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  1. Article ; Online: Carbon-infiltrated carbon nanotubes inhibit the development of Staphylococcus aureus biofilms.

    Bowden, Lucy C / Evans, Jocelyn G W / Miller, Katelyn M / Bowden, Anton E / Jensen, Brian D / Hope, Sandra / Berges, Bradford K

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 19398

    Abstract: Staphylococcus aureus forms biofilms that cause considerable morbidity and mortality in patients who receive implanted devices such as prosthetics or fixator pins. An ideal surface for such medical devices would inhibit biofilm growth. Recently, it was ... ...

    Abstract Staphylococcus aureus forms biofilms that cause considerable morbidity and mortality in patients who receive implanted devices such as prosthetics or fixator pins. An ideal surface for such medical devices would inhibit biofilm growth. Recently, it was reported that surface modification of stainless steel materials with carbon-infiltrated carbon nanotubes (CICNT) inhibits the growth of S. aureus biofilms. The purpose of this study was to investigate this antimicrobial effect on titanium materials with CICNT coated surfaces in a variety of surface morphologies and across a broader spectrum of S. aureus isolates. Study samples of CICNT-coated titanium, and control samples of bare titanium, a common implant material, were exposed to S. aureus. Viable bacteria were removed from adhered biofilms and quantified as colony forming units. Scanning electron microscopy was used to qualitatively analyze biofilms both before and after removal of cells. The CICNT surface was found to have significantly fewer adherent bacteria than bare titanium control surfaces, both via colony forming unit and microscopic analyses. This effect was most pronounced on CICNT surfaces with an average nanotube diameter of 150 nm, showing a 2.5-fold reduction in adherent bacteria. Since S. aureus forms different biofilm structures by isolate and by growth conditions, we tested 7 total isolates and found a significant reduction in the biofilm load in six out of seven S. aureus isolates tested. To examine whether the anti-biofilm effect was due to the structure of the nanotubes, we generated an unstructured carbon surface. Significantly more bacteria adhered to a nonstructured carbon surface than to the 150 nm CICNT surface, suggesting that the topography of the nanotube structure itself has anti-biofilm properties. The CICNT surface possesses anti-biofilm properties that result in fewer adherent S. aureus bacteria. These anti-biofilm properties are consistent across multiple isolates of S. aureus and are affected by nanotube diameter. The experiments performed in this study suggest that this effect is due to the nanostructure of the CICNT surface.
    MeSH term(s) Humans ; Nanotubes, Carbon ; Staphylococcus aureus ; Titanium/pharmacology ; Biofilms ; Bone Nails
    Chemical Substances Nanotubes, Carbon ; Titanium (D1JT611TNE)
    Language English
    Publishing date 2023-11-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-46748-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Chikungunya virus time course infection of human macrophages reveals intracellular signaling pathways relevant to repurposed therapeutics.

    Gray, Madison / Guerrero-Arguero, Israel / Solis-Leal, Antonio / Robison, Richard A / Berges, Bradford K / Pickett, Brett E

    PeerJ

    2022  Volume 10, Page(s) e13090

    Abstract: Background: Chikungunya virus: Methods: To better characterize the transcriptional response of macrophages during early infection, we generated RNA-sequencing data from a CHIKV-infected human macrophage cell line at eight or 24 hours post-infection ( ... ...

    Abstract Background: Chikungunya virus
    Methods: To better characterize the transcriptional response of macrophages during early infection, we generated RNA-sequencing data from a CHIKV-infected human macrophage cell line at eight or 24 hours post-infection (hpi), together with mock-infected controls. We then calculated differential gene expression, enriched functional annotations, modulated intracellular signaling pathways, and predicted therapeutic drugs from these sequencing data.
    Results: We observed 234 pathways were significantly affected 24 hpi, resulting in six potential pharmaceutical treatments to modulate the affected pathways. A subset of significant pathways at 24 hpi includes AGE-RAGE, Fc epsilon RI, Chronic myeloid leukemia, Fc gamma R-mediated phagocytosis, and Ras signaling. We found that the MAPK1 and MAPK3 proteins are shared among this subset of pathways and that Telmisartan and Dasatinib are strong candidates for repurposed small molecule therapeutics that target human processes. The results of our analysis can be further characterized in the wet lab to contribute to the development of host-based prophylactics and therapeutics.
    Language English
    Publishing date 2022-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.13090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Alphaviruses: Host pathogenesis, immune response, and vaccine & treatment updates.

    Guerrero-Arguero, Israel / Tellez-Freitas, Claudia M / Weber, K Scott / Berges, Bradford K / Robison, Richard A / Pickett, Brett E

    The Journal of general virology

    2021  Volume 102, Issue 8

    Abstract: Human pathogens belonging to ... ...

