Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-...Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.展开更多
BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,...BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.展开更多
Background: The optimal time to closure of a newborn with a myelomeningocele has been the focus of a number of evaluations. The Timing of primary surgery has received significant attention due to its relationship to r...Background: The optimal time to closure of a newborn with a myelomeningocele has been the focus of a number of evaluations. The Timing of primary surgery has received significant attention due to its relationship to repair-site infection that can lead to increased morbidity and prolonged hospital stays. It is on this basis that recommendations have utilized 48 - 72 hours post birth as ideal time of closure. This is not only prevent infection at the site but also prevent ventriculitis and neural structure damage. We therefore, hypothesized an increase in wound infection rates in those patients with delays in myelomeningocele repair. Methods: We retrospectively reviewed the records of 103 children with myelomeningocele treated between 2016 and 2023. At discharge the patients were followed up at the post-operative clinic visit 2 weeks later. Children were assigned to 1 of 2 groups, those who underwent primary neurosurgical repair within 72 hours of delivery (Group 1) and those undergoing repair after 72 hours (Group 2). We compared the infection rates. Results: 103 children who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Eight (7.8 %) patients were noted to have post-repair surgical site complications. There was no significant difference in rates of infection between Group 1 and Group 2 repair times. The presence of infection was associated increased length of stay when compared to neonates without infection. Conclusion: In children with myelomeningocele, the timing of primary neurosurgical repair appears not to have a significant impact on surgical site infection. Closure of the spinal lesion within the first 72 hours of life may be more favorable for neural damage prevention. These results suggest that early myelomeningocele repair may not impart significantly on the rate of wound-site infection.展开更多
The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental p...The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.展开更多
Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occu...Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.展开更多
BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systemati...BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based therapies show promise,but clinical trials reveal potential adverse events and limitations,underscoring the need for meticulous optimization of transplantation conditions and parameters,caution against swift clinical implementation,a deeper understanding of SCI pathophysiology,and addressing ethical,tumorigenicity,immunogenicity,and immunotoxicity concerns before gradual and careful adoption in clinical practice.展开更多
Some specially imaging of magnetic resonance imaging,the diffusion-weighted imaging(DWI),the diffusion tensor imaging and fractional anisotropy(FA),are useful to described,detect,and map the extent of spinal cord lesi...Some specially imaging of magnetic resonance imaging,the diffusion-weighted imaging(DWI),the diffusion tensor imaging and fractional anisotropy(FA),are useful to described,detect,and map the extent of spinal cord lesions.FA measurements may are used to predicting the outcome of patients who have spinal cord lesions.Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions,and this information could be used to formulating a differential diagnosis and planning biopsies or resection.In this article,we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future.展开更多
Clipping and coiling are currently the two alternatives in treatment of ruptured cerebral aneurysms. In spite of some meritorious analysis, further discussion is helpful to understand the actual state of art. Retreatm...Clipping and coiling are currently the two alternatives in treatment of ruptured cerebral aneurysms. In spite of some meritorious analysis, further discussion is helpful to understand the actual state of art. Retreatment and rebleeding rates clearly favors clipping, although short-term functional outcome seems to be beneficial for clipping, while this different is not such if we perform the comparison at a longer follow up. Longterm follow ups and cost analysis are mandatory to have a clear view of the current picture in treatment of subarachnoid hemorrhage. Treatment strategy should be made by a multi-disciplinary team in accredited centers with proficient experience in both techniques.展开更多
Surgical treatment for cervical kyphotic deformity is still controversial. Circumferential approach has been well described in the literature but long terms outcomes are not well reported. Important to decide the corr...Surgical treatment for cervical kyphotic deformity is still controversial. Circumferential approach has been well described in the literature but long terms outcomes are not well reported. Important to decide the correct treatment option is the preoperative radiological exams to value the type of deformity(flexible or fixed). We report the case of a 67-year-old woman affected by a severe cervical kyphotic deformity who underwent combined anterior/posterior surgical approach, getting a good reduction of the deformity and an optimal stability in a long term follow up.展开更多
