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Furan-based Chalcone Annihilates the Multi-Drug-Resistant Pseudomonas aeruginosa and Protects Zebra Fish Against its Infection
Santosh Pushpa Ramya Ranjan Nayak , Catharine Basty , Seenivasan Boopathi , Loganathan Sumathi Dhivya , Khaloud Mohammed Alarjani , Mohamed Ragab Abdel Gawwad , Raghda Hager , Muthu Kumaradoss Kathiravan , Jesu Arockiaraj
J. Microbiol. 2024;62(2):75-89.   Published online February 21, 2024
DOI: https://doi.org/10.1007/s12275-024-00103-6
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AbstractAbstract
The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and synthetically produced chalcones are known to have a wide array of biological activities. The antibacterial properties of synthetically produced chalcone were studied against P. aeruginosa. In vitro, study of the compound (chalcone derivative named DKO1), also known as (2E)-1-(5-methylfuran-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one, had substantial antibacterial and biofilm disruptive action. DKO1 effectively shielded against P. aeruginosa-induced inflammation, oxidative stress, lipid peroxidation, and apoptosis in zebrafish larvae. In adult zebrafish, the treatment enhanced the chances of survivability and reduced the sickness-like behaviors. Gene expression, biochemical analysis, and histopathology studies found that proinflammatory cytokines (TNF-α, IL-1β, IL-6, iNOS) were down regulated; antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) levels increased, and histoarchitecture was restored in zebrafish. The data indicate that DKO1 is an effective antibacterial agent against P. aeruginosa demonstrated both in vitro and in vivo.

