• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3721-3725
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• 2016

The liver fluke Opisthorchis viverrini is a serious health problem in Thailand. Infection is associated with cholangiocarcinoma (CCA), endemic among human populations in northeast and north Thailand where raw fish containing fluke metacercariae are frequently consumed. Recently, Thailand public health authorities have been organized to reduce morbidity and mortality particularly in the northeast through O. viverrini and CCA screening projects. Health modification is one of activities included in this campaign, but systemic guidelines of modifying and developing health behavior among liver fluke and CCA prevention in communities towards health belief and social support theory are still various and unclear. Here we review the guidelines for modifying and developing health behavior among populations in rural communities to strengthen understanding regarding perceived susceptibility, severity, benefits, and barriers to liver fluke and CCA prevention. This model may be useful for public health officers and related organizations to further health behavior change in endemic areas.

• Molecules and Cells
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• 제44권12호
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• pp.893-899
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• 2021

BLT2 is a low-affinity receptor for leukotriene B₄, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB₄ [leukotriene B₄] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-lipoxygenase (5-LO) and 12-LO, which are synthesizing enzymes for LTB₄ and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1β [interleukin-β] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

• Journal of Microbiology and Biotechnology
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• 제26권10호
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• pp.1817-1823
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• 2016

Areca nut (AN) chewing is a habit in many countries in Central, Southern, and Southeast Asia. It is strongly associated with the occurrence of oral, pharyngeal, and esophageal cancer as well as systemic inflammation. However, the association between AN intake and the development of gastric lesions has not yet been identified. The aim of this study was to investigate the effect of AN on gastric diseases using a mouse model for Helicobacter pylori infection. We studied four groups of mice: those fed a normal diet (ND), those fed a diet containing 2.5% AN (AD), those fed ND and infected with H. pylori PMSS1 strain (ND/HP), and those fed AD and infected with H. pylori PMSS1 strain (AD/HP). Food intake and body weight were monitored weekly during the experiments. At 10 weeks, the mice were sacrificed, and the stomach weight, H. pylori colonization, and gastric inflammation were evaluated. The stomach weight had increased significantly in the ND/HP and AD/HP groups along with increases in H. pylori colonization; however, there was no significant difference between these two groups with respect to stomach weight and colonization. On histological grading, mononuclear cell infiltration was severer in the AD/HP group than in the ND/HP group. These data suggest that chronic gastric inflammation was aggravated by AN treatment in the mice with H. pylori-induced gastric lesions. Furthermore, as previously suggested, this animal model is useful to determine the effect of potential carcinogens on gastric lesions induced by H. pylori infection.

• 한국산학기술학회논문지
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• 제19권1호
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• pp.121-126
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• 2018

중환자실에 입원한 환자들의 구강위생은 매우 중요한 문제이다. 중환자들은 기본적으로 면역이 저하된 환자들로 각종 병원성 세균들에 의한 감염의 기회가 높기 때문이다. 구강문제는 감염의 1차 방어선인 구강이 감염의 우선적인 부위로 작용될 뿐 아니라 전신감염을 초래하기도 한다. 본 연구에서는 중증환자의 구강청소를 용이하게 하는 마우스 피스 형태의 새로운 진공 구강 세정기 설계에 관한 연구를 수행하였다. 이중 구조 방식의 세정기와 표준 치아 모델로써 3D CAD 모델링 및 유동해석 모델을 수립하고 압력 및 유동특성을 분석하였다. 세정기 내부의 압력은 거의 일정한 분포를 보였으나, 속력분포의 경우 치아 안쪽과 바깥쪽에서 큰 차이를 보였다. 치아 안쪽에서도 가운데 부분의 속도가 가장 높고 가운데에서 멀어질수록 속력이 감소하는 특성을 보였다. 세정기의 흡입관과 배출관을 바꾸어 해석한 결과 치아 바깥쪽 가운데 부분의 속도가 가장 높게 나타났다. 세정기의 효과를 높이기 위해서 흡입-배출을 교대로 바꾸는 교번식을 제안하고, 어금니 부위의 속력을 높이는 설계 보완이 요구된다.

