28 research outputs found

    Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1-mediated inhibition of STAT3 and Akt/VEGFR2 pathway in hepatocellular carcinoma

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    Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Phloretin (PH) possesses anticancer, antitumor, and hepatoprotective effects, however, the effects and potential mechanisms of phloretin remain elusive. Methods: Five HCC cells were tested in vitro for sensitivity to PH, Sorafenib (Sor) or both and the apoptosis, signal transduction and phosphatase activity were analyzed. To validate the role of SHP-1, we used PTP inhibitor III and SHP-1 siRNA. Further, we used purified SHP-1 proteins or HCC cells expressing deletion N-SH2 domain or D61A point mutants to study the PH efficacy on SHP-1. The 'in vivo studies were conducted using HepG2 and SK-Hep1 and Sor resistant HepG2SR and Huh7SR xenografts. Molecular docking was done with Swiss dock and Auto Dock Vina. Results: PH inhibited cell growth and induced apoptosis in all HCC cells by upregulating SHP-1 expression and downregulating STAT3 expression and further inhibited pAKT/pERK signaling. PH activated SHP-1 by disruption of autoinhibition of SHP-1, leading to reduced p-STAT3Tyr705 level. PH induced apoptosis in two Sor-resistant cell lines and overcome STAT3, AKT, MAPK and VEGFR2 dependent Sor resistance in HCCs. PH potently inhibited tumor growth in both Sor-sensitive and Sor-resistant xenografts in vivo by impairing angiogenesis, cell proliferation and inducing apoptosis via targeting the SHP-1/STAT3 signaling pathway. Conclusion: Our data suggest that PH inhibits STAT3 activity in Sor-sensitive and -resistant HCCs via SHP-1-mediated inhibition of STAT3 and AKT/mTOR/JAK2/VEGFR2 pathway. Our results clearly indicate that PH may be a potent reagent for hepatocellular carcinoma and a noveltargeted therapy for further clinical investigations. Graphical abstract: [Figure not available: see fulltext]. - 2019 The Author(s).The publication of this article was funded by the Qatar National Library, Qatar. The graphical abstract was created with BioRender.comScopu

    Much ado about nothing? Tracing the progress of innovations borne on enterprise social network sites

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    Enterprise social networks are organizationally bounded online platforms for users to interact with another and maintain interpersonal relationships. The allure of these technologies is often seen in intra-organizational communication, collaboration and innovation. How these technologies actually support organizational innovation efforts remains unclear. A specific challenge is whether digital content on these platforms converts to actual innovation development efforts. In this study we set out to examine innovation-centric content flows on enterprise social networking platforms, and advance a conceptual model that seeks to explain which innovation conveyed in the digital content will traverse from the digital platform into regular processes. We describe important constructs of our model and offer strategies for the operationalization of the constructs. We conclude with an outlook to our ongoing empirical study that will explore and validate the key propositions of our model, and we sketch some potential implications for industry and academia

    Analiza fitochemiczna oraz ocena aktywności mięczakobójczej Andrographis paniculata

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    Andrographis paniculata Nees (Acanthaceae), commonly known as “Kalmegh” is traditionally used medicinal plant. In present study the laboratory evaluations were made to assess the preliminary phytochemical screening and molluscicidal activity of Andrographis paniculata. Maximum extractive value (3.134%) was found in water extract among test solvents. All the tested metabolites were qualitatively present in ethanolic extract. Regarding molluscicidal activity, the acute toxicity of the extracts on Lymnaea acuminata was evaluated by a rapid screening procedure. Among the different plant parts (root, stem and leaf) powder and ethanolic extract showed LC50 at 295.55mg/L and 19.73mg/L respectively. Screening of plant extracts represents a continuous effort to find new antiparasitic drugs.Andrographis paniculata Nees (Acanthaceae) jest tradycyjną rośliną leczniczą powszechnie znaną jako „Kalmegh”. W niniejszej pracy zaprezentowano wyniki wstępnych badań dotyczących analizy fitochemicznej oraz oceny aktywności mięczakobójczej Andrographis paniculata. Najwyższą wydajność ekstrakcji odnotowano w przypadku wyciągu wodnego – 3,134%, natomiast wszystkie bioaktywne metabolity były obecne w ilościach oznaczalnych w wyciągu alkoholowym. W przypadku działania mięczakobójczego oznaczono toksyczność ostrą z użyciem Lymnaea acuminata za pomocą szybkiego testu przesiewowego. Najwyższą LC50 spośród badanych części roślin (korzenie, łodyga i liście) odnotowano dla sproszkowanych korzeni oraz wyciągu alkoholowego, odpowiednio LC50=295,55 mg/L i 19,73 mg/L. Analiza wyciągów roślinnych potwierdza słuszność przeprowadzania dalszych badań mających na celu poszukiwanie nowych leków przeciwpasożytniczych

    SATYAPAL SINGH AND

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    The ethanolic extracts of different plant parts of Alangium salviifolium Linn, Andrographis paniculata Nees and Spilanthus acemella Murr showed significant antibacterial activity against Escherichia coli, Pseudomonas aureginosa, Staphylococcus aureus and antifungal activity against Aspergillus flavus A. niger, A. fumigatus and Fusarium oxysporium. Alangium salviifolium root extract and S. acemella leaf extract showed highest antibacterial activity against E. coli and Staphylococcus aureus. Root and stem extracts of Alangium salviifoilium recorded significant activity against all the test bacteria and fungi
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