Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and s...Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective delivery.Exosomes can also interact with viruses in diverse ways.Emerging research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and HCV.Understanding the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral therapies.An important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent characteristics.By leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune responses.They can either help or hinder viral infection by modulating the immune system.This review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or therapy.This could lead to new clinical applications of exosomes in disease management.展开更多
Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of tr...Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.展开更多
Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not b...Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.展开更多
In this study, we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne(CIL) extract, which has been used as a botanical drug in East Asia, against ischemic damage and to explore the underlying m...In this study, we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne(CIL) extract, which has been used as a botanical drug in East Asia, against ischemic damage and to explore the underlying mechanism involving the anti-inflammatory approach. A gerbil was given CIL extract for 7 consecutive days followed by bilateral carotid artery occlusion to make a cerebral ischemia/reperfusion model. Then, we found that CIL extracts protected pyramidal neurons in the hippocampal CA1 region(CA1) from ischemic damage using neuronal nucleus immunohistochemistry and Fluoro-Jade B histofluorescence. Accordingly, interleukin-13 immunoreactivities in the CA1 pyramidal neurons of CIL-pretreated animals were maintained or increased after cerebral ischemia/reperfusion. These findings indicate that the pre-treatment of CIL can attenuate neuronal damage/death in the brain after cerebral ischemia/reperfusion via an anti-inflammatory approach.展开更多
AIM:To assess the reliability of web-based version of ocular surface disease index in Chinese(C-OSDI)on clinically diagnosed dry eye disease(DE)patients.METHODS:A total of 254 Chinese participants(51%male,129/254;mean...AIM:To assess the reliability of web-based version of ocular surface disease index in Chinese(C-OSDI)on clinically diagnosed dry eye disease(DE)patients.METHODS:A total of 254 Chinese participants(51%male,129/254;mean age:27.90±9.06 y)with DED completed paper-and web-based versions of C-OSDI questionnaires in a randomized crossover design.Ophthalmology examination and DED diagnosis were performed prior to the participants being invited to join the study.Participants were randomly designated to either group A(paper-based first and webbased second)or group B(web-based first and paper-based second).Final data analysis included participants that had successfully completed both versions of the C-OSDI.Demographic characteristics,test-retest reliability,and agreement of individual items,subscales,and total score were evaluated with intraclass correlation coefficients(ICC),Spearman rank correlation,Wilcoxon test and Rasch analysis.RESULTS:Reliability indexes were adequate,Pearson correlation was greater than 0.8 and ICCs range was 0.827 to 0.982;total C-OSDI score was not statistically different between the two versions.The values of mean-squares fit statistics were very low compared to 1,indicating that the responses to the items by the model had a high degree of predictability.While comparing the favorability 72%(182/254)of the participants preferred web-based assessment.CONCLUSION:Web-based C-OSDI is reliable in assessing DED and correlation with the paper-based version is significant in all subscales and overall total score.Webbased C-OSDI can be administered to assess individuals with DED as participants predominantly favored online assessment.展开更多
Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is repo...Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We inves- tigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei (NeuN) and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia (39.5 + 0.2~C) was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neu- ronal damage/death in the pyramidal layer of CA1-3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreac- tivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immu- noreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.展开更多
Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity....Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation) and doublecortin (a marker for neuroblast). Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.展开更多
This study aimed to assess whether a daily supplementation with Lactobacillus rhamnosus GG (LGG) can alter the body composition as well as bone turnover and the mechanical properties of the bones in systemic immunodef...This study aimed to assess whether a daily supplementation with Lactobacillus rhamnosus GG (LGG) can alter the body composition as well as bone turnover and the mechanical properties of the bones in systemic immunodeficiency. For this, we use an in vivo model of severe combined immunodeficient (scid) mice supplemented daily with LGG over 8 weeks period. After 8 weeks of the treatment, the animals were assessed by DEXA and then the blood was collected from the hepatic portal vein for bone turnover biomarkers;post-mortem, the caecum was removed for isolation and enumeration of the gut bacteria, while femurs/tibiae were excised for the assessment of their mechanical properties. LGG treatment affected the composition of the gut microbiota at the order level, and it decreased (P = 0.002) total adipose tissue content. Moreover, LGG treatment decreased the stiffness (N/mm) of both femurs (P = 0.008) and tibiae (P = 0.011). To conclude, this study shows that dietary supplementation with LGG in immunodeficient animals can alter mechanical properties of the long bones and concomitantly it can modify host’s total adiposity level.展开更多
