• 생명과학회지
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• 제31권6호
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• pp.595-602
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• 2021

사람의 장내 미생물은 숙주의 대사 조절에서 중요한 역할을 한다. 장내 미생물 균총의 불균형은 비만, 대사 증후군과 밀접하게 병리학적, 생리학적 상호작용을 한다. A. muciniphila는 최근 인간의 대변에서 분리되었으며, 장내 미생물의 약 1-4%를 차지하는 우점균이다. A. muciniphila 유래 외막(external membran) 단백질 Amuc_1100과 세포외 소포(EVs)의 이용은 비만치료를 위한 새로운 전략이 될 수 있다. A. muciniphila는 비만과 같은 대사 장애치료를 위한 차세대 probiotics로 고려되고 있다. F. prausnitzii는 next-generation probiotic로서 건강한 성인의 경우 장내미생물 균총의 약 5%를 차지하며 성인 장 건강의 지표이다. F. prausnitzii는 butyrate-producing bacterium로서 항염증 효과를 나타내며, 면역 질환과 당뇨병 치료를 위한 next-generation probiotics로 기대된다. Postbiotics는 probiotics에 의해 분비되는 세포 상층액에 포함된 대사산물의 복잡한 혼합물이다. 반면, parabiotics는 probiotics를 불활성화 시킨 미생물 세포이다. Paraprobiotics와 postbiotics는 probiotics에 비해 명확한 화학구조(clear chemical structures)와 안전한 투여 용량(safety dose parameters), 장기간의 유통 기간(longer shelf life) 등 많은 장점을 가지고 있어서 probiotics를 대체할 수 있는 잠재력을 가지고 있다. 장 생태계의 불균형을 정상적으로 복원하기 위해서 장내 공생 박테리아(commensal bacteria) 중 next-generation probiotics (NGPs)를 사용하는 것이 가장 자연스런 방법이다. 따라서 next-generation probiotics 를 대상으로 parabiotics와 postbiotics와 같은 새로운 식품이나 약품으로 개발하는 것이 필요하다.

• Journal of Periodontal and Implant Science
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• 제52권3호
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• pp.206-219
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• 2022

Purpose: This study was performed to evaluate the influence of local application of thymoquinone (TQ) on bone healing in experimental bone defects infected with Porphyromonas gingivalis (PG). Methods: Forty-two female rats were randomly divided into 6 groups. A bone defect was created on the right tibia of all animals. The PG, PG/collagen membrane (COL) and PG/TQ/COL groups were infected with PG. In the COL and PG/COL groups, the defects were covered with a COL; in the TQ/COL and PG/TQ/COL groups, the defects were covered with a TQ-containing COL. After 28 days, all animals were sacrificed. Quantitative measurements of new bone formation and osteoblast lining, as well as semiquantitative measurements of capillary density and tissue response, were analyzed. Furthermore, the presence of bacterial infections in defect areas was evaluated. Results: The new bone formation, osteoblast number, and capillary density were significantly higher in the TQ groups than in the control groups (P<0.001, P<0.001, and P<0.01, respectively). In a comparison between the TQ/COL group, with a TQ-containing COL (TQ/COL), and the PG-infected TQ-containing COL (PG/TQ/COL) group, the newly formed bone and capillary density were higher in the TQ/COL group (P<0.01). When the control group was compared to the PG, PG/COL, and PG/TQ/COL groups in terms of tissue response, the differences were statistically significant (P<0.001, P=0.02, and P=0.041, respectively). The intensity of the inflammatory cell reaction was higher in the PG, PG/COL, and PG/TQ/COL groups (P<0.05). Conclusions: Within the limitations of this study, the local application of a TQ-containing COL positively affected bone healing even if the bone defects were infected. The results suggest that TQ increased angiogenesis and showed promise for accelerating bone defect healing. Further research is warranted to support these findings and reach more definitive conclusions.

• 대한본초학회지
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• 제36권6호
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• Advances in nano research
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• 제13권6호
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• pp.575-585
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• 2022