• Journal of Microbiology and Biotechnology
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• 제10권6호
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• pp.865-872
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• 2000

Helocobacter phylori is the major cause of gastritis, peptic ulcer, and a principal risk factor for gastric cancer. As the firs step towards a vaccine against H. pylori infection, Hy.pylori urease was expressed and purified as a recombinant apoenzyme (rUrease) in E. coli. In order to develop an effective immunization protocol using rUrease, the host immune responses were evaluated after the oral immunization of mice with rUrease preparations plus cholera toxin relative to various conditions, such as the physical nature of the antigen, the frequency of the booster immunization, the dose of the antigen, and the route of administration. The protective efficacy was assessed using a quantitative culture following an H. pylori SS1 challenge. It was demonstrated that rUrease, due to its particulated nature, was more superior than the UreB subunit as a vaccine antigen. The oral immunization of rUrease elicited significant systemic and secretory antibody responses, and activated predominantly Th2-type cellular responses. The bacterial colonization was significantly reduced (~100-fold) in those mice immunized with three or four weekly oran doses of rUrease plus cholera toxin (p<0.05), when compared to the non-immunized/challenged controls. The protection correlated well with the elicited secretory IgA level against rUrease, and these secretory antibody responses were highly dependent on the frequency of the booster immunization, yet unaffected by the dose of the antigen (25-200$\mu\textrm{g}$). These results demonstrate the remarkable potential of rUrease as a vaccine antigen, thereby strengthening the possibility of developing an H. pylori vaccine for humans.

• Biomolecules & Therapeutics
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• 제24권4호
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• pp.387-394
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• 2016

Sepsis, a serious clinical problem, is characterized by a systemic inflammatory response to infection and leads to organ failure. Toll-like receptor (TLR) signaling is intimately implicated in hyper-inflammatory responses and tissue injury during sepsis. Histone deacetylase (HDAC) inhibitors have been reported to exhibit anti-inflammatory properties. The aim of this study was to investigate the hepatoprotective mechanisms of trichostatin A (TSA), a HDAC inhibitor, associated with TLR signaling pathway during sepsis. The anti-inflammatory properties of TSA were assayed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP), a clinically relevant model of sepsis. The mice were intraperitoneally received TSA (1, 2 or 5 mg/kg) 30 min before CLP. The serum and liver samples were collected 6 and 24-h after CLP. TSA inhibited the increased production of tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6 in LPS-stimulated RAW264.7 cells. TSA improved sepsis-induced mortality, attenuated liver injury and decreased serum TNF-${\alpha}$ and IL-6 levels. CLP increased the levels of TLR4, TLR2 and myeloid differentiation primary response protein 88 (MyD88) protein expression and association of MyD88 with TLR4 and TLR2, which were attenuated by TSA. CLP increased nuclear translocation of nuclear factor kappa B and decreased cytosolic inhibitor of kappa B ($I{\kappa}B$) protein expression, which were attenuated by TSA. Moreover, CLP decreased acetylation of $I{\kappa}B$ kinase (IKK) and increased association of IKK with $I{\kappa}B$ and TSA attenuated these alterations. Our findings suggest that TSA attenuates liver injury by inhibiting TLR-mediated inflammatory response during sepsis.

• 약학회지
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• 제40권1호
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• pp.102-111
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• 1996

LB10522 is a new parenteral broad spectrum cephalosporin with a catechol moiety at C-7 position of beta-lactam ring. This compound can utilize tonB-dependent iron transp ort system in addition to porin proteins to enter bacterial periplasmic space and access to penicillin-binding proteins (PBPs) which are the lethal targets of ${\beta}$-lactam antibiotics. The chelating activity of LB10522 to metal iron was measured by spectrophotometrically scanning the absorbance from 200 to 900nm. When $FeCl_3$ was added, optical density was increased between 450 and 800nm. LB10522 was more active against gram-negative strains in iron-depleted media than in iron-replete media. This is due to the increased expression of iron transport channels in iron-depleted condition. LB10522 showed a similar activity against E. coli DC2 (permeability mutant) and E. coli DCO (wild type strain) in both iron-depleted and iron-replete media, indicating a minimal permeaility barrier for LB10522 uptake. LB10522 had high affinities to PBP 3 and PBP 1A, 1B of E. coli. By blocking these proteins, LB10522 caused inhibition of cell division and the eventual death of cells. This result was correlated well with the morphological changes in E. coli exposed to LB10522. Although the in vitro MIC of LB10522 against P. aeruginosa 1912E mutant (tonB) was 8-times higher than that of the P. aeruginosa 1912E parent strain, LB10522 showed a similar in vivo protection efficacy against both strains in the mouse systemic infection model. This result suggested that tonB mutant, which requires a high level of iron for normal growth, might have a difficulty in surviving in their host with an iron-limited environment.

