The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Versatile strategies for adult neurogenesis:avenues to repair the injured brain

Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.

Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.

脊髓损伤后神经源性膀胱患者的康复护理

脊髓损伤属于中枢神经系统疾病,其致残率较高,脊髓损伤后运动功能障碍给患者生活带来了极大的影响,特别是脊髓损伤后导致的神经源性膀胱,更是让患者痛苦不堪。研究发现通过膀胱训练结合中药热敷,及使用电生理适宜技术有助于脊髓损伤后神经源性膀胱的康复,且无明显不良反应。本文从神经源性膀胱的护理展开综述,旨在为广大患者提供相应的帮助,为疾病的恢复研究提供参考。

Research Progress of Acupuncture Treatment of Neurogenic Bladder after Spinal Cord Injury

Neurogenic bladder (NB) mainly occurs in patients with spinal cord injury (SCI). The pathological basis of NB is the occurrence of lesions in the urination control center, which requires systematic treatment. Western medicine has many treatment methods for this disease, which can alleviate the symptoms of the disease. However, the radical effect is not ideal and there are many adverse reactions. In comparison, acupuncture can improve the residual urine volume of NB patients and regulate the related indexes of urodynamics. There are many kinds of acupuncture therapies, such as simple acupuncture and moxibustion, which can comprehensively improve the therapeutic effect and obtain a better disease prognosis. Therefore, this article elaborates on the pathogenesis of SCI complicated with NB, the treatment mechanism, and treatment methods of acupuncture and moxibustion to provide a reference for clinical treatment.

Rehabilitation care of patients with neurogenic bladder after spinal cord injury:A literature review

This article reviews the research progress of rehabilitation treatment and nursing care of patients with neurogenic bladder after spinal cord injury,in order to provide reference for the rehabilitation treatment and nursing care of patients.We reviewed recent medical literature on patients with neurogenic bladder,focusing on neurogenic bladder caused by spinal cord injury.We analyzed 30 recent of publications in patients with neurogenic bladder after spinal cord injury,in addition to reviewing and evaluating the commonly used rehabilitation nursing methods for neurogenic bladder.Psychological counseling is a vital aspect which cannot be neglected in the process of neurogenic bladder rehabilitation.Hitherto,the commonly used drug and surgical treatments may have negatively impacted the mental health of patients in varying degrees.However,in clinical practice,applying intermittent catheterization in patients who have neurogenic bladder with spinal cord injury may help improve patients’life quality,mitigate psychological burden,and reduce negative emotions.

MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1

Mesenchymal stem cell(MSC)-based therapy has emerged as a promising treatment for spinal cord injury(SCI),but improving the neurogenic potential of MSCs remains a challenge.Mixed lineage leukemia 1(MLL1),an H3K4me3 methyltransferases,plays a critical role in regulating lineage-specific gene expression and influences neurogenesis.In this study,we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla(SCAPs).We examined the expression of neural markers,and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells,immunofluorescence staining,and a SCI model.We employed a coimmunoprecipitation(Co-IP)assay,real-time RT-PCR,microarray analysis,and chromatin immunoprecipitation(ChIP)assay to investigate the molecular mechanism.The results showed that MLL1 knock-down increased the expression of neural markers,including neurogenic differentiation factor(NeuroD),neural cell adhesion molecule(NCAM),tyrosine hydroxylase(TH),βIII-tubulin and Nestin,and promoted neuron-like cell formation in SCAPs.In vivo,a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model.MLL1 can combine with WD repeat domain 5(WDR5)and WDR5 inhibit the expression of neural markers in SCAPs.MLL1 regulates Hairy and enhancer of split 1(HES1)expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5.Additionally,HES1 enhances the expression of neural markers in SCAPs.Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1.These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.

