• Nonlinear Functional Analysis and Applications
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• 제26권3호
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• pp.629-648
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• 2021

In this paper, we study a within-host mathematical model of HCV infection and carry out mathematical analysis of the global dynamics and bifurcations of the model in different parameter regimes. We explore the effect of reverse transcriptase inhibitors (RTI) on spontaneous HCV clearance. The model can produce all clinically observed patient profiles for realistic parameter values; it can also be used to estimate the efficacy and/or duration of treatment that will ensure permanent cure for a particular patient. From the results of the model, we infer possible measures that could be implemented in order to reduce the number of infected individuals.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.272-281
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• 2020

Environmental agents, including viral and bacterial infectious agents, are involved in the alteration of physicochemical and biological parameters in the nasal epithelium. Hyaluronan (HA) has an important role in the regulation of tissue healing properties. High molecular weight HA (HMW-HA) shows greater anti-inflammatory responses than medium molecular weight HA (MMW-HA) and low molecular weight HA (LMW-HA). We investigated the effect of HMW-HA, MMW-HA and LMW-HA on the regulation of physicochemical and biological parameters in an "in vitro" model that might mimic viral infections of the nasal epithelium. Human nasal epithelial cell line RPMI2650 was stimulated with double-stranded RNA (dsRNA) Poly(I:C) for 5 days in air-liquid-interface (ALI) culture (3D model of airway tissue). dsRNA Poly(I:C) treatment significantly decreased transepithelial electrical resistance (TEER) in the stratified nasal epithelium of RPMI2650 and increased pH values, rheological parameters (elastic G' and viscous G''), and Muc5AC and Muc5B production in the apical wash of ALI culture of RPMI2650 in comparison to untreated cells. RPMI2650 treated with dsRNA Poly(I:C) in the presence of HMW-HA showed lower pH values, Muc5AC and Muc5B production, and rheological parameters, as well as increased TEER values in ALI culture, compared to cells treated with Poly(I:C) alone or pretreated with LMW-HA and MMW-HA. Our 3D "in vitro" model of epithelium suggests that HMW-HA might be a coadjuvant in the pharmacological treatment of viral infections, allowing for the control of some physicochemical and biological properties affecting the epithelial barrier of the nose during infection.

• 대한본초학회지
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• 제28권4호
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• pp.57-62
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• 2013

Objectives : Lonicerae Japonicae Flos (LJF) has been shown anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits skin injury against oxidative stress in human keratinocyte, HaCaT cells. The purpose of this study was to evaluate the protective effects of LJF against hydrogen peroxide($H_2O_2$)-induced oxidative stress in human keratinocytes, HaCaT cells. Methods : To evaluate out the protective effects of LJF on oxidative injury in HaCaT cells, an oxidative stress model of HaCaT cells was established under a suitable concentration (500 ${\mu}M$) hydrogen peroxide. HaCaT keratinocyte cells were pre-treated with LJF (0.1, 0.25 or 0.5 mg/ml), and then stimulated with $H_2O_2$. Then, the cells were harvested to measure the cell viability, DNA damage, and release of reactive oxygen species (ROS). Results : LJF (0.1, 0.25 or 0.5 mg/ml) itself did not show any significant toxicity in HaCaT cells. The treatment of $H_2O_2$ caused the oxidative stress, leading to the cell death, and DNA injury. However, pretreatment with LJF reduced cell death, and DNA injury. The stimulation of $H_2O_2$ on HaCaT cells resulted in excessive release of ROS, which is the main factor of oxidative stress. The excessive release of ROS was inhibited by LJF treatment significantly. Conclusions : These results could suggest that LJF exhibited the protective effects of HaCaT cells against $H_2O_2$-induced oxidative stress by inhibiting ROS release. It could be explained that LJF inhibit skin damages against oxidative stress. Thus, LJF would be useful for the development of drug or cosmetics treating skin troubles.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVI)
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• pp.35-35
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• 2005

