• Journal of Veterinary Science
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• 제24권1호
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• pp.2.1-2.14
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• 2023

Background: Hypothermia is a crucial environmental factor that elevates the risk of cardiovascular disease, but the underlying effect is unclear. Objectives: This study examined the role of cold stress (CS) in cardiac injury and its underlying mechanisms. Methods: In this study, a chronic CS-induced myocardial injury model was used; mice were subjected to chronic CS (4℃) for three hours per day for three weeks. Results: CS could result in myocardial injury by inducing the levels of heat shock proteins 70 (HSP70), enhancing the generation of creatine phosphokinase-isoenzyme (CKMB) and malondialdehyde (MDA), increasing the contents of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1) interleukin1b (IL-1β), IL-18, IL-6, and triggering the depletion of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Multiple signaling pathways were activated by cold exposure, including pyroptosis-associated NOD-like receptor 3 (NLRP3)-regulated caspase-1-dependent/Gasdermin D (GSDMD), inflammation-related toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK), as well as oxidative stressinvolved thioredoxin-1/thioredoxin-interacting protein (Txnip) signaling pathways, which play a pivotal role in myocardial injury resulting from hypothermia. Conclusions: These findings provide new insights into the increased risk of cardiovascular disease at extremely low temperatures.

• 한국ITS학회 논문지
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• 제3권2호
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• pp.55-68
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• 2004

본 연구에서는 고속도로 교통정보의 적정 가치를 산정하고자 비 시장재의 가치 추정에 많이 적용되고 있으며 환경경제학 분야에서 발전되어온 조건부 가치측정법을 사용하였다. 비 시장재인 고속도로 교통정보의 적정한 가치를 추정하기 위하여 가상 시나리오를 설계하고 설문의 신뢰도를 높이기 위하여 교통관련 분야의 전공자를 설문자로 하였으며 일대일 면접을 실시하였다. 또한 질문 방법으로 개방형 질문과 지불카드 방법을 혼용하여 사용하였다. 교통정보의 가치추정식으로 다중회귀 모형을 사용하여 교통정보의 가치에 영향을 미치는 정도를 알아보았다. 연구결과 정보별 1회 이용시 지불하고자 하는 가격은 현재 제공되는 가격보다 다소 비싼 가격을 지불할 의사를 보였으나 전체적인 가격을 묻는 월정액은 낮게 지불의사를 표시하였다. 이는 개별적인 정보에 대한 가치나 유용성은 수긍하나 공공의 정보는 무료로 제공되어야 한다는 다수 이용객들의 인식이 지불 의사를 낮게 표시한 것으로 판단된다.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.62-64
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• 2008

A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.295-302
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• 2021

Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons's disease, which is aggravated by systemic inflammation.

• 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.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.1011-1018
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• 1997

연구배경 : 이 연구의 목적은 자동생검장치를 이용한 경피적 폐생검의 유용성과 안전성에 대하여 알아보기 위함이다. 방 법 : 저자들은 폐종괴를 가진 114명의 환자를 대상으로 18-gauge 자동생검장치(ASAP 18, Microvasive)를 사용하여 경피적 폐생검올 시행하였다. 이중 16명에서는 1회의 반복생검을 하여 총 130예의 폐생검의 이루어졌다. 130예중 83예는 숙련된 방사건과의사에 의하여 나머지 47예는 비교적 덜 숙련된 여러명의 방사선과의사들에 의하여 생검이 시행되었다. 모든 생검은 투시유도하에 시술되었다. 결 과 : 130예중 128예(98%)에서 2mm 이상의 충분한 검체를 얻을 수 있었다. 전체 114 명중 97명(85%)에서 조직학적 진단을 내릴 수 있었으며, 이중 악성질환을 가진 89명중 78명(88%)과 양성질환을 가진 21명 중 19명(90%)에서 특이적 진단을 얻을 수 있었다. 조직학적 진단이 가능하였던 폐암에서는 전례(74/74)에서 소세포암과 비소세포암의 구분이 가능하였다. 진단에 필요한 조직을 얻는데 숙련자와 비숙련자간의 유의한 차이는 없었다. 총 130예중 생검후 13예(10%)에서 기흉이 발생하였으나 이중 2예(2%)에서만 삽관술을 필요로 하였고, 7예(5%)에서 경미한 객혈이 발생하였으나 치료를 요한 경우는 1예도 없었다. 결 론 : 자동생검장치를 이용한 경피적 폐생검은 악성과 양성 폐질환의 특이적 진단을 내리는데 유용한 검사이며 합병증의 발생 빈도도 낮은 안전한 시술이다.