Polyneuropathy organomegaly endocrinopathy M-protein and skin changes syndrome with ascites as an early-stage manifestation:A case report

BACKGROUND Polyneuropathy organomegaly endocrinopathy M-protein and skin changes(POEMS)syndrome is a rare paraneoplastic syndrome caused by a potential plasma cell tumor.The clinical manifestations of POEMS syndrome are diverse.Due to the insidious onset and lack of specific early-stage manifestations,POEMS syndrome is easily misdiagnosed or never diagnosed,leading to delayed treatment.Neurological symptoms are usually the first clinical manifestation,while ascites is a rare symptom in patients with POEMS syndrome.CASE SUMMARY A female patient presented with unexplained ascites as an initial symptom,which is a rare early-stage manifestation of the condition.After 1 year,the patient gradually developed progressive renal impairment,anemia,polyserosal effusion,edema,swollen lymph nodes on the neck,armpits,and groin,and decreased muscle strength of the lower extremities.The patient was eventually diagnosed with POEMS syndrome after multidisciplinary team discussion.Treatment comprised bortezomib+dexamethasone,continuous renal replacement therapy,chest and abdominal closed drainage,transfusions of erythrocytes and platelets,and other symptomatic and supportive treatments.The patient’s condition initially improved after treatment.However,then her symptoms worsened,and she succumbed to the illness and died.CONCLUSION Ascites is a potential early manifestation of POEMS syndrome,and this diagnosis should be considered for patients with unexplained ascites.Furthermore,multidisciplinary team discussion is helpful in diagnosing POEMS syndrome.

Experimental study on the regulation effect of Qiaoqin Qingfei agent on cough variant asthma based on airway neurogenic inflammation

Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model group,montelukast sodium group(1.05 mg/kg)and high,medium and low dose groups(26,13,6.5 g/kg),with 8 rats in each group.The rat CVA model was established by the method of ovalbumin(OVA)combined with aluminum hydroxide(Al(OH)3)sensitization and repeated stimulation.From the second day of sensitization,the rat CVA model was given by gavage for 28 days.The pathological changes of lung tissue were observed under microscope by HE staining.The content changes of nerve growth factor(NGF)and substance P(SP)in alveolar lavage fluid(BALF)were determined by double-antibody sandwich ABC-ELISA,and the protein expression levels of NGF and SP in lung tissue were detected by immunohistochemistry.Results:Pathological findings showed significant inflammatory manifestations in the model group,and the inflammatory infiltration in the high-dose,medium-dose and low-dose groups of Qiaoqin Qingfei agent and montelukast sodium groups were alleviated to varying degrees.Compared with blank group,the protein expression levels of NGF and SP in lung tissue of model group were significantly increased(P<0.01).Compared with model group,the protein expression levels of NGF and SP in lung tissue and the contents of NGF and SP in alveolar lavage fluid in high-dose,medium-dose and low-dose groups and montelukast sodium group were significantly decreased(P<0.05).Conclusion:Qiaoqin Qingfei agent may reduce airway inflammation and relieve cough variant asthma by regulating the protein expression levels of NGF and SP in airway neurogenic inflammation.

The body can heal itself in trauma:concept and practical exercises

Post-traumatic stress disorder is caused by a traumatic experience,for example rape,a natural disaster,war,serious accidents.Memories of the trauma often haunt the affected person in everyday life.Anyone who has to survive one or more such extreme situations can suffer from post-traumatic stress disorder,even witnesses of a traumatic event[1].If the disorder is not treated,it can become chronic and massively limit the quality of life.With timely and correct therapy,the chances of recovery are good.In the experience and psychological processing of those affected,there is a difference whether this catastrophe was a natural disaster or a“man made disaster”in a war or post-war area.It becomes very difficult when the two come together,as for example in Banda Aceh in 2004.The associated individual experience of fear of death,panic,helplessness,loss of control and powerlessness is the same for both types of disaster at the moment it happens.However,the processing of the traumatising experience is different.Traumas caused by people are more difficult for the individual to process than natural disasters.The article describes in detail what happens in the body and in the person during traumatisation.It also describes how the body can heal itself.The second part of the article presents the concrete exercise programme for practice.

