• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.59-68
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• 2021

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

• Journal of Ginseng Research
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• 제45권1호
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• pp.66-74
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• 2021

Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. Results: RGAE (at 30㎍/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = ㎂/㎠)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 ㎛ vs control, 3.9+/-0.09 ㎛; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제47권6호
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• pp.445-453
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• 2021

Objectives: Periodontitis is the most common chronic disease that causes tooth loss and is related to systemic diseases such as cardiovascular disease and diabetes. An objective indicator of the current activity of periodontitis is necessary. Soluble forms of the receptor for advanced glycation end products (sRAGE) are markers that reflect the status of inflammatory diseases. In this study, the relationship between sRAGE and periodontitis was analyzed to determine whether it can be used to diagnose the current state of periodontitis. Patients and Methods: Eighty-four patients without any systemic diseases were diagnosed with periodontitis using three classifications of periodontitis. Demographics and oral examination data such as plaque index (PI), bleeding on probing (BOP) index, and probing pocket depth (PPD) were analyzed according to each classification. In addition, correlation and partial correlation between sRAGE and the values indicating periodontitis were analyzed. Results: In each classification, the level of sRAGE tended to decrease if periodontitis was present or severe, but this change was not statistically significant. sRAGE and periodontitis-related variables exhibited a weak correlation, among which the BOP index showed a relatively strong negative correlation (ρ=-0.20). Based on this, on analyzing the correlation between the BOP index and sRAGE in the group with more severe periodontitis (PPD≥5 mm group, severe group of AAP/CDC [American Academy of Periodontology/Centers for Disease Control and Prevention], periodontitis group of López), the correlation further increased (ρ=-0.23, -0.40, -0.50). Partial correlation analysis of the sRAGE and BOP index showed a stronger negative correlation (ρ=-0.36, -0.55, -0.45). Conclusion: sRAGE demonstrated a tendency to decrease upon increased severity of periodontitis according to the classifications used. Above all, the correlation with the BOP index, which reflects the current state of periodontitis, was higher in the group with severe periodontitis. This indicates that the current status of periodontitis can be diagnosed through sRAGE.

• Animal Bioscience
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• 제35권1호
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• pp.87-95
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• 2022

Objective: This study was conducted to investigate the effect of associating calcium butyrate with tannin extract, compared to an antimicrobial on the growth performance, incidence of diarrhea, intestinal histology, immune-expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNF-α) in piglets. Methods: Seventy-two piglets (36 barrows and 36 gilts) weaned at 28±2 d and initial body weight of 7.17±1.07 kg were allocated to 3 treatments in a randomized complete block design with 8 replicates per treatment and 3 animals per experimental unit. Treatments were composed of NC, negative control: basal diet without additives; PC, positive control: basal diet + 40 mg/kg of colistin sulfate; or BT, basal diet + calcium butyrate + tannin extract. The butyrate and tannin inclusion levels were 0.15% in the pre-starter phase and 0.075% in the starter phase. Incidence of diarrhea was monitored daily, and on d 14 and 35 of experiment, 1 animal from each experimental unit was slaughtered to collect intestinal samples. Results: No significant differences were observed for growth performance. The butyrate-and tannin-based additive resulted in reduced (p<0.05) incidence of diarrhea in piglets during d 1 to 14 and d 1 to 35 in comparison with the other treatments. Piglets that consumed the diet containing the calcium-butyrate and tannin showed a lower (p<0.05) crypt depth in the duodenum than those receiving the NC treatment at 14 d of experimentation. The BT treatment provided a lower (p<0.05) immune-expression of COX-2 at 14 d and TNF-α at 35 d in the duodenum. Conclusion: Association between calcium butyrate and tannin extract resulted in a significant decrease in the incidence of diarrhea and inflammatory process in the duodenum of piglets. Therefore, calcium-butyrate combined with tannin could be a part of an alternative program to reduce the use of antimicrobials in the diet of weaned piglets.

• Journal of Microbiology and Biotechnology
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• 제32권9호
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• pp.1154-1167
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• 2022

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta_1-42 (Aβ_1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ_1-42-induced cognitive impairment in mice.

• 한국식품위생안전성학회지
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• 제37권3호
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• pp.198-205
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• 2022

본 연구에서는 경증 또는 중등도 간기능 이상 소견자를 대상으로 ESE의 간기능 개선 효과를 평가하기 위해 시험식품군과 대조식품군으로 나누어 단일기관, 위약대조, 무작위배정, 이중눈가림 평행 인체적용시험으로 연구를 수행하였다. 12주간 ESE 420 mg(210 mg/포, 1일 2회)을 함유한 시험식품 또는 대조식품을 섭취하였을 때 ESE의 간 기능 개선 유효성과 안전성을 평가하였다. 유효성 평가 결과, 섭취 후 시험식품군은 대조식품군과 비교하여 ALT, AST, γ-GT 수준이 유의하게 감소하였다. 반면, 지질대사 지표는 두 군간의 의미 있는 차이를 보이지 않았다. 또한, 비알콜성 시험대상자군을 대상으로 분석하였을 때도 ALT 및 AST 수준이 유의하게 감소하였으며 γ-GT의 경우 감소하는 경향성을 보였다. 안전성 평가로서 혈액, 소변, 활력 징후를 검사한 결과 대부분 항목에서 시험식품군과 대조식품군 군간 차이가 없었으며 몇몇 유의성이 나타난 지표도 임상적 의미는 없었다. 따라서 ESE는 간기능 개선에 도움을 줄 수 있을 것으로 보이며 안전한 식품 소재로 판단된다.