We describe the case of a 67-year-old woman with L5-S1 ontogenetic spondylolisthesis treated with pedicle fixation associated with interbody arthrodesis performed with S1-L5 trans-sacral screwing according to the tech...We describe the case of a 67-year-old woman with L5-S1 ontogenetic spondylolisthesis treated with pedicle fixation associated with interbody arthrodesis performed with S1-L5 trans-sacral screwing according to the technique of Bartolozzi. The procedure was followed by a wide decompressive laminectomy. The patient had a progressive improvement of the symptoms which gradually disappeared in 12 mo. The radiograph at 6 and 12 mo showed complete fusion system. The choice of treatment in L5-S1 ontogenetic spondylolithesis is related to a correct clinical and diagnostic planning(X-ray, computer tomography magnetic resonance imaging, Measurement). In particular, the severity index and the square of unstable zone, and the standard measurements already described in the literature, are important to understand and to plane the correct surgical strategy, that require, in most of the times, fusion and interbody artrodesis.展开更多
With an aging patient population and an increased burden of neurological disease,the demand for noninvasive alternatives to open neurosurgical procedures is imperative.Noninvasive or minimally invasive approaches to t...With an aging patient population and an increased burden of neurological disease,the demand for noninvasive alternatives to open neurosurgical procedures is imperative.Noninvasive or minimally invasive approaches to targeting brain regions include transcranial magnetic stimulation(TMS),transcranial direct current stimulation,temporally interfering electric fields,and focused ultrasound(FUS).Among these modalities,FUS offers a unique combination of target specificity,deep brain penetration,and compatibility with real-time structural and thermal monitoring using magnetic resonance imaging(MRI)and MR thermometry.Depending on the intensity and frequency used,ultrasound can have either modulating or ablative effects on brain tissue.High-intensity MR-guided FUS(MRgFUS)is a noninvasive and effective alternative to conventional deep-brain stimulation and radiofrequency lesioning for essential tremor(ET),and is being investigated for other movement disorders,particularly Parkinson’s disease.Wider clinical implementation of high-intensity ultrasound is challenged by limitations in target selection precision,technical barriers(such as variable penetration and heat deposition)and the possibility of lesion-related adverse effects(Schwartz et al.,2018).Emerging studies,including those from our group(Boutet et al.,2018)are striving to refine targeting of MRgFUS to improve safety and patient clinical outcomes.At the same time,low-intensity FUS(LIFUS)has been found to safely modulate brain activity in rodents,primates,and healthy human subjects(Fomenko et al.,2018).Clinical translation of LIFUS has been hampered however,by a poor understanding of the mechanisms of action,uncertainty over effective sonication parameters and intensities,and conflicting study results due to heterogeneous experimental protocols.In this perspective,the current state of both MRgFUS ablation and LIFUS neuromodulation will be presented.Ongoing technical challenges to delivering ultrasound to the brain,recent innovations in target and parameter selection,and future directions for this emerging nonsurgical alternative are also discussed.展开更多
Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland. According to the World Health Organization there are "organotypic"(types A, AB, B1, B2, and B3) and "non-o...Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland. According to the World Health Organization there are "organotypic"(types A, AB, B1, B2, and B3) and "non-organotypic"(thymic carcinomas) thymomas. Type B3 thymomas are aggressive tumors, which can metastasize. Due to the rarity of these lesions, only 7 cases of extradural metastasis are described in the literature. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis. A 46-year-old man underwent thymoma surgical removal. The year after the procedure he was treated for a parietal pleura metastasis. In 2006 he underwent cervical-dorsal extradural metastasis removal and C5-Th1 stabilization. Seven years after he came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. He underwent a cervical spine magnetic resonance imaging, which showed a new lesion at the C5-C7 level. The patient underwent a surgery for the intradural B3 thymoma metastasis. Neurological symptoms improved although the removal was subtotal. He went through postoperative radiation therapy with further mass reduction. Spinal metastases are extremely rare. To date, only 7 cases of spinal extradural metastasis have been described in the literature. This is the first case of spinal intradural metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma.展开更多
Additional hemodynamic parameters are highly desirable in the clinical management of intracranial aneurysm rupture as static medical images cannot demonstrate the blood flow within aneurysms. There are two ways of obt...Additional hemodynamic parameters are highly desirable in the clinical management of intracranial aneurysm rupture as static medical images cannot demonstrate the blood flow within aneurysms. There are two ways of obtaining the hemodynamic information-by phase-contrast magnetic resonance imaging (PCMRI) and computational fluid dynamics (CFD). In this paper, we compared PCMRI and CFD in the analysis of a stable patient's specific aneurysm. The results showed that PCMRI and CFD are in good agreement with each other. An additional CFD study of two stable and two ruptured aneurysms revealed that ruptured aneurysms have a higher statistical average blood velocity, wall shear stress, and oscillatory shear index (OSI) within the aneurysm sac compared to those of stable aneurysms. Furthermore, for ruptured aneurysms, the OSI divides the positive and negative wall shear stress divergence at the aneurysm sac.展开更多
