.05),a higher disease knowledge mastery rate,higher safety and quality,and a higher overall nursing satisfaction rate(P<0.05).CONCLUSION The precision rehabilitation nursing model for chronic disease management improves the clinical symptoms of patients with cerebral infarction,reducing the incidence of total complications and improving the clinical outcome of patients,and is worthy of application in clinical practice.
文摘Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectious rate,a long incubation period and a variety of manifestations.In the absence of effective treatments for the virus,it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission.Hereby we focused on the surgical practice in Neurosurgery Department,Tongji Hospital,Wuhan,and drafted several recommendations based on the latest relevant guidelines and our experience.These recommendations have helped us until now to achieve'zero infection'of doctors and nurses in our department,we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.
文摘BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.
文摘BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.
