• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권4호
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• pp.308-316
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• 2006

Objectives Despite considerable advances in technique, experience and skill, the precise place of surgery in the treatment of facial nerve injury remains uncertain. We designed a facial nerve crush injury model in rats and evaluated the recovery of crushed nerve which is the most common injury type of facial nerve using adenovirus vector mediated in vivo gene transfer of Brain derived neurotrophic factor(BDNF). Materials and methods In 48 Sprague Dawley rats, we made a facial nerve crush injury model to main trunk before the furcation, and injected a $10^{11}$pfu adenoviral BDNF in experimental group(BDNF adenoviral injection group; ad-BDNF) and $3{\mu}l$ saline in control group(Saline injection group; saline). After a period of regeneration from 10 to 40 days, nerve regeneration was evaluated with functioinal test (vibrissae and ocular movement), electrophysiologic study(threshold, peak voltage, conduction velocity) and histomorphometric study of axon density. Results Vibrissae and ocular movement, threshold and conduction velocity improved as time elapse in both group, however axon density was increased significantly only in experimental group. Functional test in 10 days and 20 days showed no difference between experimental group and control group. Vibrissae movement, threshold, conduction velocity and axon density in 30 days revealed that the regeneration in quality of experimental group was significantly superior to that of control group. Conclusion In general, there is tendency for nerve regeneration in experimental group (BDNF-adenovirus injection group) during 40 days, functional recovery was detected successfully after facial nerve crush in 30 days postoperatively.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제27권1호
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• pp.72-81
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• 2016

Objectives: The purpose of this study was to evaluate anti-depressive effects of exercise on child and adolescent and its association with brain derived neurotrophic factor (BDNF). Methods: Twenty nine middle school boys (age $13.3{\pm}0.7$) were divided into two groups, 15 boys for control group and 14 in the experimental group. The control group participated in a regular exercise program, 3 times a week for 15 weeks. During the same period, the experimental group participated in an aerobic exercise program specifically designed to enhance anti-depressive effect of exercise. Serum BDNF level and its performance of each group on the Beck Depression Index (BDI), Children's Depression Inventory (CDI), Screen for Child Anxiety Related Emotional Disorders (SCARED), Aggression Questionnaire (AK-Q), and Stroop task were compared before and after the exercise program. Results: Scores of BDI, CDI, SCARED, and AK-Q were significantly lower in both groups after the exercise programs compared to those before the programs. The Stroop task performances were significantly improved after the programs. However, there were no significant differences between two exercise programs, except SCARED separation anxiety, AK-Q physical, and verbal aggression scores. Also, no association was found between serum BDNF level and anti-depressive effects of exercise. Conclusion: Our preliminary results suggest a possible effect of exercise on depression, anxiety, aggression, and cognition of child and adolescents.

• 한국수정란이식학회지
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• 제29권3호
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• pp.221-228
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• 2014

Despite that porcine spermatogonial stem cells (pSSCs) have been regarded as a practical tool for preserving eternally genetic backgrounds derived from pigs with high performance in the economic traits or phenotypes of specific human diseases, there were no reports about precise definition of niche conditions promoting proliferation and maintenance of pSSCs. Accordingly, we tried to determine niche conditions supporting proliferation and maintenance of undifferentiated pSSCs for short-term. For these, undifferentiated pSSCs were progressively cultured in different composition of culture medium, seeding density of pSSCs, type of feeder cells and concentration of growth factors, and then total number of and alkaline phosphatase (AP) activity of pSSCs were investigated at post-6 day culture. As the results, the culture of $4{\times}10^5$ pSSCs on mitotically in activated $2{\times}10^5$ STO cells in the mouse embryonic stem cell culture medium (mESCCM) supplemented with 30 ng/ml glial cell line-derived neurotrophic factor (GDNF) was identified as the best niche condition supporting effectively the short-term maintenance of undifferentiated pSSCs. Moreover, the optimized short-term culture system will be a basis for developing long-term culture system of pSSCs in the following researches.