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  • Chalcone derivative enhance poultry meat preservation through quorum sensing inhibition against Salmonella (Salmonella enterica serovar Typhi) contamination
    S.P. Ramya Ranjan Nayak, Pratik Pohokar, Anamika Das, L.S. Dhivya, Mukesh Pasupuleti, Ilavenil Soundharrajan, Bader O. Almutairi, Kathiravan Muthu Kumaradoss, Jesu Arockiaraj
    Food Control.2025; 171: 111155.     CrossRef
  • Harnessing Cyclic di-GMP Signaling: A Strategic Approach to Combat Bacterial Biofilm-Associated Chronic Infections
    P. Snega Priya, Ramu Meenatchi, Mukesh Pasupuleti, S. Karthick Raja Namasivayam, Jesu Arockiaraj
    Current Microbiology.2025;[Epub]     CrossRef
  • Targeted inhibition of PqsR in Pseudomonas aeruginosa PAO1 quorum-sensing network by chalcones as promising antibacterial compounds
    Negin Arami, Amineh Sadat Tajani, Maryam Hashemi, Tahoura Rezaei, Razieh Ghodsi, Vahid Soheili, Bibi Sedigheh Fazly Bazzaz
    Molecular Biology Reports.2025;[Epub]     CrossRef
  • Exposure to bisphenol A and sodium nitrate found in processed meat induces endocrine disruption and dyslipidemia through PI3K/AKT/SREBP pathway in zebrafish larvae
    S. P. Ramya Ranjan Nayak, Anamika Das, Karthikeyan Ramamurthy, Mukesh Pasupuleti, Rajakrishnan Rajagopal, Jesu Arockiaraj
    The Journal of Nutritional Biochemistry.2025; : 109887.     CrossRef
  • Testing of Anti-EMT, Anti-Inflammatory and Antibacterial Activities of 2′,4′-Dimethoxychalcone
    Peiling Zhao, Mengzhen Xu, Kai Gong, Kaihui Lu, Chen Ruan, Xin Yu, Jiang Zhu, Haixing Guan, Qingjun Zhu
    Pharmaceuticals.2024; 17(5): 653.     CrossRef
  • Furan-based chalcone protects β-cell damage and improves glucose uptake in alloxan-induced zebrafish diabetic model via influencing Peroxisome Proliferator-Activated Receptor agonists (PPAR-γ) signaling
    S.P. Ramya Ranjan Nayak, B. Haridevamuthu, Raghul Murugan, L.S. Dhivya, S. Venkatesan, Mikhlid H. Almutairi, Bader O. Almutairi, M.K. Kathiravan, S. Karthick Raja Namasivayam, Jesu Arockiaraj
    Process Biochemistry.2024; 142: 149.     CrossRef
  • Protective role of 2-aminothiazole derivative against ethanol-induced teratogenic effects in-vivo zebrafish
    S. Madesh, Gokul Sudhakaran, Karthikeyan Ramamurthy, Avra Sau, Kathiravan Muthu Kumaradoss, Mikhlid H. Almutairi, Bader O. Almutairi, Senthilkumar Palaniappan, Jesu Arockiaraj
    Biochemical Pharmacology.2024; 230: 116601.     CrossRef
  • Tissue damage alleviation and mucin inhibition by P5 in a respiratory infection mouse model with multidrug-resistant Acinetobacter baumannii
    Jun Hee Oh, Jonggwan Park, Hee Kyoung Kang, Hee Joo Park, Yoonkyung Park
    Biomedicine & Pharmacotherapy.2024; 181: 117724.     CrossRef
  • Toxicity and therapeutic property of dioxopiperidin derivative SKT40 demonstrated in-vivo zebrafish model due to inflammatory bowel disease
    B. Aswinanand, S.P. Ramya Ranjan Nayak, S. Madesh, Suthi Subbarayudu, S. Kaliraj, Rajakrishnan Rajagopal, Ahmed Alfarhan, Muthu Kumaradoss Kathiravan, Jesu Arockiaraj
    Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology.2024; 284: 109990.     CrossRef
Ultrasonic Treatment Enhanced Astaxanthin Production of Haematococcus pluvialis
Yun Hwan Park , Jaewon Park , Jeong Sik Choi , Hyun Soo Kim , Jong Soon Choi , Yoon-E Choi
J. Microbiol. 2023;61(6):633-639.   Published online June 13, 2023
DOI: https://doi.org/10.1007/s12275-023-00053-5
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AbstractAbstract
In this study, effects of ultrasonic treatment on Haematococcus pluvialis (H. pluvialis) were investigated. It has been confirmed that the ultrasonic stimulation acted as stress resources in the red cyst stage H. pluvialis cells containing astaxanthin,
result
ing in additional astaxanthin production. With the increase in production of astaxanthin, the average diameter of H. pluvialis cells increased accordingly. In addition, to determine how ultrasonic stimulation had an effect on the further biosynthesis of astaxanthin, genes related to astaxanthin synthesis and cellular ROS level were measured. As a result, it was confirmed that astaxanthin biosynthesis related genes and cellular ROS levels were increased, and thus ultrasonic stimulation acts as an oxidative stimulus. These results support the notion on the effect of the ultrasonic treatment, and we believe our novel approach based on the ultrasonic treatment would help to enhance the astaxanthin production from H. pluvialis.

Citations

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  • Recent Advances in Astaxanthin as an Antioxidant in Food Applications
    Yimeng Dang, Zhixi Li, Fanqianhui Yu
    Antioxidants.2024; 13(7): 879.     CrossRef
  • Effect of reduced atmospheric pressures on the morphology and astaxanthin biosynthesis of microalga Haematococcus lacustris
    Sangui Kim, Rendi Mahadi, Aditya Lakshmi Narasimhan, Catherine Christabel, Hyoji Yu, Eui-Jin Kim, You-Kwan Oh
    Biotechnology and Bioprocess Engineering.2024; 29(6): 1131.     CrossRef
Review
The crosstalk between bacteria and host autophagy: host defense or bacteria offense
Lin Zheng , Fang Wei , Guolin Li
J. Microbiol. 2022;60(5):451-460.   Published online April 29, 2022
DOI: https://doi.org/10.1007/s12275-022-2009-z
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AbstractAbstract
Xenophagy is a specific selective autophagy for the elimination of intracellular bacteria. Current evidence suggests that the processes for host autophagy system to recognize and eliminate invading bacteria are complex, and vary according to different pathogens. Although both ubiquitin-dependent and ubiquitin-independent autophagy exist in host to defense invading bacteria, successful pathogens have evolved diverse strategies to escape from or paralyze host autophagy system. In this review, we discuss the mechanisms of host autophagy system to recognize and eliminate intracellular pathogens and the mechanisms of different pathogens to escape from or paralyze host autophagy system, with a particular focus on the most extensively studied bacteria.

