A novel CD4 knockout mouse strain with a spontaneous frameshift mutation in the CD4 locus.

T cells express co-receptors CD4 and CD8, which are involved in the recognition of antigen presented to T cell receptors. The expression of CD4 in thymic hematopoietic cells is crucial for the thymic development and selection of T cells. In this study, we identified a novel CD4 mutant allele that emerged spontaneously in our mouse colony. The frameshift mutation led to a truncated CD4 protein which failed to reach the plasma membrane resulting in impaired development of CD4+ helper T cells. The CRISPR mediated correction of mutant allele restored the membrane CD4 expression. Further, using an adoptive transfer of T cells, we show that this model is an ideal recipient mouse for the study of CD4+ T cells.

Targeted Expression of Myelin Autoantigen in the Periphery Induces Antigen-Specific T and B Cell Tolerance and Ameliorates Autoimmune Disease.

There is a great interest in developing antigen-specific therapeutic approaches for the treatment of autoimmune diseases without compromising normal immune function. The key challenges are to control all antigen-specific lymphocyte populations that contribute to pathogenic inflammatory processes and to provide long-term protection from disease relapses. Here, we show that myelin oligodendrocyte glycoprotein (MOG)-specific tolerance can be established by ectopic expression of MOG in the immune organs. Using transgenic mice expressing MOG-specific CD4, CD8, and B cell receptors, we show that MOG expression in the bone marrow cells results in impaired development of MOG-specific lymphocytes. Ectopic MOG expression has also resulted in long-lasting protection from MOG-induced autoimmunity. This finding raises hope that transplantation of autoantigen-expressing bone marrow cells as a therapeutic strategy for specific autoantigen-driven autoimmune diseases.

High-salt diet suppresses autoimmune demyelination by regulating the blood-brain barrier permeability.

Sodium chloride, "salt," is an essential component of daily food and vitally contributes to the body's homeostasis. However, excessive salt intake has often been held responsible for numerous health risks associated with the cardiovascular system and kidney. Recent reports linked a high-salt diet (HSD) to the exacerbation of artificially induced central nervous system (CNS) autoimmune pathology through changes in microbiota and enhanced TH17 cell differentiation [M. Kleinewietfeld et al., Nature 496, 518-522 (2013); C. Wu et al., Nature 496, 513-517 (2013); N. Wilck et al., Nature 551, 585-589 (2017)]. However, there is no evidence that dietary salt promotes or worsens a spontaneous autoimmune disease. Here we show that HSD suppresses autoimmune disease development in a mouse model of spontaneous CNS autoimmunity. We found that HSD consumption increased the circulating serum levels of the glucocorticoid hormone corticosterone. Corticosterone enhanced the expression of tight junction molecules on the brain endothelial cells and promoted the tightening of the blood-brain barrier (BBB) thereby controlling the entry of inflammatory T cells into the CNS. Our results demonstrate the multifaceted and potentially beneficial effects of moderately increased salt consumption in CNS autoimmunity.

Preliminary Study of the Antioxidant Effects of Oenanthe javanica Extract on the Skin of Aged Mice / 대한피부과학회지

No abstract available.

Extract Promotes Neurogenesis in the Hippocampal Dentate Gyrus of the Adult Mouse through Increasing Expressions of Brain-Derived Neurotrophic Factor and Tropomyosin-Related Kinase B / 中华医学杂志(英文版)

<p><b>Background</b>Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice.</p><p><b>Methods</b>A total of 39 male ICR mice (12 weeks old) were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups (n = 13 in each group). Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects of G. littoralis extract, we performed immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU, an indicator for cell proliferation) and doublecortin (DCX, an immature neuronal marker) and double immunofluorescence staining for BrdU and neuronal nuclear antigen (NeuN, a mature neuronal marker). In addition, we examined expressional changes of brain-derived neurotrophic factor (BDNF) and its major receptor tropomyosin-related kinase B (TrkB) using Western blotting analysis.</p><p><b>Results</b>Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive () and DCX cells (48.0 ± 3.1 and 72.0 ± 3.8 cells/section, respectively) in the subgranular zone (SGZ) of the dentate gyrus (DG) and BrdU/NeuN cells (17.0 ± 1.5 cells/section) in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and TrkB (about 232% and 244% of the vehicle-treated group, respectively) were significantly increased in the DG of the mice treated with 200 mg/kg of G. littoralis extract.</p><p><b>Conclusion</b>G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases of BDNF and TrkB proteins by G. littoralis extract treatment.</p>

Risk Factors for an Iatrogenic Mallory-Weiss Tear Requiring Bleeding Control during a Screening Upper Endoscopy.