Minimally Invasive Hind-Foot Fusion in Charcot Patients

Background: Hindfoot fusion, is a fusion of the talonavicular, talocalcaneal, and calcaneocuboid joints and is commonly performed for patients complaining of pain, chronic instability and gross deformity as a result of hindfoot pathology. Objective: This study aimed to assess the functional outcomes of the patients underwent hindfoot fusion, the post-operative complications and patient’s satisfaction. Methodology: This study is a prospective cohort study was conducted in Future hospital, in Khartoum, Sudan. It involved 30 patients from July 2015-July 2022. Data was collected by the primary researcher using data collection sheet, then it was cleaned and entered into Microsoft excel data sheet and was analysed using SPSS version 28 software. Results: 33.3% of the patients are aged 51 - 60 years, and >60 years. Male: Female equals 1:1. 56.7% are for the left side, only 23.3% developed complications. 63.3% patients are fully satisfied. There is a significant correlation between the AOFAS score before and after the operation. Also, a significant correlation between the means of AOFAS score after with the complications and the satisfaction of the patients. Conclusion: Minimally invasive tibio-talo-calcaneal is an alternative procedure for the treatment of severe Charcot arthropathy of the ankle. The expected functional outcome is impressive and comparable with the open surgery. However, the post-operative complications are prevalent in 23.3% of patients. Most candidates are fully satisfied with the procedure.

A New Device for Intermittent Emptying of the Bladder in Children and Adults: A Long-Term Follow-Up

Contextualization: Emptying the bladder is a challenging problem for the urological community. Intermittent catheterization is the most widely used method to restore bladder emptying mechanism. However, this procedure can have a negative impact on self-image and result in a decline in the quality of life of patients. In this context, the use of a bladder emptying device (SVCATH3D) proposes to be effective and have a positive impact on the quality of life of different patients. Objective: The objective of the study was to evaluate the functionality of a new device for both intermittent and controlled emptying of the bladder in both sexes and ages. Materials and methods: A randomized clinical trial was conducted with 251 patients, with different bladder problems, from March 2013 to January 2023. After randomization, the patients were divided into two groups: Group I (SVCATH3D) and Group II (Clean Intermittent Catheterization). The primary outcome was defined as the impact on quality of life. Data on episodes of urinary tract infection, adverse effects, number of diaper use and treatment costs were analyzed. Results: The apposition of the SVCATH3D was performed on an outpatient basis, with no complications during the procedures. The patients were followed up for 10 years. There was a significant improvement in quality of life when comparing the moments before and after the use of SVCATH3D (p Conclusion: The study using SVCATH3D showed promising results in relation to functionality, showing improvement in quality of life with a reduction in episodes of urinary infection and amount of diapers/day. This allows us to conclude that SVCATH3D can represent an important step in the treatment of patients suffering from various bladder problems both incontinence and affecting emptying mechanism.

改良铺灸对脊髓损伤所致神经源性膀胱的临床疗效观察

神经源性膀胱（neurogenic bladder,NB）是脊髓损伤（spinal cord injury,SCI）的常见并发症之一,常表现为排尿困难、尿潴留、充盈性尿失禁等症状,容易出现泌尿系统的感染,导致肾盂肾炎、肾积水甚至肾功能衰竭,严重者可危及患者生命（[1—2]）。有研究表明,69%—92%的SCI患者会伴发神经源性膀胱,所以积极采取有效、最佳的方法治疗神经源性膀胱对改善患者生存质量意义重大（[3]）。

Neuro-rejuvenation for neuronal function

Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.

神经源性膀胱过度活动研究进展

神经源性膀胱过度活动（neurogenic overactive bladder,NOAB）是因疾病或外伤造成神经损害引起的排尿功能障碍,主要临床表现为尿急、尿频、夜尿、尿失禁等症状。神经源性膀胱过度活动严重影响患者的生活质量,其身体功能、情感、社会关系也受到影响,同时还给患者及家庭带来了巨大的经济负担。

神经源性膀胱功能障碍47例泌尿系统感染情况及护理干预

泌尿系统感染是神经源性膀胱（neurogenic bladder,NB）功能障碍患者最常见的并发症,反复感染可导致患者肾功能受损、败血症、死亡等严重后果。本文报告47例NB患者泌尿系统感染情况及护理干预,旨在探讨如何通过适宜的护理干预降低感染率。