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  • Complement C3 deposition restricts the proliferation of internalized Staphylococcus aureus by promoting autophagy
    Yining Deng, Yunke Zhang, Tong Wu, Kang Niu, Xiaoyu Jiao, Wenge Ma, Chen Peng, Wenxue Wu
    Frontiers in Cellular and Infection Microbiology.2024;[Epub]     CrossRef
  • Innate immune response of host cells infected with Salmonella
    Hongfei Fan, Juane Lu, Hao Wu, Haihua Ruan, Wenjun Song, Y.-T. Yu, P.P. Piccaluga, S. Xie
    BIO Web of Conferences.2024; 111: 01022.     CrossRef
  • Exploring the Connections: Autophagy, Gut Microbiota, and Inflammatory Bowel Disease Pathogenesis
    Arunkumar Subramanian, Afrarahamed J, Tamilanban T, Vinoth Kumarasamy, M Yasmin Begum, Mahendran Sekar, Vetriselvan Subramaniyan, Ling Shing Wong, Adel Al Fatease
    Journal of Inflammation Research.2024; Volume 17: 10453.     CrossRef
  • Programmed cell death and Salmonella pathogenesis: an interactive overview
    Yu Zhang, Maodou Xu, Yujiao Guo, Li Chen, Wanwipa Vongsangnak, Qi Xu, Lizhi Lu
    Frontiers in Microbiology.2024;[Epub]     CrossRef
  • Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
    Shanshan Jiang, Jinyao He, Lijie Zhang, Qiaojiajie Zhao, Shuqi Zhao
    Open Life Sciences.2023;[Epub]     CrossRef
  • Xenophagy as a Strategy for Mycobacterium leprae Elimination during Type 1 or Type 2 Leprosy Reactions: A Systematic Review
    Débora Dantas Nucci Cerqueira, Ana Letícia Silva Pereira, Ana Elisa Coelho da Costa, Tarcísio Joaquim de Souza, Matheus Santos de Sousa Fernandes, Fabrício Oliveira Souto, Patrícia d’Emery Alves Santos
    Pathogens.2023; 12(12): 1455.     CrossRef
  • Brucella BtpB Manipulates Apoptosis and Autophagic Flux in RAW264.7 Cells
    Junmei Li, Lin Qi, Ziyang Diao, Mengyu Zhang, Bin Li, Yunyi Zhai, Mingyue Hao, Dong Zhou, Wei Liu, Yaping Jin, Aihua Wang
    International Journal of Molecular Sciences.2022; 23(22): 14439.     CrossRef
Journal Article
[PROTOCOL]A Signature-Tagged Mutagenesis (STM)-based murine-infectivity assay for Cryptococcus neoformans
Kwang-Woo Jung , Kyung-Tae Lee , Yong-Sun Bahn
J. Microbiol. 2020;58(10):823-831.   Published online September 29, 2020
DOI: https://doi.org/10.1007/s12275-020-0341-8
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AbstractAbstract
Signature-tagged mutagenesis (STM) is a high-throughput genetic technique that can be used to investigate the function of genes by constructing a large number of mutant strains with unique DNA identification tags, pooling them, and screening them for a particular phenotypic trait. STM was first designed for the identification of genes that contribute to the virulence or infectivity of a pathogen in its host. Recently, this
method
has also been applied for the identification of mutants with specific phenotypes, such as antifungal drug resistance and proliferation. In the present study, we describe an STM
method
for the identification of genes contributing to the infectivity of Cryptococcus neoformans using a mutant library, in which each strain was tagged with a unique DNA sequence.

