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
Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord ...Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.展开更多
Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknow...Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs.This study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs.Methods:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BSI(N-BSI,n=14);a history of 1 lower extremity BSI(1-BSI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BSIs(M-BSI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit.The vertical average loading rate(VALR),vertical instantaneous loading rate(VILR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run.Results:There were no differences between groups in VALR,VILR,vertical stiffness,or tibial shock in a fresh or exerted condition.However,compared to N-BSI,women with M-BSI had greater increase with exertion in VALR(-1.8%vs.6.1%,p=0.01)and VILR(1.5%vs.4.8%,p=0.03).Similarly,compared to N-BSI,vertical stiffness increased more with exertion among women with M-BSI(-0.9%vs.7.3%,p=0.006)and 1-BSI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BSI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI(0.9%vs.5.5%,p=0.03)and 1-BSI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI.These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.展开更多
Spinal cord injury(SCI)is a devastating condition with complex pathological mechanisms that lead to sensory,motor,and autonomic dysfunction below the site of injury.To date,no effective therapy is available for the tr...Spinal cord injury(SCI)is a devastating condition with complex pathological mechanisms that lead to sensory,motor,and autonomic dysfunction below the site of injury.To date,no effective therapy is available for the treatment of SCI.Recently,bone marrow-derived mesenchymal stem cells(BMMSCs)have been considered to be the most promising source for cellular therapies following SCI.The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI.In this work,we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects:Neuroprotection,axon sprouting and/or regeneration,myelin regeneration,inhibitory microenvironments,glial scar formation,immunomodulation,and angiogenesis.Additionally,we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.展开更多
Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment ...Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.展开更多
Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hi...Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.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
A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researche...A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.展开更多
Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins ...Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.展开更多
In this case report, we discuss a patient who presented with Tullio’s phenomenon, who also experienced bone-conduction induced seizures on two occasions. Tullio’s phenomenon refers to sound induced vestibular sympto...In this case report, we discuss a patient who presented with Tullio’s phenomenon, who also experienced bone-conduction induced seizures on two occasions. Tullio’s phenomenon refers to sound induced vestibular symptoms, including disequilibrium oscillopsia, and vertical nystagmus. We were ultimately able to rule out some of the more common pathologies associated with Tullio’s phenomenon for this patient based on imaging findings. However, given the specific nature of her chronic symptoms, as well as her seizure like activity in clinic, we performed a literature search to investigate other less common pathologies associated with Tullio’s phenomenon. Given her past medical history of mixed psychogenic non-epileptic seizures (PNES), there is likely a somatic component to her presentation. However, given the specific and unexpected nature of these events, we propose that her symptoms may also be related to a unique inner ear pathology. Specifically, we feel that she may have exhibited symptoms of vestibular atelectasis, a relatively new otologic diagnosis characterizing the pathologic collapse of the ampulla and utricle, such that the membranous labyrinth contacts the stapes. In this way, loud sounds or changes in pressure may induce vestibular symptoms. Dizzy patients can be a difficult demographic to diagnose and manage, especially when their presentation is complicated by other functional neurologic disorders. Ultimately, we believe that this case report offers helpful insights into a new disease process associated with Tullio’s phenomenon.展开更多
Background:Sports medicine(injury and illnesses)requires distinct coding systems because the International Classification of Diseases is insuf-ficient for sports medicine coding.The Orchard Sports Injury and Illness C...Background:Sports medicine(injury and illnesses)requires distinct coding systems because the International Classification of Diseases is insuf-ficient for sports medicine coding.The Orchard Sports Injury and Illness Classification System(OSIICS)is one of two sports medicine coding systems recommended by the International Olympic Committee.Regular updates of coding systems are required.Methods:For Version 15,updates for mental health conditions in athletes,sports cardiology,concussion sub-types,infectious diseases,and skin and eye conditions were considered particularly important.Results:Recommended codes were added from a recent International Olympic Committee consensus statement on mental health conditions in athletes.Two landmark sports cardiology papers were used to update a more comprehensive list of sports cardiology codes.Rugby union protocols on head injury assessment were used to create additional concussion codes.Conclusion:It is planned that OSIICS Version 15 will be translated into multiple new languages in a timely fashion to facilitate international accessibility.The large number of recently published sport-specific and discipline-specific consensus statements on athlete surveillance warrant regular updating of OSIICS.展开更多
