• BMB Reports
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• v.56 no.4
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• pp.234-239
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• 2023

Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H₂O₂-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury.

• Korean Journal of Animal Reproduction
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• v.25 no.4
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• pp.389-397
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• 2001

Cocaine-amphetamine regulated transcript (CART), a satiety factor regulated by leptin, is associated with food intake and motor behavior. In knock out studies, Leu34Phe mutation of human CART gene resulted in obese phenotype but mice carrying a targeted deletion of the CART gene exhibited no dramatic increase of body weight on normal fat diet. To establish a new transgenic mouse model for determining the function of CART on feeding behavior in vivo, we constructed the fusion gene, CART gene under the control of neurofilament light chain promoter, which regulates gene expression at the stage of neuronal differentiation. Transgenic mice were generated by microinjection method and screened by PCR and Southern blot analyses. In these transgenic mice, overexpression of CART was detected by in situ hybridization in spinal cords and brains at 13.5 days post-coitum embryos. At six weeks of age, RT-PCR analysis showed that exogenous CART mRNA was expressed strongly in brains and spinal cords, but not much in other tissues. Our results suggest that these transgenic mice provide a new model to investigate the function of CART gene in neuronal network associated with feeding behavior.

• Journal of agriculture & life science
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• v.50 no.3
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• pp.129-139
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• 2016

Curcumin plays a protective role in brain injury through its anti-oxidant and anti-inflammatory activities. Moreover, peroxiredoxin-5 exerts a protective effect against oxidative stress. The aim of this study was to investigate whether curcumin modulated the peroxiredoxin-5 expression in focal cerebral ischemic animal model. Middle cerebral artery occlusion(MCAO) was performed to induce cerebral ischemic injury in rats. Adult male rats were injected intraperitoneally with vehicle or curcumin(50mg/kg B.W.) 1 h after MCAO and cerebral cortex tissues were collected 24 h after MCAO. Photographs of hematoxylin and eosin staining showed that MCAO induced necrotic changes with scalloped shrunken form and apoptotic changes with nuclear chromatin condensations. However, curcumin treatment attenuated MCAO-induced histopathological changes. Moreover, this study clearly showed that peroxiredoxin-5 expression was decreased in MCAO operated animal with vehicle using a proteomics approach. However, this decrease in peroxiredoxin-5 expression was attenuated by curcumin treatment. Reverse-transcription PCR and Western blot analyses confirmed that curcumin treatment alleviated the MCAO injury-induced decrease in peroxiredoxin-5 expression(p<0.05). These results demonstrated that curcumin regulates peroxiredoxin-5 expression in MCAO animal model. In conclusion, our findings suggest that curcumin exerts a neuroprotective effect in cerebral ischemia by attenuating the MCAO-induced decrease in peroxiredoxin-5 expression.

• Industry Promotion Research
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• v.8 no.3
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• pp.95-109
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• 2023

The purpose of this paper is to empirically grasp the influence on self-efficacy and depression and the relationship between variables, focusing on middle-aged women in their 40s and 50s who are psychologically and socially vulnerable. Through this, it was intended to explore the psychological problems of highly educated careerinterrupted women from a personal perspective and further derive implications for the development of policies and services for socially highly educated career-interrupted women. The relationship between variables was analyzed through a survey based on measurement tools structured by variables of Saju factors, self-efficacy, and depression, and the effect of the sub-dimensional characteristics of Saju structure on self-efficacy, and the resulting level of depression were verified through structural equation model analysis. Bigeop, Jaeseong, and Kwanseong have been found to have a positive and direct effect on self-efficacy and negative direct effect on depression, eventually increasing self-efficacy and lowering depression. It was found that Siksang had a positive (+) relationship with depression and a negative (-) relationship with self-efficacy, but Inseong did not directly affect self-efficacy and depression. In addition, the indirect effects between variables and the effects between self-efficacy and depression were identified.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.40.1-40.15
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• 2020