Background and Aim. In some cases of iatrogenic Mallory-Weiss tears (MWTs), hemostasis is needed due to severe mucosal tearing with bleeding. Therefore, we aimed to evaluate the risk factors for severe iatrogenic MWTs and the methods of endoscopic bleeding control. Materials and Methods. Between January 2008 and December 2012, 426,085 cases of screening upper endoscopy were performed at the Asan Medical Center. We retrospectively analyzed the risk factors for severe iatrogenic MWTs requiring an endoscopic procedure and the treatment modalities of bleeding control. Results. Iatrogenic MWTs occurred in 546 cases (0.13%) of screening upper endoscopy in 539 patients. Bleeding control due to severe bleeding was applied in 71 cases (13.0%), and rebleeding after initial bleeding control occurred in 1 case. Multivariate analysis showed that old age, a history of distal gastrectomy, and a less-experienced endoscopist (fewer than 2,237.5 endoscopic procedures at the time of the MWT) were associated with severe iatrogenic MWTs requiring an endoscopic procedure. Among 71 cases requiring bleeding control, a hemoclip was used in 81.7% (58 cases). Conclusions. Screening endoscopy procedures should be carefully performed when patients are in their old age and have a history of distal gastrectomy, particularly if the endoscopist is less experienced.

A Mouse Model of Post-Stroke Pneumonia Induced by Intra-Tracheal Inoculation with Streptococcus pneumoniae.

BACKGROUND: Stroke-induced immunodeficiency increases the risk of infectious complications, which adversely affects neurological outcome. Among those, pneumonia affects as many as one third of stroke patients and is the main contributor to mortality in the post-acute phase of stroke. Experimental findings on post-stroke susceptibility to spontaneous pneumonia in mice are contradictory. Here, we established a mouse model inducing standardized bacterial pneumonia and characterized the impaired pulmonary cellular and humoral immune responses after experimental stroke. METHODS: Bacterial pneumonia was induced by intra-tracheal inoculation with Streptococcus pneumoniae at different time points after transient middle cerebral artery occlusion (MCAO). Bacterial counts in lungs and blood, histological changes, and cytokine production in the lungs were assessed. Furthermore, we investigated the effect of pneumonia on stroke outcome. RESULTS: Intra-tracheal inoculation resulted in reproducible pneumonia and bacteraemia, and demonstrated post-stroke susceptibility to streptococcal pneumonia developing with a delay of at least 24 h after MCAO. Higher bacterial counts in mice infected 3 days after stroke induction correlated with reduced neutrophil and macrophage infiltration in the lungs and lower levels of pro-inflammatory cytokines in the broncho-alveolar lavage compared to sham-operated animals. Pneumonia increased mortality without affecting brain-infiltrating leukocytes. CONCLUSIONS: In this standardized mouse model of post-stroke pneumonia, we describe attenuated leukocyte infiltration and cytokine production in response to bacterial infection in the lungs that has a profound effect on outcome.

Clinical features of postoperative anastomotic bleeding after gastrectomy and efficacy of endoscopic hemostasis: a case-control study.

BACKGROUND: Postoperative anastomotic bleeding (PAB) is relatively rare; however, it can be lethal if not treated immediately. The aim of our study was to investigate the clinical features of PAB and the efficacy of endoscopic hemostasis (EH) for PAB. METHODS: Between January 2004 and May 2013, 16,591 patients underwent gastrectomy for gastric cancer at Asan Medical Center. Among them, 36 patients who experienced PAB within 2 months after the gastrectomy were enrolled as a case group. Each subject was matched at a ratio of 1:5 with randomly selected patients without bleeding during the same period (n = 180, control group). The clinical outcomes and risk factors for patients with PAB were compared with those of the control group, and the results of EH were evaluated retrospectively. RESULTS: The incidence of PAB was 0.22% (n = 36), and the median duration from gastrectomy to PAB was 34.5 h (interquartile range, 12.3-132.8 h). EH was attempted in 25 patients (69.4%); surgery was performed in 6 patients (16.7%); and conservative management was applied in 5 patients (13.9%). PAB-related death occurred in three patients (8.3%; one in each treatment modality). Among 25 patients with primary EH, 16 were treated successfully (64%) and hemoclip was the most commonly used endoscopic tool (52%). In the multivariate analysis, the type of gastrectomy was found to be a risk factor for PAB (odds ratio 3.448, 95% confidence interval, 1.138-10.448, p = .029). CONCLUSIONS: Although PAB is an infrequent and potentially life-threatening complication, endoscopy can be considered as a useful method to avoid additional surgery in properly selected patients.

