LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 38

Search options

  1. Article: MET Receptor Tyrosine Kinase Inhibition Reduces Interferon-Gamma (IFN-γ)-Stimulated PD-L1 Expression through the STAT3 Pathway in Melanoma Cells.

    Song, Kyu Young / Han, Yong Hwan / Roehrich, Heidi / Brown, Mary E / Torres-Cabala, Carlos / Giubellino, Alessio

    Cancers

    2023  Volume 15, Issue 13

    Abstract: Melanoma is the leading cause of death from cutaneous malignancy. While targeted therapy and immunotherapy with checkpoint inhibitors have significantly decreased the mortality rate of this disease, advanced melanoma remains a therapeutic challenge. Here, ...

    Abstract Melanoma is the leading cause of death from cutaneous malignancy. While targeted therapy and immunotherapy with checkpoint inhibitors have significantly decreased the mortality rate of this disease, advanced melanoma remains a therapeutic challenge. Here, we confirmed that interferon-gamma (IFN-γ)-induced PD-L1 expression in melanoma cell lines. This increased expression was down-regulated by the reduction in phosphorylated STAT3 signaling via MET tyrosine kinase inhibitor treatment. Furthermore, immunoprecipitation and confocal immunofluorescence microscopy analysis reveals MET and PD-L1 protein-protein interaction and colocalization on the cell surface membrane of melanoma cells. Together, these findings demonstrate that the IFN-γ-induced PD-L1 expression in melanoma cells is negatively regulated by MET inhibition through the JAK/STAT3 signaling pathway and establish the colocalization and interaction between an RTK and a checkpoint protein in melanoma cells.
    Language English
    Publishing date 2023-06-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15133408
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface.

    Roehrich, Heidi / Yuan, Ching / Hou, Joshua H

    Cornea

    2020  Volume 39, Issue 12, Page(s) 1556–1562

    Abstract: Purpose: To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry.: Methods: Fresh donor corneas and primary ... ...

    Abstract Purpose: To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry.
    Methods: Fresh donor corneas and primary explant cultures of corneal, limbal, and conjunctival epithelial cells were evaluated for the expression of viral entry factors. Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2).
    Results: In total, 5 donor corneas were evaluated for the expression of viral entry factors. In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. DC-SIGN/DC-SIGNR expression varied between donor specimens. Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells.
    Conclusions: Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium. Cultured corneal, limbal, and conjunctival epithelial cells mimic the expression of viral entry factors in fresh donor tissue and may be useful for future in vitro SARS-CoV-2 infection studies.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus/physiology ; COVID-19 ; Cell Adhesion Molecules/metabolism ; Cells, Cultured ; Conjunctiva/cytology ; Conjunctiva/metabolism ; Coronavirus Infections/immunology ; Epithelial Cells/metabolism ; Epithelium, Corneal/metabolism ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Lectins, C-Type/metabolism ; Limbus Corneae/cytology ; Male ; Microscopy, Fluorescence ; Middle Aged ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/immunology ; Receptors, Cell Surface/metabolism ; SARS-CoV-2 ; Serine Endopeptidases/metabolism ; Tissue Donors ; Viral Tropism/physiology ; Virus Internalization ; Young Adult
    Chemical Substances CLEC4M protein, human ; Cell Adhesion Molecules ; DC-specific ICAM-3 grabbing nonintegrin ; Lectins, C-Type ; Receptors, Cell Surface ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
    Keywords covid19
    Language English
    Publishing date 2020-08-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604826-2
    ISSN 1536-4798 ; 0277-3740
    ISSN (online) 1536-4798
    ISSN 0277-3740
    DOI 10.1097/ICO.0000000000002509
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Mice Lacking the Systemic Vitamin A Receptor RBPR2 Show Decreased Ocular Retinoids and Loss of Visual Function.

    Radhakrishnan, Rakesh / Leung, Matthias / Roehrich, Heidi / Walterhouse, Stephen / Kondkar, Altaf A / Fitzgibbon, Wayne / Biswal, Manas R / Lobo, Glenn P

    Nutrients

    2022  Volume 14, Issue 12

    Abstract: The systemic transport of dietary vitamin A/all- ...

    Abstract The systemic transport of dietary vitamin A/all-
    MeSH term(s) Animals ; Carrier Proteins/metabolism ; Mammals/metabolism ; Mice ; Mice, Knockout ; Retina/metabolism ; Retinoids/metabolism ; Retinol-Binding Proteins/metabolism ; Vitamin A ; Zebrafish
    Chemical Substances Carrier Proteins ; Retinoids ; Retinol-Binding Proteins ; Vitamin A (11103-57-4)
    Language English
    Publishing date 2022-06-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu14122371
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface

    Roehrich, Heidi / Yuan, Ching / Hou, Joshua H.

