• Title/Summary/Keyword: molecular pathogenesis

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Bioactive secondary metabolites in sea cucumbers and their potential to use in the functional food industry

  • KK Asanka Sanjeewa;KHINM Herath
    • Fisheries and Aquatic Sciences
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    • v.26 no.2
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    • pp.69-86
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    • 2023
  • The bioactive secondary metabolites produced by sea cucumbers are very diverse with differences in composition, linkages, molecular weight, and various functional properties. Due to their physicochemical properties, these bioactive molecules in sea cucumbers have found applications in various market segments such as functional foods and cosmetics. Sea cucumber side dishes are a prominent food item in traditional cuisine in East Asian countries such as South Korea, China, and Japan. In addition, many studies have reported that the consumption of sea cucumbers can reduce the risk of cardiovascular disease, the pathogenesis of cancer cells, chronic inflammatory diseases, etc. In particular, many studies have recently reported the potential of sea cucumbers to develop functional products to reduce inflammation, oxidative stress, diabetes, and cancer. Additionally, these bioactive properties associated with sea cucumbers make them ideal compounds for use as functional ingredients in functional food products. However, no report has yet reviewed the properties of sea cucumbers related to functional foods. Therefore, in this review, the primary focus is given to collecting published scientific data (from 2019 to 2023) on the bioactive properties of sea cucumbers relevant to the functional food industry.

Pathogenesis of Oncoviruses: A Systemic Review

  • Zain Ul Abedien;Kainat Gul;Sara Khan;Maheen Shafiq;Khizar Rahman;Muhammad Hassan Nawaz
    • Microbiology and Biotechnology Letters
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    • v.51 no.2
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    • pp.135-146
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    • 2023
  • Viral oncology is focused on understanding the relationship between cancer and viruses, which are known to play a role in the development of certain types of cancer. Approximately 15-20% of human cancers are believed to be caused by oncogenic viruses, and as a result, there is significant interest in understanding how these viruses contribute to cancer development. There are several viruses that have been linked to cancer, including human papillomavirus, hepatitis B and C virus, Epstein-Barr virus, human T-cell lymphotropic virus type 1, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. Each of these viruses is associated with different types of cancer, and the mechanisms by which they contribute to cancer development are diverse. This article discusses these mechanisms as well as current and future strategies for preventing and treating virus-associated cancers with the goal of presenting a thorough review of the current state of knowledge in viral oncology and to highlight the importance of continued research in this field.

The role of cellular prion protein in immune system

  • Seunghwa Cha;Mi-Yeon Kim
    • BMB Reports
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    • v.56 no.12
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    • pp.645-650
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    • 2023
  • Numerous studies have investigated the cellular prion protein (PrPC) since its discovery. These investigations have explained that its structure is predominantly composed of alpha helices and short beta sheet segments, and when its abnormal scrapie isoform (PrPSc) is infected, PrPSc transforms the PrPC, leading to prion diseases, including Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Given its ubiquitous distribution across a variety of cellular types, the PrPC manifests a diverse range of biological functions, including cell-cell adhesion, neuroprotection, signalings, and oxidative stress response. PrPC is also expressed in immune tissues, and its functions in these tissues include the activation of immune cells and the formation of secondary lymphoid tissues, such as the spleen and lymph nodes. Moreover, high expression of PrPC in immune cells plays a crucial role in the pathogenesis of prion diseases. In addition, it affects inflammation and the development and progression of cancer via various mechanisms. In this review, we discuss the studies on the role of PrPC from various immunological perspectives.

Unraveling flavivirus pathogenesis: from bulk to single-cell RNA-sequencing strategies

  • Doyeong Kim;Seonghun Jeong;Sang-Min Park
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.5
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    • pp.403-411
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    • 2024
  • The global spread of flaviviruses has triggered major outbreaks worldwide, significantly impacting public health, society, and economies. This has intensified research efforts to understand how flaviviruses interact with their hosts and manipulate the immune system, underscoring the need for advanced research tools. RNA-sequencing (RNA-seq) technologies have revolutionized our understanding of flavivirus infections by offering transcriptome analysis to dissect the intricate dynamics of virus-host interactions. Bulk RNA-seq provides a macroscopic overview of gene expression changes in virus-infected cells, offering insights into infection mechanisms and host responses at the molecular level. Single-cell RNA sequencing (scRNA-seq) provides unprecedented resolution by analyzing individual infected cells, revealing remarkable cellular heterogeneity within the host response. A particularly innovative advancement, virus-inclusive single-cell RNA sequencing (viscRNA-seq), addresses the challenges posed by non-polyadenylated flavivirus genomes, unveiling intricate details of virus-host interactions. In this review, we discuss the contributions of bulk RNA-seq, scRNA-seq, and viscRNA-seq to the field, exploring their implications in cell line experiments and studies on patients infected with various flavivirus species. Comprehensive transcriptome analyses from RNA-seq technologies are pivotal in accelerating the development of effective diagnostics and therapeutics, paving the way for innovative treatments and enhancing our preparedness for future outbreaks.