Due to its biofilm formation and colonization of the osteocyte-lacuno canalicular network (OLCN), Staphylococcus aureus (S.aureus) implant-associated bone infection (SIABI) is difficult to cure thoroughly, and may occur recurrently subsequently after a long period dormant. It is essential to explore an alternative therapeutic strategy that can eradicate the pathogens in the infected foci. To address this, the polymethylmethacrylate (PMMA) bone cement and Fe3O4 nanoparticles compound cylinder were developed as implants based on their size and mechanical properties for the alternative magnetic field (AMF) induced thermal ablation, The PMMA mixed with optimized 2% Fe₃O₄ nanoparticles showed an excellent antibacterial efficacy in vitro. It was evaluated by the CFU, CT scan and histopathological staining on a rabbit 1-stage transtibial screw model. The results showed that on week 7, the CFU of infected soft tissue and implants, and the white blood cells (WBCs) of the PMMA+2% Fe₃O₄+AMF group decreased significantly from their controls (p<0.05). PMMA+2% Fe₃O₄+AMF group did not observe bone resorption, periosteal reaction, and infectious reactive bone formation by CT images. Further histopathological H&E and Gram Staining confirmed there was no obvious inflammatory cell infiltration, neither pathogens residue nor noticeably burn damage around the infected screw channel in the PMMA+2% Fe₃O₄+AMF group. Further investigation of nanoparticle distributions in bone marrow medullary and vital organs of heart, liver, spleen, lung, and kidney. There were no significantly extra Fe₃O₄ nanoparticles were observed in the medullary cavity and all vital organs either. In the current study, PMMA+2% Fe₃O₄+AMF shows promising therapeutic potential for SIABI by providing excellent mechanical support, and promising efficacy of eradicating the residual pathogenic bacteria in bone infected lesions.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.335-345
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• 2022

Pyroptosis is an inflammatory form of programmed cell death that is linked with invading intracellular pathogens. Cardiac pyroptosis has a significant role in coronary microembolization (CME), thus causing myocardial injury. Tanshinone IIA (Tan IIA) has powerful cardioprotective effects. Hence, this study aimed to identify the effect of Tan IIA on CME and its underlying mechanism. Forty Sprague-Dawley (SD) rats were randomly grouped into sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA groups. Except for the sham group, polyethylene microspheres (42 ㎛) were injected to establish the CME model. The Tan-L and Tan-H groups received intraperitoneal Tan IIA for 7 days before CME. After CME, cardiac function, myocardial histopathology, and serum myocardial injury markers were assessed. The expression of pyroptosis-associated molecules and TLR4/MyD88/NF-κB/NLRP3 cascade was evaluated by qRT-PCR, Western blotting, ELISA, and IHC. Relative to the sham group, CME group's cardiac functions were significantly reduced, with a high level of serum myocardial injury markers, and microinfarct area. Also, the levels of caspase-1 p20, GSDMD-N, IL-18, IL-1β, TLR4, MyD88, p-NF-κB p65, NLRP3, and ASC expression were increased. Relative to the CME group, the Tan-H and Tan-L groups had considerably improved cardiac functions, with a considerably low level of serum myocardial injury markers and microinfarct area. Tan IIA can reduce the levels of pyroptosis-associated mRNA and protein, which may be caused by inhibiting TLR4/MyD88/NF-κB/NLRP3 cascade. In conclusion, Tanshinone IIA can suppress cardiomyocyte pyroptosis probably through modulating the TLR4/MyD88/NF-κB/NLRP3 cascade, lowering cardiac dysfunction, and myocardial damage.

• 생명과학회지
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• 제33권3호
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• pp.287-294
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• 2023

건강한 adipose tissue는 대사 항상성 통해 비만을 막는데 중요하다고 할 수 있다. Adipose tissue는 포도당과 지질 대사를 통해 에너지 균형에 중요한 역할을 한다. 영양분 상태에 따라, adipose tissue는 지질을 저장하여 커지기도 하고, 지질 분해를 통해 에너지를 소비하기도 한다. 게다가, adipose tissue는 호르몬 분비기관으로 작용이 부각되고 있다. 다양한 adipose tissue 호르몬이 존재하며, metabolic signaling을 통해 다른장기와 조직에 영향을 준다. 예를 들면, adipose tissue에서 분비하는 대표적인 펩타이드 호르몬(adipokine)은 섭식조절을 위해 뇌의 중추신경을 자극한다. 또한 adipocytes도 염증성 cytokines을 분비하여 adipose tissue의 immune cells을 표적으로 한다. 당연하게도, adipocytes는 지질에서 만들어지는 호르몬(lipokine)이 분비되어 특정 수용체와 결합하여 paracrine 및 endocrine으로 영향을 준다. 이러한 adipose tissue 호르몬에 의한 장기 조직 간의 상호작용을 이해하기 위해서는, 세부적인 adipocytes 및 다른 표적 세포에서 metabolic sig- naling이 규명되어야 한다. 그러므로, 과체중이나 비만의 건강하지 못한 adipose tissue에서는 metabolic sig- naling의 비정상적인 조절이 일어난다고 할 수 있다. 새로운 adipose metabolic signaling을 표적으로 하는 치료제는 항 비만 약물개발을 이끌어 낼 수 있다. 본 총설논문은 비만과 대사질환 관점에서 adipose tissue 호르몬과 metabolic signaling의 최신 연구결과를 요약 정리한다.

• Journal of Ginseng Research
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• 제47권2호
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• pp.337-346
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• 2023

Background: Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated. Methods: We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs. Results: Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-I to LC3-II and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence. Conclusion: Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.