In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause e...In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.展开更多
Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychoso...Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.展开更多
Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,...Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal regrowth.During development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).展开更多
1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, ...1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, comprised of the tegmen tympani(To′th et al., 2007), and a posterior one, formed by the tegmen antri and the tegmen mastoideum(Makki et al., 2011). In some patients, the tegmental region of the temporal bone can be interrupted, causing a tegmen defect(TD). A TD is sometimes associated with a meningoencephalic herniation(MEH), in which brain tissue herniates through a TD.展开更多
Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control...Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.展开更多
BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,neces...BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.展开更多
Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain...Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking examples.Traumatic brain injury(TBI)is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death rate.TBI is characterized by two pathologically distinct but strictly consequential phases:a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue,which involves widespread cell death and tissue degeneration,followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient’s pre-existing health status.Secondary processes,including inflammatory phenomena,oxidative stress associated with metabolic,vascular,and neuro-modulatory deficits,are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities(Kaur and Sharma,2018).展开更多
Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA...Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA) assay, digital rectal examination (DRE) and prostate biopsy, its incidence has increased significantly. The aim of our study was to analyse aspects of bone scintigraphy (BS) as part of the metastatic extension assessment of prostate cancer in Senegal. Patients and Methods: This was a retrospective descriptive and analytical study, running from January 1<sup>er</sup> 2022 to August 31 2023. Patients with histologically confirmed prostate cancer were included. Whole-body scans (WBS) were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of <sup>99m</sup>Tc-HMDP. Results: A total of 288 patients with a mean age of 68.37 ± 7.79 years were included. The median total PSA level was 97.6 ng/ml, with 144 patients having a level greater than or equal to 20 ng/ml. All patients had adenocarcinoma, and the Gleason score was available in 202 (70.13%) patients, 75.75% of whom had a score greater than or equal to 7. BS was contributory in 70.48% of cases, with 30.90% positive and 39.58% negative. The result was inconclusive in 85 patients (29.51%). The mean PSA for patients with a positive scan was 190.2 ng/ml and 40.6 ng/ml for those with a negative scan. Multiple metastatic lesions predominated (87.35% of cases). Metastatic lesions occurred preferentially in the axial skeleton, with a proportion of 68% versus 32% in the appendicular skeleton. Classification of bone metastases according to the SOLOWAY score revealed grade I (62.07%), grade II (35.63%) and grade IV (2.30%). Conclusion: In Senegal, prostate cancer is generally diagnosed in men of advanced age. The presence of bone metastases is frequent in its evolution, transforming a curable localized disease into a generalized disease with a compromised prognosis. Bone scintigraphy remains an essential part of the initial work-up and evaluation of response to treatment.展开更多
Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site....Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.展开更多
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 the National Key R&D Program of China,No.2020YFC2008502 (to QW)the National Natural Science Foundation of China,No. 82172534 (to QW)。
文摘Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.
基金supported in part by appointments to the Department of Defense Research Participation Program at the U.S.Army Research Institute of Environmental Medicine administered by the Oak Ridge Institute for Science and Educationsupport from the U.S.Department of Defense+2 种基金Defense Health ProgramJoint Program Committee(W81XWH-16-1-0652)the National Institutes of Health shared instrumentation grant(S10 RR023405)。
文摘Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs.This study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs.Methods:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BSI(N-BSI,n=14);a history of 1 lower extremity BSI(1-BSI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BSIs(M-BSI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit.The vertical average loading rate(VALR),vertical instantaneous loading rate(VILR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run.Results:There were no differences between groups in VALR,VILR,vertical stiffness,or tibial shock in a fresh or exerted condition.However,compared to N-BSI,women with M-BSI had greater increase with exertion in VALR(-1.8%vs.6.1%,p=0.01)and VILR(1.5%vs.4.8%,p=0.03).Similarly,compared to N-BSI,vertical stiffness increased more with exertion among women with M-BSI(-0.9%vs.7.3%,p=0.006)and 1-BSI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BSI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI(0.9%vs.5.5%,p=0.03)and 1-BSI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI.These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.