• Journal of Nutrition and Health
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• 제56권4호
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• pp.361-376
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• 2023

본 연구에서는 햄프씨드 오일이 고콜레스테롤혈증을 개선시키는 지 확인하기 위하여 Sprague-Dawley rat에 1.25% 콜레스테롤식이를 8주 동안 급여하였으며, 햄프씨드 오일을 두 농도 (저농도, 고농도)로 경구 투여한 후 혈액, 조직 분석을 통하여 지질개선 및 염증 완화 효과를 발휘하는지 분석하였다. 햄프씨드 오일 식이는AMPK/SREBP-2 경로를 경유하여 혈중 콜레스테롤의 합성을 효과적으로 억제하였으며, PI3IK/Akt/NF-κB의 경로를 유의하게 억제하여 항염증 효과를 발휘함을 알 수 있었다. 이러한 신호전달의 경로는 간 조직에서 지질축적의 감소와도 관련이 있는 것으로 보인다. 이상의 결과를 종합해보면 햄프씨드 오일은 고콜레스테롤혈증의 예방 및 치료를 위한 잠재적 후보소재로서 가능성이 있음을 시사한다.

• IMMUNE NETWORK
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• 제23권6호
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• 한방재활의학과학회지
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• 제34권1호
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• pp.65-81
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• 2024

Objectives This study aimed to understand the general research trends, applicated disease, and methodology of transcutaneous/percutaneous vagus nerve stimulation, contemplating its clinical use in traditional Korean medicine and future research directions. Methods A scoping review was conducted following Arksey and O'Malley Framework Stage and adhering to the PRISMA extension for scoping reviews: checklist and explanation. Papers published until October 30, 2023, were investigated across 10 databases (PubMed, Embase, Scopus, Web of Science, China National Knowledge Infrastructure, Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, KMbase, Science ON, Research Information Sharing Service. The search terms used were 'Transcutaneous/Percutaneous vagus nerve stimulation'. Results Since 2021, the application of transcutaneous/percutaneous vagus nerve stimulation for musculoskeletal symptoms has been actively researched, predominantly in Asia (37%), Europe (37%), and North America (21%). All 19 papers were part of clinical studies. Chronic pain was noted that most applied disease, it also was found to potentially aid in acute post-surgical pain relief. Major assessment tools include not only simple pain metrics but also pain perception, vagal nerve tension, quality of life, and inflammatory markers. Most procedures were carried out through the ear, which offers a favorable site for therapeutic stimulation without notable side effects. And parameter analysis, frequencies typically ranged around 25 Hz to 30 Hz, while pulse widths were commonly set at 250 ㎲ or 300 ㎲. Conclusions Transcutaneous/percutaneous vagus nerve stimulation is easily accessible through acupuncture in Korean medicine. Therefore, if future studies establish parameters and clinical significance, it could be utilized as a therapeutic modality.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.369-378
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• 2023

본 연구는 청가시덩굴 에탄올 추출물을 이용하여 3T3-L1 지방전구세포에서 지방세포를 통해 항비만 활성을 확인하고자 하였다. 청가시덩굴 에탄올 추출물에 의한 지방세포 분화 억제 활성 및 지방형성에 미치는 영향을 확인하기 위해 3T3-L1 지방전구세포에 분화를 유도하여 추출물을 농도별로 처리하였다. 그 결과 청가시덩굴 에탄올 추출물 처리 시 지방세포 분화 및 세포 내 중성지방 축적 수준이 농도 의존적으로 감소하였다. 이러한 지방형성 억제 효과가 어떠한 작용기전에 의해 유도되는지 확인하기 위해 청가시덩굴 추출물과 그로부터 분리된 화합물인 acertannin을 이용하여 지방세포 분화 조절인자들의 유전자 및 단백질 발현을 확인하고자 하였다. 청가시덩굴 에탄올 추출물은 지방형성 및 지방산 합성 관련 인자인 PPARγ, C/EBPα, ADD1/SREBP1c, FAS, aP2의 유전자 및 단백질 발현을 유의적으로 억제하였다. 이러한 결과들로 볼 때 청가시덩굴 에탄올 추출물은 지방세포분화 및 지방축적 인자의 조절 효과를 나타냄으로써 산림자원의 항비만 및 고지혈증 개선 기능성 소재로의 활용 가능성을 확인하였다.