• Korean Journal of Acupuncture
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• 제35권4호
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• pp.187-202
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• 2018

Objectives : Non-invasive transcranial electrical stimulation is one of therapeutic interventions to change in neural excitability of the cortex. Transcranial electro-acupuncture (TEA) can modulate brain functions through changes in cortical excitability as a model of non-invasive transcranial electrical stimulation. Some composites of fermented Scutellaria baicalenis (FSB) can activate intercellular signaling pathways for activation of brain-derived neurotrophic factor that is critical for formation of neural plasticity in stroke patients. This study was aimed at evaluation of combinatory treatment of TEA and FSB on behavior recovery and cortical neural excitability in rodent focal stroke model. Methods : Focal ischemic stroke was induced by photothrombotic injury to the motor cortex of adult rats. Application of TEA with 20 Hz and $200{\mu}A$ in combination with daily oral treatment of FBS was given to stroke animals for 3 weeks. Motor recovery was evaluated by rotating bean test and ladder working test. Electrical activity of cortical pyramidal neurons of stroke model was evaluated by using multi-channel extracellular recording technique and thallium autometallography. Results : Compared with control stroke group who did not receive any treatment, Combination of TEA and FSB treatment resulted in more rapid recovery of forelimb movement following focal stroke. This combination treatment also elicited increase in spontaneous firing rate of putative pyramidal neurons. Furthermore expression of metabolic marker for neural excitability was upregulated in peri-infract area under thallium autometallography. Conclusions : These results suggest that combination treatment of TEA and FSB can be a possible remedy for motor recovery in focal stroke.

• 대한한의학방제학회지
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• 제27권2호
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• pp.121-136
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• 2019

Objective : To investigate the effect of sihogayonggolmoryeotang (SY) on Single Prolonged Stress(SPS)-induced Post Traumatic Stress Disorder(PTSD). Method : To confirm the effects of SY on SPS-induced PTSD, Changes in body weight, sucrose intake open field test(OFT) and forced swimming test(FST)were observed. After behavioral tests, the plasma corticosterone(CORT) from the abdominal aorta, serotonin(5-HT) from prefrontal cortex, hippocampus, amygdala and striatum, norepinephrine(NE) and dopamine(DA) from hippocampus was measured by ELISA. mRNA expression of brain-derived neurotrophic factor(BDNF) and cAMP response element-binding protein(CREB) in hippocampus was measured by RT-PCR. Result : Weight change and sucrose intakes of rats in 14th day after the administration of SY were significantly increased in the SPS + SY450 group compared to the SPS group (p<0.05). Numbers of crossing in the central zone in the OFT were significantly increased in the SPS + SY450 group (p<0.05) compared with the SPS group. The immobility time of FST was significantly decreased in SPS + SY450 group compared with SPS group (p<0.05). The change of plasma CORT concentration was significantly decreased in SPS + SY450 group compared with that in SPS group (p<0.05). The change of 5-HT concentration was significantly increased in the SPS + SY450 group at hippocampus and amygdala compared with the SPS group (p<0.05). The concentration of DA was significantly increased in the SPS + SY450 group compared with the SPS group (p<0.05). The expression of BDNF and CREB were significantly increased in SPS + SY450 group compared with the SPS group (p<0.05). Conclusion : SY administration lowered the increase of CORT caused by PTSD and increases the 5-HT concentration and reversed the decreased expression of NE and DA and BDNF and CREB by PTSD. It is postulated that SY is effective in treating PTSD by restoring cognitive function, memory impairment, unstable emotional disturbances.

• Animal Bioscience
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• 제34권1호
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• pp.143-153
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• 2021