    Cornea

    2020  Volume Publish Ahead of Print

    Keywords Ophthalmology ; covid19
    Language English
    Publisher Ovid Technologies (Wolters Kluwer Health)
    Publishing country us
    Document type Article ; Online
    ZDB-ID 604826-2
    ISSN 1536-4798 ; 0277-3740
    ISSN (online) 1536-4798
    ISSN 0277-3740
    DOI 10.1097/ico.0000000000002509
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  5. Article ; Online: Parabiosis reveals the correlation between the recruitment of circulating antigen presenting cells to the retina and the induction of spontaneous autoimmune uveoretinitis.

    McPherson, Scott W / Heuss, Neal D / Abedin, Md / Roehrich, Heidi / Pierson, Mark J / Gregerson, Dale S

    Journal of neuroinflammation

    2022  Volume 19, Issue 1, Page(s) 295

    Abstract: Background: Characterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of ... ...

    Abstract Background: Characterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of antigen presenting cells associated with the induction of retinal autoimmunity using a system that relies on spontaneous autoimmunity, thus avoiding uncertainties associated with immunization with adjuvants at remotes sites or adoptive transfer of in vitro activated T cells.
    Methods: R161H mice (B10.RIII background), which spontaneously and rapidly develop severe spontaneous autoimmune uveoretinitis (SAU), were crossed to CD11c
    Results: Onset of SAU in R161H
    Conclusions: Our results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile mechanical injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve, thus highlighting a unique facet of retinal autoimmunity.
    MeSH term(s) Mice ; Animals ; Mice, Transgenic ; Disease Models, Animal ; Retina/pathology ; Antigen-Presenting Cells ; Parabiosis ; Autoimmune Diseases ; Mice, Inbred C57BL
    Language English
    Publishing date 2022-12-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2156455-3
    ISSN 1742-2094 ; 1742-2094
    ISSN (online) 1742-2094
    ISSN 1742-2094
    DOI 10.1186/s12974-022-02660-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article: Human iPSC- and Primary-Retinal Pigment Epithelial Cells for Modeling Age-Related Macular Degeneration.

    Fisher, Cody R / Ebeling, Mara C / Geng, Zhaohui / Kapphahn, Rebecca J / Roehrich, Heidi / Montezuma, Sandra R / Dutton, James R / Ferrington, Deborah A

    Antioxidants (Basel, Switzerland)

    2022  Volume 11, Issue 4

    Abstract: Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related ... ...

    Abstract Primary cultures of retinal pigment epithelium (RPE) from human adult donors (haRPE) and induced pluripotent stem cell derived-RPE (iPSC-RPE) are valuable model systems for gaining mechanistic insight and for testing potential therapies for age-related macular degeneration (AMD). This study evaluated the treatment response of haRPE and iPSC-RPE to oxidative stress and potential therapeutics addressing mitochondrial defects. haRPE and iSPC-RPE were derived from donors with or without AMD. Mitochondrial function was measured after treatment with menadione, AICAR, or trehalose and the response to treatment was compared between cell models and by disease status. In a subset of samples, haRPE and iPSC-RPE were generated from the same human donor to make a side-by-side comparison of the two cell models' response to treatment. Disease-specific responses to all three treatments was observed in the haRPE. In contrast, iPSC-RPE had a similar response to all treatments irrespective of disease status. Analysis of haRPE and iPSC-RPE generated from the same human donor showed a similar response for donors without AMD, but there were significant differences in treatment response between cell models generated from AMD donors. These results support the use of iPSC-RPE and haRPE when investigating AMD mechanisms and new therapeutics but indicates that attention to experimental conditions is required.
    Language English
    Publishing date 2022-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11040605
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article: Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration.

    Ebeling, Mara C / Geng, Zhaohui / Stahl, Madilyn R / Kapphahn, Rebecca J / Roehrich, Heidi / Montezuma, Sandra R / Ferrington, Deborah A / Dutton, James R

    Pharmaceuticals (Basel, Switzerland)

    2022  Volume 15, Issue 1

    Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or "dry" AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts ... ...

    Abstract Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or "dry" AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.
    Language English
    Publishing date 2022-01-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph15010062
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Differences in Oxygen-Induced Retinopathy Susceptibility Between Two Sprague Dawley Rat Vendors: A Comparison of Retinal Transcriptomes.

    Lee, Haeyeon / Molomjamts, Mandkhai / Roehrich, Heidi / Gudvangen, Sydney / Asuncion, Chanel / Georgieff, Michael K / Tran, Phu / McLoon, Linda K / Ingolfsland, Ellen C

    Current eye research

    2023  Volume 49, Issue 4, Page(s) 425–436

    Abstract: Purpose: To determine the retinal transcriptomic differences underlying the oxygen-induced retinopathy phenotypes between Sprague Dawley rat pups from two commonly used commercial vendors. This will allow us to discover genes and pathways that may be ... ...

