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  1. Article ; Online: Apoptotic caspase inhibits innate immune signaling by cleaving NF-κBs in both Mammals and Flies.

    Wu, Di / Wang, Zhaowei / Zhang, Jing / Robinson, Adam G / Lyu, Bao / Chen, Ziyu / Wang, Chong / Wei, Bin / Xia, Xiaojun / Zhang, Qing / Zhou, Xi

    Cell death & disease

    2022  Volume 13, Issue 8, Page(s) 731

    Abstract: Host organisms use different innate immune mechanisms to defend against pathogenic infections, while tight control of innate immunity is essential for proper immune induction and balance. Here, we reported that apoptotic induction or caspase-3 ... ...

    Abstract Host organisms use different innate immune mechanisms to defend against pathogenic infections, while tight control of innate immunity is essential for proper immune induction and balance. Here, we reported that apoptotic induction or caspase-3 overexpression caused dramatic reduction of differently triggered cytokine signalings in human cells, murine primary cells and mouse model, while the loss of caspase-3 or inhibiting apoptosis markedly enhances these immune signalings. Furthermore, caspase-3 can mediate the cleavage of NF-κB members p65/RelA, RelB, and c-Rel via its protease activity. And the caspase-3-resistant p65/RelA, RelB, or c-Rel mutant mostly restored the caspase-3-induced suppression of cytokine production. Interestingly, we further uncovered that apoptotic induction also dramatically inhibited Toll immune signaling in Drosophila, and the Drosophila effector caspases, drICE and DCP-1, also mediated the degradation of DIF, the NF-κB of Toll signaling. Together, our findings demonstrate apoptotic effector caspases, including mammalian caspase-3 and fly drICE/DCP-1, can function as repressors of NF-κB-mediated innate immune signalings.
    MeSH term(s) Animals ; Apoptosis ; Caspase 3 ; Caspases/metabolism ; Cytokines ; DNA-Binding Proteins/metabolism ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Humans ; Immunity, Innate ; Mammals ; Mice ; NF-kappa B/metabolism ; Transcription Factor RelA/metabolism ; Transcription Factors
    Chemical Substances Cytokines ; DNA-Binding Proteins ; Dif protein, Drosophila ; Drosophila Proteins ; NF-kappa B ; Transcription Factor RelA ; Transcription Factors ; Caspase 3 (EC 3.4.22.-) ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2022-08-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-022-05156-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effect of Flavonoid Supplementation on Alveolar Bone Healing-A Randomized Pilot Trial.

    Souza, Jose Moises / Tuin, Stephen A / Robinson, Adam G / Souza, Joao Gustavo Oliveira de / Bianchini, Marco Aurelio / Miguez, Patricia A

    Dentistry journal

    2020  Volume 8, Issue 3

    Abstract: We investigated the effects of two common dietary supplements on bone healing in dental extraction sockets in humans. In this randomized pilot trial, male subjects took Grape Seed Extract [GSE] or Grapefruit Extract [GFE] starting two weeks prior to ... ...

    Abstract We investigated the effects of two common dietary supplements on bone healing in dental extraction sockets in humans. In this randomized pilot trial, male subjects took Grape Seed Extract [GSE] or Grapefruit Extract [GFE] starting two weeks prior to dental extraction and maintained this regimen for sixty days after surgery. Extraction sockets were filled with a collagen plug. After 24 h, a socket sample was collected and processed for quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and an 84-gene wound healing assay. Sixty days after tooth extraction, a core of newly formed bone was obtained prior to dental implant placement and processed for histology. qRT-PCR revealed that GFE led to a significant decrease in platelet-derived growth factor and interleukin (IL)1-β compared to GSE, and a significant decrease in IL-6 and CXCL2 compared to control. GSE led to a significant increase in coagulation factor Von Willebrand and inflammatory marker IL1-β compared to GFE. WISP1 and CXCL5 were upregulated in both groups. Overall, GFE showed a downregulation of inflammation and GSE led to a decrease in collagen density and increased osteoclasts. This pilot trial highlights the need for further investigation on the mechanism of action of such supplements on bone healing and oral health.
    Language English
    Publishing date 2020-08-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681351-8
    ISSN 2304-6767 ; 2304-6767
    ISSN (online) 2304-6767
    ISSN 2304-6767
    DOI 10.3390/dj8030086
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo.

