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  1. Article ; Online: SARS-CoV-2 spike protein expressing epithelial cells promotes senescence associated secretory phenotype in endothelial cells and increased inflammatory response

    Meyer, Keith / Patra, Tapas / Mahantesh, Vijay / Ray, Ranjit

    bioRxiv

    Abstract: Increased mortality in COVID-19 often associates with thrombotic and microvascular complications. We have recently shown that SARS-CoV-2 spike protein promotes inflammatory cytokine IL-6/IL-6R induced trans-signaling responses which modulate MCP-1 ... ...

    Abstract Increased mortality in COVID-19 often associates with thrombotic and microvascular complications. We have recently shown that SARS-CoV-2 spike protein promotes inflammatory cytokine IL-6/IL-6R induced trans-signaling responses which modulate MCP-1 expression in human endothelial cells. MCP-1 is secreted as a major component of the senescence associated secretory phenotype (SASP). Virus infected or Spike transfected human pulmonary epithelial cells (A549) exhibited an increase in senescence related marker proteins. TMNK; as a representative human endothelial cell line, when exposed to cell culture supernatant derived from A549 cells expressing SARS-CoV-2 spike protein (Spike CM) exhibited a senescence phenotype with enhanced p16, p21, and SA-β-galactosidase expression. Inhibition of IL-6 trans-signaling by Tocilizumab, prior to exposure of supernatant to endothelial cells, inhibited p16 and p21 induction. Likewise, inhibition of receptor signaling by Zanabrutinib or Brd4 function by AZD5153 also led to limited induction of p16 expression. Senescence lead to an enhanced level of adhesion molecule, ICAM-1 and VCAM-1 in human endothelial cells, and TPH1 attachment by in vitro assay. Inhibition of senescence or SASP function prevented ICAM/VCAM expression and leukocyte attachment. We also observed an increase in oxidative stress in A549 spike transfected and endothelial cells exposed to Spike CM. ROS generation in TMNK was reduced after treatment with the IL-6 specific inhibitor Tociliximab, and with the specific inhibitors Zanabrutinib and AZD5153. Taken together, we identified that the exposure of human endothelial cells to cell culture supernatant derived from SARS-CoV-2 spike protein expression displayed cellular senescence markers leading to enhanced leukocyte adhesion with coronary blockade potential.
    Keywords covid19
    Language English
    Publishing date 2021-04-16
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.04.16.440215
    Database COVID19

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  2. Article: Validating Immunomodulatory Responses of r-

    Pandey, Rajkishor / Gautam, Rohit Kumar / Sharma, Simran / Tedla, Mebrahtu G / Mahantesh, Vijay / Dikhit, Manas Ranjan / Kumar, Akhilesh / Pandey, Krishna / Bimal, Sanjiva

    Pathogens (Basel, Switzerland)

    2022  Volume 12, Issue 1

    Abstract: Vaccination is considered the most appropriate way to control visceral leishmaniasis (VL). With this background, the r- ...

    Abstract Vaccination is considered the most appropriate way to control visceral leishmaniasis (VL). With this background, the r-
    Language English
    Publishing date 2022-12-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens12010016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immunomodulation mediated through Leishmania donovani protein disulfide isomerase by eliciting CD8+ T-cell in cured visceral leishmaniasis subjects and identification of its possible HLA class-1 restricted T-cell epitopes.

    Amit, Ajay / Dikhit, Manas R / Mahantesh, Vijay / Chaudhary, Rajesh / Singh, Ashish Kumar / Singh, Ashu / Singh, Shubhankar Kumar / Das, V N R / Pandey, Krishna / Ali, Vahab / Narayan, Shyam / Sahoo, Ganesh C / Das, Pradeep / Bimal, Sanjiva

    Journal of biomolecular structure & dynamics

    2017  Volume 35, Issue 1, Page(s) 128–140

    Abstract: Protein disulphide isomerase (PDI) is one of the key enzymes essential for the survival of Leishmania donovani in the host. Our study suggested that PDI is associated with the generation of Th1-type of cellular responses in treated Visceral leishmaniasis ...

    Abstract Protein disulphide isomerase (PDI) is one of the key enzymes essential for the survival of Leishmania donovani in the host. Our study suggested that PDI is associated with the generation of Th1-type of cellular responses in treated Visceral leishmaniasis (VL) subjects. The stimulation of Peripheral blood mononuclear cells (PBMCs) with recombinant Protein Disulphide Isomerase upregulated the reactive oxygen species generation, Nitric oxide release, IL12 and IFN-γ production indicating its pivotal role in protective immune response. Further, a pre-stimulation of PBMCs with Protein disulphide isomerase induced a strong IFN-γ response through CD8+ T cells in treated VL subjects. These findings also supported through the evidence that this antigen was processed and presented by major histocompatibility complex class I (MHC-1) dependent pathway and had an immunoprophylactic potential which can induce CD8+ T cell protective immune response in MHC class I dependent manner against VL. To find out the possible epitopes that might be responsible for CD8+ T cell specific IFN-γ response, computational approach was adopted. Six novel promiscuous epitopes were predicted to be highly immunogenic and can be presented by 32 different HLA allele to CD8+ T cells. Further investigation will explore more about their immunological relevance and usefulness as vaccine candidates.
    MeSH term(s) Adolescent ; Adult ; Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cytokines/metabolism ; Epitopes, T-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/immunology ; Female ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class I/immunology ; Humans ; Immunomodulation ; Leishmania donovani/enzymology ; Leishmania donovani/immunology ; Leishmaniasis, Visceral/immunology ; Male ; Protein Disulfide-Isomerases/chemistry ; Protein Disulfide-Isomerases/immunology ; Protozoan Proteins/chemistry ; Protozoan Proteins/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Young Adult
    Chemical Substances Cytokines ; Epitopes, T-Lymphocyte ; Histocompatibility Antigens Class I ; Protozoan Proteins ; Protein Disulfide-Isomerases (EC 5.3.4.1)
    Language English
    Publishing date 2017-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2015.1134349
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2093: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  4. Book ; Online: A Navigation Algorithm Inspired by Human Navigation

    M., Vijesh / Iyengar, Sudarshan / Mahantesh, Vijay / Ramesh, Amitash / Madhavan, Veni

    2011  

    Abstract: Human navigation has been a topic of interest in spatial cognition from the past few decades. It has been experimentally observed that humans accomplish the task of way-finding a destination in an unknown environment by recognizing landmarks. ... ...