Pre-treated Populus tomentiglandulosa extract inhibits neuronal loss and alleviates gliosis in the gerbil hippocampal CA1 area induced by transient global cerebral ischemia / 대한해부학회지

The genus Populus (poplar) belonging to the Salicaceae family has been used in traditional medicine, and its several species show various pharmacological properties including antioxidant and anti-inflammatory effects. No study regarding protective effects of Populus species against cerebral ischemia has been reported. Therefore, in the present study, we examined neuroprotective effects of ethanol extract from Populus tomentiglandulosa (Korea poplar) in the hippocampal cornu ammonis (CA1) area of gerbils subjected to 5 minutes of transient global cerebral ischemia. Pretreatment with 200 mg/kg of P. tomentiglandulosa extract effectively protected CA1 pyramidal neurons from transient global cerebral ischemia. In addition, glial fibrillary acidic protein immunoreactive astrocytes and ionized calcium binding adapter molecule 1 immunoreactive microglia were significantly diminished in the ischemic CA1 area by pretreatment with 200 mg/kg of P. tomentiglandulosa extract. Briefly, our results indicate that pretreatment with P. tomentiglandulosa extract protects neurons from transient cerebral ischemic injury and diminish cerebral ischemia-induced reactive gliosis in ischemic CA1 area. Based on these results, we suggest that P. tomentiglandulosa can be used as a potential candidate for prevention of ischemic injury.

Nutritional Evaluation of Convenience Meals in Convenience Stores near the Universities / 대한지역사회영양학회지

OBJECTIVES: Rapid economic growth and industrial development in South Korea have led to a great change in dietary patterns, and the use of convenience foods has continuously increased. This study was performed to evaluate the energy and nutrient contents of convenience foods at convenience stores near the universities as a meal. METHODS: Data was collected by visiting 22 convenience stores near some universities in Chungbuk and Seoul and by checking nutrition labels on convenience foods at the stores. Data of a total of 338 food items were collected, and divided into five groups according to the food categories; rice products (n=156), noodles (n=101), burger/sandwiches (n=62), Tteokbokkis (n=11), and dumplings (n=8). Further, rice products, noodles, and burger/sandwiches were divided into subcategories. RESULTS: The proportion of calories from carbohydrates was high in the rice products and tteokbokki, while the rate of calories from fat was high in burger/sandwiches and dumplings. Among the rice products, the proportion of carbohydrate calories was high in a one-dish food, rice with soup, and triangular kimbap, while the proportion of calories from fat in lunch boxes was high. In the noodles category, ramyeon and spaghetti had a high percentage of fat calories, while udong had a high percentage of carbohydrate calories. The ratio of the calorie content in relation to the KDRIs for adults aged 19-29 years, lunch boxes provided about 1/3 of daily required energy. However, the amount of calories as one meal was not enough for other types of rice products except for lunch boxes. Ramyeon was high in calories, fat, and sodium, but low in protein content. The burger/sandwiches had a high percentage of fat and sodium. CONCLUSIONS: Our results showed several nutritional limitations of convenience meals in convenience stores according to the type of food. Therefore, college students should limit excessive intake of convenience meals on a regular basis in order to avoid unhealthy food intake patterns. Our results demonstrate the need for educating college students with regard to checking nutrition labels when choosing convenience meals in order to facilitate the selection of food items that contribute to a balanced diet.

PretreatedExtract Prevents Neuronal Death Following Transient Global Cerebral Ischemia through Increases of Superoxide Dismutase 1 and Brain-derived Neurotrophic Factor Expressions in the Gerbil Hippocampal Cornu Ammonis 1 Area / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glehnia littoralis, as a traditional herbal medicine to heal various health ailments in East Asia, displays various therapeutic properties including antioxidant effects. However, neuroprotective effects of G. littoralis against cerebral ischemic insults have not yet been addressed. Therefore, in this study, we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia (TGCI).</p><p><b>METHODS</b>Gerbils were subjected to TGCI for 5 min. G. littoralis extract (GLE; 100 and 200 mg/kg) was administrated orally once daily for 7 days before ischemic surgery. Neuroprotection was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. Gliosis was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1. For neuroprotective mechanisms, immunohistochemistry for superoxide dismutase (SOD) 1 and brain-derived neurotrophic factor (BDNF) was done.</p><p><b>RESULTS</b>Pretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 (CA1) area from ischemic insult area (F = 29.770, P < 0.05) and significantly inhibited activations of astrocytes (F = 22.959, P < 0.05) and microglia (F = 44.135, P < 0.05) in the ischemic CA1 area. In addition, pretreatment with GLE significantly increased expressions of SOD1 (F = 28.561, P < 0.05) and BDNF (F = 55.298, P < 0.05) in CA1 pyramidal neurons of the sham- and ischemia-operated groups.</p><p><b>CONCLUSIONS</b>Our findings indicate that pretreatment with GLE can protect neurons from ischemic insults, and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD1 and BDNF expressions as well as attenuation of glial activation.</p>

Time interval after ischaemic preconditioning affects neuroprotection and gliosis in the gerbil hippocampal CA1 region induced by transient cerebral ischaemia.