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  • Genome-wide phenotypic profiling of transcription factors and identification of novel targets to control the virulence of Vibrio vulnificus
    Dayoung Sung, Garam Choi, Minji Ahn, Hokyung Byun, Tae Young Kim, Hojun Lee, Zee-Won Lee, Ji Yong Park, Young Hyun Jung, Ho Jae Han, Sang Ho Choi
    Nucleic Acids Research.2024;[Epub]     CrossRef
  • Zinc-binding domain mediates pleiotropic functions of Yvh1 in Cryptococcus neoformans
    Jae-Hyung Jin, Myung Kyung Choi, Hyun-Soo Cho, Yong-Sun Bahn
    Journal of Microbiology.2021; 59(7): 658.     CrossRef
Research Support, Non-U.S. Gov'ts
A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis
Fei-yu Wang , Yu-qing Zhang , Xin-min Wang , Chan Wang , Xiao-fang Wang , Jiang-dong Wu , Fang Wu , Wan-jiang Zhang , Le Zhang
J. Microbiol. 2016;54(4):330-337.   Published online April 1, 2016
DOI: https://doi.org/10.1007/s12275-016-5627-5
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AbstractAbstract
Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.

Citations

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  • Tolerance of Listeria monocytogenes to biocides used in food processing environments
    Sanelisiwe Thinasonke Duze, Musa Marimani, Mrudula Patel
    Food Microbiology.2021; 97: 103758.     CrossRef
  • Regulatory role and mechanism of the inhibition of the Mcl-1 pathway during apoptosis and polarization of H37Rv-infected macrophages
    Ling Han, Yang Lu, Xiaofang Wang, Shujun Zhang, Yingzi Wang, Fang Wu, Wanjiang Zhang, Xinmin Wang, Le Zhang
    Medicine.2020; 99(42): e22438.     CrossRef
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    Philip Arandjelovic, Marcel Doerflinger, Marc Pellegrini
    Current Opinion in Pharmacology.2019; 48: 33.     CrossRef
  • PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis
    Eusondia Arnett, Ashlee M. Weaver, Kiersten C. Woodyard, Maria J. Montoya, Michael Li, Ky V. Hoang, Andrew Hayhurst, Abul K. Azad, Larry S. Schlesinger, Thomas R. Hawn
    PLOS Pathogens.2018; 14(6): e1007100.     CrossRef
  • Effect of gap junctions on RAW264.7 macrophages infected with H37Rv
    Yang Lu, Xin-min Wang, Pu Yang, Ling Han, Ying-zi Wang, Zhi-hong Zheng, Fang Wu, Wan-jiang Zhang, Le Zhang
    Medicine.2018; 97(35): e12125.     CrossRef
Characterization of cell death in Escherichia coli mediated by XseA, a large subunit of exonuclease VII
Hyeim Jung , Junwei Liang , Yuna Jung , Dongbin Lim
J. Microbiol. 2015;53(12):820-828.   Published online December 2, 2015
DOI: https://doi.org/10.1007/s12275-015-5304-0
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AbstractAbstract
Exonuclease VII (ExoVII) of Escherichia coli is a single strandspecific DNA nuclease composed of two different subunits: the large subunit, XseA, and the small subunit, XseB. In this study, we found that multicopy single-stranded DNAs (msDNAs), Ec83 and Ec78, are the in vivo substrates of ExoVII; the enzyme cuts the phosphodiester bond between the fourth and fifth nucleotides from the 5′ end. We used this msDNA cleavage to assess ExoVII activity in vivo. Both subunits were required for enzyme activity. Expression of XseA without XseB caused cell death, even though no ExoVII activity was detected. The lethality caused by XseA was rescued by surplus XseB. In XseA-induced death, cells were elongated and multinucleated, and their chromosomes were fragmented and condensed; these are the morphological hallmarks of apoptotic cell death in bacteria. A putative caspase recognition sequence (FVAD) was found in XseA, and its hypothetical caspase product with 257 amino acids was as active as the intact protein in inducing cell death. We propose that under ordinary conditions, XseA protects chromosome as a component of the ExoVII enzyme, but in some conditions, the protein causes cell death; the destruction of cell is probably carried out by the amino terminal fragment derived from the cleavage of XseA by caspase-like enzyme.