Objective To investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. Methods Orchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related ost...Objective To investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. Methods Orchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. A rat vertebral body can be longitudinally divided into central portion, which contain more trabecular bone, and para-endplate portions which contain more compact bone. In matured male and female Wistar and Sprague-Dawley rat lumbar spines, we investigated baseline bone mineral density (BMD) characteristics and the differential segmental responses in bone loss within the lumbar vertebral body post gonadal surgery with clinical multidetector computed tomography. Results Para-endplate sections had a higher BMD than central sections. The cephalad para-endplate sections had a higher BMD than the caudad para-endplate sections. Eight weeks after gonadal removal, there was more bone loss in central sections than para-endplate sections. The relative difference of bone loss between para-endplate and central sections was more apparent in male rats than in female rats. There was more bone loss in caudad sections than cephalad sections; this lead to a further increase of BMD difference between caudad para-endplate sections and cephalad para-endplate sections post gonadal surgery. Conclusion The approach described in this study provided a consistent way to study BMD change within predominantly compact bone portion and trabecular bone portion of the vertebral body.展开更多
Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effe...Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.展开更多
Intracranial aneurysm, a localized dilation of arterial blood vessels in the Circle of Willis and its branches, is potentially life threatening, due to massive bleeding in the subarachnoid space upon rupture. In clini...Intracranial aneurysm, a localized dilation of arterial blood vessels in the Circle of Willis and its branches, is potentially life threatening, due to massive bleeding in the subarachnoid space upon rupture. In clinical practice, one minimally invasive surgical procedure is the implantation of a metallic stent to cover the aneurysm neck. This flow diverting device can reduce the flow into the aneurysm and enhance the prospect of thrombosis, a condition expected to reduce the risk of growth and rupture. The biomechanical and haemo-dynamic factors in stented and nonstented situations are studied by computational fluid dynamics. Unlike earlier models with straight or curved parent blood vessels, the aneurysm is now located near an arterial bifurcation. The influence of the aspect (depth to neck) ratio of the aneurysm on the flow dynamics will be emphasized, especially in the post-operation stages. More precisely, the maximum flow velocity, the variations of wall shear stress, the risk of stent migration and volumetric flow rate after endovascular treatment will be studied. Aneurysms with larger aspect ratios (i.e. smaller neck sizes for constant depth) generally pose a greater risk in terms of these flow parameters. These results will assist the applications and design of stents in future neurosurgical therapy. The approach is limited to a nonelastic model, without taking into account of questions like stent expansion and interaction with tissue.展开更多
Posterior fossa ependymoma comprises two distinct molecular entities,ependymoma_posterior fossa A(EPN_PFA)and ependymoma_posterior fossa B(EPN_PFB),with differentiable gene expression profiles.As yet,the response of t...Posterior fossa ependymoma comprises two distinct molecular entities,ependymoma_posterior fossa A(EPN_PFA)and ependymoma_posterior fossa B(EPN_PFB),with differentiable gene expression profiles.As yet,the response of the two entities to treatment is unclear.To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment,we studied a cohort of 820 patients with molecularly profiled,clinically annotated posterior fossa ependymomas.We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA,which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era:a retrospective multicohort analysis" in the Journal ofClinical Oncology.Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy,whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.展开更多
Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study...Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study analyzed MASTL expression in gastric cancer vs.adjacent normal tissue for elucidating the association with clinicopathological data from patients.This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro.The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN,GEPIA,and Oncomine online databases.Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells.RT-qPCR,Western blotting,cell viability,cell counting,flow cytometric apoptosis and cell cycle,and colony formation assays were performed.MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue,and the MASTL expression was associated with advanced tumor stage,Helicobacter pylori infection and histological subtypes.On the other hand,knockdown of MASTL expression significantly reduced tumor cell viability and proliferation,and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis.At protein level,knockdown of MASTL expression enhanced levels of cleaved PARP1,cleaved caspase-3,Bax and p-ERK1/2 expression,but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells.MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression,whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis.Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.展开更多
Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan(CGM)...Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan(CGM). Matrix metalloproteinases(MMPs) may play an important role in neurogenesis but there is currently a lack of studies displaying the relationship between the stimulation of MMPs and neurogenesis after collagen glycosaminoglycan implantation following surgical brain trauma. The present study was carried out to further examine the expression of MMP2 and MMP9 after implantation of collagen glycosaminoglycan(CGM) following surgical brain trauma. Using the animal model of surgically induced brain lesion, we implanted CGM into the surgical trauma. Rats were thus divided into three groups:(1) sham operation group: craniotomy only;(2) lesion(L) group: craniotomy + surgical trauma lesion;(3) lesion + CGM(L + CGM) group: CGM implanted following craniotomy and surgical trauma lesion. Cells positive for SOX2(marker of proliferating neural progenitor cells) and matrix metalloproteinases(MMP2 and MMP9) in the lesion boundary zone were assayed and analyzed by immunofluorescence and ELISA commercial kits, respectively. Our results demonstrated that following implantation of CGM after surgical brain trauma, significant increases in MMP2^+/SOX2^+ cells and MMP9^+/SOX2^+ cells were seen within the lesion boundary zone in the L + CGM group. Tissue protein concentrations of MMP2 and MMP9 also increased after CGM scaffold implantation. These findings suggest that implantation of a CGM scaffold alone after surgical brain trauma can enhance the expression of MMP2 and MMP9 accompanied by neurogenesis.展开更多
OBJECTIVE: Tuberculum sellae meningiomas traditionally have been removed through a transcranial approach. More recently, the sublabial transsphenoidal approach has been used to remove such tumors. Here, we describe us...OBJECTIVE: Tuberculum sellae meningiomas traditionally have been removed through a transcranial approach. More recently, the sublabial transsphenoidal approach has been used to remove such tumors. Here, we describe use of the direct endonasal transsphenoidal approach for removal of suprasellar meningiomas. METHODS: Three women, aged 32, 34, and 55 years, each sought treatment for visual loss and headaches. In each patient, magnetic resonance imaging (MRI) showed a suprasellar mass causing optic chiasmal and optic nerve compression (average size, 2cm x2 cm). All three patients underwent tumor removal via an endonasal approach with展开更多
基金supported by the Robert Campeau Family Foundation/Dr.C.H.Tator Chair in Brain and Spinal Cord Research(to MGF)。
文摘Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our society.Moreove r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal cord.This makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative capacity.For these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory response.This review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after injury.Further,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural lesions.Both the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous system.Recent advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are directed.Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.
文摘BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
文摘Background: The optimal time to closure of a newborn with a myelomeningocele has been the focus of a number of evaluations. The Timing of primary surgery has received significant attention due to its relationship to repair-site infection that can lead to increased morbidity and prolonged hospital stays. It is on this basis that recommendations have utilized 48 - 72 hours post birth as ideal time of closure. This is not only prevent infection at the site but also prevent ventriculitis and neural structure damage. We therefore, hypothesized an increase in wound infection rates in those patients with delays in myelomeningocele repair. Methods: We retrospectively reviewed the records of 103 children with myelomeningocele treated between 2016 and 2023. At discharge the patients were followed up at the post-operative clinic visit 2 weeks later. Children were assigned to 1 of 2 groups, those who underwent primary neurosurgical repair within 72 hours of delivery (Group 1) and those undergoing repair after 72 hours (Group 2). We compared the infection rates. Results: 103 children who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Eight (7.8 %) patients were noted to have post-repair surgical site complications. There was no significant difference in rates of infection between Group 1 and Group 2 repair times. The presence of infection was associated increased length of stay when compared to neonates without infection. Conclusion: In children with myelomeningocele, the timing of primary neurosurgical repair appears not to have a significant impact on surgical site infection. Closure of the spinal lesion within the first 72 hours of life may be more favorable for neural damage prevention. These results suggest that early myelomeningocele repair may not impart significantly on the rate of wound-site infection.
文摘The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.
文摘Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.
文摘BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based therapies show promise,but clinical trials reveal potential adverse events and limitations,underscoring the need for meticulous optimization of transplantation conditions and parameters,caution against swift clinical implementation,a deeper understanding of SCI pathophysiology,and addressing ethical,tumorigenicity,immunogenicity,and immunotoxicity concerns before gradual and careful adoption in clinical practice.