• Toxicological Research
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• 제34권3호
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• pp.221-229
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• 2018

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권4호
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• pp.300-305
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• 2005

Purpose: For the reconstruction of maxillofacial defect created by trauma, infection, or tumor etc, the role of microvascular anastomosis or vessel graft has been increased. Many methods has been tried to increase the success rate of microvascular anastomosis. Various anticoagulants and thrombolytic agents have been used to reduce the failure rate of microvascular anastomosis and avoid re-operation. Many drugs, however, have been used in the limited cases because most of these drugs may cause complications, such as allergy, fever or systemic bleeding. This study was performed to evaluate the influence of the Argatroban on patency and thrombosis in microvascular anastomosis when it is used for local irrigation or general administration. Materials & methods: Eight mature rabbits, weighing 2kg, were used. After exposing both femoral veins, the artificial thrombotic model was made by crushing injury using a smooth needle holder, and the transverse incision were made on femoral vein. The animals were divided into 4 groups according to Argatroban administration methods; control group (n=4), topical irrigation of lumen with saline solution; experimental group 1 (n=4), topical irrigation of lumen with Argatroban saline solution; experimental group 2 (n=4), topical irrigation of lumen with heparin followed by intravenous injection of Argatroban; experimental group 3 (n=4), topical irrigation of lumen with Argatroban followed by IV of Argatroban. Microvascular anastomosis was done with 10-0 Ethilon. The patency was evaluated by empty-and-refill test 30 minutes and 3 days after microanastomosis. The thrombus formation was examined 3 days after microanastomosis by surgical microscope. The histologic findings were also examined. Results: 1. Thirty minutes after microvascular anastomosis, the patency of all experimental groups was better than that of control group, but there was no significant difference among groups. 2. Three days after microvascular anastomosis, the patency of all experimental groups was more improved than that of control group (p<0.05). There was no significant difference among experimental groups. 3. Three days after microvascular anastomosis, the amount of thrombus in all experimental groups was less than that of control group (p<0.05). There was no significant difference among experimental groups. 4. Histologically, a lot of luminal thrombus was observed around sutured area in control group. Few luminal thrombus was observed in all experimental groups. The necrotic changes were observed on the sutured vein wall in all specimens. Conclusion: These results indicate that topical irrigation and/or intravenous administration of Argatroban is effective in improving patency and preventing thrombus formation after microvascular anastomosis.

• 생명과학회지
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• 제29권6호
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• pp.747-753
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• 2019

인지기능 저하는 장 단기 기억 및 주의력 소실과 우울증, 불안증의 증가를 특징으로 한다. 또한, 인지기능 저하는 알츠하이머, 파킨슨병과 같은 다양한 퇴행성 뇌질환과 연관되어 있다. 경제적 부담, 안전 위협을 포함하는 인지기능 저하와 관련된 사회적 문제는 고령화가 진행됨에 따라 증가하고 있다. 이러한 문제를 해결하기 위해 전 세계적으로 많은 연구가 수행되고 있다. 일반적으로 인지기능 저하를 유발할 가능성이 있는 원인으로는 노화에 따른 대사 및 호르몬 불균형, 감염, 약물 오남용, 신경세포 손상 등이 알려져 있지만 다양한 요인이 관련되어 있으므로 원인 규명이 어려운 한계점 때문에 뚜렷한 치료전략 수립이 어려운 실정이다. 최근의 연구에 따르면 퇴행성 뇌질환 발생의 원인과 이에 대한 치료전략 수립에 있어서 장내미생물의 역할이 중요하게 제시되고 있다. 특히, 알츠하이머병과 파킨슨병에서 장내미생물 조성의 변화 및 이들에 의한 대사산물에 따른 분자생물학적, 신경행동학적 증상의 변화가 밝혀졌다. 알츠하이머병 동물모델에서 장내미생물의 변화는 NMDA 수용체와 글루탐산의 변화를 통해 기억능력 소실을 야기하였다. 반면, 알츠하이머병 동물모델에 프로바이오틱스를 투여하였을 때, 비정상적인 신경학적 행동이 유의적으로 감소하였다. 파킨슨병은 장내미생물 군집의 변화와 직접적인 연관성을 보였으며 이는 이차적 증상인 변비 발생에도 영향을 미치는 것으로 나타났다. 파킨슨병 동물모델에 투여한 프로바이오틱스는 단쇄지방산 중 하나인 뷰티르산 증가를 통한 신경세포 보호효과를 나타내었다. 또한, 알츠하이머병과 파킨슨병에서 뇌-혈관장벽의 기능이상이 밝혀졌으며, 뇌-혈관장벽 변화는 장내미생물 불균형에 의한 전신성 염증에 따른 미세소관의 파괴 및 투과성 증가와 연관된 것으로 나타났다. 더불어 장내미생물 대사과정에서 생성된 대사산물은 퇴행성 뇌질환의 발생과 치료에 영향을 미친다. 본 논문에서는 인지기능 저하의 진행을 지연시킴으로써 심화를 방지할 수 있는 효과적인 접근법을 제시하기 위하여 인지기능 저하와 장내미생물의 연관성을 심층적으로 고찰하여 치료적 대안으로 제시하고자 한다.