    Abstract Human navigation has been a topic of interest in spatial cognition from the past few decades. It has been experimentally observed that humans accomplish the task of way-finding a destination in an unknown environment by recognizing landmarks. Investigations using network analytic techniques reveal that humans, when asked to way-find their destination, learn the top ranked nodes of a network. In this paper we report a study simulating the strategy used by humans to recognize the centers of a network. We show that the paths obtained from our simulation has the same properties as the paths obtained in human based experiment. The simulation thus performed leads to a novel way of path-finding in a network. We discuss the performance of our method and compare it with the existing techniques to find a path between a pair of nodes in a network.

    Comment: Human Navigation, Path Concatenation, Hotspots, Center Strategic Paths, Approximation Algorithm
    Keywords Computer Science - Social and Information Networks ; Physics - Physics and Society
    Subject code 000
    Publishing date 2011-11-21
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of Leishmania in visceral leishmaniasis.

    Yadav, Anupam / Amit, Ajay / Chaudhary, Rajesh / Chandel, Arvind Singh / Mahantesh, Vijay / Suman, Shashi Shekhar / Singh, Subhankar Kumar / Dikhit, Manas Ranjan / Ali, Vahab / Rabidas, Vidyanand / Pandey, Krishna / Kumar, Anil / Das, Pradeep / Bimal, Sanjiva

    International journal for parasitology

    2015  Volume 45, Issue 1, Page(s) 33–42

    Abstract: Ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthesis pathway, is significant in the synthesis of trypanothione, T(SH)2, the major reduced thiol which is responsible for the modulation of the immune response and pathogenesis in ... ...

    Abstract Ornithine decarboxylase, the rate limiting enzyme of the polyamine biosynthesis pathway, is significant in the synthesis of trypanothione, T(SH)2, the major reduced thiol which is responsible for the modulation of the immune response and pathogenesis in visceral leishmaniasis. Data on the relationship between ornithine decarboxylase and the cellular immune response in VL patients are limited. Therefore, we purified a recombinant ornithine decarboxylase from Leishmania donovani (r-LdODC) of approximately 77kDa and examined its effects on the immunological responses in peripheral blood mononuclear cells of human visceral leishmaniasis cases. For these studies, α-difluoromethylornithine was tested as an inhibitor and was used in parallel in all experiments. The r-LdODC was identified as having a direct correlation with parasite growth and significantly increased the number of promastigotes as well as axenic amastigotes after 96h of culture. The stimulation of peripheral blood mononuclear cells with r-LdODC up-regulated IL-10 production but not IFN-γ production from CD4(+) T cells in active as well as cured visceral leishmaniasis cases, indicating a pivotal role for r-LdODC in causing strong immune suppression in a susceptible host. In addition, severe hindrance of the immune response and anti-leishmanial macrophage function due to r-LdODC, as revealed by decreased IL-12 and nitric oxide production, and down-regulation in mean fluorescence intensities of reactive oxygen species, occurred in visceral leishmaniasis patients. There was little impact of r-LdODC in the killing of L. donovani amastigotes in macrophages of visceral leishmaniasis patients. In contrast, when cultures of promastigotes and amastigotes, and patients' blood samples, were directed against α-difluoromethylornithine, parasite numbers significantly reduced in culture, whereas the levels of IFN-γ and IL-12, and the production of reactive oxygen species and nitric oxide, were significantly elevated. Therefore, we demonstrated cross-talk with the use of α-difluoromethylornithine which can reduce the activity of ornithine decarboxylase of L. donovani, eliminating the parasite-induced immune suppression and inducing collateral host protective responses in visceral leishmaniasis.
    MeSH term(s) Adolescent ; Adult ; Cytokines/secretion ; Female ; Humans ; Immune Evasion ; Immune Tolerance ; Immunity, Cellular ; Leishmania donovani/immunology ; Leishmania donovani/physiology ; Leishmaniasis, Visceral/immunology ; Leishmaniasis, Visceral/parasitology ; Leukocytes, Mononuclear/immunology ; Male ; Nitric Oxide/metabolism ; Ornithine Decarboxylase/genetics ; Ornithine Decarboxylase/immunology ; Ornithine Decarboxylase/isolation & purification ; Ornithine Decarboxylase/metabolism ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Recombinant Proteins/isolation & purification ; Recombinant Proteins/metabolism ; Virulence Factors/genetics ; Virulence Factors/immunology ; Virulence Factors/isolation & purification ; Virulence Factors/metabolism ; Young Adult
    Chemical Substances Cytokines ; Recombinant Proteins ; Virulence Factors ; Nitric Oxide (31C4KY9ESH) ; Ornithine Decarboxylase (EC 4.1.1.17)
    Language English
    Publishing date 2015-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120518-3
    ISSN 1879-0135 ; 0020-7519
    ISSN (online) 1879-0135
    ISSN 0020-7519
    DOI 10.1016/j.ijpara.2014.08.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 789: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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