Recombinant human $interferon-{\beta}-1a(rIFN-{\beta})$ is a single glycosylated protein (at N80, 1N) with anti-viral activity. However, present drugs have a relatively short serum half-life of $rIFN-{\beta}$, thus patients suffer from frequent $infections.^{1)}$ To improve its half-life, eight glycosylation analogs were prepared, which have additional N-linked glycosylation consensus sequences (N-X-T/S) within the $IFN-{\beta}$ molecule and/or at C-terminal. Each $rIFN-{\beta}$ analog was examined for the presence of additional N-linked glycosylation and the maintenance of anti-viral activity in CHO cells. The molecular weights of five analogs were not changed. However, two analogs, R27T within $rIFN-{\beta}$ (27 kDa, 2N) and GNITVNITV at C-terminal (29kDa, 2N), showed a clear increase in molecular weights, compared to native $rIFN-{\beta}$ (23 kDa, 1N). And another combined analog of R27T+GNITVNITV showed increased molecular weight (33 kDa, 3N). It was confimed that the molecular weight increment of analogs was caued by the N-linked glycosylation with the treatment of N-glycansae. In the case of anti-viral activity, the analog GNITVNITV showed a reduction in activity compared to native $IFN-{\beta}$, whereas the analogs R27T and R27T+GNITVNITV were found to have distinctly increased activities. Pharmacokinetic study in rats also disclosed that the analogs R27T and R27T+GNITVNITV had 2 3 fold increased serum half-life, respectively. In conclusion, the addition of N-linked glycosylation in $rIFN-{\beta}$ increased serum half-life, thereby its less frequent administration will be expected.

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.172-177
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• 2020

Influenza viruses cause respiratory diseases in humans and animals with high morbidity and mortality rates. Conventional anti-influenza drugs are reported to exert side effects and newly emerging viral strains tend to develop resistance to these commonly used agents. Fritillaria thunbergii (FT) is traditionally used as an expectorant for controlling airway inflammatory disorders. Here, we evaluated the therapeutic effects of FT extracts against influenza virus type A (H1N1) infection in vitro, in ovo, and in vivo. In the post-treatment assay, FT extracts showed high CC50 (7,500 ㎍/ml), indicating low toxicity, and exerted moderate antiviral effects compared to oseltamivir (SI 50.6 vs. 222) in vitro. Antiviral activity tests in ovo revealed strong inhibitory effects of both FT extract and oseltamivir against H1N1 replication in embryonated eggs. Notably, at a treatment concentration of 150 mg/kg, only half the group administered oseltamivir survived whereas the FT group showed 100% survival, clearly demonstrating the low toxicity of FT extracts. Consistent with these findings, FT-administered mice showed a higher survival rate with lower body weight reduction relative to the oseltamivir group upon treatment 24 h after viral infection. Our collective results suggest that FT extracts exert antiviral effects against influenza H1N1 virus without inducing toxicity in vitro, in ovo or in vivo, thereby supporting the potential utility of FT extract as a novel candidate therapeutic drug or supplement against influenza.

• 대한한방내과학회지
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• 제30권2호
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• pp.270-287
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• 2009

Objective : Yinjinchunggan-tang(YJCGT) is reported previously as having theraputic effects on hepatitis such as anti-implammatory, anti-apoptotic, anti-viral(HBV), etc. Though this prescription is not studied on its anti-fibrogenic effect, it is still expected to have the effect in the liver. Thus, this study was performed to investigate the anti-fibrogenic effect of YJCGT on thioacetamide(TAA)-induced liver fibrosis in rats. Method: Rat liver fibrosis was induced by intraperitoneal TAA injection(150mg/kg) 3 times a week for 5 weeks. After the YJCGT (YJCGT 1g/kg, YJCGT 2g/kg)-treatment, body weight, liver and spleen weights, liver function test, the complete blood count and the portal pressure were studied. In addition, gene expressions of ASMA, procollagen type Ia2, MMP2, TIMP1 and TIMP2, all of which are known to be associated with liver fibrosis, were analyzed by RT-PCR. After YJCGT (YJCGT 1g/kg, YJCGT 2g/kg) treatment, percentages of collagen in TAA-induced rat liver tissue were measured by image analyzer. Results : The body weight of the normal group increased more than that of the control and YJCGT-treated groups. The AST level of the YJCGT lg/kg-treated group significantly decreased compared to that of the control. The ALT and the GGT levels of the YJCGT 2g/kg-treated group significantly increased compared to those of the control. In the YJCGT-treated groups. WBC, RBC and Hgb elevated by TAA injection decreased but platelet count increased. In the YJCGT lg/kg-treated group, the portal pressure elevated by TAA injection significantly decreased. The significant decreases in the gene expressions of procollagen type Ia2, MMP2 and TIMP2 were observed in the YJCGT-treated groups. In histological findings. TAA injections caused severe liver fibrosis, but the YJCGT treatment significantly reduced the amounts of hepatic collagens. Conclusions: These results suggest that YJCGT has beneficial effects on the treatment of patients with liver cirrhosis as well as chronic hepatitis. Further study should be done to decide the optimal concentration of the YJCGT for the treatment of liver cirrhosis.