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain. Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord. Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM-19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.154-161
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• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• Journal of Pharmacopuncture
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• v.27 no.3
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• pp.211-222
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• 2024

Objectives: Tilia viridis (Bayer) Simonk. (Malvaceae) is widely distributed in Argentina and employed for its tranquilizing properties. Other species of the genus (Tilia europaea L., Tilia cordata Mill., Tilia platyphyllos Scop.) have been traditionally used for the treatment of epilepsy. Epilepsy affects approximately 65 million people worldwide and is characterized by an imbalance between excitatory and inhibitory processes in the brain, leading to unpredictable, unprovoked, recurrent seizures. Current pharmacological interventions often present mild to moderately severe side effects. Epilepsy has been associated with oxidative and nitrative stress as well as neuroinflammation. Herbal medicine therapies may offer new treatment options with multi-target antioxidant and anticonvulsant effects for patients whose seizures remain uncontrolled, potentially providing cost-effective solutions for individuals worldwide suffering from uncontrolled epilepsy.The aim of this study was to demonstrate the anticonvulsant activity of a standardized T. viridis aqueous extract (TE). Methods: Study of the constituents of TE, TE's antioxidant and anticonvulsant activities and toxicity, and analysis of the possible relation between the potential activities and the compounds present in the extract. In order to demonstrate TE's anticonvulsant activity a zebrafish model was used. The study also assessed TE's toxicity and antioxidant activity. To standardize the extract, total polyphenols and flavonoids were quantified and specific flavonoids were identified and quantified using HPLC-MS/MS and HPLC-UV. Results: TE exhibited anticonvulsant activity at low concentrations and demonstrated antioxidant effects by scavenging free radicals, exhibiting superoxide dismutase and peroxidase-like activities, as well as inhibiting lipoperoxidation. These actions can be attributed to the presence of polyphenols, particularly flavonoids. Conclusion: TE holds promise as a complementary herbal medicine in the treatment of epilepsy and may also offer benefits for other neuropathies associated with oxidative stress, such as Parkinson's disease and Alzheimer's disease.

• Tuberculosis and Respiratory Diseases
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• v.65 no.3
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• pp.177-182
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• 2008

Background: Isoniazid (INH, H) is a key drug of the standard first-line regimen for the treatment of tuberculosis (TB), yet some reports have suggested that treatment efficacy was maintained even though INH was omitted from the treatment regimen. Methods: One hundred forty C57BL/6 mice were infected with the H37Rv strain of M. tuberculosis with using a Glas-Col aerosol generation device, and this resulted in depositing about 100 bacilli in the lung. Four weeks after infection, anti-TB treatment was initiated with varying regimens for 4-8 weeks; Group 1: no treatment (control), Group 2 (4HREZ): 4 weeks of INH, rifampicin (R), pyrazinamide (Z) and ethambutol (E), Group 3: 1HREZ/3REZ, Group 4: 4REZ, Group 5: 4HREZ/4HRE, Group 6: 1HREZ/3REZ/4RE, and Group 7: 4REZ/4RE. The lungs and spleens were harvested at several time points until 28 weeks after infection, and the colony-forming unit (CFU) counts were determined. Results: The CFU counts increased steadily after infection in the control group. In the 4-week treatment groups (Group 2-4), even though the culture was negative at treatment completion, the bacilli grew again at the 12-week and 20-week time points after completion of treatment. In the 8-week treatment groups (Groups 5-7), the bacilli did not grow in the lung at 4 weeks after treatment initiation and thereafter. In the spleens of Group 7 in which INH was omitted from the treatment regimen, the culture was negative at 4-weeks after treatment initiation and thereafter. However, in Groups 5 and 6 in which INH was taken continuously or intermittently, the bacilli grew in the spleen at some time points after completion of treatment. Conclusion: TThe exclusion of INH from the standard first-line regimen did not affect the treatment outcome in a murine model of TB in the early stage of disease. Further studies using a murine model of chronic TB are necessary to clarify the role of INH in the standard first-line regimen for treating TB.