基金Supported by the National Key R&D Program of China,No.2020YFC2008502。
文摘Spinal cord injury(SCI)is a devastating condition with complex pathological mechanisms that lead to sensory,motor,and autonomic dysfunction below the site of injury.To date,no effective therapy is available for the treatment of SCI.Recently,bone marrow-derived mesenchymal stem cells(BMMSCs)have been considered to be the most promising source for cellular therapies following SCI.The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI.In this work,we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects:Neuroprotection,axon sprouting and/or regeneration,myelin regeneration,inhibitory microenvironments,glial scar formation,immunomodulation,and angiogenesis.Additionally,we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.
基金supported by the National Defense Science and Technology Outstanding Youth Science Fund Project,No.2021-JCJQ-ZQ-035National Defense Innovation Special Zone Project,No.21-163-12-ZT-006-002-13Key Program of the National Natural Science Foundation of China,No.11932013(all to XuC).
文摘Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.
基金supported by the Key Projects of the National Natural Science Foundation of China,No.11932013(to XC)Key Military Logistics Research Projects,No.B WJ21J002(to XC)+4 种基金the Key projects of the Special Zone for National Defence Innovation,No.21-163-12-ZT006002-13(to XC)the National Nature Science Foundation of China No.82272255(to XC)the National Defense Science and Technology Outstanding Youth Science Fund Program,No.2021-JCIQ-ZQ-035(to XC)the Scientific Research Innovation Team Project of Armed Police Characteristic Medical Center,No.KYCXTD0104(to ZL)the National Natural Science Foundation of China Youth Fund,No.82004467(to BC)。
文摘Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.
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 Natural Science Foundation of Beijing,No.L222126(to LD)。
文摘A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XH)+1 种基金Everest Project of Military Medicine of Air Force Medical University,No.2018RCFC02(to XH)Boosting Project of the First Affiliated Hospital of Air Force Medical University,No.XJZT19Z22(to ZW)。
文摘Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.
文摘In this case report, we discuss a patient who presented with Tullio’s phenomenon, who also experienced bone-conduction induced seizures on two occasions. Tullio’s phenomenon refers to sound induced vestibular symptoms, including disequilibrium oscillopsia, and vertical nystagmus. We were ultimately able to rule out some of the more common pathologies associated with Tullio’s phenomenon for this patient based on imaging findings. However, given the specific nature of her chronic symptoms, as well as her seizure like activity in clinic, we performed a literature search to investigate other less common pathologies associated with Tullio’s phenomenon. Given her past medical history of mixed psychogenic non-epileptic seizures (PNES), there is likely a somatic component to her presentation. However, given the specific and unexpected nature of these events, we propose that her symptoms may also be related to a unique inner ear pathology. Specifically, we feel that she may have exhibited symptoms of vestibular atelectasis, a relatively new otologic diagnosis characterizing the pathologic collapse of the ampulla and utricle, such that the membranous labyrinth contacts the stapes. In this way, loud sounds or changes in pressure may induce vestibular symptoms. Dizzy patients can be a difficult demographic to diagnose and manage, especially when their presentation is complicated by other functional neurologic disorders. Ultimately, we believe that this case report offers helpful insights into a new disease process associated with Tullio’s phenomenon.