Quantification of Her-2/Neu Gene in Breast Cancer Patients using Real Time-Polymerase Chain Reaction (Q-PCR) and Correlation with Immunohistochemistry Findings

  • Abdul Murad, Nor Azian;Razak, Zuraini Abdul;Hussain, Rosniza Muhammmad;Syed Hussain, Sharifah Noor Akmal;Ching Huat, Clarence Ko;Siti Aishah, Che Md. Ali;Abdullah, Norlia;Muhammad, Rohaizak;Ibrahim, Naqiyah;Jamal, Rahman
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1655-1659
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    • 2013
  • Background: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR). Materials and Methods: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification. Results: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR. Conclusion: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.

Crystal Structure of the Regulatory Domain of AphB from Vibrio vulnificus, a Virulence Gene Regulator

  • Park, Nohra;Song, Saemee;Choi, Garam;Jang, Kyung Ku;Jo, Inseong;Choi, Sang Ho;Ha, Nam-Chul
    • Molecules and Cells
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    • v.40 no.4
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    • pp.299-306
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    • 2017
  • The transcriptional activator AphB has been implicated in acid resistance and pathogenesis in the food borne pathogens Vibrio vulnificus and Vibrio cholerae. To date, the full-length AphB crystal structure of V. cholerae has been determined and characterized by a tetrameric assembly of AphB consisting of a DNA binding domain and a regulatory domain (RD). Although acidic pH and low oxygen tension might be involved in the activation of AphB, it remains unknown which ligand or stimulus activates AphB at the molecular level. In this study, we determine the crystal structure of the AphB RD from V. vulnificus under aerobic conditions without modification at the conserved cysteine residue of the RD, even in the presence of the oxidizing agent cumene hydroperoxide. A cysteine to serine amino acid residue mutant RD protein further confirmed that the cysteine residue is not involved in sensing oxidative stress in vitro. Interestingly, an unidentified small molecule was observed in the inter-subdomain cavity in the RD when the crystal was incubated with cumene hydroperoxide molecules, suggesting a new ligand-binding site. In addition, we confirmed the role of AphB in acid tolerance by observing an aphB-dependent increase in cadC transcript level when V. vulnificus was exposed to acidic pH. Our study contributes to the understanding of the AphB molecular mechanism in the process of recognizing the host environment.

Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation of IL-17R in Human Bronchial Epithelial Cells

  • Lee, Kyoung-Hee;Lee, Chang-Hoon;Woo, Jisu;Jeong, Jiyeong;Jang, An-Hee;Yoo, Chul-Gyu
    • Molecules and Cells
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    • v.41 no.4
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    • pp.282-289
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    • 2018
  • Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$) via the PI3K/Akt pathway. Blockade of $GSK-3{\beta}$ inactivation by overexpression of constitutively active $GSK-3{\beta}$ (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of $GSK-3{\beta}$ via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.

Identification of disease resistance to soft rot in transgenic potato plants that overexpress the soybean calmodulin-4 gene (GmCaM-4) (대두 칼모듈린 단백질, GmCaM-4를 발현하는 형질전환 감자의 무름병 저항성 확인)

