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.

Commentary on "Association of daily sitting time and leisure-time physical activity with body fat among U.S.adults"

In their study,association of daily sitting time and leisure-time physical activity (LTPA) with body fat among U.S.Adults,Liao et al.^(1) analyzed data from the 2011-2018 National Health and Examination Survey to examine associations between h/day sitting,meeting (or not meeting) the U.S.Physical Activity Guidelines of≥150 min/week of moderate-and vigorous-intensity LTPA,and combinations of sitting time and LTPA on totaland trunk percent body fat (BF%).

Adult localized Langerhans cell histiocytosis:A case report

BACKGROUND Langerhans cell histiocytosis(LCH)is a rare clonal proliferative disease of Langerhans cells with unknown pathogenesis.An increasing number of clinicians recognize that LCH has a wide clinical spectrum and a highly varied course.Adults rarely develop LCH.Here,we report a case of adult localized LCH.CASE SUMMARY A 32-year-old woman presented with plaques and ulcers on the vulva and crissum,accompanied by pain that persisted for more than one year.Physical examination revealed a red-infiltrating plaque with ulcerations and exudates in the vulva and crissum.Pathological examination revealed a diffuse infiltration of lymphocytes,eosinophilic granulocytes,and histiocytoid cells in the superficial dermis.Proliferative histiocytoid cells showed mild atypia,partly with kidneyshaped nuclei.Immunohistochemical examination showed that the histiocytoid cells were positive for S100 protein and CD1 and weakly positive for CD68(20%+),with a Ki-67 index of 30%.Laboratory tests did not reveal any other systemic damage.The patient was diagnosed with adult localized LCH and was prescribed oral prednisone(20 mg)once daily.The skin lesions gradually improved and are still being followed-up.CONCLUSION Adult localized LCH is rare and must be differentiated from other common conditions.

Child’s Point of View vs.Adult’s in Melville’s Early Two Stories

This paper aims to study the functions of two different points of view from the perspective of narratology,namely,the point of view of the adult and the one of the child,in two of Herman Melville’s early stories.By contrasting these two functions of the different perspectives,the author of this paper draws the conclusion that the child has a unique and significant perspective in Melville’s works.

成人病毒性脑炎患者血清和脑脊液GFAP CPK-BB NSES-100B表达在病情监测中的作用

目的 探究成人病毒性脑炎(VE)患者血清和脑脊液胶质纤维酸性蛋白(GFAP)、肌酸激酶脑型同工酶(CPK-BB)、神经元特异性烯醇化酶(NSE)、星形胶质源性蛋白(S-100B)表达在病情监测中的作用。方法 选取2021-02—2022-10河北中石油中心医院收治的102例成人VE患者(VE组)为研究对象,其中轻度感染39例,中度34例,重度29例。选取同期头痛入院有腰椎穿刺指征,最终确诊为偏头痛、上呼吸道感染的患者50例为对照组,比较VE组与对照组、不同病情程度患者血清和脑脊液GFAP、CPK-BB、NSE、S-100B水平,应用Pearson分析血清GFAP、CPK-BB、NSE、S-100B水平与脑脊液对应指标的相关性,应用Spearman分析血清和脑脊液GFAP、CPK-BB、NSE、S-100B与病情程度的相关性。结果 VE组急性期、恢复期血清和脑脊液GFAP、CPK-BB、NSE、S-100B水平高于对照组(P<0.05),急性期血清和脑脊液GFAP、CPK-BB、NSE、S-100B水平高于恢复期(P<0.05)。VE组急性期血清GFAP、CPK-BB、NSE、S-100B水平与脑脊液对应指标呈正相关(r=0.806、0.728、0.819、0.781,均P<0.001),恢复期血清GFAP、CPK-BB、NSE、S-100B水平与脑脊液对应指标呈正相关(r=0.746、0.807、0.728、0.769,均P<0.001)。VE患者急性期、恢复期重度感染患者血清和脑脊液GFAP、CPK-BB、NSE、S-100B水平高于中度和轻度,中度患者高于轻度(P<0.05)。与恢复期对应感染程度比较,急性期轻度、中度、重度患者血清和脑脊液GFAP、CPK-BB、NSE、S-100B水平升高(P<0.05),急性期、恢复期血清和脑脊液GFAP、CPK-BB、NSE、S-100B水平均与感染程度呈正相关(P<0.05)。结论 成人VE患者血清和脑脊液GFAP、CPK-BB、NSE、S-100B表达升高,与病情严重程度、所处的病程阶段有关,且血清GFAP、CPK-BB、NSE、S-100B表达与脑脊液显著相关,有望作为VE病情监测的便捷、无创标志物。

A Comparison of the lexical processing in Children's Word Acquisition and in Adults' Word Learning

Children can acquire knowledge of their mother tongue easily in a relatively short time,whereas adults are too inferior to bear the comparison in learning a second language.This paper sets out to study the background and process of children's and adults' language learning,make comparison and contrast,and find out an effective way to promote adults' second language learning.