    Abstract Human pathogens belonging to the
    MeSH term(s) Alphavirus/immunology ; Alphavirus/pathogenicity ; Alphavirus Infections/epidemiology ; Alphavirus Infections/prevention & control ; Alphavirus Infections/virology ; Animals ; Humans ; Viral Vaccines/immunology
    Chemical Substances Viral Vaccines
    Language English
    Publishing date 2021-08-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/jgv.0.001644
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comparison of Intracellular Transcriptional Response of NHBE Cells to Infection with SARS-CoV-2 Washington and New York Strains.

    Scott, Tiana M / Solis-Leal, Antonio / Lopez, J Brandon / Robison, Richard A / Berges, Bradford K / Pickett, Brett E

    Frontiers in cellular and infection microbiology

    2022  Volume 12, Page(s) 1009328

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial epithelial (NHBE) cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at 6, 12, and 24 hours post-infection (hpi) to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes (DEGs), enriched Gene Ontology (GO) terms and dysregulated signaling pathways. We detected over 2,000 DEGs, over 600 GO terms, and 29 affected pathways between the two infections. Many of these entities play a role in immune signaling and response. A comparison between strains and time points showed a higher similarity between matched time points than across different time points with the same strain in DEGs and affected pathways, but found more similarity between strains across different time points when looking at GO terms. A comparison of the affected pathways showed that the 24hpi samples of the New York strain were more similar to the 12hpi samples of the Washington strain, with a large number of pathways related to translation being inhibited in both strains. These results suggest that the various mutations contained in the genome of these two viral isolates may cause distinct effects on the host transcriptional response in infected host cells, especially relating to how quickly translation is dysregulated after infection. This comparison of the intracellular host response to infection with these two SARS-CoV-2 isolates suggest that some of the mechanisms associated with more severe disease from these viruses could include virus replication, metal ion usage, host translation shutoff, host transcript stability, and immune inhibition.
    MeSH term(s) COVID-19 ; Humans ; New York ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Viral Proteins ; Washington
    Chemical Substances Spike Glycoprotein, Coronavirus ; Viral Proteins ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-09-20
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2022.1009328
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Chikungunya virus time course infection of human macrophages reveals intracellular signaling pathways relevant to repurposed therapeutics

    Madison Gray / Israel Guerrero-Arguero / Antonio Solis-Leal / Richard A. Robison / Bradford K. Berges / Brett E. Pickett

    PeerJ, Vol 10, p e

    2022  Volume 13090

    Abstract: Background Chikungunya virus (CHIKV) is a mosquito-borne pathogen, within the Alphavirus genus of the Togaviridae family, that causes ~1.1 million human infections annually. CHIKV uses Aedes albopictus and Aedes aegypti mosquitoes as insect vectors. ... ...

    Abstract Background Chikungunya virus (CHIKV) is a mosquito-borne pathogen, within the Alphavirus genus of the Togaviridae family, that causes ~1.1 million human infections annually. CHIKV uses Aedes albopictus and Aedes aegypti mosquitoes as insect vectors. Human infections can develop arthralgia and myalgia, which results in debilitating pain for weeks, months, and even years after acute infection. No therapeutic treatments or vaccines currently exist for many alphaviruses, including CHIKV. Targeting the phagocytosis of CHIKV by macrophages after mosquito transmission plays an important role in early productive viral infection in humans, and could reduce viral replication and/or symptoms. Methods To better characterize the transcriptional response of macrophages during early infection, we generated RNA-sequencing data from a CHIKV-infected human macrophage cell line at eight or 24 hours post-infection (hpi), together with mock-infected controls. We then calculated differential gene expression, enriched functional annotations, modulated intracellular signaling pathways, and predicted therapeutic drugs from these sequencing data. Results We observed 234 pathways were significantly affected 24 hpi, resulting in six potential pharmaceutical treatments to modulate the affected pathways. A subset of significant pathways at 24 hpi includes AGE-RAGE, Fc epsilon RI, Chronic myeloid leukemia, Fc gamma R-mediated phagocytosis, and Ras signaling. We found that the MAPK1 and MAPK3 proteins are shared among this subset of pathways and that Telmisartan and Dasatinib are strong candidates for repurposed small molecule therapeutics that target human processes. The results of our analysis can be further characterized in the wet lab to contribute to the development of host-based prophylactics and therapeutics.
    Keywords Chikungunya virus ; Transcriptomics ; Signaling pathways ; Drug repurposing ; Macrophage ; Virology ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: A comparison of Chikungunya virus infection, progression, and cytokine profiles in human PMA-differentiated U937 and murine RAW264.7 monocyte derived macrophages.