文摘Background:Sports medicine(injury and illnesses)requires distinct coding systems because the International Classification of Diseases is insuf-ficient for sports medicine coding.The Orchard Sports Injury and Illness Classification System(OSIICS)is one of two sports medicine coding systems recommended by the International Olympic Committee.Regular updates of coding systems are required.Methods:For Version 15,updates for mental health conditions in athletes,sports cardiology,concussion sub-types,infectious diseases,and skin and eye conditions were considered particularly important.Results:Recommended codes were added from a recent International Olympic Committee consensus statement on mental health conditions in athletes.Two landmark sports cardiology papers were used to update a more comprehensive list of sports cardiology codes.Rugby union protocols on head injury assessment were used to create additional concussion codes.Conclusion:It is planned that OSIICS Version 15 will be translated into multiple new languages in a timely fashion to facilitate international accessibility.The large number of recently published sport-specific and discipline-specific consensus statements on athlete surveillance warrant regular updating of OSIICS.
文摘In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.
文摘Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.
基金supported by grants from The University of Connecticut School of Medicine (StartUp Fund)the National Institutes of Health (NIH)(Grant R01-EY029 739)+1 种基金the Connecticut Institute for the Brain and Cognitive Sciences (Research Seed Grant)the BrightFocus Foundation (Grant G2017204)(all to EFT)
文摘Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal regrowth.During development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).
文摘1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, comprised of the tegmen tympani(To′th et al., 2007), and a posterior one, formed by the tegmen antri and the tegmen mastoideum(Makki et al., 2011). In some patients, the tegmental region of the temporal bone can be interrupted, causing a tegmen defect(TD). A TD is sometimes associated with a meningoencephalic herniation(MEH), in which brain tissue herniates through a TD.
基金supported by the Veterans Administration (I01RX002264-01A2)(to PL)Wings For Life (WFL-US-10/21)(to CMF)。
文摘Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in humans.This system has historically been the most refractory to regenerative efforts after SCI.The "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.
文摘BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.
文摘Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of biomedicine.And among these,the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking examples.Traumatic brain injury(TBI)is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death rate.TBI is characterized by two pathologically distinct but strictly consequential phases:a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue,which involves widespread cell death and tissue degeneration,followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient’s pre-existing health status.Secondary processes,including inflammatory phenomena,oxidative stress associated with metabolic,vascular,and neuro-modulatory deficits,are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities(Kaur and Sharma,2018).
文摘Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA) assay, digital rectal examination (DRE) and prostate biopsy, its incidence has increased significantly. The aim of our study was to analyse aspects of bone scintigraphy (BS) as part of the metastatic extension assessment of prostate cancer in Senegal. Patients and Methods: This was a retrospective descriptive and analytical study, running from January 1<sup>er</sup> 2022 to August 31 2023. Patients with histologically confirmed prostate cancer were included. Whole-body scans (WBS) were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of <sup>99m</sup>Tc-HMDP. Results: A total of 288 patients with a mean age of 68.37 ± 7.79 years were included. The median total PSA level was 97.6 ng/ml, with 144 patients having a level greater than or equal to 20 ng/ml. All patients had adenocarcinoma, and the Gleason score was available in 202 (70.13%) patients, 75.75% of whom had a score greater than or equal to 7. BS was contributory in 70.48% of cases, with 30.90% positive and 39.58% negative. The result was inconclusive in 85 patients (29.51%). The mean PSA for patients with a positive scan was 190.2 ng/ml and 40.6 ng/ml for those with a negative scan. Multiple metastatic lesions predominated (87.35% of cases). Metastatic lesions occurred preferentially in the axial skeleton, with a proportion of 68% versus 32% in the appendicular skeleton. Classification of bone metastases according to the SOLOWAY score revealed grade I (62.07%), grade II (35.63%) and grade IV (2.30%). Conclusion: In Senegal, prostate cancer is generally diagnosed in men of advanced age. The presence of bone metastases is frequent in its evolution, transforming a curable localized disease into a generalized disease with a compromised prognosis. Bone scintigraphy remains an essential part of the initial work-up and evaluation of response to treatment.
基金supported by the patient organizations“Verticale”(to YNG and FEP).
文摘Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.