Critical analysis of the literature investigating urogenital function preservation following robotic rectal cancer surgery

AIM To analyses the current literature regarding the urogenital functional outcomes of patients receiving robotic rectal cancer surgery. METHODS A comprehensive literature search of electronic databases was performed in October 2015. The following search terms were applied: "rectal cancer" or "colorectal cancer" and robot* or "da Vinci" and sexual or urolog* or urinary or erect* or ejaculat* or impot* or incontinence. All original studies examining the urological and/or sexual outcomes of male and/or female patients receiving robotic rectal cancer surgery were included. Reference lists of all retrieved articles were manually searched for further relevant articles. Abstracts were independently searched by two authors. RESULTS Fifteen original studies fulfilled the inclusion criteria. A total of 1338 patients were included; 818 received robotic, 498 laparoscopic and 22 open rectal cancer surgery. Only 726(54%) patients had their urogenital function assessed via means of validated functional questionnaires. From the included studies, three found that robotic rectal cancer surgery leads to quicker recovery of male urological function and five of male sexual function as compared to laparoscopic surgery. It is unclear whether robotic surgery offers favourable urogenital outcomes in the long run for males. In female patients only two studies assessed urological and threesexual function independently to that of males. In these studies there was no difference identified between patients receiving robotic and laparoscopic rectal cancer surgery. However, in females the presented evidence was very limited making it impossible to draw any substantial conclusions. CONCLUSION There seems to be a trend towards earlier recovery of male urogenital function following robotic surgery. To evaluate this further, larger well designed studies are required.

Long-term anodal block stimulation at sacral anterior roots promoted recovery of neurogenic bladder function in a rabbit model of complete spinal cord injury

A complete spinal cord injury model was established in experimental rabbits using the spinal cord clip compression method. Urodynamic examination was performed 2 weeks later to determine neurogenic bladder status. The rabbits were treated with anodal block stimulation at sacral anterior roots for 4 weeks. Electrical stimulation of sacral anterior roots improved urodynamic parameters of neurogenic bladder in rabbit models of complete spinal cord injury, effectively promoted urinary function, and relieved urinary retention. Immunohistochemistry results showed that a balance was achieved among expression of muscarinic receptor subunits M2, M3, ATP-gated ion channel P2X3 receptors, and 132-adrenergic receptor, and nerve growth factor expression decreased. These results suggested that long-term sacral anterior root stimulation of anodal block could＇be used to treat neurogenic bladder in a rabbit model of complete spinal cord injury.

Diet in neurogenic bowel management:A viewpoint on spinal cord injury

The aim of this review is to offer dietary advice for individuals with spinal cord injury(SCI)and neurogenic bowel dysfunction.With this in mind,we consider health conditions that are dependent on the level of lesion including skeletal muscle atrophy,autonomic dysreflexia and neurogenic bladder.In addition,SCI is often associated with a sedentary lifestyle,which increases risk for osteoporosis and diseases associated with chronic low-grade inflammation,including cardiovascular and chronic kidney diseases.The Mediterranean diet,along with exercise and dietary supplements,has been suggested as an anti-inflammatory intervention in individuals with SCI.However,individuals with chronic SCI have a daily intake of whole fruit,vegetables and whole grains lower than the recommended dietary allowance for the general population.Some studies have reported an increase in neurogenic bowel dysfunction symptoms after high fiber intake;therefore,this finding could explain the low consumption of plant foods.Low consumption of fibre induces dysbiosis,which is associated with bothendotoxemia and inflammation.Dysbiosis can be reduced by exercise and diet in individuals with SCI.Therefore,to summarize our viewpoint,we developed a Mediterranean diet-based diet and exercise pyramid to integrate nutritional recommendations and exercise guidelines.Nutritional guidelines come from previously suggested recommendations for military veterans with disabilities and individuals with SCI,chronic kidney diseases,chronic pain and irritable bowel syndrome.We also considered the recent exercise guidelines and position stands for adults with SCI to improve muscle strength,flexibility and cardiorespiratory fitness and to obtain cardiometabolic benefits.Finally,dietary advice for Paralympic athletes is suggested.