    Guerrero-Arguero, Israel / Høj, Taalin R / Tass, E Shannon / Berges, Bradford K / Robison, Richard A

    PloS one

    2020  Volume 15, Issue 3, Page(s) e0230328

    Abstract: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes rash, fever and severe polyarthritis that can last for years in humans. Murine models display inflammation and macrophage infiltration only in the adjacent tissues at the site of ... ...

    Abstract Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes rash, fever and severe polyarthritis that can last for years in humans. Murine models display inflammation and macrophage infiltration only in the adjacent tissues at the site of inoculation, showing no signs of systemic polyarthritis. Monocyte-derived macrophages are one cell type suspected to contribute to a systemic CHIKV infection. The purpose of this study was to analyze differences in CHIKV infection in two different cell lines, human U937 and murine RAW264.7 monocyte derived macrophages. PMA-differentiated U937 and RAW264.7 macrophages were infected with CHIKV, and infectious virus production was measured by plaque assay and by reverse transcriptase quantitative PCR at various time points. Secreted cytokines in the supernatants were measured using cytometric bead arrays. Cytokine mRNA levels were also measured to supplement expression data. Here we show that CHIKV replicates more efficiently in human macrophages compared to murine macrophages. In addition, infected human macrophages produced around 10-fold higher levels of infectious virus when compared to murine macrophages. Cytokine induction by CHIKV infection differed between human and murine macrophages; IL-1, IL-6, IFN-γ, and TNF were significantly upregulated in human macrophages. This evidence suggests that CHIKV replicates more efficiently and induces a much greater pro-inflammatory cytokine profile in human macrophages, when compared to murine macrophages. This may shed light on the critical role that macrophages play in the CHIKV inflammatory response.
    MeSH term(s) Animals ; Chikungunya Fever/immunology ; Chikungunya virus/physiology ; Cytokines/immunology ; Disease Progression ; Humans ; Macrophages/virology ; Mice ; RAW 264.7 Cells ; U937 Cells ; Virus Replication
    Chemical Substances Cytokines
    Language English
    Publishing date 2020-03-12
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0230328
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  7. Article: Artesunate Regulates Neurite Outgrowth Inhibitor Protein B Receptor to Overcome Resistance to Sorafenib in Hepatocellular Carcinoma Cells.

    He, Wubin / Huang, Xiaoxu / Berges, Bradford K / Wang, Yue / An, Ni / Su, Rongjian / Lu, Yanyan

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 615889

    Abstract: The multireceptor tyrosine kinase inhibitor sorafenib is a Food and Drug Administration-approved first-line drug for the treatment of advanced liver cancer that can reportedly extend overall survival in patients with advanced hepatocellular carcinoma ( ... ...

    Abstract The multireceptor tyrosine kinase inhibitor sorafenib is a Food and Drug Administration-approved first-line drug for the treatment of advanced liver cancer that can reportedly extend overall survival in patients with advanced hepatocellular carcinoma (HCC). Primary and acquired resistance to sorafenib are gradually increasing however, leading to failure of HCC treatment with sorafenib. It is therefore crucial to study the potential mechanism of sorafenib resistance. The results of the current study indicate that neurite outgrowth inhibitor protein B receptor (NgBR) is overexpressed in cultured sorafenib-resistant cells, and that its expression is negatively correlated with the sensitivity of liver cancer cells to sorafenib. Artesunate can inhibit the expression of NgBR, and it may block sorafenib resistance. Herein we report that sorafenib treatment in combination with artesunate overcomes HCC resistance to sorafenib alone in a cell culture model.
    Language English
    Publishing date 2021-02-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.615889
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Carbon-infiltrated carbon nanotubes inhibit the development of Staphylococcus aureus biofilms

    Lucy C. Bowden / Jocelyn G. W. Evans / Katelyn M. Miller / Anton E. Bowden / Brian D. Jensen / Sandra Hope / Bradford K. Berges

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract Staphylococcus aureus forms biofilms that cause considerable morbidity and mortality in patients who receive implanted devices such as prosthetics or fixator pins. An ideal surface for such medical devices would inhibit biofilm growth. Recently, ...