  • Park, Hyeong Cheol;Chun, Hyun Jin;Kim, Min Chul;Lee, Sin Woo;Chung, Woo Sik
    • Journal of Plant Biotechnology
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    • v.47 no.2
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    • pp.157-163
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    • 2020
  • Calmodulin (CaM) mediates cellular Ca2+ signals in the defense responses of plants. We previously reported that GmCaM-4 and 5 are involved in salicylic acid-independent activation of disease resistance responses in soybean (Glycine max). Here, we generated a GmCaM-4 cDNA construct under the control of the cauliflower mosaic virus (CaMV) 35S promoter and transformed this construct into potato (Solanum tuberosum L.). The constitutive over-expression of GmCaM-4 in potato induced high-level expression of pathogenesis-related (PR) genes, such as PR-2, PR-3, PR-5, phenylalanine ammonia-lyase (PAL), and proteinase inhibitorII (pinII). In addition, the transgenic potato plants exhibited enhanced resistance against a bacterial pathogen, Erwinia carotovora ssp. Carotovora (ECC), that causes soft rot disease and showed spontaneous lesion phenotypes on their leaves. These results strongly suggest that a CaM protein in soybean, GmCaM-4, plays an important role in the response of potato plants to pathogen defense signaling.

Immunological Detection of Garlic Latent Virus (마늘 잠복 바이러스의 면역학적 진단)

  • Choi, Jin-Nam;Song, Jong-Tae;Song, Sang-Ik;Ahn, Ji-Hoon;Choi, Yang-Do;Lee, Jong-Seob
    • Applied Biological Chemistry
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    • v.38 no.1
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    • pp.49-54
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    • 1995
  • To understand the molecular structure and pathogenesis mechanism of Korean garlic viruses, we have isolated cDNA clones for garlic viruses. The partial nucleotide sequences of 24 cDNA clones were determined and those of five clones containing poly(A) tail were compared with sequences of other plant viruses. One of these clones, V9, has a primary structure similar to the carlavirus group, suggesting that the clone V9 derived from a part of garlic latent virus (GLV). Northern blot analysis with the clone V9 as a probe demonstrated that GLV genome is 8.5 knt long and has a poly(A) tail. The clone V9 encodes coat protein (CP) of 33 kDa and nucleic acid binding protein of 10 kDa in different reading frame. The hexanucleotide motif, 5'-ACCUAA, which is conserved in the 3' noncoding region arid was proposed to be a cis-acting element involved in the production of negative strand genomic RNA was noticed. Complementary sequence to the hexanucleotide motif, 5'-TTAGGT, is also found in the positive strand of V9 RNA. The putative CP gene was cloned into the pRSET-A expression vector and expressed in E. coli BL21. The expressed recombinant V9CP protein was purified by $Ni^{2+}$ NTA affinity chromatography. The anti-V9CP antibody recognizes 34 kDa polypeptide which could be CP of GLV in infected garlic leaf extract. Immunoblot and Northern blot analysis of various cultivars shows wide occurrence of GLV in Korean garlic plants.

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AtCBP63, a Arabidopsis Calmodulin-binding Protein 63, Enhances Disease Resistance Against Soft Rot Disease in Potato (애기장대 칼모듈린 결합 단백질 AtCBP63을 발현시킨 형질전환 감자의 무름병 저항성 증가)

  • Chun, Hyun-Jin;Park, Hyeong-Cheol;Goo, Young-Min;Kim, Tae-Won;Cho, Kwang-Soo;Cho, Hyeon-Seol;Yun, Dae-Jin;Chung, Woo-Sik;Lee, Shin-Woo
    • Journal of Plant Biotechnology
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    • v.38 no.1
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    • pp.62-68
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    • 2011
  • Calmodulin (CaM), a $Ca^{2+}$ binding protein in eukaryotes, mediates cellular $Ca^{2+}$ signals in response to a variety of biotic and abiotic external stimuli. The $Ca^{2+}$-bound CaM transduces signals by modulating the activities of numerous CaM-binding proteins. As a CaM binding protein, AtCBP63 ($\b{A}$rabidopsis thaliana $\b{C}$aM-binding protein $\underline{63}$ kD) has been known to be positively involved in plant defense signaling pathway. To investigate the pathogen resistance function of AtCBP63 in potato, we constructed transgenic potato (Solanum tuberosum L.) plants constitutively overexpressing AtCBP63 under the control of cauliflower mosaic virus (CaMV) 35S promoter. The overexpression of the AtCBP63 in potato plants resulted in the high level induction of pathogenesis-related (PR) genes such as PR-2, PR-3 and PR-5. In addition, the AtCBP63 transgenic potato showed significantly enhanced resistance against a pathogen causing bacterial soft rot, Erwinia carotovora ssp. Carotovora (ECC). These results suggest that a CaM binding protein from Arabidopsis, AtCBP63, plays a positive role in pathogen resistance in potato.