• 제목/요약/키워드: Therapeutic vaccine

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Antibiotic resistance in Neisseria gonorrhoeae: broad-spectrum drug target identification using subtractive genomics

  • Umairah Natasya Mohd Omeershffudin;Suresh Kumar
    • Genomics & Informatics
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    • 제21권1호
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    • pp.5.1-5.13
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    • 2023
  • Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.

Re-defining T-Cell Exhaustion: Subset, Function, and Regulation

  • Se Jin Im;Sang-Jun Ha
    • IMMUNE NETWORK
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    • 제20권1호
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    • pp.2.1-2.19
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    • 2020
  • Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

Bioactive Lipids and Their Derivatives in Biomedical Applications

  • Park, Jinwon;Choi, Jaehyun;Kim, Dae-Duk;Lee, Seunghee;Lee, Bongjin;Lee, Yunhee;Kim, Sanghee;Kwon, Sungwon;Noh, Minsoo;Lee, Mi-Ock;Le, Quoc-Viet;Oh, Yu-Kyoung
    • Biomolecules & Therapeutics
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    • 제29권5호
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    • pp.465-482
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    • 2021
  • Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

토픽모델링을 활용한 COVID-19 학술 연구 기반 연구 주제 분류에 관한 연구 (A study on the classification of research topics based on COVID-19 academic research using Topic modeling)

  • 유소연;임규건
    • 지능정보연구
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    • 제28권1호
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    • pp.155-174
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    • 2022
  • 2020년 1월부터 2021년 10월 현재까지 COVID-19(치명적인 호흡기 증후군인 코로나바이러스-2)와 관련된 학술 연구가 500,000편 이상 발표되었다. COVID-19와 관련된 논문의 수가 급격하게 증가함에 따라 의료 전문가와 정책 담당자들이 중요한 연구를 신속하게 찾는 것에 시간적·기술적 제약이 따르고 있다. 따라서 본 연구에서는 LDA와 Word2vec 알고리즘을 사용하여 방대한 문헌의 텍스트 자료로부터 유용한 정보를 추출하는 방안을 제시한다. COVID-19와 관련된 논문에서 검색하고자 하는 키워드와 관련된 논문을 추출하고, 이를 대상으로 세부 주제를 파악하였다. 자료는 Kaggle에 있는 CORD-19 데이터 세트를 활용하였는데, COVID-19 전염병에 대응하기 위해 주요 연구 그룹과 백악관이 준비한 무료 학술 자료로서 매주 자료가 업데이트되고 있다. 연구 방법은 크게 두 가지로 나뉜다. 먼저, 47,110편의 학술 논문의 초록을 대상으로 LDA 토픽 모델링과 Word2vec 연관어 분석을 수행한 후, 도출된 토픽 중 'vaccine'과 관련된 논문 4,555편, 'treatment'와 관련된 논문 5,791편을 추출한다. 두 번째로 추출된 논문을 대상으로 LDA, PCA 차원 축소 후 t-SNE 기법을 사용하여 비슷한 주제를 가진 논문을 군집화하고 산점도로 시각화하였다. 전체 논문을 대상으로 찾을 수 없었던 숨겨진 주제를 키워드에 따라 문헌을 분류하여 토픽 모델링을 수행한 결과 세부 주제를 찾을 수 있었다. 본 연구의 목표는 대량의 문헌에서 키워드를 입력하여 특정 정보에 대한 문헌을 분류할 수 있는 방안을 제시하는 것이다. 본 연구의 목표는 의료 전문가와 정책 담당자들의 소중한 시간과 노력을 줄이고, 신속하게 정보를 얻을 수 있는 방법을 제안하는 것이다. 학술 논문의 초록에서 COVID-19와 관련된 토픽을 발견하고, COVID-19에 대한 새로운 연구 방향을 탐구하도록 도움을 주는 기초자료로 활용될 것으로 기대한다.

쯔쯔가무시병의 임상 양상에 대한 소아와 성인의 비교 (A Comparison of Clinical Manifestations of Patients with Tsutsugamushi Disease between Children and Adults)

  • 호요한;박기철;장영택
    • Pediatric Infection and Vaccine
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    • 제21권2호
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    • pp.104-113
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    • 2014
  • 목적: 본 연구는 최근 10년 동안 전주 예수병원에 쯔쯔가무시병으로 입원한 환자를 조사하여 소아와 성인의 임상 양상을 비교하고자 하였다. 방법: 2003년 1월부터 2012년 12월까지, 쯔쯔가무시병의 진단 기준에 포함되는 768명의 환자를 후향적으로 검토하여, 소아 49명, 성인 719명의 임상적 특징과 검사소견 및 합병증 등을 분석 비교하였다. 결과: 연도별 환자의 증가 추세는 소아와 성인 모두에서 뚜렷하게 보이지 않았고, 10월과 11월에 환자가 가장 많이 발생하였다. 남녀비에서 소아는 남아가 많은 반면에, 성인은 여자가 많았고, 거주 지역은 소아가 성인에 비해 도시가 더 많았다. 증상은 소아에서 발진과 가피가 많았고, 근육통은 성인에서 더 많았다. 검사상 소아는 빈혈이 많은 반면에, 혈소판, 간기능, 신기능의 이상 소견이 적었다. 입원 기간과 합병증에서는 성인보다 양호한 결과를 보였다. 소아에서 독시사이클린과 마크로라이드계열 항생제의 치료 효과를 비교하였을 때, 두 약제 간에 유의한 차이는 보이지 않았다. 결론: 쯔쯔가무시병 환자에서 소아는 남아에서 많았고, 발진 및 가피의 발생이 더 많았다. 검사상 이상 소견은 성인에 비해 경하였으며, 입원 기간이 짧고, 합병증이 적으며, 마크로라이드계열 항생제에도 동일한 치료 효과를 보였다. 따라서 유행 시기에, 소아에서 쯔쯔가무시병이 의심될 때에는, 세밀한 이학적 진찰과 혈청학적 검사를 실시하여 빠른 진단을 내릴 수 있도록 노력해야 하며, 상대적으로 부작용이 적은 마크로라이드계 항생제로도 좋은 치료 결과를 기대해 볼 수 있다.

Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine

  • Lee, Jun-Sik;Kim, Dae-Hyun;Lee, Chang-Min;Ha, Tae-Kwun;Noh, Kyung-Tae;Park, Jin-Wook;Heo, Deok-Rim;Son, Kwang-Hee;Jung, In-Duk;Lee, Eun-Kyung;Shin, Yong-Kyoo;Ahn, Soon-Cheol;Park, Yeong-Min
    • IMMUNE NETWORK
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    • 제11권1호
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    • pp.79-94
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    • 2011
  • Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

Strategies Against Human Papillomavirus Infection and Cervical Cancer

  • Jung Woon-Won;Chun Taehoon;Sul Donggeun;Hwang Kwang Woo;Kang Hyung-Sik;Lee Duck Joo;Han In-Kwon
    • Journal of Microbiology
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    • 제42권4호
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    • pp.255-266
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    • 2004
  • Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well char­acterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clin­ical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now rec­ognized to be a major risk factor in at least $95\%$ of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demon­strating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.

항암치료 중 RSV에 감염된 백혈병 영아에서의 리바비린 흡입치료 1례 (A Case of Therapy of Aerosolized Ribavirin in a Leukemia Infant with RSV Infection)

  • 권효진;오명진;이재욱;정낙균;조빈;김학기;강진한
    • Pediatric Infection and Vaccine
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    • 제19권3호
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    • pp.162-167
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    • 2012
  • RSV는 2세 미만의 소아에서 급성 하기도 감염으로 인한 입원의 주원인이다. 특히 미숙아, 선천성 심폐질환, 면역결핍이 동반된 경우 주요 위험군으로 알려져 있다. 고위험군의 소아에서 중증 RSV 감염의 경우 리바비린 흡입요법이 허가가 되어 있으나 고비용, 안전성 등의 문제로 국내 임상에서의 사용은 매우 제한적인 실정이다. 저자들은 8개월 여환이 급성 림프구성 백혈병으로 관해유도요법 항암치료 중 발생한 RSV 폐렴으로 기흉, 기종격동, 호흡부전이 동반된 중증 감염을 경험하였다. 정맥용 면역글로불린, 경구 리바비린 투여에 반응이 없어 리바비린 흡입 치료를 시행하였고, 이후 임상적 호전을 경험하였기에 보고하는 바이다.

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Multifactorial Traits of SARS-CoV-2 Cell Entry Related to Diverse Host Proteases and Proteins

  • You, Jaehwan;Seok, Jong Hyeon;Joo, Myungsoo;Bae, Joon-Yong;Kim, Jin Il;Park, Man-Seong;Kim, Kisoon
    • Biomolecules & Therapeutics
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    • 제29권3호
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    • pp.249-262
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    • 2021
  • The most effective way to control newly emerging infectious disease, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, is to strengthen preventative or therapeutic public health strategies before the infection spreads worldwide. However, global health systems remain at the early stages in anticipating effective therapeutics or vaccines to combat the SARS-CoV-2 pandemic. While maintaining social distance is the most crucial metric to avoid spreading the virus, symptomatic therapy given to patients on the clinical manifestations helps save lives. The molecular properties of SARS-CoV-2 infection have been quickly elucidated, paving the way to therapeutics, vaccine development, and other medical interventions. Despite this progress, the detailed biomolecular mechanism of SARS-CoV-2 infection remains elusive. Given virus invasion of cells is a determining factor for virulence, understanding the viral entry process can be a mainstay in controlling newly emerged viruses. Since viral entry is mediated by selective cellular proteases or proteins associated with receptors, identification and functional analysis of these proteins could provide a way to disrupt virus propagation. This review comprehensively discusses cellular machinery necessary for SARS-CoV-2 infection. Understanding multifactorial traits of the virus entry will provide a substantial guide to facilitate antiviral drug development.

African swine fever: Etiology, epidemiological status in Korea, and perspective on control

  • Yoo, Dongwan;Kim, Hyunil;Lee, Joo Young;Yoo, Han Sang
    • Journal of Veterinary Science
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    • 제21권2호
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    • pp.38.1-38.24
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    • 2020
  • African swine fever (ASF), caused by the ASF virus, a member of the Asfarviridae family, is one of the most important diseases in the swine industry due to its clinical and economic impacts. Since the first report of ASF a century ago, ample information has become available, but prevention and treatment measures are still inadequate. Two waves of epizootic outbreaks have occurred worldwide. While the first wave of the epizootic outbreak was controlled in most of the infected areas, the second wave is currently active in the European and Asian continents, causing severe economic losses to the pig industry. There are different patterns of spreading in the outbreaks between those in European and Asian countries. Prevention and control of ASF are very difficult due to the lack of available vaccines and effective therapeutic measures. However, recent outbreaks in South Korea have been successfully controlled on swine farms, although feral pigs are periodically being found to be positive for the ASF virus. Therefore, we would like to share our story regarding the preparation and application of control measures. The success in controlling ASF on farms in South Korea is largely due to the awareness and education of swine farmers and practitioners, the early detection of infected animals, the implementation of strict control policies by the government, and widespread sharing of information among stakeholders. Based on the experience gained from the outbreaks in South Korea, this review describes the current understanding of the ASF virus and its pathogenic mechanisms, epidemiology, and control.