• 대한의용생체공학회:의공학회지
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• 제43권1호
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• pp.19-26
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• 2022

The Comprehensive in vitro Proarrhythmic Assay(CiPA) project was launched for solving the hERG assay problem of being classified as high-risk groups even though they are low-risk drugs due to their high sensitivity. CiPA presented a protocol to predict drug toxicity using physiological data calculated based on the in-silico model. in this study, features calculated through the in-silico model are analyzed for correlation of changing action potential in the near future, and features are verified through predictive performance according to drug datasets. Using the O'Hara Rudy model modified by Dutta et al., Pearson correlation analysis was performed between 13 features(dVm/dtmax, APpeak, APresting, APD90, APD50, APDtri, Ca_peak, Ca_resting, CaD90, CaD50, CaDtri, qNet, qInward) calculated at 100 pacing, and between dVm/d_{tmax_repol} calculated at 1,000 pacing, and linear regression analysis was performed on each of the 12 training drugs, 16 verification drugs, and 28 drugs. Indicators showing high coefficient of determination(R²) in the training drug dataset were qNet 0.93, AP resting 0.83, APDtri 0.78, Ca resting 0.76, dVm/dt_max 0.63, and APD90 0.61. The indicators showing high determinants in the validated drug dataset were APDtri 0.94, APD90 0.92, APD50 0.85, CaD50 0.84, qNet 0.76, and CaD90 0.64. Indicators with high coefficients of determination for all 28 drugs are qNet 0.78, APD90 0.74, and qInward 0.59. The indicators vary in predictive performance depending on the drug dataset, and qNet showed the same high performance of 0.7 or more on the training drug dataset, the verified drug dataset, and the entire drug dataset.

• 한국물환경학회지
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• 제38권1호
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• pp.19-30
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• 2022

Climate change has increased the average air temperature. Rising air temperature are absorbed by water bodies, leading to increasing water temperature. Increased water temperature will cause eutrophication and excess algal growth, which will reduce water quality. In this study, long-term trends of air and water temperatures in the Han-river basin over the period of 1997-2020 were discussed to assess the impacts of climate change. Future (~2100s) levels of air temperature were predicted based on the climate change scenarios (Representative concentration pathway (RCP) 2.6, 4.5, 6.0, and 8.5). The results showed that air and water temperatures rose at an average rate of 0.027℃ year^-1 and 0.038℃ year^-1 respectively, over the past 24 years (1997 to 2020). Future air temperatures under RCP 2.6, 4.5, 6.0, and 8.5 increased up to 0.32℃ 1.18℃, 2.14℃, and 3.51℃, respectively. An increasing water temperature could dissolve more minerals from the surrounding rock and will therefore have a higher electrical conductivity. It is the opposite when considering a gas, such as oxygen, dissolved in the water. Water temperature also governs the kinds of organisms that can live in rivers and lakes. Fish, insects, zooplankton, phytoplankton, and other aquatic species all have a preferred temperature range. As temperatures get too far above or below this preferred range, the number of individuals of the species decreases until finally there are none. Therefore, changes of water temperature that are induced by climate change have important implications on water supplies, water quality, and aquatic ecosystems of a watershed.

• 생명과학회지
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• 제32권4호
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• pp.290-297
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• 2022