Citations

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  • ReaL-MGE is a tool for enhanced multiplex genome engineering and application to malonyl-CoA anabolism
    Wentao Zheng, Yuxuan Wang, Jie Cui, Guangyao Guo, Yufeng Li, Jin Hou, Qiang Tu, Yulong Yin, Francis Stewart, Youming Zhang, Xiaoying Bian, Xue Wang
    Nature Communications.2024;[Epub]     CrossRef
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    Ronald R. Breaker, Kimberly A. Harris, Seth E. Lyon, Freya D. R. Wencker, Chrishan M. Fernando
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    Santi Bhattarai-Kline, Sierra K. Lear, Chloe B. Fishman, Santiago C. Lopez, Elana R. Lockshin, Max G. Schubert, Jeff Nivala, George M. Church, Seth L. Shipman
    Nature.2022; 608(7921): 217.     CrossRef
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    Roman Kogay, Olga Zhaxybayeva, Rachel Poretsky
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    Jacob Bobonis, Karin Mitosch, André Mateus, Nicolai Karcher, George Kritikos, Joel Selkrig, Matylda Zietek, Vivian Monzon, Birgit Pfalz, Sarela Garcia-Santamarina, Marco Galardini, Anna Sueki, Callie Kobayashi, Frank Stein, Alex Bateman, Georg Zeller, Mik
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    Christina Palka, Chloe B Fishman, Santi Bhattarai-Kline, Samuel A Myers, Seth L Shipman
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    Ya-jing XIAO, Tan-tan GAO, Qi PENG, Jie ZHANG, Dong-mei SUN, Fu-ping SONG
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Anti-tumor effect of Cordyceps militaris in HCV-infected human hepatocarcinoma 7.5 cells
Seulki Lee , Hwan Hee Lee , Jisung Kim , Joohee Jung , Aree Moon , Choon-Sik Jeong , Hyojeung Kang , Hyosun Cho
J. Microbiol. 2015;53(7):468-474.   Published online June 27, 2015
DOI: https://doi.org/10.1007/s12275-015-5198-x
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AbstractAbstract
Cordyceps extract has been reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris on hepatitis C virus-infected human hepatocarcinoma 7.5 cells (J6/JFH1-huh 7.5 cells). The huh7.5 cells with or without HCV infection were treated with various concentrations of ethanol extract of Cordyceps militaris (CME) for 48 h and the cytotoxicity was measured by CCK-8 assay. Both J6/JFH1- huh7.5 cells and huh7.5 cells were highly susceptible to CME. To examine the molecular mechanisms of the inhibitory effect on huh7.5 cells, the effect of CME on cell apoptosis was measured using flow cytometry and the expressions of p53, Bim, Bax, PARP, (cleaved) caspase-9, and (cleaved) caspase- 3 in huh 7.5 cells were detected by western blot assays. CME significantly increased early apoptosis and up-regulated the expression of Bim, Bax, cleaved PARP, cleaved caspase 9 and cleaved caspase-3. We also found the decrease of HCV Core or NS3 protein by CME in HCV-infected huh 7.5 cells.

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VvpM, an Extracellular Metalloprotease of Vibrio vulnificus, Induces Apoptotic Death of Human Cells
Mi-Ae Lee , Jeong-A Kim , Yu Jin Yang , Mee-Young Shin , Soon-Jung Park , Kyu-Ho Lee
J. Microbiol. 2014;52(12):1036-1043.   Published online November 3, 2014
DOI: https://doi.org/10.1007/s12275-014-4531-0
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AbstractAbstract
A pathogenic bacterium, Vibrio vulnificus produces various extracellular proteases including the elastolytic metalloprotease, VvpE. In silico analysis of its genome revealed a VvpEhomologous protease, VvpM whose proteolytic activity was abolished by specific inhibitors against metalloproteases. To investigate whether this newly identified protease has pathogenic role in host interaction in addition to proteolytic role, human cell lines were incubated with recombinant VvpM (rVvpM). rVvpM-challenged cells showed typical morphological changes found in cells under apoptosis. Apoptotic cell death was further evidenced by estimating the Annexin V-stained cells, whose proportions were dependent upon the concentrations of rVvpM treated to human cells. To elucidate the signaling pathway for VvpM-induced apoptosis, three MAPKs were tested if their activation were mediated by rVvpM. ERK1/2 was phosphorylated by treatment of rVvpM and rVvpM-induced cell death was blocked by a specific inhibitor against ERK1/2. In rVvpM-treated cells, the cytosolic levels of cytochrome c were increased in a VvpM concentration- dependent manner, while the levels of cytochrome c in mitochondria were decreased. Cell deaths were accompanied by apparent cleavages of procaspases-9 and -3 to the active caspases-9 and -3, respectively. Therefore, this study demonstrates that an extracellular metalloprotease of V. vulnificus, VvpM induces apoptosis of human cells via a pathway consisting of ERK activation, cytochrome c release, and then activation of caspases-9 and -3.