• 생명과학회지
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• 제30권3호
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• pp.221-229
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• 2020

비만의 원인은 유전적, 대사적 및 환경적 요인 등 다양한 가운데 특정 세균 및 바이러스 감염에 의해 비만이 유도되는 것이 확인되며 이러한 비만은 감염성 비만이라고 한다. 또한 감염성 비만을 유발하는 병원체 가운데 아데노바이러스 36이 밝혀졌다. 현재 비만 예방 및 치료제 개발에 대한 연구가 활발히 진행되는 가운데 감염성 비만의 예방 및 치료제 개발에 대한 연구는 불충불한 실정이다. 이와 관련하여 본 연구에서는 제주에 자생하는 조록나무 잎을 이용하여 분획물을 제조하고, 비만을 유도하는 사람아데노바이러스 36 증식에 미치는 영향을 평가하고자 한다. A549세포에 사람아데노바이러스 36을 감염시키고, 조록나무 잎 에틸 아세테이트 분획물을 처리하여 바이러스 역가를 측정하였다. 그 결과, 조록나무 잎 에틸 아세테이트 분획물을 처리한군에서 농도 의존적으로 바이러스 증식 억제능을 확인하였다. 또한 조록나무 에틸 아세테이트 분획물의 물질 분리를 한 결과, quercitrin이 확인되었으며, 표준물질 quercitrin의 사람아데노바이러스 36에 대한 증식 억제능을 확인하였다. 이러한 결과 조록나무 잎 에틸 아세테이트 분획물은 감염성 비만 치료제 개발을 위한 효과적인 후보 물질로 사료되며, 본 연구는 감염성 비만 치료제 개발을 위한 기초 자료로 유용할 것으로 보인다.

• 한국어병학회지
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• 제26권2호
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• pp.111-116
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• 2013

본 연구에서는 4급 암모늄에 속하는 didecyldimethylammonium chloride (DDAC)와 유카추출물 (Yucca extract)의 합제인 아쿠아 팜세이프$^{(R)}$의 어류 질병 병원체에 대한 살균효과를 확인하기 위하여 농림수산검역검사본부의 소독제 효력시험 중 세균 및 바이러스 소독제 효력시험에 따라 수행하였다. 소독제와 병원체를 증류수, 경수 그리고 유기물 조건에서 반응시킨 후, 중화액을 이용하여 중화시킨 다음, 중화된 용액을 배지 및 주화세포에서 접종시켜 세균의 성장 및 세포변성효과를 통해 소독제의 효력배수를 결정하였다. 본 연구의 결과, 아쿠아 팜세이프$^{(R)}$는 식중독을 일으키는 공시균주 살모넬라균 (S. typhimurim)에 비하여, 어병세균이 30~40배 이상 높은 희석농도에서 소독효과를 나타내었으며, VHSV에 대하여서는 2,000~3,600배의 유효한 효력배수를 나타내었다. 따라서, 향후, 야외적용시험을 통해 실제 적용에 따른 효과를 확인할 필요가 있을 것으로 사료된다.

• 대한한의정보학회지
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• 제21권1호
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• pp.14-22
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• 2015

Flavonoids show diverse bioactivities, such as anti-oxidant, anti-cancer, anti-allergic, anti-inflammatory, and anti-viral. Quercetin is one of the flavonoids present in a wide range of plants, especially onions and consumed all over the world. Recently, it is known that quercetin induces mitochondrial biogenesis in vivo and in vitro. However, detail mechanism of these actions remains unknown. We investigated quercetin's effects on mitochondrial biogenesis in HepG2 cells, and determined the mechanisms involved. We found that quercetin treatment induced the expression of mitochondrial biogenesis activators, $PGC-1{\alpha}$, NRF-1, TFAM, and mitochondrial proteins, cytochorome c and complex IV (COXIV). Moreover, amount of mitochondrial DNA was also increased by quercetin. Quercetin has been known to induce heme oxygenase (HO)-1 in several types of cells. Here, we found quercetin induces HO-1, and inhibition of HO-1 or CO, which is product of HO-1, decreased quercetin-induced mitochondrial biogenesis such as induction of $PGC-1{\alpha}$, NRF-1, TFAM, cytochorome c, COXIV, and mitochondrial DNA. These findings imply that quercetin can increase mitochondrial biogenesis via HO-1/CO system. High glucose results in dysfunction of mitochondria biogenesis. In the present study, 25 mM glucose decreased mitochondrial biogenesis and this damage was restored by quercetin. Conversely, inhibition of HO-1 or CO inhibited quercetin-induced mitochondrial biogenesis rescue. These results suggest that quercetin enhances mitochondrial biogenesis via HO-1/CO system and hence, can rescue mitochondria from damage by high glucose.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.641-647
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• 2017

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.