• Progress in Medical Physics
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• v.19 no.2
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• pp.95-101
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• 2008

In this study, we observed the alteration of choline signal intensity in hippocampus region of the depressive rat model induced by forced swimming test (FST). The purpose of this study was to evaluate the antidepressant efficacy in the depressive animal model using MR spectroscopy. Fourteen experimentally naive male Sprague-Dawley rats weighting $160{\sim}180\;g$ were used as subjects. Drug injection group was exposed to the FST except for control group. The drugs were administered subcutaneously (SC) in a volume equivalent to 2ml/kg. And three injections were administered 23, 5, and 1h before beginning the given test. 1H MR spectra were obtained with use of a point resolved spectroscopy (PRESS) localization sequence performed according to the following parameters: repetition time, 2500 ms; echo time, 144 ms; 512 average; 2048 complex data points; voxel dimensions, $1.5{\times}2.5{\times}2.5\;mm^3$ ; acquisition time, 25min. There were no differences in NAA/Cr and Cho/Cr ratio between the right and the left hippocampus both normal control rats and antidepressant-injected rats. Also, no differences were observed in NAA/Cr and Cho/Cr ratio between the normal control rats and the antidepressant-injected rats both the right and the left hippocampus. In this study, we found the recovery of choline signals in the depressive animal model similar to normal control groups as injecting desipramine-HCl which was antidepressant causing anti-immobility effects. Thus, we demonstrated that MR spectroscopy was able to aid in evaluating the antidepressant effect of desipramine-HCl.

• Progress in Medical Physics
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• v.14 no.1
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• pp.34-42
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• 2003

In medical imaging, three-dimensional (3D) display using Virtual Reality Modeling Language (VRML) as a portable file format can give intuitive information more efficiently on the World Wide Web (WWW). The web-based 3D visualization of functional images combined with anatomical images has not studied much in systematic ways. The goal of this study was to achieve a simultaneous observation of 3D anatomic and functional models with planar images on the WWW, providing their locational information in 3D space with a measuring implement using VRML. MRI and ictal-interictal SPECT images were obtained from one epileptic patient. Subtraction ictal SPECT co-registered to MRI (SISCOM) was performed to improve identification of a seizure focus. SISCOM image volumes were held by thresholds above one standard deviation (1-SD) and two standard deviations (2-SD). SISCOM foci and boundaries of gray matter, white matter, and cerebrospinal fluid (CSF) in the MRI volume were segmented and rendered to VRML polygonal surfaces by marching cube algorithm. Line profiles of x and y-axis that represent real lengths on an image were acquired and their maximum lengths were the same as 211.67 mm. The real size vs. the rendered VRML surface size was approximately the ratio of 1 to 605.9. A VRML measuring tool was made and merged with previous VRML surfaces. User interface tools were embedded with Java Script routines to display MRI planar images as cross sections of 3D surface models and to set transparencies of 3D surface models. When transparencies of 3D surface models were properly controlled, a fused display of the brain geometry with 3D distributions of focal activated regions provided intuitively spatial correlations among three 3D surface models. The epileptic seizure focus was in the right temporal lobe of the brain. The real position of the seizure focus could be verified by the VRML measuring tool and the anatomy corresponding to the seizure focus could be confirmed by MRI planar images crossing 3D surface models. The VRML application developed in this study may have several advantages. Firstly, 3D fused display and control of anatomic and functional image were achieved on the m. Secondly, the vector analysis of a 3D surface model was defined by the VRML measuring tool based on the real size. Finally, the anatomy corresponding to the seizure focus was intuitively detected by correlations with MRI images. Our web based visualization of 3-D fusion image and its localization will be a help to online research and education in diagnostic radiology, therapeutic radiology, and surgery applications.