본 연구에서는 전통적인 방법으로 제조한 황칠 식초의 유기산 함량을 측정하고 항산화 효과와 항당뇨 효과, 알코올 대사 효소 활성 및 HepG2 세포에 대한 간보호 효과를 알아보았다. 황칠 식초의 유기산 분석결과 acetic acid가 91.72 mg/ml로 가장 높았고, 그 다음으로는 lactic acid (7.31 mg/ml), malic acid (1.36 mg/ml), succinic acid (1.20 mg/ml) 순으로 나타났다. 황칠 식초의 총 폴리페놀 함량은 13.73 ㎍ TAE/ml으로 나타났다. DPPH radical 소거능은 농도 의존적으로 증가하였으며 60% 농도에서 76.04%로 나타났고, SOD 활성은 60% 농도에서 95.14%로 나타났다. 황칠 식초 10% 농도에서의 α-glucosidase 저해 효과는 98.94%로 높게 나타났다. 알코올 분해 활성을 알아보기 위해 ADH 및 ALDH 활성을 측정한 결과, 두 가지 효소 모두 황칠 식초의 농도 의존적으로 증가하였으며 60% 농도에서의 ADH 및 ALDH 활성은 각각 43.62% 및 60.39%로 나타났다. 황칠 식초 0.6% 농도에서는 tacrine으로 유도된 HepG2 세포주에 대하여 간보호 활성이 높게 나타났다. 이상의 결과에서 전통적인 방법으로 제조한 황칠 식초는 기능성 건강 음료로서 활용 가능성이 높은 것으로 생각된다.

• Journal of Ginseng Research
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• 제46권2호
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• pp.255-265
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• 2022

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.246-256
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• 2022

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

• 한국미생물·생명공학회지
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• 제50권2호
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• pp.301-309
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• 2022

본 연구에서는 제럼본에 처리에 의해 유도된 H. pylori 유전자의 전사적 변화를 분석하였다. NGS를 사용하여 RNA 발현 변화를 분석한 다음 그 결과를 검증하기 위해 RT-PCR을 수행하였다. NGS 분석 결과, 1,632개의 유전자 중 총 23개가 제럼본 처리에 의해 유의하게 발현이 변화된 특이발현 유전자로 분석되었다. DNA 복제와 전사, 병원성 인자 및 T4SS 성분과 관련된 유전자 중 10개는 현저하게 하향 조절되었고 5개는 상향 조절되었다. RT-PCR을 이용하여 유전자의 발현 수준을 재확인하였고 그 결과, 14개 유전자에서 NGS와 동일하게 발현 양상이 변화하였다. RT-PCR은 제럼본 처리에 의해 10개의 유전자(dnaE, dnaQ, rpoA, rpoD, secA, flgE, flhA, virB5, virB8, virB9)의 발현 감소와 4개의 유전자(flaA, flaB, virB4, virD4)의 발현 증가를 보였다. 이러한 본 연구의 결과는 제럼본이 다양한 H. pylori의 병원성과 관련된 인자들을 조절함으로써 H. pylori 감염의 잠재적인 치료제가 될 수 있음을 시사한다.

• Journal of Ginseng Research
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• 제46권6호
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• pp.780-789
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• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

• BMB Reports
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• 제54권5호
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• pp.266-271
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• 2021

Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

• 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.

• 대한본초학회지
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• 제28권4호
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• pp.93-100
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• 2013

Objectives : This study was to evaluate the anti-inflammatory and anti-pruritic effects of WSY-1075 composited with Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Ginseng Radix, Cervi parvum Cornu and Cinnamomi Cortex in rat peritoneal mast cells (RPMCs) and scratching mouse model. Methods : WSY-1075 was prepared by extracting with 30% ethanol. In the present study, we investigated the effect of WSY-1075 on the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and histamine in rat peritoneal mast cells (RPMCs) activated with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187, and on the scratching behavior in mice treated with pruriogens. Results : WSY-1075 was not cytotoxic effect in used all concentration. PMA plus A23187 treatment significantly increased TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production compared with media control in RPMCs. However, TNF-${\alpha}$, $IL1{\beta}$ and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by WSY-1075 (200 ${\mu}g/mL$ and 400 ${\mu}g/mL$). WSY-1075 also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, WSY-1075 administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin and substence P) in ICR mice. Conclusion : These results suggest that WSY-1075 administration (200 mg/kg or 400 mg/kg) has the anti-inflammatory and anti-pruritic effects on the activated rat peritoneal mast cell and mouse pruritus. WSY-1075 has a potential use as a composition of medicinal plants for treatment against inflammation- and pruritus-related disease.