Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking
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Abstract Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn 2+ ) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO 2 group, Zn 2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn 2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO 2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.Most of advanced hypopharyngeal squamous cell carcinoma (HSCC) are resistant to chemotherapy, and there is still lack of effective treatment for HSCC now. The present study aimed to investigate whether downregulation of RNA-binding motif protein 17 (RBM17) could enhance cisplatin sensitivity and inhibit cell invasion in HSCC and the underlying mechanism. We observed that RBM17 was upregulated in tumor tissues and associated with poor progression. Treatment of FaDu cells with cisplatin increased RBM17 expression in mRNA levels. Downregulation of RBM17 enhanced cisplatin-mediated inhibition of FaDu cells. In addition, downregulation of RBM17 effectively suppressed tumor cell migration and invasion through the reversion of epithelial-mesenchymal transition. Moreover, downregulation of RBM17 could significantly slow tumor growth in FaDu xenograft tumor model. Liquid chromatography-mass spectrometry/mass spectrometry detection and independent PRM analysis showed that 21 differentially expressed proteins were associated with the downregulation of RBM17. Taken together, our study implied that downregulation of RBM17 could serve as a novel approach to enhance cisplatin sensitivity in HSCC.
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Maternal viral infection is known to increase the risk for schizophrenia and autism in their offspring (Brown et al, 2004). C57BL/6 mice were infected with human influenza virus on day E18 of pregnancy and brains were collected at PN days 0, 14, or 56, from virally-exposed (N=3) or sham-infected control's (N=3) offspring. Microarray analysis of virally-exposed mouse brains showed significant (p<0.05) upregulation of 15 genes and downregulation of 3 genes in cerebellum, upregulation of 42 genes and downregulation of 9 genes in hippocampus, and upregulation of 4 genes and downregulation of 5 genes in prefrontal cortex vs. controls in day 0 mice. At day 14, there was a significant upregulation of 2 genes and downregulation of 0 genes in cerebellum, upregulation of 1 gene and downregulation of 1 gene in hippocampus, and upregulation of 3 genes and downregulation of 3 genes in prefrontal cortex vs. controls. At day 56, there was a significant upregulation of 13 genes and downregulation of 2 genes in cerebellum, upregulation of 4 genes and downregulation of 3 genes in hippocampus, and upregulation of 4 genes and downregulation of 1 gene in prefrontal cortex vs. controls. Implications of changes in brain genes for development of abnormal brain structure and function will be discussed. The generous support by the National Institute for Child Health and Human Development (1-R01-HD046589-01A2) to S.H.F. is greatly appreciated.
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Li, Xiaoyan; Wang, Xiaofang; Jiang, Li; Harris, Peter C.; Li, Xiaogang; Torres, Vicente E. Author Information
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Dual layer
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Cancer cells differ from normal cells in both gain of functions (i.e., upregulation) and loss of functions (i.e., downregulation). While it is common to suppress gain of function for chemotherapy, it remains challenging to target downregulation in cancer cells. Here we show the combination of enzyme-instructed assembly and disassembly to target downregulation in cancer cells by designing peptidic precursors as the substrates of both carboxylesterases (CESs) and alkaline phosphatases (ALPs). The precursors turn into self-assembling molecules to form nanofibrils upon dephosphorylation by ALP, but CES-catalyzed cleavage of the ester bond on the molecules results in disassembly of the nanofibrils. The precursors selectively inhibit the cancer cells that downregulate CES (e.g., OVSAHO) but are innocuous to a hepatocyte that overexpresses CES (HepG2), while the two cell lines exhibit comparable ALP activities. This work illustrates a potential approach for the development of chemotherapy via targeting downregulation (or loss of functions) in cancer cells.
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Check lamps and lanterns of injection molded parts vacuum coating adhesion is to verify coating parts surface coating quality level of an important indicator, Coating adhesion direct impact on coating parts and corrosion prevention sex and using effect. In this paper application of national standard, and in combination with the actual situation, Introduces the coating adhesion test methods and other test items for adhesion effect of elaboration, Aimed to help everyone to the vacuum coating adhesion check, With the correct choice of methods for determination of adhesion etc,Coated,Ensure coating quality.
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"Downregulation of miR-140-3p Is a Cause of Upregulation of RhoA Protein in Bronchial Smooth Muscle of Murine Experimental Asthma." American Journal of Respiratory Cell and Molecular Biology, 64(1), pp. 138–140
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