Use of exclusive enteral nutrition in adults with Crohn's disease: A review

Exclusive enteral nutrition(EEN)is well-established as a first line therapy instead of corticosteroid(CS)therapy to treat active Crohn’s disease(CD)in children.It also has been shown to have benefits over and above induction of disease remission in paediatric populations.However,other than in Japanese populations,this intervention is not routinely utilised in adults.To investigate potential reasons for variation in response between adult studies of EEN and CS therapy.The Ovid database was searched over a 6-mo period.Articles directly comparing EEN and CS therapy in adults were included.Eleven articles were identified.EEN therapy remission rates varied considerably.Poor compliance with EEN therapy due to unpalatable formula was an issue in half of the studies.Remission rates of studies that only included patients with previously untreated/new CD were higher than studies including patients with both existing and new disease.There was limited evidence to determine if disease location,duration of disease or age of diagnosis affected EEN therapy outcomes.There is some evidence to support the use of EEN as a treatment option for a select group of adults,namely those motivated to adhere to an EEN regimen and possibly those newly diagnosed with CD.In addition,the use of more palatable formulas could improve treatment compliance.

Inverted Meckel’s diverticulum manifested as adult intussusception: Age does not matter

Adult intussusception due to Meckel’s diverticulum (MD) is an uncommon cause of intestinal obstruction. However, the surgeon should still be suspicious of this condition since the non specific symptoms and the rarity of it make a preoperative diagnosis uncertain. Considering the secondary nature of adult intussusception and the necessity of early surgical intervention to avoid morbidity and mortality, we report two cases of intussusception due to MD in adults. A diverticulectomy using a TA stapler was performed in the first patient. In the second patient extensive fibrosis of the adjacent mesentery and thickening of jejunal mucosa were observed, so a segmental resection of the small bowel or affected ileal part and a hand-sewn anastomosis was performed. The postoperative period along with the long term follow-up was uneventful for both patients. The decision between diverticulectomy vs bowel resection can be based on the intussuscepted bowel condition. Early surgical intervention may ensure a favorable outcome.

Decreased osteogenesis of adult mesenchymal stem cel s by reactive oxygen species under cyclic stretch: a possible mechanism of age related osteoporosis

Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.

Acquired segmental colonic hypoganglionosis in an adult Caucasian male:A case report

BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). The adult-onset form(acquired hypoganglionosis) is extremely uncommon and is thought to arise due to cellular remodelling as a result of chronic inflammation. It differs from Hirschprung's disease in that there is a reduction in ganglion cells in the colonic neural plexuses as opposed to being completely absent.CASE SUMMARY A 31 year-old male presented to hospital with recurrent abdominal pain and vomiting over thirteen months. Abdominal computed tomography scans demonstrated thickening and stranding affecting the transverse, descending and sigmoid colon. Endoscopic appearances were non-specific but confirmed a mixed picture of mucosal inflammation and necrosis in various stages of healing.Numerous investigations were performed to elucidate an underlying aetiology but neither an infective nor ischaemic cause could be proven. Biopsy features were not typical of inflammatory bowel disease. Due to persistence of his symptoms and failure of medical management, a segmental colectomy was performed. Histological examination of the specimen revealed an unexpected finding of segmental hypoganglionosis. Complete surgical excision of the diseased segment of colon was curative and since his operation the patient has had no recurrence of symptoms requiring hospitalisation.CONCLUSION Our case serves to raise awareness of acquired hypoganglionosis as a rare condition that can result from chronic colitis.

A new age in understanding adult hippocampal neurogenesis in Alzheimer’s disease

Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.

Adult hippocampal neurogenesis and its impairment in Alzheimer's disease

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain.Recent evidence suggests that adult hippocampal neurogenesis(AHN)persists throughout life in mammals,including humans.These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory.Importantly,studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases.Alzheimer’s disease(AD)is one of the most common forms of dementia affecting millions of people.Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus.Therefore,there has been growing interest in identifying how hippocampal neurogenesis is affected in AD.However,the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood.In this review,we summarized the recent literature on AHN and its impairments in AD.