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  • Pathology and pathogenesis of Vibrio infection in fish: A review
    Tilusha Manchanayake, Annas Salleh, Mohammad Noor Azmai Amal, Ina Salwany Md Yasin, Mohd Zamri-Saad
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Effects of Fengycin from Bacillus subtilis fmbJ on Apoptosis and Necrosis in Rhizopus stolonifer
Qunyong Tang , Xiaomei Bie , Zhaoxin Lu , Fengxia Lv , Yang Tao , Xiaoxu Qu
J. Microbiol. 2014;52(8):675-680.   Published online August 1, 2014
DOI: https://doi.org/10.1007/s12275-014-3605-3
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AbstractAbstract
The lipopeptide antibiotic fengycin, produced by Bacillus subtilis, strongly inhibits growth of filamentous fungi. In this study, we evaluated the effects of fengycin treatment on apoptosis and necrosis in Rhizopus stolonifer by means of cell staining and epifluorescence microscopy. At fengycin concentrations less than 50 μg/ml, treated fungal cells demonstrated a dose-dependent increase in apoptosis-associated markers compared with the untreated control. These markers included chromatin condensation, reactive oxygen species accumulation, mitochondrial membrane potential depolarization, phosphatidylserine externalization, and the occurrence of DNA strand breaks. These results showed that fungal cells were impaired in a number of important functions and entered apoptosis upon treatment with low concentrations of fengycin. In contrast, high concentrations (>50 μg/ml) induced necrosis, indicating that the fungicidal action of fengycin operates via two modes: apoptosis at low concentrations and necrosis at high concentrations. Additionally, the apoptotic effect that we have shown suggests that lower concentrations of fengycin than previously thought may be effective for food preservation.

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Lithium Inhibits Growth of Intracellular Mycobacterium kansasii through Enhancement of Macrophage Apoptosis
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J. Microbiol. 2014;52(4):299-306.   Published online February 17, 2014
DOI: https://doi.org/10.1007/s12275-014-3469-6
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AbstractAbstract
Mycobacterium kansasii (Mk) is an emerging pathogen that causes a pulmonary disease similar to tuberculosis. Macrophage apoptosis contributes to innate host defense against mycobacterial infection. Recent studies have suggested that lithium significantly enhances the cytotoxic activity of death stimuli in many cell types. We examined the effect of lithium on the viability of host cells and intracellular Mk in infected macrophages. Lithium treatment resulted in a substantial reduction in the viability of intracellular Mk in macrophages. Macrophage cell death was significantly enhanced after adding lithium to Mk-infected cells but not after adding to uninfected macrophages. Lithium-enhanced cell death was due to an apoptotic response, as evidenced by augmented DNA fragmentation and caspase activation. Reactive oxygen species were essential for lithium-induced apoptosis. Intracellular scavenging by N-acetylcysteine abrogated the lithiummediated decrease in intracellular Mk growth as well as apoptosis. These data suggest that lithium is associated with control of intracellular Mk growth through modulation of the apoptotic response in infected macrophages.