• 대한한의학방제학회지
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• 제31권1호
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• pp.53-65
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• 2023

Objectives : Present study investigated the hepatoprotective effects and the optimal mixing ratio of fermented Schizandrae Fructus Pomace (fSFP) and Hoveniae Semen Cum Fructus (HSCF) extract combination in carbon tetrachloride (CCl₄)-induced acute liver injury mice. Methods : ICR mice were orally administered with 200 mg/kg of fSFP, HSCF and mixtures of fSFP and HSCF [MSH (w:w); 1:1, 1:2, 1:4, 1:6, 2:1, 4:1, 6:1, and 8:1] for 7 consecutive days. Silymarin (100 mg/kg) was administered as a reference drug. 0.5 mL/kg of CCl₄ was injected intraperitoneally to induce acute liver injury. Body weight gain, relative liver weight, serum chemistry, histopathological analysis, and hepatic endogenous antioxidants capacities were observed. Results : All diverse combinations of MSH significantly reduced relative liver weight increase by CCl₄. In addition, MSH administrations significantly decreased the elevation of serum alanine aminotransferase and aspartate aminotransferase activities by CCl₄. Histopathological observation indicated that all MSH treatments significantly reduced the increase of degenerated hepatocytes, inflammatory cell infiltration, and histological activity index score by CCl₄. Moreover, all MSH administrations reduced the elevation of malondialdehyde contents, and ameliorated the reduction of hepatic glutathione contents, superoxide dismutase activity, and catalase activity. Among the various mixing ratio of MSH combinations, MSH 1:1 and 2:1 showed the most potent anti-oxidative stress, and hepatoprotective effect. Conclusion : Present results suggest that 1:1 and 2:1 combinations of MSH is promising herbal formulation with the hepatoprotective effect against oxidative stress.

• 생명과학회지
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• 제33권9호
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• pp.703-712
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• 2023

기존 혈관에서 새로운 혈관을 형성하는 혈관 신생은 혈관 신생 조절인자에 의해 조절되는 다단계 과정이며 배아 발달, 만성 염증 및 상처 복구를 포함한 다양한 생리학적 과정에 필수적이다. 혈관 신생의 조절장애는 암, 자가 면역 질환, 류마티스 관절염, 심혈관 질환 및 상처 치유 지연과 같은 많은 질병을 유발한다. 그러나 효과적인 혈관신생 억제 약물은 제한되어 있으며, 최근 연구에서는 천연 자원에서 잠재적인 약물후보를 식별하는 데 중점을 두고 있다. 예를 들어, 해양 천연물은 항암, 항산화, 항염증, 항바이러스 및 상처 치유 효과를 입증했다. 따라서 본 연구에서는 톳(갈조류) 추출물의 혈관 신생 억제 효과를 확인했습니다. H. fusiformis 추출물은 인간 제대 정맥 내피 세포(HUVECs)에서 세포 이동, 침윤 및 관 형성을 억제하며, 동시에 Matrigel 겔 플러그 분석을 통해 생체 내 혈관 신생을 억제를 확인했다. 또한, 톳 추출물 처리 후 VEGF, Erk, Akt의 활성이 감소하는 것을 확인했다. 이 결과를 토대로 H. fusiformis 추출물이 in vitro 및 in vivo 혈관 신생을 억제함을 시사한다.

• Restorative Dentistry and Endodontics
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• 제48권1호
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• pp.6.1-6.14
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• 2023

Objectives: This study evaluated the effects of high-plasticity mineral trioxide aggregate (MTA-HP) on the activity of M1 and M2 macrophages, compared to white MTA (Angelus). Materials and Methods: Peritoneal inflammatory M1 (from C57BL/6 mice) and M2 (from BALB/c mice) macrophages were cultured in the presence of the tested materials. Cell viability (MTT and trypan blue assays), adhesion, phagocytosis, reactive oxygen species (ROS) production, and tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β production were evaluated. Parametric analysis of variance and the non-parametric Kruskal-Wallis test were used. Results were considered significant when p < 0.05. Results: The MTT assay revealed a significant decrease in M1 metabolism with MTA-HP at 24 hours, and with MTA and MTA-HP later. The trypan blue assay showed significantly fewer live M1 at 48 hours and live M2 at 48 and 72 hours with MTA-HP, compared to MTA. M1 and M2 adherence and phagocytosis showed no significant differences compared to control for both materials. Zymosan A stimulated ROS production by macrophages. In the absence of interferon-γ, TNF-α production by M1 did not significantly differ between groups. For M2, both materials showed higher TNF-α production in the presence of the stimulus, but without significant between-group differences. Likewise, TGF-β production by M1 and M2 macrophages was not significantly different between the groups. Conclusions: M1 and M2 macrophages presented different viability in response to MTA and MTA-HP at different time points. Introducing a plasticizer into the MTA vehicle did not interfere with the activity of M1 and M2 macrophages.