Nigral dopaminergic neuron replenishment in adult mice through VE-cadherin-expressing neural progenitor cells

The function of dopaminergic neurons in the substantia nigra is of central importance to the coordination of movement by the brain＇s basal ganglia circuitry. This is evidenced by the loss of these neurons, resulting in the cardinal motor deficits associated with Parkinson＇s disease. In order to fully understand the physiology of these key neurons and develop potential therapies for their loss, it is essential to determine if and how dopaminergic neurons are replenished in the adult brain. Recent work has presented evidence for adult neurogenesis of these neurons by Nestin＋/Sox2 neural progenitor cells. We sought to further validate this finding and explore a potential atypical origin for these progenitor cells. Since neural progenitor cells have a proximal association with the vasculature of the brain and subsets of endothelial cells are Nestin＋, we hypothesized that dopaminergic neural progenitors might share a common cell lineage. Therefore, we employed a VE-cadherin promoter-driven CREERT2：TIlox/Tlox transgenic mouse line to ablate the tyrosine hydroxylase gene from endothelial cells in adult animals. After 26 weeks, but not 13 weeks, following the genetic blockade of tyrosine hydroxylase expression in VE-cadherin＋ cells, we observed a significant reduction in tyrosine hydroxylase＋ neurons in the substantia nigra. The results from this genetic lineage tracing study suggest that dopaminergic neurons are replenished in adult mice by a VE-cadherin＋ progenitor cell population potentially arising from an endothelial lineage.

A Case of Ewing’s Sarcoma of the Clavicle in Adults

The Clavicle is a rare primary site for Ewing sarcoma (ES). We report one case of patient with clavicular ES under our tracking and review the related literatures on management of this rare tumor. The patient was age of 35 years and were non metastaticat presentation. The patient received chemotherapy before and after the surgery. Claviculectomy was used. The patient had good functional outcomes with no pain of the shoulder at the follow-up of ten months. In conclusion, Ewing sarcoma of clavicle is a very rare tumor and different methods of surgical treatment can be used. Clavicle often can be resected without a need of reconstruction.

Cow’s milk-induced gastrointestinal disorders:From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders.Cow’s milk protein allergy(CMPA)is the most common food allergy,especially in infancy and childhood,which may persist into adulthood.There are three main types of CMPA;immunoglobulin E(IgE)-mediated CMPA,non-IgEmediated CMPA,and mixed type.CMPA appears before the first birthday in almost all cases.Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis.CMPA(often non-IgE mediated)can present with symptoms of gastroesophageal reflux,eosinophilic esophagitis,hemorrhagic gastritis,food protein-induced protein-losing enteropathy,and food protein-induced enterocolitis syndrome.Most CMPAs are benign and outgrown during childhood.CMPA is not as common in adults as in children,but when present,it is usually severe with a protracted course.Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose.Lactose intolerance has four typical types:Developmental,congenital,primary,and secondary.Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults.They are also common in inflammatory bowel diseases.Milk consumption may have preventive or promoter effects on cancer development.Milk may also become a source of microbial infection in humans,causing a wide array of diseases,and may help increase the prevalence of antimicrobial resistance.This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.

Novel case of Trevor's disease:Adult onset and later recurrence

Dysplasia epiphysealis hemimelica(DEH),or Trevor’s disease,is an osteocartilaginous epiphyseal overgrowth typically occurring in children.The literature reports6 adult cases and none describe recurrence requiring additional procedures.We present a new-onset proximal tibial DEH in an adult recurring approximately 3 years after open excision.A 39-year-old female presented with a history of right knee pain,swelling,and instability.Physical examination revealed a firm proximal tibial mass.Computed tomography(CT)imaging showed an exophytic,lobulated,sclerotic mass involving the anterolateral margin of the lateral tibial plateau.Magnetic resonance imaging was suggestive of an osteochondroma.The patient underwent curettage of the lesion due to its periarticular location.Histology revealed benign and reactive bone and cartilage consistent with periosteal chondroma.Two and a half years later,the patient presented with a firm,palpable mass larger than the initial lesion.CT revealed a lateral tibial plateau sclerotic mass consistent with recurrent intraarticular DEH.A complete excision was performed and histology showed sclerotic bone with overlying cartilage consistent with exostosis.DEH is a rare epiphyseal osteocartilaginous outgrowth frequently occurring in the long bones of children less than 8 years old.DEH resembles an osteochondroma due to its pediatric presentation and similar histologic appearance.Adultonset cases comprise less than 1%of reported cases.Recurrence rate after surgical intervention is unknown.Only 1 such case,occurring in a child,has been described.Clinicians contemplating operative treatment for DEH should note the potential for recurrence and consider complete excision.A follow-up period of several years may be warranted to identify recurrent lesions.