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    Kang-In Lee, Seunga Choi, Han-Gyu Choi, Sintayehu Gurmessa Kebede, Thi Binh Dang, Yong Woo Back, Hye-Soo Park, Hwa-Jung Kim
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Journal Article
Porphyromonas gingivalis-Derived Lipopolysaccharide-Mediated Activation of MAPK Signaling Regulates Inflammatory Response and Differentiation in Human Periodontal Ligament Fibroblasts
Taegun Seo , Seho Cha , Tae-Il Kim , Hee-Jung Park , Jeong-Soon Lee , Kyung Mi Woo
J. Microbiol. 2012;50(2):311-319.   Published online April 27, 2012
DOI: https://doi.org/10.1007/s12275-012-2146-x
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  • 28 Crossref
AbstractAbstract
Porphyromonas gingivalis (P.g.), which is a potential pathogen for periodontal diseases, contains lipopolysaccharide (LPS), and this endotoxin stimulates a variety of cellular responses. At present, P.g.-derived LPS-induced cellular responses in human periodontal ligament fibroblasts (PDLFs) are not well characterized. Here, we demonstrate that P.gderived LPS regulates inflammatory responses, apoptosis and differentiation in PDLFs. Interleukin-6 (IL-6) and -8 (IL-8) were effectively upregulated by treatment of P.g.-derived LPS, and we confirmed apoptosis markers including elevated cytochrome c levels, active caspase-3 and morphological change in the presence of P.g.-derived LPS. Moreover, when PDLFs were cultured with differentiation media, P.g.- derived LPS reduced the expression of differentiation marker genes, as well as reducing alkaline phosphatase (ALP) activity and mineralization. P.g.-derived LPS-mediated these cellular responses were effectively abolished by treatment of mitogen-activated protein kinase (MAPK) inhibitors. Taken together, our results suggest that P.g.-derived LPS regulates several cellular responses via activation of MAPK signaling pathways in PDLFs.