    Miguez, Patricia A / Tuin, Stephen A / Robinson, Adam G / Belcher, Joyce / Jongwattanapisan, Prapaporn / Perley, Kimberly / de Paiva Gonҫalves, Vinicius / Hanifi, Arash / Pleshko, Nancy / Barton, Elisabeth R

    International journal of molecular sciences

    2021  Volume 22, Issue 6

    Abstract: This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and ... ...

    Abstract This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.
    MeSH term(s) Animals ; Bone Morphogenetic Protein 2/pharmacology ; Bone Regeneration ; Calcification, Physiologic/drug effects ; Cell Line ; Cells, Cultured ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Hesperidin/pharmacology ; Mice ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Osteogenesis/drug effects ; Rats
    Chemical Substances Bmp2 protein, mouse ; Bone Morphogenetic Protein 2 ; Collagen (9007-34-5) ; Hesperidin (E750O06Y6O)
    Language English
    Publishing date 2021-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22063223
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The function and regulation of the GATA factor ELT-2 in the C. elegans endoderm.

    Wiesenfahrt, Tobias / Berg, Janette Y / Osborne Nishimura, Erin / Robinson, Adam G / Goszczynski, Barbara / Lieb, Jason D / McGhee, James D

    Development (Cambridge, England)

    2016  Volume 143, Issue 3, Page(s) 483–491

    Abstract: ELT-2 is the major regulator of genes involved in differentiation, maintenance and function of C. elegans intestine from the early embryo to mature adult. elt-2 responds to overexpression of the GATA transcription factors END-1 and END-3, which specify ... ...

    Abstract ELT-2 is the major regulator of genes involved in differentiation, maintenance and function of C. elegans intestine from the early embryo to mature adult. elt-2 responds to overexpression of the GATA transcription factors END-1 and END-3, which specify the intestine, as well as to overexpression of the two GATA factors that are normally involved in intestinal differentiation, ELT-7 and ELT-2 itself. Little is known about the molecular mechanisms underlying these interactions, how ELT-2 levels are maintained throughout development or how such systems respond to developmental perturbations. Here, we analyse elt-2 gene regulation through transgenic reporter assays, ELT-2 ChIP and characterisation of in vitro DNA-protein interactions. Our results indicate that elt-2 is controlled by three discrete regulatory regions conserved between C. elegans and C. briggsae that span >4 kb of 5' flanking sequence. These regions are superficially interchangeable but have quantitatively different enhancer properties, and their combined activities indicate inter-region synergies. Their regulatory activity is mediated by a small number of conserved TGATAA sites that are largely interchangeable and interact with different endodermal GATA factors with only modest differences in affinity. The redundant molecular mechanism that forms the elt-2 regulatory network is robust and flexible, as loss of end-3 halves ELT-2 levels in the early embryo but levels fully recover by the time of hatching. When ELT-2 is expressed under the control of end-1 regulatory elements, in addition to its own endogenous promoter, it can replace the complete set of endoderm-specific GATA factors: END-1, END-3, ELT-7 and (the probably non-functional) ELT-4. Thus, in addition to controlling gene expression during differentiation, ELT-2 is capable of specifying the entire C. elegans endoderm.
    MeSH term(s) 5' Flanking Region/genetics ; Animals ; Base Sequence ; Caenorhabditis elegans/embryology ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Cell Differentiation/genetics ; Chromatin Immunoprecipitation ; Conserved Sequence ; DNA/metabolism ; Endoderm/embryology ; Endoderm/metabolism ; GATA Transcription Factors/genetics ; GATA Transcription Factors/metabolism ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Intestines/metabolism ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Binding/genetics ; Transcription Factors/metabolism ; Transcription, Genetic
    Chemical Substances Caenorhabditis elegans Proteins ; ELT-2 protein, C elegans ; END-3 protein, C elegans ; GATA Transcription Factors ; Transcription Factors ; DNA (9007-49-2)
    Language English
    Publishing date 2016-02-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.130914
    Database MEDical Literature Analysis and Retrieval System OnLINE

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