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  1. Article ; Online: Enhancement of innate immunity in gingival epithelial cells by vitamin D and HDAC inhibitors.

    Figgins, Erika L / Arora, Payal / Gao, Denny / Porcelli, Emily / Ahmed, Rabab / Daep, Carlo Amorin / Keele, Garrett / Ryan, Lisa K / Diamond, Gill

    Frontiers in oral health

    2024  Volume 5, Page(s) 1378566

    Abstract: Introduction: The human host defense peptide LL-37 is a component of the innate immune defense mechanisms of the oral cavity against colonization by microbes associated with periodontal disease. We have previously shown that the active form of vitamin D, ...

    Abstract Introduction: The human host defense peptide LL-37 is a component of the innate immune defense mechanisms of the oral cavity against colonization by microbes associated with periodontal disease. We have previously shown that the active form of vitamin D, 1,25(OH)
    Methods: We treated 3-dimensional primary cultures of GEC topically with the inactive form of vitamin D, in the presence and absence of selected histone deacetylase (HDAC) inhibitors. LL-37 mRNA levels were quantified by quantitative RT-PCR, and inhibition of invasion of bacteria was measured by fluorescence microscopy.
    Results: Vitamin D treatment led to an induction of LL-37 mRNA levels, as well as an inhibition of pro-inflammatory cytokine secretion. This effect was further enhanced by HDAC inhibitors, most strongly when the HDAC inhibitor, phenyl butyrate (PBA) was combined with Vitamin D
    Conclusions: Our results demonstrate that a combination of inactive vitamin D and sodium butyrate could be developed as a safe treatment for periodontal disease.
    Language English
    Publishing date 2024-03-14
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2673-4842
    ISSN (online) 2673-4842
    DOI 10.3389/froh.2024.1378566
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  2. Article ; Online: Porin loss in Klebsiella pneumoniae clinical isolates impacts production of virulence factors and survival within macrophages.

    Brunson, Debra N / Maldosevic, Emir / Velez, Amanda / Figgins, Erika / Ellis, Terri N

    International journal of medical microbiology : IJMM

    2019  Volume 309, Issue 3-4, Page(s) 213–224

    Abstract: Clinical isolates of Klebsiella pneumoniae are often resistant to beta-lactam antibiotics via the acquisition of extended spectrum beta lactamase (ESBL) enzymes paired with loss of one or both major outer membrane porins. It has been well established ... ...

    Abstract Clinical isolates of Klebsiella pneumoniae are often resistant to beta-lactam antibiotics via the acquisition of extended spectrum beta lactamase (ESBL) enzymes paired with loss of one or both major outer membrane porins. It has been well established that loss of OmpK35 and/or OmpK36 correlates with increased minimum inhibitory concentrations of antibiotics that target the peptidoglycan. However, little is known concerning the downstream effects porin loss might have on other major virulence factors such as the polysaccharide capsule or LPS. Furthermore, it is unknown whether these cumulative changes impact pathogenesis. Therefore, the focus of this study was to identify alterations in production of the major virulence factors due to porin loss; and to investigate the effect these changes have on host pathogen interactions. Our data demonstrates that loss of a single porin is paired with reductions in capsule, increased LPS content, and up-regulated transcription of compensatory porin genes. In contrast, loss of both porins resulted in a significant increase in capsule production. Loss of OmpK35 alone or dual porin loss was further associated with reduced oxidative burst by macrophages and increased ability of the bacteria to survive phagocytic killing. These data indicate that porin loss is accompanied by a suite of changes in other virulence-associated factors. These cumulative changes act to nullify any negative fitness effect due to lack of the nonspecific porin proteins, allowing the bacteria to grow and survive phagocytic immune responses.
    MeSH term(s) Animals ; Bacterial Capsules/metabolism ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Outer Membrane Proteins/metabolism ; Host-Pathogen Interactions ; Humans ; Klebsiella Infections/microbiology ; Klebsiella pneumoniae/genetics ; Klebsiella pneumoniae/isolation & purification ; Klebsiella pneumoniae/pathogenicity ; Klebsiella pneumoniae/physiology ; Lipopolysaccharides/metabolism ; Macrophages/metabolism ; Macrophages/microbiology ; Mice ; Microbial Viability ; Porins/deficiency ; Porins/genetics ; RAW 264.7 Cells ; Transcription, Genetic ; Virulence Factors/genetics ; Virulence Factors/metabolism ; beta-Lactamases/genetics ; beta-Lactamases/metabolism
    Chemical Substances Bacterial Outer Membrane Proteins ; Lipopolysaccharides ; Porins ; Virulence Factors ; beta-Lactamases (EC 3.5.2.6)
    Language English
    Publishing date 2019-04-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2006518-8
    ISSN 1618-0607 ; 1438-4221
    ISSN (online) 1618-0607
    ISSN 1438-4221
    DOI 10.1016/j.ijmm.2019.04.001
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  3. Article: Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids.