    Abstract Abstract Staphylococcus aureus forms biofilms that cause considerable morbidity and mortality in patients who receive implanted devices such as prosthetics or fixator pins. An ideal surface for such medical devices would inhibit biofilm growth. Recently, it was reported that surface modification of stainless steel materials with carbon-infiltrated carbon nanotubes (CICNT) inhibits the growth of S. aureus biofilms. The purpose of this study was to investigate this antimicrobial effect on titanium materials with CICNT coated surfaces in a variety of surface morphologies and across a broader spectrum of S. aureus isolates. Study samples of CICNT-coated titanium, and control samples of bare titanium, a common implant material, were exposed to S. aureus. Viable bacteria were removed from adhered biofilms and quantified as colony forming units. Scanning electron microscopy was used to qualitatively analyze biofilms both before and after removal of cells. The CICNT surface was found to have significantly fewer adherent bacteria than bare titanium control surfaces, both via colony forming unit and microscopic analyses. This effect was most pronounced on CICNT surfaces with an average nanotube diameter of 150 nm, showing a 2.5-fold reduction in adherent bacteria. Since S. aureus forms different biofilm structures by isolate and by growth conditions, we tested 7 total isolates and found a significant reduction in the biofilm load in six out of seven S. aureus isolates tested. To examine whether the anti-biofilm effect was due to the structure of the nanotubes, we generated an unstructured carbon surface. Significantly more bacteria adhered to a nonstructured carbon surface than to the 150 nm CICNT surface, suggesting that the topography of the nanotube structure itself has anti-biofilm properties. The CICNT surface possesses anti-biofilm properties that result in fewer adherent S. aureus bacteria. These anti-biofilm properties are consistent across multiple isolates of S. aureus and are affected by nanotube diameter. The ...
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Modelling of human herpesvirus infections in humanized mice.

    Berges, Bradford K / Tanner, Anne

    The Journal of general virology

    2014  Volume 95, Issue Pt 10, Page(s) 2106–2117

    Abstract: The human herpesviruses (HHVs) are remarkably successful human pathogens, with some members of the family successfully establishing infection in the vast majority of humans worldwide. Although many HHV infections result in asymptomatic infection or mild ... ...

    Abstract The human herpesviruses (HHVs) are remarkably successful human pathogens, with some members of the family successfully establishing infection in the vast majority of humans worldwide. Although many HHV infections result in asymptomatic infection or mild disease, there are rare cases of severe disease and death found with nearly every HHV. Many of the pathogenic mechanisms of these viruses are poorly understood, and in many cases, effective antiviral drugs are lacking. Only a single vaccine exists for the HHVs and researchers have been unable to develop treatments to cure the persistent infections associated with HHVs. A major hindrance to HHV research has been the lack of suitable animal models, with the notable exception of the herpes simplex viruses. One promising area for HHV research is the use of humanized mouse models, in which human cells or tissues are transplanted into immunodeficient mice. Current humanized mouse models mostly transplant human haematopoietic stem cells (HSCs), resulting in the production of a variety of human immune cells. Although all HHVs are thought to infect human immune cells, the beta- and gammaherpesviruses extensively infect and establish latency in these cells. Thus, mice humanized with HSCs hold great promise to study these herpesviruses. In this review, we provide a historical perspective on the use of both older and newer humanized mouse models to study HHV infections. The focus is on current developments in using humanized mice to study mechanisms of HHV-induced pathogenesis, human immune responses to HHVs and effectiveness of antiviral drugs.
    MeSH term(s) Animals ; Disease Models, Animal ; Herpesviridae Infections/pathology ; Herpesviridae Infections/virology ; Humans ; Mice ; Mice, SCID
    Language English
    Publishing date 2014-07-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/vir.0.067793-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Characterization of HIV-1 infection in the humanized Rag2-/-γc-/- mouse model.

    Sanchez, Freddy M / Berges, Bradford K

    Methods in molecular biology (Clifton, N.J.)

    2013  Volume 1031, Page(s) 215–222

    Abstract: Engraftment of immunodeficient mice with a human immune system (humanized mice) provides a model system to study pathogens that target human immune cells. Humanized Rag2(-/-)γc(-/-) mice produce the major target cells of HIV-1 and these cells can be ... ...

    Abstract Engraftment of immunodeficient mice with a human immune system (humanized mice) provides a model system to study pathogens that target human immune cells. Humanized Rag2(-/-)γc(-/-) mice produce the major target cells of HIV-1 and these cells can be detected in primary and secondary lymphoid tissues, as well as in the vaginal and rectal mucosa and brain tissues. This humanized model has already yielded important findings on HIV-1 transmission, mechanisms of pathogenesis, and testing of novel antiviral strategies in vivo. Here, we describe the methods used to infect humanized mice with HIV-1 and to characterize plasma viral load and blood CD4(+) T cell depletion.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; DNA-Binding Proteins/deficiency ; DNA-Binding Proteins/genetics ; Disease Models, Animal ; Female ; HIV Infections/drug therapy ; HIV Infections/genetics ; HIV Infections/virology ; HIV-1/immunology ; HIV-1/pathogenicity ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune System ; Mice ; Mucous Membrane/pathology ; Mucous Membrane/virology ; Vagina/pathology ; Vagina/virology
    Chemical Substances DNA-Binding Proteins ; Rag2 protein, mouse
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-481-4_24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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