Objective: To explore the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in laying hens, an experiment was conducted to reveal the differences in histopathological observation and gene expression between FLHS group and normal group. Methods: We compared the histopathological difference using hematoxylin and eosin staining and proceeded with RNA sequencing of adipose tissue to search differentially expressed genes and enriched biological processes and pathways. Then we validated the mRNA expression levels by real-time polymerase chain reaction and quantified protein levels in the circulation by enzyme-linked immunosorbent assay. Results: We identified 100 differentially expressed transcripts corresponding to 66 genes (DEGs) were identified between FLHS-affected group and normal group. Seven DEGs were significantly enriched in the immune response process and lipid metabolic process, including phospholipase A2 group V, WAP kunitz and netrin domain containing 2, delta 4-desaturase sphingolipid 2, perilipin 3, interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and suppressor of cytokine signaling 3 (SOCS3). And these genes could be the targets of immune response and be involved in metabolic homeostasis during the process of FLHS in laying hens. Based on functional categories of the DEGs, we further proposed a model to explain the etiology and pathogenesis of FLHS. IL-6 and SOCS3 mediate inflammatory responses and the satiety hormone of leptin, induce dysfunction of Jak-STAT signaling pathway, leading to insulin resistance and lipid metabolic disorders. Conversely, CNTF may reduce tissue destruction during inflammatory attacks and confer protection from inflammation-induced insulin resistance in FLHS chickens. Conclusion: These findings highlight the therapeutic implications of targeting the JAK-STAT pathway. Inhibition of IL6 and SOCS3 and facilitation of CNTF could serve as a favorable strategy to enhance insulin action and improve glucose homoeostasis, which are of importance for treating obesity-related disorders for chickens.

• Journal of Ginseng Research
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• 제46권3호
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• pp.376-386
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• 2022

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

• 대한본초학회지
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• 제37권4호
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• pp.39-48
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• 2022

Objectives : In the present study, we assessed the effects of water extract of Ulmus davidiana(UED) on the learning and memory impairments induced by scopolamine in mice through its favorable acetylcholinesterase (AChE) activity and antioxidant effect. Methods : The memory and cognitive enhancing effect of the UDE was investigated using a passive avoidance test, the Morris water maze test and Y-maze test in mice. In addition, to examine the mechanism of UDE using acetylcholinesterase (AChE) and antioxidant activity. Results : The water extract of UDE (100, and 200 mg/kg) significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (P < 0.05). Moreover, UDE (100, and 200 mg/kg) also improved escape latencies in training trials and increased swimming times and distances within the target zone of the Morris water maze (P < 0.05). On the Y-maze test, UDE (100, and 200 mg/kg) also significantly reversed scopolamine-induced cognitive impairments in mice (P < 0.05). In an in vitro study, UDE was found to inhibit acetylcholinesterase, changes in neurotrophic factor (CREB), and antioxidant activity in a dose-dependent manner. Conclusions : The water extract of UDE dramatically possesses the anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent on the learning models. These results suggest that the administration of UDE enhances learning and memory, and that this effect is partially mediated by ERK-CREB-BDNF signaling and the survival of immature neurons.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.360-367
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• 2022

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor. Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion. KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.

• 대한한의학방제학회지
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• 제30권3호
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• pp.109-121
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• 2022

Objective : This study is conducted to investigate the effect of Astragali Radix on Post Traumatic Stress Disorder(PTSD) induced by the Single Proposed Stress(SPS). Methods : The experiment was conducted with five groups; SAL groups with only saline treatment, SPS group, SPS + ARX25 group, SPS + ARX50 group, and SPS + ARX100 group. After applying SPS, saline and ARX were administered for 14 days to identify the change of body weight, sucrose intake amount, and behavioral changes through Open Field Test(OFT) and Forced Swimming Test(FST). After the behavioral experiment, plasma corticosterone levels, serotonin, norepinephrine and dopamine concentrations were measured by enzyme-linked immunoassay in medical prefrontal cortex, hippocampus, and amygdala. Brain-derived neurotrophic factor(BDNF) in the hippocampus was measured using Reverse Transcription Polymerase Chain Reaction. Results : Weight change has significantly decreased in the SPS group compared to the SAL group(p<0.05). On day 14, the sucrose intake of rats has significantly increased in the SPS + ARX100 group compared to the SPS group(p<0.05). In OFT, the number of staying in the central space has significantly increased in the SPS + ARX100 group(p<0.01). In FST, immobility has significantly decreased in SPS + ARX50 group and SPS + ARX100 group(p<0.05). The concentration of serotonine, dopamine and BDNF expression has increased significantly in SPS + ARX100 group compared to SPS group(p<0.05) Conclusions : In the SPS-induced PTSD experiment, ARX increased sucrose intake and the numbers of crossing in the central zone space in OFT, decreased immobility time in FST, and increased concentration of serotonin, dopamine, and BDNF. It can be postulated that the ARX could be effective for the treatment of PTSD.