OBJECTIVES: Ischaemic preconditioning (IPC) can increase ischaemic tolerance of the central nervous system (CNS) to a subsequent longer or lethal period of transient ischaemia. In this study, we examined neuroprotective effects of time intervals after IPC against ischaemic insult in the hippocampus. METHODS: Animals were randomly assigned to six groups; sham-operated-group, ischaemia-operated-group, and three IPC (12 hours, 1- and 2-day intervals after IPC) plus ischaemia-groups (IPC-12 hour, 1 and 2-day interval-ischaemia-operated-groups). For neuroprotection, we carried out cresyl violet (CV) staining neuronal nuclei (NeuN) immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, we examined gliosis using immunohistochemistry for GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia). RESULTS: A significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) in the ischaemia-operated-group and IPC-12 hours interval-ischaemia-operated-groups. In the IPC-1 day interval-ischaemia-operated-group, CA1 pyramidal neurons were well protected from ischaemic insult; the neuroprotective effect in the IPC-2 day interval-ischaemia-operated-group was less than that in the IPC-1 day interval-ischaemia-operated-group. On the other hand, we observed changes in glial cells (astrocytes and microglia) in the CA1 of all groups. The distribution pattern of glial cells only in the IPC-1 day interval-ischaemia-operated-group was similar to that in the sham-group. CONCLUSION: In brief, our findings indicate that 1 day after IPC displays a mighty neuroprotection and shows an inhibition of glial activation in the CA1 induced by transient ischaemic insult.

Erratum: Prescribing Patterns of Codeine among Children under aged 12 in Korea

Erratum agreed to by all authors, editor in chief, publisher, and scientific society.

Delayed Bleeding Rate According to the Forrest Classification in Second-Look Endoscopy After Endoscopic Submucosal Dissection.

BACKGROUND AND AIM: Forrest classification is a valid tool to predict rebleeding rate in peptic ulcer, not in post-endoscopic resection ulcer. We evaluated the delayed bleeding rate in Forrest classification II and III lesions when they were not treated in second-look endoscopy. METHODS: Between July 2011 and February 2012, 706 lesions in 656 consecutive patients who underwent second-look endoscopy performed on the second day after endoscopic submucosal dissection (ESD) were prospectively investigated. Endoscopic findings were described according to Forrest classification, and late delayed bleeding was defined as bleeding from second-look endoscopy to 1 month. We evaluated the rate of late delayed bleeding in untreated Forrest classification II and III lesions during second-look endoscopy. RESULTS: Among the 706 gastric tumors analyzed, late delayed bleeding after ESD occurred in 29 lesions (4.1%). At second-look endoscopy, Forrest I lesions (immediately treated by endoscopic hemostasis) were found in 63 cases [Ia, 8 lesions (1.1%); Ib, 55 lesions (7.8%)]; there was no further bleeding after discharge. Forrest II and III lesions (not treated in second-look endoscopy) were found in 643 cases [IIa, 62 lesions (8.8%); IIb, 119 lesions (16.9%); IIc, 460 lesions (65.2 %); III, 2 lesions (0.3%)]; and there was no significant difference in the late delayed bleeding rate between these groups [IIa, 2/62 (3.2%); IIb, 5/119 (4.2%); IIc and III, 22/462 (4.8%); P = 1.000]. CONCLUSIONS: The rate of late delayed bleeding of post-ESD ulcers with non-bleeding visible vessels was not significantly different from that of ulcers with non-visible vessels ( http://cris.nih.go.kr , identifier KCT0000268).

Idarucizumab Improves Outcome in Murine Brain Hemorrhage Related to Dabigatran.

Lack of specific antidotes is a major concern in intracerebral hemorrhage (ICH) related to direct anticoagulants including dabigatran (OAC-ICH). We examined the efficacy of idarucizumab, an antibody fragment binding to dabigatran, in a mouse model of OAC-ICH. Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab. Pretreatment with DE increased intracerebral hematoma volume and cerebral hemoglobin content. Idarucizumab in equimolar dose prevented excess hematoma expansion for both DE doses. In more extensive ICH, idarucizumab significantly reduced mortality. Thus, idarucizumab prevents excess intracerebral hematoma formation in mice anticoagulated with dabigatran and reduces mortality.