c-Fos is a good biological marker for detecting the pathogenesis of central nervous system disorders. Few studies are reported on the change in myocardial infarction-induced c-Fos expression in the paralimbic regions....c-Fos is a good biological marker for detecting the pathogenesis of central nervous system disorders. Few studies are reported on the change in myocardial infarction-induced c-Fos expression in the paralimbic regions. Thus, in this study, we investigated the changes in c-Fos expression in the rat cingulate and piriform cortices after myocardial infarction. Neuronal degeneration in cingulate and piriform cortices after myocardial infarction was detected using cresyl violet staining, Neu N immunohistochemistry and Fluoro-Jade B histofluorescence staining. c-Fos-immunoreactive cells were observed in cingulate and piriform cortices at 3 days after myocardial infarction and peaked at 7 and 14 days after myocardial infarction. But they were hardly observed at 56 days after myocardial infarction. The chronological change of c-Fos expression determined by western blot analysis was basically the same as that of c-Fos immunoreactivity. These results indicate that myocardial infarction can cause the chronological change of immediate-early response gene c-Fos protein expression, which might be associated with the neural activity induced by myocardial infarction.展开更多
Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest(CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their b...Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest(CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet(CV) and Fluore-Jade B(F-J B) staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1(Iba-1), glial fibrillary acidic protein(GFAP), and tumor necrosis factor-alpha(TNF-α) immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA(about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day postCA, and they were activated(enlarged cell bodies with short and thicken processes) in all layers 2 days postCA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-α immunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.展开更多
Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the n...Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning(2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult(5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.展开更多
Quercetin(QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprot...Quercetin(QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprotective mechanisms of QE after ischemic insults. Therefore, in this study, we investigated the effects of QE on ischemic injury and the expression of antioxidant enzymes in the hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, pretreatment with QE significantly increased the expression levels of endogenous antioxidant enzymes Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic injury. These findings demonstrate that pretreated QE displayed strong neuroprotective effects against transient cerebral ischemia by increasing the expression of antioxidant enzymes.展开更多
Salmonella enterica serovar Rissen has been recognised as a common serovar in humans and pigs around the world. This study investigated S. Rissen prevalence in pigs slaughtered in Northern Ireland additionally looking...Salmonella enterica serovar Rissen has been recognised as a common serovar in humans and pigs around the world. This study investigated S. Rissen prevalence in pigs slaughtered in Northern Ireland additionally looking at antibiotic susceptibility profiles, genetic profiles and plasmid profiles to provide information on an emerging non-typhoid Salmonella serotype with the potential to cause disease in humans. S. Rissen were isolated on five separate sampling occasions from both the boning hall and slaughter line of a randomly selected single pig abattoir in Northern Ireland (NI). Following antibiotic susceptibility testing against 16 antibiotics, all S. Rissen isolates were identified as susceptible to 15 antibiotics but resistant to tetracycline (R-type: Te). Of the 29 S. Rissen, 27 were isolated from pigs originating in NI and two S. Rissen were isolated from pigs originating in the Republic of Ireland (RoI). The combined results of the PFGE and plasmid profiling analyses were capable of subdividing the S. Rissen isolates into three distinct groups. The data suggests that S. Rissen is an emerging serovar in Northern Ireland and continued surveillance of this serovar is warranted as it has the potential to cause disease in humans.展开更多
Waterpipe(WP),a less common method of tobacco smoking than cigarette smoking(CS),has become increasingly popular over the last decade.Contrary to popular belief,WP smoking is far from harmless and has multiple health ...Waterpipe(WP),a less common method of tobacco smoking than cigarette smoking(CS),has become increasingly popular over the last decade.Contrary to popular belief,WP smoking is far from harmless and has multiple health risks similar to,or even exceeding,those seen in CS[1,2].展开更多
The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not bee...The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1-3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group, p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.展开更多
Ischemic preconditioning(IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult.We,in this study,examined the neuroprotective effect...Ischemic preconditioning(IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult.We,in this study,examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase(SOD) 1 and SOD2,catalase(CAT) and glutathione peroxidase(GPX) in the gerbil hippocampal CA1 region after transient forebrain ischemia.Pyramidal neurons of the stratum pyramidale(SP) in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC(8.6%(ratio of remanent neurons) of the sham-operated group);however,IPC prevented the pyramidal neurons from subsequent lethal ischemic injury(92.3%(ratio of remanent neurons) of the sham-operated group).SOD1,SOD2,CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale(SP) of the hippocampal CA1 region,while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without IPC.Meanwhile,their immunoreactivities in the sham-operated animals with IPC were similar to(SOD1,SOD2 and CAT) or higher(GPX) than those in the sham-operated animals without IPC.Furthermore,their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/reperfusion.Results of western blot analysis for SOD1,SOD2,CAT and GPX were similar to immunohistochemical data.In conclusion,IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia.展开更多