Physical Conditions of China's Adult Population

Ｐｈｙｓｉｃａｌｍｏｎｉｔｏｒｉｎｇｓｈｏｗｓｔｈｅｐｈｙｓｉｃａｌｃｏｎｄｉｔｉｏｎｓｏｆ７１．４％ｏｆＣｈｉｎｅｓｅａｄｕｌｔｐｏｐｕｌａｔｉｏｎｈａｖｅｒｅａｃｈｅｄｒｅｑｕｉｒｅｄｓｔａｎｄａｒｄｓ，ｏｆｗｈｉｃｈｍｅｎａｒｅ７１．２％ａｎｄ...

Comparison of adults with attention-deficit/hyperactivity disorder versus Asperger’s disorder using the WAIS-R

Objective: The present study compared results on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) among adult patients with attention-deficit/hyperactivity disorder (AD/HD) and those with Asperger’s disorder (AD). Method: WAIS-R results were compared between 16 adults with AD/HD (8 men and 8 women;mean age, 33.81 years;mean full-scale IQ, 101.5) and 15 adults with AD (12 men and 3 women;mean age, 30.93 years;mean full-scale IQ, 104.6). Results: Verbal IQ was significantly higher than performance IQ in the AD group. Among various subtests, scores were the highest for similarities in the AD/HD group and for block design in the AD group. Picture completion test scores were the lowest scores obtained in both groups. A comparison of subtest scores between the AD/HD and AD groups showed scores for information to be significantly higher in the AD group than in the AD/HD group. Conclusions: Our results suggest that there are no differences in verbal IQ, performance IQ, and full-scale IQ scores (except for scores on the information subtest) among adult patients with AD/HD compared with adult patients with AD.

Anti-CD-20 Therapy in Refractory Adult Still’s Disease

Adult Still’s disease is a relatively rare form of rheumatoid arthritis with systemic inflammatory features. The prevalence is around 1.5 cases per 100,000 - 1000,000. In the current case we display a 30-year-old male patient with refractory adult still’s disease who suffered recurrent attacks of fever 39.5°C, arthritis in proximal interphalangeal joints (PIPs), wrists, tempromandibular joints (TMJs), knees and ankles, stitching chest pain, dyspnea, erythematous rash over the trunk, sore throat, weight loss (15 Kilograms in 4 months). The patients’ disease remained uncontrolled despite of synthetic disease modifying anti-rheumatic drugs and repeated intramuscular corticosteroid injections. Laboratory workup revealed erythrocyte sedimentation rate (ESR) of 95, C-reactive protein (CRP) of 100 mg/L, hemoglobin 10.5 gm%, leukocytosis 12,000/microlitre, mild elevation of liver function tests and dyslipidemia. Serology revealed negative rheumatoid factor, anti-nuclear antibody titre of 1:80, elevated serum ferritin 4000 micrograms/litre. The patient was started on rituximab (375 mg/m2), prednisolone 20 mg/day and selective Cox-2 inhibitor. Follow up for over three months following the completion of his pulse therapy, revealed no relapse of fever or fatigue, with morning stiffness of 5 - 10 minutes, VAS of 3, DAS28 of 3.8, HAQDI of 0.62, ESR 23, CRP 4.9, Hb 12.5 gm%, leucocytic count 9000/microlitre, the dose of prednisolone was successfully reduced to a dose of 5 mg/day orally. Conclusion: Anti-CD20 therapy successfully controlled systemic and articular refractory disease with sustained efficacy over a follow up period of up to 24 weeks.

Adult Onset Still’s Disease

The adult onset Still’s disease is a rare affection characterised by occurrence of fever, arthralgia or arthritis and evanescent cutaneous eruption. Multiple other systemic lesions make the diagnosis more difficult. Several diagnostic criteria were formulated to confirm this disease. The physiopathology of the adult onset Still’s disease is not well elucidated. However, several studies based on new facts in physiopathology, improved the therapy of refractory forms for which the biotherapy was an interesting alternative. The TNF alpha receptor antagonists are efficient on systemic and articular manifestations of this disease and allow a corticosteroid’s saving. Tocilizumab (interleukin 6 receptor antagonist), and Anakinra (interleukin 1 receptor antagonist) are also new promising treatments for resistant forms.