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    Kübra Aral, Michael R. Milward, Paul R. Cooper
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  • Bambusae Caulis in Taeniam modulates neuroprotective and anti-neuroinflammatory effects in hippocampal and microglial cells via HO-1- and Nrf-2-mediated pathways
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Research Support, Non-U.S. Gov't
Functional Analysis of the Inhibitor of Apoptosis Genes in Antheraea pernyi Nucleopolyhedrovirus
Feng Yan , Xiaobei Deng , Junpeng Yan , Jiancheng Wang , Lunguang Yao , Songya lv , Yipeng Qi , Hua Xu
J. Microbiol. 2010;48(2):199-205.   Published online May 1, 2010
DOI: https://doi.org/10.1007/s12275-010-9108-y
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  • 14 Scopus
AbstractAbstract
The inhibitor of apoptosis proteins (IAP) plays an important role in cell apoptosis. We cloned two novel IAP family members, Ap-iap1 and Ap-iap2, from Antheraea pernyi nucleopolyhedrovirus (ApNPV) genome. Ap-IAP1 contains two baculoviral IAP repeat (BIR) domains followed by a RING domain, but Ap-IAP2 has only one BIR domain and RING. The result of transient expression in Spodoptera frugiperda (Sf21) showed that Ap-iap1 blocked cell apoptosis induced by actinomycin D treatment and also rescued the p35 deficient Autographa californica nucleopolyhedrovirus (AcNPV) to replicate in Sf9 cells, while Ap-iap2 does not have this function. Several Ap-IAP1 truncations were constructed to test the activity of BIRs or RING motif to inhibit cell apoptosis. The results indicated that BIRs or RING of Ap-IAP1 had equally function to inhibit cell apoptosis. Therefore deletion of above both of the above domains could not block apoptosis induced by actinomycin D or rescue the replication of AcMNPV△p35. We also screened two phage-display peptides that might interact with Ap-IAP1.
Journal Article
Ethanol Extract of Fermented Soybean, Chungkookjang, Inhibits the Apoptosis of Mouse Spleen, and Thymus Cells
Han Bok Kim , Hye Sung Lee , Sook Jin Kim , Hyung Jae Yoo , Jae Sung Hwang , Gang Chen , Hyun Joo Youn
J. Microbiol. 2007;45(3):256-261.
DOI: https://doi.org/2534 [pii]
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AbstractAbstract
Apoptosis is a step of the cell cycle which is important in the regulation of immune cell populations. Chungkookjang is a Korean traditional fermented soybean containing microorganisms, enzymes, and bioactive compounds which was used in the treatment of mouse spleen as well as thymus cells (CH1-fermented soybean containing barley, wormwood, and sea tangle; CH2-fermented soybean) and was found to exhibit substantially reduced small DNA fragmentation. An MTT assay showed that the treatment of CH1 and CH2 into the mouse splenocytes and thymocytes sharply increased their survival. Moreover, a FACS analysis also showed that CH1 and CH2 are effective at suppressing the apoptosis of splenocytes and thymocytes. The fermented soybean isoflavone concentrations, which are implicated in lowering breast and prostate cancers, lowering the risk of cardiovascular diseases, and improving bone health, were determined using Capillary Electrophoresis-Electrochemical Detection (CE-ED). The amount of Daidzein in fermented soybean significantly increased by 44-fold dramatically, compared with those in unfermented soybean. In this study, we demonstrated that ethanol extracts of Chungkookjang promote the survival of the mouse spleen and thymus cells in culture by suppressing their apoptotic death. Future studies should investigate which genes are related to apoptosis of the immune cells.
Research Support, Non-U.S. Gov't
Molecular Taxonomy of a Soil Actinomycete Isolate, KCCM10454 Showing Neuroprotective Activity by 16S rRNA and rpoB Gene Analysis
Bong-Hee Lee , Hong Kim , Hyun-Ju Kim , Yoon-Kyu Lim , Kyung-Hee Byun , Brian Hutchinson , Chang-Jin Kim , Young-Hwan Ko , Keun-Hwa Lee , Chang-Yong Cha , Yoon-Hoh Kook , Bum-Joon Kim
J. Microbiol. 2005;43(2):213-218.
DOI: https://doi.org/2158 [pii]
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AbstractAbstract
Epilepsy constitutes a significant public health problem, and even the newest drugs and neurosurgical techniques have proven unable to cure the disease. In order to select a group of isolates which could generate an active compound with neuroprotective or antiepileptic properties, we isolated 517 actinomycete strains from soil samples taken from Jeju Island, in South Korea. We then screened these strains for possible anti-apoptotic effects against serum deprivation-induced hippocampal cell death, using the 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay as an in vitro test. The excitotoxic glutamate analog, kainic acid (KA), was used to induce seizures in experimental mice in our in vivo tests. As a result of this testing, we located one strain which exhibited profound neuroprotective activity. This strain was identified as a Streptomyces species, and exhibited the rifampin-resistant genotype, Asn(AAC)^442, according to the results of 16S rRNA and rpoB gene analyses
Hepatitis C Virus Core Protein Sensitizes Cells to Apoptosis Induced by Anti-Cancer Drug
Kang, Mun Il , Cho, Mong , Kim, Sun Hee , Kang, Chi Dug , Kim, Dong Wan
J. Microbiol. 1999;37(2):90-96.
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AbstractAbstract
The core protein of the hepatitis C virus (HCV) is a multifunctional protein. The HCV core protein was reported to regulate cellular gene expression and transform primary rat embryo fibroblast cells. However, the role of the core protein in the pathogenesis of HCV-associated liver diseases is not well understood. To investigate the functional role of the core protein in cytophathogenicity, we have constructed stable expression systems of full length or truncated HCV core protein lacking the C-terminal hyderophobic domains and established HepG2 cell clones constitutively expressing the core protein. The full length core protein was localized in the cytoplasm and the C-terminal truncated core protein was localized in the nucleus. HepG2 cells expressing nuclear, truncated core protein showed elevated cell death during cultivation compared to untransfected cells and full length core-expressing cells. In the treatment with bleomycin, both cell clones expressing full length or truncated core protein appeared to be more sensitive to bleomycin than the parental HepG2 cells. These results suggest that the core protein may play a role in HCV pathogenesis promoting apoptotic cell death of infected cells.

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