Background Oenanthe javanica is an aquatic perennial herb originated from East Asia.Nowadays,the effects of Oenanthe javanica have been proven in various disease models.Studies regarding the antioxidant effect of Oena...Background Oenanthe javanica is an aquatic perennial herb originated from East Asia.Nowadays,the effects of Oenanthe javanica have been proven in various disease models.Studies regarding the antioxidant effect of Oenanthe javanica in the kidney are still unclear.Methods This study was therefore performed to investigate the effect of the Oenanthe javanica extract (OJE) in the rat kidney using immunohistochemistry for antioxidant enzymes,copper,zinc-superoxide dismutase (SOD1),manganese superoxide dismutase (SOD2),catalase (CAT) and glutathione peroxidase (GPx).Sprague-Dawley rats were randomly assigned to three groups:(1) normal diet fed-group (normal-group),(2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control,(3) diet containing OJE-fed group (OJE-group).AA and OJE were supplied during 28 days.Results The side-effects were not observed in all the groups.Immunoreactivities of SOD1,SOD2,CAT and GPx were easily detected in the distal tubules of the kidney,and their immunoreactivities in the AA-and OJE-groups were increased to about 1.4-1.5 times and 2 times,respectively,compared with those in the normal-group.Conclusion OJE significantly increased expressions of SOD1 & 2,CAT and GPx immunoreactivities in the distal tubules of the rat kidney,and this finding suggests that significant enhancements of endogenous enzymatic antioxidants by OJE treatment may be a legitimate strategy for decreasing oxidative stresses in the kidney.展开更多
文摘Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective delivery.Exosomes can also interact with viruses in diverse ways.Emerging research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and HCV.Understanding the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral therapies.An important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent characteristics.By leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune responses.They can either help or hinder viral infection by modulating the immune system.This review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or therapy.This could lead to new clinical applications of exosomes in disease management.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2016R1D1A1B01011790 to JHC)+3 种基金Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2017R1A2B4009079 to MHW)Cooperative Research Program for Agriculture Science and Technology Development(Project No.PJ01329401to MHW) Rural Development Administration,Republic of Korea
文摘Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2017R1D1A1B03033271,to JDK)the Bio-Synergy Research Project(NRF-2018M3A9C4076478,to IJK)of the Ministry of Science,ICT and Future Planning through the National Research Foundation
文摘Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science,ICT and Future Planning(NRF-2013R1A2A2A01068190)Hallym University Specialization Fund(HRF-S-13)
文摘In this study, we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne(CIL) extract, which has been used as a botanical drug in East Asia, against ischemic damage and to explore the underlying mechanism involving the anti-inflammatory approach. A gerbil was given CIL extract for 7 consecutive days followed by bilateral carotid artery occlusion to make a cerebral ischemia/reperfusion model. Then, we found that CIL extracts protected pyramidal neurons in the hippocampal CA1 region(CA1) from ischemic damage using neuronal nucleus immunohistochemistry and Fluoro-Jade B histofluorescence. Accordingly, interleukin-13 immunoreactivities in the CA1 pyramidal neurons of CIL-pretreated animals were maintained or increased after cerebral ischemia/reperfusion. These findings indicate that the pre-treatment of CIL can attenuate neuronal damage/death in the brain after cerebral ischemia/reperfusion via an anti-inflammatory approach.
文摘AIM:To assess the reliability of web-based version of ocular surface disease index in Chinese(C-OSDI)on clinically diagnosed dry eye disease(DE)patients.METHODS:A total of 254 Chinese participants(51%male,129/254;mean age:27.90±9.06 y)with DED completed paper-and web-based versions of C-OSDI questionnaires in a randomized crossover design.Ophthalmology examination and DED diagnosis were performed prior to the participants being invited to join the study.Participants were randomly designated to either group A(paper-based first and webbased second)or group B(web-based first and paper-based second).Final data analysis included participants that had successfully completed both versions of the C-OSDI.Demographic characteristics,test-retest reliability,and agreement of individual items,subscales,and total score were evaluated with intraclass correlation coefficients(ICC),Spearman rank correlation,Wilcoxon test and Rasch analysis.RESULTS:Reliability indexes were adequate,Pearson correlation was greater than 0.8 and ICCs range was 0.827 to 0.982;total C-OSDI score was not statistically different between the two versions.The values of mean-squares fit statistics were very low compared to 1,indicating that the responses to the items by the model had a high degree of predictability.While comparing the favorability 72%(182/254)of the participants preferred web-based assessment.CONCLUSION:Web-based C-OSDI is reliable in assessing DED and correlation with the paper-based version is significant in all subscales and overall total score.Webbased C-OSDI can be administered to assess individuals with DED as participants predominantly favored online assessment.