• 대한임상검사과학회지
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• 제52권3호
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• pp.253-260
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• 2020

알츠하이머 병은 인지 기능 저하로 인한 치매 발생으로 설명할 수 있는 만성 및 진행성 신경 퇴행성 질환이다. 알츠하이머 병의 특징은 세포 외 및 세포 내 아밀로이드 플라크의 형성이다. 아밀로이드 베타는 알츠하이머 병의 특징이며 미세아교세포는 아밀로이드 베타의 존재하에 활성화될 수 있다. 활성화된 미세아교세포는 전 염증성 사이토카인을 분비한다. 게다가, S100A9는 염증의 중요한 선천성 전 염증 기여자이며 알츠하이머 병에 잠재적인 기여자로 알려져 있다. 이 연구는 아밀로이드 베타 및 S100A9이 처리된 BV-2 세포에서 염증반응 및 NLRP3 인플라마솜 활성화에 대한 메트포르민 및 알파리포산의 효과를 조사했다. 메트포르민과 알파-리포산은 종양 괴사 인자-알파 및 일터루킨-6와 같은 염증성 사이토카인을 약화시킨다. 또한 메트포르민과 알파-리포산은 JNK, ERK, p38의 인산화를 억제하고, NF-kB 경로 및 NLRP3 인플라마솜의 활성화를 억제했다. 또한 메트포르민과 알파-리포산은 M1 표현형인 ICAM1의 수준을 감소시킨 반면 M2 표현형인 ARG1은 증가시켰다. 이러한 발견은 메트포르민과 알파-리포산이 아밀로이드베타 및 S100A9에 의한 신경 염증 반응에 대한 치료제가 될 수 있음을 시사한다.

• Journal of Preventive Medicine and Public Health
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• 제34권1호
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• pp.89-99
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• 2001

Objectives : To describe the characteristics of a mumps epidemic in Cheju-do, 1998 and to identify the risk factors associated with mumps infection. Methods : To estimate attack rate, previously collected data from the Nationally Notifiable Communicable Disease Reporting System and School Health Reporting System, temporarily administered by Division of Education. as well as additional surveillance data were used. In order to identify the clinical characteristics and risk factors associated with mumps, we conducted a questionnaire survey in 17 schools (9 elementary, 4 middle, and 4 high schools) among a population that included healthy students. Results : From March 3 to August 31, 2,195 cases of mumps were identified, and patients under 20 years of age accounted for 2,162 cases (attack rate 13.2, 95% CI 12.6-13.7/1,000). The attack rate for the population under 20 years of age was the highest in Nam county (44.7/1,000), nod in the 7-12 years old sub-group(>20.0/1,000). There was no sexual difference. 80.5% and 59.7% of patients presented periauricular and submandibular swelling respectively. Aseptic meningitis was a complication in 2.9% of cases, orchitis in 1.3%, epididymitis in 0.9% and oophoritis in 0.6% respectively. The overall MMR vaccination rate was 59.1% and it decreased in accordance with increasing age. In students aged 10 years old or below, household contact and MMR vaccination status was significantly associated with infection, and only among students with household contact, the risk of one dose MMR(OR=10.22, 95% CI 2.92-35.78) and non-vaccination (OR=11.62, 95% CI 1.96-68.96) was significantly greater when. compared with that of two dose vaccination. Among students aged 11 years old or above, household contact history was significantly associated and MMR vaccination status was not associated. Conclusions : Low vaccination rate and vaccine failure were thought to predispose the population for this large outbreak. To prevent sustained mumps outbreaks, a second MMR vaccination should be encouraged and catch up vaccinations should be given to elderly children who remain susceptible.

• 한국식품영양과학회지
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• 제42권10호
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• pp.1576-1584
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• 2013

이상의 결과를 종합해 볼 때, 높은 수준의 포도당 섭취는 공복혈당과 공복혈당면적을 높이고 혈중 인슐린 농도와 아티포넥틴의 수준을 낮추어 혈당조절 능력을 억제시켰다. 반면, 높은 수준의 과당 섭취는 인슐린을 요구하지 않는 과당대사의 특이성으로 인해 혈당조절에는 효과적으로 보인다. 그러나 고과당 섭취는 간 조직 및 혈중 중성지방의 농도를 높이고 염증조절복합체 구성단백질의 발현을 조절하여 전염증인자의 발현을 증가시켰다. 이는 간조직에 있어 과당이 포도당보다 높은 수준의 염증반응을 유도하여 NAFLD의 발병과 진행에 보다 유의적인 영향을 준다는 것을 보여준다. 본 연구의 제한점은 일상에서 과당이나 포도당을 단독으로 섭취하는 경우가 드물다는 점과 3주라는 짧은 중재기간에 의한 실험 결과라는 것이다. 앞으로의 연구는 단순당을 장기간 섭취했을 때 혈청과 간 조직을 포함한 다른 대사 관련조직에서 나타나는 변화에 초점을 맞출 필요가 있으며, 염증조절복합체가 염증인자의 발현을 증가시키는 기전을 구체화하는 것이 요구된다.

• Journal of Periodontal and Implant Science
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• 제47권5호
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• pp.292-311
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• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.