文摘Some specially imaging of magnetic resonance imaging,the diffusion-weighted imaging(DWI),the diffusion tensor imaging and fractional anisotropy(FA),are useful to described,detect,and map the extent of spinal cord lesions.FA measurements may are used to predicting the outcome of patients who have spinal cord lesions.Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions,and this information could be used to formulating a differential diagnosis and planning biopsies or resection.In this article,we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future.
文摘Clipping and coiling are currently the two alternatives in treatment of ruptured cerebral aneurysms. In spite of some meritorious analysis, further discussion is helpful to understand the actual state of art. Retreatment and rebleeding rates clearly favors clipping, although short-term functional outcome seems to be beneficial for clipping, while this different is not such if we perform the comparison at a longer follow up. Longterm follow ups and cost analysis are mandatory to have a clear view of the current picture in treatment of subarachnoid hemorrhage. Treatment strategy should be made by a multi-disciplinary team in accredited centers with proficient experience in both techniques.
文摘Surgical treatment for cervical kyphotic deformity is still controversial. Circumferential approach has been well described in the literature but long terms outcomes are not well reported. Important to decide the correct treatment option is the preoperative radiological exams to value the type of deformity(flexible or fixed). We report the case of a 67-year-old woman affected by a severe cervical kyphotic deformity who underwent combined anterior/posterior surgical approach, getting a good reduction of the deformity and an optimal stability in a long term follow up.
文摘We describe the case of a 67-year-old woman with L5-S1 ontogenetic spondylolisthesis treated with pedicle fixation associated with interbody arthrodesis performed with S1-L5 trans-sacral screwing according to the technique of Bartolozzi. The procedure was followed by a wide decompressive laminectomy. The patient had a progressive improvement of the symptoms which gradually disappeared in 12 mo. The radiograph at 6 and 12 mo showed complete fusion system. The choice of treatment in L5-S1 ontogenetic spondylolithesis is related to a correct clinical and diagnostic planning(X-ray, computer tomography magnetic resonance imaging, Measurement). In particular, the severity index and the square of unstable zone, and the standard measurements already described in the literature, are important to understand and to plane the correct surgical strategy, that require, in most of the times, fusion and interbody artrodesis.
基金supported by the Canada Research Chair in Neuroscience(to AML)the University of Manitoba Clinician Investigator Program(to AF)
文摘With an aging patient population and an increased burden of neurological disease,the demand for noninvasive alternatives to open neurosurgical procedures is imperative.Noninvasive or minimally invasive approaches to targeting brain regions include transcranial magnetic stimulation(TMS),transcranial direct current stimulation,temporally interfering electric fields,and focused ultrasound(FUS).Among these modalities,FUS offers a unique combination of target specificity,deep brain penetration,and compatibility with real-time structural and thermal monitoring using magnetic resonance imaging(MRI)and MR thermometry.Depending on the intensity and frequency used,ultrasound can have either modulating or ablative effects on brain tissue.High-intensity MR-guided FUS(MRgFUS)is a noninvasive and effective alternative to conventional deep-brain stimulation and radiofrequency lesioning for essential tremor(ET),and is being investigated for other movement disorders,particularly Parkinson’s disease.Wider clinical implementation of high-intensity ultrasound is challenged by limitations in target selection precision,technical barriers(such as variable penetration and heat deposition)and the possibility of lesion-related adverse effects(Schwartz et al.,2018).Emerging studies,including those from our group(Boutet et al.,2018)are striving to refine targeting of MRgFUS to improve safety and patient clinical outcomes.At the same time,low-intensity FUS(LIFUS)has been found to safely modulate brain activity in rodents,primates,and healthy human subjects(Fomenko et al.,2018).Clinical translation of LIFUS has been hampered however,by a poor understanding of the mechanisms of action,uncertainty over effective sonication parameters and intensities,and conflicting study results due to heterogeneous experimental protocols.In this perspective,the current state of both MRgFUS ablation and LIFUS neuromodulation will be presented.Ongoing technical challenges to delivering ultrasound to the brain,recent innovations in target and parameter selection,and future directions for this emerging nonsurgical alternative are also discussed.