基金supported by the Biomedical Technology Development Program of the NRF funded by the Korean Government,MSIP(NRF-2015M3A9B6066835)by the Bio-Synergy Research Project(NRF-2015M3A9C4076322)of the Ministry of Science,ICT and Future Planning through the National Research Foundation
文摘Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We inves- tigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei (NeuN) and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia (39.5 + 0.2~C) was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neu- ronal damage/death in the pyramidal layer of CA1-3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreac- tivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immu- noreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.
基金supported by Hallym University Specialization Fund,No.HRF-S-12
文摘Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation) and doublecortin (a marker for neuroblast). Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.
文摘This study aimed to assess whether a daily supplementation with Lactobacillus rhamnosus GG (LGG) can alter the body composition as well as bone turnover and the mechanical properties of the bones in systemic immunodeficiency. For this, we use an in vivo model of severe combined immunodeficient (scid) mice supplemented daily with LGG over 8 weeks period. After 8 weeks of the treatment, the animals were assessed by DEXA and then the blood was collected from the hepatic portal vein for bone turnover biomarkers;post-mortem, the caecum was removed for isolation and enumeration of the gut bacteria, while femurs/tibiae were excised for the assessment of their mechanical properties. LGG treatment affected the composition of the gut microbiota at the order level, and it decreased (P = 0.002) total adipose tissue content. Moreover, LGG treatment decreased the stiffness (N/mm) of both femurs (P = 0.008) and tibiae (P = 0.011). To conclude, this study shows that dietary supplementation with LGG in immunodeficient animals can alter mechanical properties of the long bones and concomitantly it can modify host’s total adiposity level.
基金supported by Hallym University Research Fund,No.01-2012-10
文摘c-Fos is a good biological marker for detecting the pathogenesis of central nervous system disorders. Few studies are reported on the change in myocardial infarction-induced c-Fos expression in the paralimbic regions. Thus, in this study, we investigated the changes in c-Fos expression in the rat cingulate and piriform cortices after myocardial infarction. Neuronal degeneration in cingulate and piriform cortices after myocardial infarction was detected using cresyl violet staining, Neu N immunohistochemistry and Fluoro-Jade B histofluorescence staining. c-Fos-immunoreactive cells were observed in cingulate and piriform cortices at 3 days after myocardial infarction and peaked at 7 and 14 days after myocardial infarction. But they were hardly observed at 56 days after myocardial infarction. The chronological change of c-Fos expression determined by western blot analysis was basically the same as that of c-Fos immunoreactivity. These results indicate that myocardial infarction can cause the chronological change of immediate-early response gene c-Fos protein expression, which might be associated with the neural activity induced by myocardial infarction.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)the Ministry of Education(NRF-2014R1A1A2057263)+2 种基金by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2017R1A2B4009079&NRF-2017R1A2B4008403)by the Bio-Synergy Research Project(NRF-2015M3A9C4076322)of the Ministry of ScienceICT and Future Planning through the National Research Foundation
文摘Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest(CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet(CV) and Fluore-Jade B(F-J B) staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1(Iba-1), glial fibrillary acidic protein(GFAP), and tumor necrosis factor-alpha(TNF-α) immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA(about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day postCA, and they were activated(enlarged cell bodies with short and thicken processes) in all layers 2 days postCA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-α immunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.
基金supported by Hallym University Research Fund,2016(HRF-201605-012)Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2016R1A6A3A01011698)
文摘Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning(2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult(5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(NRF-2015R1D1A1A01059728)Hallym University Research Fund 2014(HURF-2014-25)
文摘Quercetin(QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprotective mechanisms of QE after ischemic insults. Therefore, in this study, we investigated the effects of QE on ischemic injury and the expression of antioxidant enzymes in the hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, pretreatment with QE significantly increased the expression levels of endogenous antioxidant enzymes Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic injury. These findings demonstrate that pretreated QE displayed strong neuroprotective effects against transient cerebral ischemia by increasing the expression of antioxidant enzymes.