    Diamond, Gill / Molchanova, Natalia / Herlan, Claudine / Fortkort, John A / Lin, Jennifer S / Figgins, Erika / Bopp, Nathen / Ryan, Lisa K / Chung, Donghoon / Adcock, Robert Scott / Sherman, Michael / Barron, Annelise E

    Pharmaceuticals (Basel, Switzerland)

    2021  Volume 14, Issue 4

    Abstract: Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of ... ...

    Abstract Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific
    Language English
    Publishing date 2021-03-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph14040304
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  4. Article ; Online: Examination of gene expression in saliva samples from COVID-19 patients to study the host defense response against SARS-CoV-2 in the oral cavity.

    Diamond, Gill / Figgins, Erika L / Robinson, Tanya / Senitko, Michal / Abraham, George E / Williams, Haley B / Sloan, Meredith / Owings, Anna / Laird, Hannah / Pride, Yilianys / Wilson, Kenneth J / Hasan, Mohammad / Parker, Adam / Glover, Sarah C

    Molecular oral microbiology

    2020  Volume 36, Issue 2, Page(s) 157–158

    MeSH term(s) COVID-19 ; Gene Expression ; Humans ; Mouth ; SARS-CoV-2 ; Saliva
    Language English
    Publishing date 2020-12-08
    Publishing country Denmark
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2537726-7
    ISSN 2041-1014 ; 2041-1006
    ISSN (online) 2041-1014
    ISSN 2041-1006
    DOI 10.1111/omi.12327
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  5. Article ; Online: Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy.

    Liu, Julia J / Sloan, Meredith E / Owings, Anna H / Figgins, Erika / Gauthier, Josee / Gharaibeh, Raad / Robinson, Tanya / Williams, Haley / Sindel, Campbell B / Backus, Fremel / Ayyalasomayajula, Krishna / Parker, Adam / Senitko, Michal / Abraham, George E / Claggett, Brian / Horwitz, Bruce H / Jobin, Christian / Adelman, Robert M / Diamond, Gill /
    Glover, Sarah C

    The American journal of gastroenterology

    2021  Volume 116, Issue 8, Page(s) 1638–1645

    Abstract: Introduction: Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The underlying mechanism(s) for this association are ... ...

    Abstract Introduction: Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The underlying mechanism(s) for this association are unclear.
    Methods: We performed a prospective study of hospitalized coronavirus disease 2019 (COVID-19) patients and COVID-negative controls to understand how PPI use may affect angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, 2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors of in-hospital mortality.
    Results: Control PPI users had higher salivary ACE2 mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 (P = 0.02), respectively. Salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In 694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors of mortality by logistic regression were PPI use (adjusted odds ratio [aOR] = 2.72, P < 0.001), age (aOR = 1.66 per decade, P < 0.001), race (aOR = 3.03, P = 0.002), cancer (aOR = 2.22, P = 0.008), and diabetes (aOR = 1.95, P = 0.003). The PPI-associated mortality risk was higher in black patients (aOR = 4.16, 95% confidence interval: 2.28-7.59) than others (aOR = 1.62, 95% confidence interval: 0.82-3.19, P = 0.04 for interaction).
    Discussion: COVID-negative PPI users had higher salivary ACE2 expression. PPI use was associated with increased mortality risk in patients with COVID-19, particularly African Americans.
    MeSH term(s) Adult ; Aged ; Angiotensin-Converting Enzyme 2/blood ; COVID-19/blood ; COVID-19/mortality ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/adverse effects ; Retrospective Studies ; Risk Assessment
    Chemical Substances Proton Pump Inhibitors ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2021-05-31
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 390122-1
    ISSN 1572-0241 ; 0002-9270
    ISSN (online) 1572-0241
    ISSN 0002-9270
    DOI 10.14309/ajg.0000000000001311
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