DAMP signaling is a key pathway inducing immune modulation after brain injury.

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and investigated its inflammatory potency and signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, was studied in various transgenic animal models and by pharmacological blockade. Our results indicate that the cytokine-inducing, fully reduced isoform of HMGB1 was released from the ischemic brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted in the periphery in response to brain injury induced sickness behavior, which could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine neutralization. Subsequently, HMGB1-release induced bone marrow egress and splenic proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling resulted in functional exhaustion of mature monocytes and lymphopenia, the hallmarks of immune suppression after extensive ischemia. This study introduces the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex postischemic brain-immune interactions.

Endoscopic resection for synchronous esophageal squamous cell carcinoma and gastric adenocarcinoma in early stage is a possible alternative to surgery.

BACKGROUND/AIMS: We investigated the clinical outcomes according to the method of treatment in synchronous esophageal and gastric cancer. METHODS: Synchronous esophageal squamous cell carcinoma and gastric adenocarcinoma were diagnosed in 79 patients between 1996 and 2010. We divided the patients into four groups according to treatment; Group 1 received surgical resection for both cancers or surgery for gastric cancer with chemoradiotherapy for esophageal cancer (n=27); Group 2 was treated by endoscopic resection with or without additional treatment (n=14); Group 3 received chemoradiotherapy only (n=18); and Group 4 received supportive care only (n=20). RESULTS: The median survival times in groups 1 and 2 were 86 and 60 months, respectively. The recurrence rate and mortality were 23% and 48%, respectively, in group 1 and 21% and 4%, respectively, in group 2. The median survival time was 12 months in group 3 and 9 months in group 4. Multivariate analysis showed that age (p<0.001) and treatment group (p=0.019) were significantly associated with death. Compared with group 1, treatment in the intensive care unit (p=0.003), loss of body weight (p=0.042), and decrease in hemoglobin (p=0.033) were worse in group 1. CONCLUSIONS: Endoscopic resection for synchronous esophageal and gastric cancer could be considered as a possible alternative to surgery for early-stage cancer.

Amplification of regulatory T cells using a CD28 superagonist reduces brain damage after ischemic stroke in mice.

BACKGROUND AND PURPOSE: Neuroinflammation plays an important role in ischemic brain injury. Regulatory T cells (Treg) are important endogenous immune modulators. We tested the hypothesis that Treg amplification with a CD28 superagonistic monoclonal antibody (CD28SA) reduces brain damage in murine cerebral ischemia. METHODS: Cerebral ischemia was induced by coagulation of the distal middle cerebral artery or by 60 minutes filament occlusion of the proximal middle cerebral artery in C57BL6 mice. 150 µg CD28SA was injected intraperitoneally 3 or 6 hours after ischemia onset. Outcome was determined by infarct volumetry and behavioral testing. Brain-infiltrating leukocyte subpopulations were analyzed by flow cytometry and immunohistochemistry 3 and 7 days after middle cerebral artery occlusion. RESULTS: CD28SA reduced infarct size in both models and attenuated functional deficit 7 days after stroke induction. Mice treated with CD28SA increased numbers of Treg in spleen and brain. Tregs were functionally active and migrated into the brain where they accumulated and proliferated in the peri-infarct area. More than 60% of brain infiltrating Treg produced interleukin-10 in CD28SA compared with 30% in control. CONCLUSIONS: In vivo expansion and amplification of Treg by CD28SA attenuates the inflammatory response and improves outcome after experimental stroke.

Effect of Oenanthe Javanica Extract on Antioxidant Enzyme in the Rat Liver / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Oenanthe javanica (O. javanica) has been known to have high antioxidant properties via scavenging reactive oxygen species. We examined the effect of O. javanica extract (OJE) on antioxidant enzymes in the rat liver.</p><p><b>METHODS</b>We examined the effect of the OJE on copper, zinc-superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPx) in the rat liver using immunohistochemistry and western blot analysis. 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).</p><p><b>RESULTS</b>In this study, no histopathological finding in the rat liver was found in all the experimental groups. Numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the normal-group. On the other hand, in the OJE-group, numbers of SOD1, SOD2, CAT, and GPx immunoreactive cells in the liver were significantly increased by about 190%, 478%, 685%, and 346%, respectively, compared with those in the AA-group. In addition, protein levels of SOD1, SOD2, CAT, and GPx in the OJE-group were also significantly much higher than those in the AA-group.</p><p><b>CONCLUSION</b>OJE significantly increased expressions of SOD1 and SOD2, CAT, and GPx in the liver cells of the rat, and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver.</p>