文摘Salmonella enterica serovar Rissen has been recognised as a common serovar in humans and pigs around the world. This study investigated S. Rissen prevalence in pigs slaughtered in Northern Ireland additionally looking at antibiotic susceptibility profiles, genetic profiles and plasmid profiles to provide information on an emerging non-typhoid Salmonella serotype with the potential to cause disease in humans. S. Rissen were isolated on five separate sampling occasions from both the boning hall and slaughter line of a randomly selected single pig abattoir in Northern Ireland (NI). Following antibiotic susceptibility testing against 16 antibiotics, all S. Rissen isolates were identified as susceptible to 15 antibiotics but resistant to tetracycline (R-type: Te). Of the 29 S. Rissen, 27 were isolated from pigs originating in NI and two S. Rissen were isolated from pigs originating in the Republic of Ireland (RoI). The combined results of the PFGE and plasmid profiling analyses were capable of subdividing the S. Rissen isolates into three distinct groups. The data suggests that S. Rissen is an emerging serovar in Northern Ireland and continued surveillance of this serovar is warranted as it has the potential to cause disease in humans.
基金supported by the National Natural Science Foundation of China[82003401&81972981]the Key Projects of Colleges and Universities of Henan Education Department[21A330006]the Opening Foundation of National Health Commission Key Laboratory of Birth Defects Prevention and Henan Key Laboratory of Population Defects Prevention[ZD202001]。
文摘Waterpipe(WP),a less common method of tobacco smoking than cigarette smoking(CS),has become increasingly popular over the last decade.Contrary to popular belief,WP smoking is far from harmless and has multiple health risks similar to,or even exceeding,those seen in CS[1,2].
基金supported by 2013 Research Grant from Kangwon National University(120131480)Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2014R1A6A3A01056005)
文摘The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1-3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group, p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.
基金supported by a Priority Research Center Program grant(No.NRF-2009-0093812)through the National Research Foundation of Korea funded by the Ministry of Science,ICT and Future Planning2015 Research Grant from Kangwon National UniversityBasic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.NRF-2014R1A1A2057013)
文摘Ischemic preconditioning(IPC) is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic insult.We,in this study,examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase(SOD) 1 and SOD2,catalase(CAT) and glutathione peroxidase(GPX) in the gerbil hippocampal CA1 region after transient forebrain ischemia.Pyramidal neurons of the stratum pyramidale(SP) in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC(8.6%(ratio of remanent neurons) of the sham-operated group);however,IPC prevented the pyramidal neurons from subsequent lethal ischemic injury(92.3%(ratio of remanent neurons) of the sham-operated group).SOD1,SOD2,CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale(SP) of the hippocampal CA1 region,while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without IPC.Meanwhile,their immunoreactivities in the sham-operated animals with IPC were similar to(SOD1,SOD2 and CAT) or higher(GPX) than those in the sham-operated animals without IPC.Furthermore,their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/reperfusion.Results of western blot analysis for SOD1,SOD2,CAT and GPX were similar to immunohistochemical data.In conclusion,IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia.
文摘Background Oenanthe javanica is an aquatic perennial herb originated from East Asia.Nowadays,the effects of Oenanthe javanica have been proven in various disease models.Studies regarding the antioxidant effect of Oenanthe javanica in the kidney are still unclear.Methods This study was therefore performed to investigate the effect of the Oenanthe javanica extract (OJE) in the rat kidney using immunohistochemistry for antioxidant enzymes,copper,zinc-superoxide dismutase (SOD1),manganese superoxide dismutase (SOD2),catalase (CAT) and glutathione peroxidase (GPx).Sprague-Dawley rats were randomly assigned to three groups:(1) normal diet fed-group (normal-group),(2) diet containing ascorbic acid (AA)-fed group (AA-group) as a positive control,(3) diet containing OJE-fed group (OJE-group).AA and OJE were supplied during 28 days.Results The side-effects were not observed in all the groups.Immunoreactivities of SOD1,SOD2,CAT and GPx were easily detected in the distal tubules of the kidney,and their immunoreactivities in the AA-and OJE-groups were increased to about 1.4-1.5 times and 2 times,respectively,compared with those in the normal-group.Conclusion OJE significantly increased expressions of SOD1 & 2,CAT and GPx immunoreactivities in the distal tubules of the rat kidney,and this finding suggests that significant enhancements of endogenous enzymatic antioxidants by OJE treatment may be a legitimate strategy for decreasing oxidative stresses in the kidney.