    Abstract Purpose: To determine the retinal transcriptomic differences underlying the oxygen-induced retinopathy phenotypes between Sprague Dawley rat pups from two commonly used commercial vendors. This will allow us to discover genes and pathways that may be related to differences in disease severity in similarly aged premature babies and suggest possible new treatment approaches.
    Methods: We analyzed retinal vascular morphometry and transcriptomes from Sprague Dawley rat pups from Charles River Laboratories and Envigo (previously Harlan). Room air control and oxygen-induced retinopathy groups were compared. Oxygen-induced retinopathy was induced with the rat 50/10 model.
    Results: Pups from Charles River Laboratories developed a more severe oxygen-induced retinopathy phenotype, with 3.6-fold larger percent avascular area at P15 and twofold larger % neovascular area at P20 than pups from Envigo. Changes in retinal transcriptomes of rat pups from both vendors were substantial at baseline and in response to oxygen-induced retinopathy. Baseline differences centered on activated pathways of neuronal development in Charles River Laboratories pups. In response to oxygen-induced retinopathy, during the neovascular phase, retinas from Charles River Laboratories pups exhibited activation of pathways regulating necrosis, neuroinflammation, and interferon signaling, supporting the observed increase of neovascularization. Conversely, retinas from Envigo pups showed decreased necrosis and increased focal adhesion kinase signaling, supporting more normal vascular development. Comparing oxygen-induced retinopathy transcriptomes at P15 to those at P20, canonical pathways such as phosphate and tensin homolog, interferon, and coordinated lysosomal expression and regulation element signaling were identified, highlighting potential novel mechanistic targets for future research.
    Conclusion: Transcriptomic profiles differ substantially between rat pup retinas from Charles River Laboratories and Envigo at baseline and in response to oxygen-induced retinopathy, providing insight into vascular morphologic differences. Comparing transcriptomes identified new pathways for further research in oxygen-induced retinopathy pathogenesis and increased scientific rigor of this model.
    MeSH term(s) Rats ; Animals ; Oxygen/toxicity ; Rats, Sprague-Dawley ; Retinopathy of Prematurity/chemically induced ; Retinopathy of Prematurity/genetics ; Transcriptome ; Retinal Neovascularization/genetics ; Retinal Neovascularization/pathology ; Animals, Newborn ; Necrosis/complications ; Necrosis/pathology ; Interferons ; Disease Models, Animal ; Retinal Vessels/pathology
    Chemical Substances Oxygen (S88TT14065) ; Interferons (9008-11-1)
    Language English
    Publishing date 2023-12-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 82079-9
    ISSN 1460-2202 ; 0271-3683
    ISSN (online) 1460-2202
    ISSN 0271-3683
    DOI 10.1080/02713683.2023.2297346
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article: Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface

    Roehrich, Heidi / Yuan, Ching / Hou, Joshua H

    Cornea

    Abstract: PURPOSE: To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry. METHODS: Fresh donor corneas and primary ... ...

    Abstract PURPOSE: To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry. METHODS: Fresh donor corneas and primary explant cultures of corneal, limbal, and conjunctival epithelial cells were evaluated for the expression of viral entry factors. Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2). RESULTS: In total, 5 donor corneas were evaluated for the expression of viral entry factors. In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. DC-SIGN/DC-SIGNR expression varied between donor specimens. Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells. CONCLUSIONS: Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium. Cultured corneal, limbal, and conjunctival epithelial cells mimic the expression of viral entry factors in fresh donor tissue and may be useful for future in vitro SARS-CoV-2 infection studies.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #725424
    Database COVID19

    Kategorien

  10. Article ; Online: Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration.

    Ebeling, Mara C / Geng, Zhaohui / Kapphahn, Rebecca J / Roehrich, Heidi / Montezuma, Sandra R / Dutton, James R / Ferrington, Deborah A

    Cells

    2021  Volume 10, Issue 4

    Abstract: Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial ... ...

    Abstract Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the complement pathway. This study used RPE generated from induced pluripotent stem cells (iPSC-RPE), which were derived from human donors with or without AMD and genotyped for the complement factor H (CFH) AMD high-risk allele (rs1061170, Y402H) to investigate whether donor disease state or genotype had a detrimental effect on mitochondrial function and inflammation. Results show that cells derived from donors with AMD display decreased mitochondrial function under conditions of stress and elevated expression of inflammatory markers compared to iPSC-RPE from individuals without AMD. A more pronounced reduction in mitochondrial function and increased inflammatory markers was observed in CFH high-risk cells, irrespective of disease state. These results provide evidence for a previously unrecognized link between CFH and mitochondrial function that could contribute to RPE loss in AMD patients harboring the CFH high-risk genotype.
    MeSH term(s) Aged ; Aged, 80 and over ; Biomarkers/metabolism ; Cell Line ; Complement Factor H/genetics ; Complement System Proteins/metabolism ; Epithelial Cells/pathology ; Female ; Humans ; Induced Pluripotent Stem Cells/pathology ; Inflammation/pathology ; Macular Degeneration/genetics ; Male ; Middle Aged ; Mitochondria/metabolism ; Mitochondria/pathology ; Mitochondrial Proteins/metabolism ; Models, Biological ; Polymorphism, Genetic ; Retinal Pigment Epithelium/pathology ; Risk ; Tissue Donors
    Chemical Substances Biomarkers ; Mitochondrial Proteins ; Complement Factor H (80295-65-4) ; Complement System Proteins (9007-36-7)
    Language English
    Publishing date 2021-04-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10040789
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top