文摘Thymoma and thymic carcinoma are rare epithelial tumors, which originate from the thymus gland. According to the World Health Organization there are "organotypic"(types A, AB, B1, B2, and B3) and "non-organotypic"(thymic carcinomas) thymomas. Type B3 thymomas are aggressive tumors, which can metastasize. Due to the rarity of these lesions, only 7 cases of extradural metastasis are described in the literature. We report the first and unique case of a man with cervical intradural B3 thymoma metastasis. A 46-year-old man underwent thymoma surgical removal. The year after the procedure he was treated for a parietal pleura metastasis. In 2006 he underwent cervical-dorsal extradural metastasis removal and C5-Th1 stabilization. Seven years after he came to our observation complaining left cervicobrachialgia and a reduction of strength of the left arm. He underwent a cervical spine magnetic resonance imaging, which showed a new lesion at the C5-C7 level. The patient underwent a surgery for the intradural B3 thymoma metastasis. Neurological symptoms improved although the removal was subtotal. He went through postoperative radiation therapy with further mass reduction. Spinal metastases are extremely rare. To date, only 7 cases of spinal extradural metastasis have been described in the literature. This is the first case of spinal intradural metastasis. Early individuation of these tumors and surgical treatment improve neurological outcome in patients with spinal cord compression. A multimodal treatment including neoadjuvant chemotherapy, surgery and postoperative radiation therapy seems to improve survival in patients with metastatic thymoma.
基金supported by the Independent Research Fund of Tsinghua University (Grant 20141081265)
文摘Additional hemodynamic parameters are highly desirable in the clinical management of intracranial aneurysm rupture as static medical images cannot demonstrate the blood flow within aneurysms. There are two ways of obtaining the hemodynamic information-by phase-contrast magnetic resonance imaging (PCMRI) and computational fluid dynamics (CFD). In this paper, we compared PCMRI and CFD in the analysis of a stable patient's specific aneurysm. The results showed that PCMRI and CFD are in good agreement with each other. An additional CFD study of two stable and two ruptured aneurysms revealed that ruptured aneurysms have a higher statistical average blood velocity, wall shear stress, and oscillatory shear index (OSI) within the aneurysm sac compared to those of stable aneurysms. Furthermore, for ruptured aneurysms, the OSI divides the positive and negative wall shear stress divergence at the aneurysm sac.
基金Supported by GRF of Hong Kong SAR (project no. 464508)a direct grant for research from the Chinese University of Hong Kong (project no.2041501)
文摘Objective To investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. Methods Orchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. A rat vertebral body can be longitudinally divided into central portion, which contain more trabecular bone, and para-endplate portions which contain more compact bone. In matured male and female Wistar and Sprague-Dawley rat lumbar spines, we investigated baseline bone mineral density (BMD) characteristics and the differential segmental responses in bone loss within the lumbar vertebral body post gonadal surgery with clinical multidetector computed tomography. Results Para-endplate sections had a higher BMD than central sections. The cephalad para-endplate sections had a higher BMD than the caudad para-endplate sections. Eight weeks after gonadal removal, there was more bone loss in central sections than para-endplate sections. The relative difference of bone loss between para-endplate and central sections was more apparent in male rats than in female rats. There was more bone loss in caudad sections than cephalad sections; this lead to a further increase of BMD difference between caudad para-endplate sections and cephalad para-endplate sections post gonadal surgery. Conclusion The approach described in this study provided a consistent way to study BMD change within predominantly compact bone portion and trabecular bone portion of the vertebral body.
文摘Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,ependymoma research was hindered by the small number of tumors available for study,low resolution of cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic(copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.
文摘Intracranial aneurysm, a localized dilation of arterial blood vessels in the Circle of Willis and its branches, is potentially life threatening, due to massive bleeding in the subarachnoid space upon rupture. In clinical practice, one minimally invasive surgical procedure is the implantation of a metallic stent to cover the aneurysm neck. This flow diverting device can reduce the flow into the aneurysm and enhance the prospect of thrombosis, a condition expected to reduce the risk of growth and rupture. The biomechanical and haemo-dynamic factors in stented and nonstented situations are studied by computational fluid dynamics. Unlike earlier models with straight or curved parent blood vessels, the aneurysm is now located near an arterial bifurcation. The influence of the aspect (depth to neck) ratio of the aneurysm on the flow dynamics will be emphasized, especially in the post-operation stages. More precisely, the maximum flow velocity, the variations of wall shear stress, the risk of stent migration and volumetric flow rate after endovascular treatment will be studied. Aneurysms with larger aspect ratios (i.e. smaller neck sizes for constant depth) generally pose a greater risk in terms of these flow parameters. These results will assist the applications and design of stents in future neurosurgical therapy. The approach is limited to a nonelastic model, without taking into account of questions like stent expansion and interaction with tissue.
文摘Posterior fossa ependymoma comprises two distinct molecular entities,ependymoma_posterior fossa A(EPN_PFA)and ependymoma_posterior fossa B(EPN_PFB),with differentiable gene expression profiles.As yet,the response of the two entities to treatment is unclear.To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment,we studied a cohort of 820 patients with molecularly profiled,clinically annotated posterior fossa ependymomas.We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA,which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era:a retrospective multicohort analysis" in the Journal ofClinical Oncology.Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy,whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.
基金grants from Lanzhou Science and Technology Planning Project(No.2016-3-113)University Research Project of Gansu Province(No.2018A049)+2 种基金the Foundation of the Fundamental Scientific Research Funds for Colleges and Universities in Gansu Province[No.(2014)63-15]the China’s National Science and Technology Program for Public Wellbeing(No.2012GS620101)National Key Research and Development Planning(No.2017YFC0908302).
文摘Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study analyzed MASTL expression in gastric cancer vs.adjacent normal tissue for elucidating the association with clinicopathological data from patients.This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro.The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN,GEPIA,and Oncomine online databases.Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells.RT-qPCR,Western blotting,cell viability,cell counting,flow cytometric apoptosis and cell cycle,and colony formation assays were performed.MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue,and the MASTL expression was associated with advanced tumor stage,Helicobacter pylori infection and histological subtypes.On the other hand,knockdown of MASTL expression significantly reduced tumor cell viability and proliferation,and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis.At protein level,knockdown of MASTL expression enhanced levels of cleaved PARP1,cleaved caspase-3,Bax and p-ERK1/2 expression,but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells.MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression,whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis.Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.
基金supported by grants from the National Science Council of China(NSC 102-2314-B-303-004)the Tzu Chi Medical Mission Project 105-06,Buddhist Tzu Chi Medical Foundation
文摘Surgical brain injury may result in irreversible neurological deficits. Our previous report showed that partial regeneration of a traumatic brain lesion is achieved by implantation of collagen glycosaminoglycan(CGM). Matrix metalloproteinases(MMPs) may play an important role in neurogenesis but there is currently a lack of studies displaying the relationship between the stimulation of MMPs and neurogenesis after collagen glycosaminoglycan implantation following surgical brain trauma. The present study was carried out to further examine the expression of MMP2 and MMP9 after implantation of collagen glycosaminoglycan(CGM) following surgical brain trauma. Using the animal model of surgically induced brain lesion, we implanted CGM into the surgical trauma. Rats were thus divided into three groups:(1) sham operation group: craniotomy only;(2) lesion(L) group: craniotomy + surgical trauma lesion;(3) lesion + CGM(L + CGM) group: CGM implanted following craniotomy and surgical trauma lesion. Cells positive for SOX2(marker of proliferating neural progenitor cells) and matrix metalloproteinases(MMP2 and MMP9) in the lesion boundary zone were assayed and analyzed by immunofluorescence and ELISA commercial kits, respectively. Our results demonstrated that following implantation of CGM after surgical brain trauma, significant increases in MMP2^+/SOX2^+ cells and MMP9^+/SOX2^+ cells were seen within the lesion boundary zone in the L + CGM group. Tissue protein concentrations of MMP2 and MMP9 also increased after CGM scaffold implantation. These findings suggest that implantation of a CGM scaffold alone after surgical brain trauma can enhance the expression of MMP2 and MMP9 accompanied by neurogenesis.
文摘OBJECTIVE: Tuberculum sellae meningiomas traditionally have been removed through a transcranial approach. More recently, the sublabial transsphenoidal approach has been used to remove such tumors. Here, we describe use of the direct endonasal transsphenoidal approach for removal of suprasellar meningiomas. METHODS: Three women, aged 32, 34, and 55 years, each sought treatment for visual loss and headaches. In each patient, magnetic resonance imaging (MRI) showed a suprasellar mass causing optic chiasmal and optic nerve compression (average size, 2cm x2 cm). All three patients underwent tumor removal via an endonasal approach with