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981.
982.
Excessive activation of immune cells plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of immune cells by miRNAs is a research hotspot. In this study, second-generation high-throughput sequencing revealed a reduction in miR-99a-3p expression in patients with SLE; however, the specific mechanism underlying this phenomenon remains unclear. After transfection with an miR-99a-3p agomir, the proliferation of Ball-1 cells decreased and the levels of their apoptosis increased. The opposite effects were observed in cells transfected with the miR-99a-3p antagomir. Luciferase reporter assay indicated that miR-99a-3p directly targeted EIF4EBP1. Rescue experiments confirmed the proposed interaction between miR-99a-3p and EIF4EBP1. In vitro, in vivo and clinical investigations further confirmed that the miR-99a-3p agomir reduced the expression of EIF4EBP1, LC3B and LAMP-2A. In the in vivo experiments, serum levels of anti-nuclear antibodies, double-stranded DNA, IgE, IgM, IL-6, IL-10 and B lymphocyte stimulator were higher in mice from the antagomir group than those in mice from the MRL/lpr group. Furthermore, the protein and mRNA levels of EIF4EBP1, LC3B and LAMP-2A, the intensity of immunohistochemical staining of EIF4EBP1, LC3B and LAMP-2A, the urinary protein levels, and the C3 immunofluorescence deposition increased in mice from the antagomir group. The upregulation of miR-99a-3p expression protected B cells from EIF4EBP1-mediated autophagy, whilst the downregulation of miR-99a-3p expression induced autophagy via the EIF4EBP1-mediated regulation of the autophagy signalling pathway in B cells isolated from individuals with SLE. Based on these results, miR-99a-3p and EIF4EBP1 may be considered potential targets for SLE treatment.  相似文献   
983.
984.
The interaction between hepatitis C virus (HCV) and human hepatic innate antiviral responses is unclear. The aim of this study was to examine how human hepatocytes respond to HCV infection. An infectious HCV isolate, JFH1, was used to infect a newly established human hepatoma cell line HLCZ01. Viral RNA or NS5A protein was examined by real-time PCR or immunofluorescence respectively. The mechanisms of HCV-induced IFN-β and apoptosis were explored. Our data showed that HLCZ01 cells supported the entire HCV lifecycle and IFN-β and interferon-stimulated genes (ISGs) were induced in HCV-infected cells. Viral infection caused apoptosis of HLCZ01 cells. Silencing of RIG-I, IRF3 or TRAIL inhibited ISG12a expression and blocked apoptosis of viral-infected HLCZ01 cells. Knockdown ISG12a blocked apoptosis of viral-infected cells. MiR-942 is a candidate negative regulator of ISG12a predicted by bioinformatics search. Moreover, HCV infection decreased miR-942 expression in HLCZ01 cells and miR-942 was inversely correlated with ISG12a expression in both HCV-infected cells and liver biopsies. MiR-942 forced expression in HLCZ01 cells decreased ISG12a expression and subsequently suppressed apoptosis triggered by HCV infection. Conversely, silencing of miR-942 expression by anti-miR-942 increased ISG12a expression and enhanced apoptosis in HCV-infected cells. Induction of Noxa by HCV infection contributed to ISG12a-mediated apoptosis. All the data indicated that innate host response is intact in HCV-infected hepatocytes. MiR-942 regulates HCV-induced apoptosis of human hepatocytes by targeting ISG12a. Our study provides a novel mechanism by which human hepatocytes respond to HCV infection.  相似文献   
985.
Electrical stimulation (ES) has long been used as an alternative clinical treatment and an effective approach to modulate cellular behaviours. In this work we investigated the effects of ES on human skin fibroblast activity, myofibroblast transdifferentiation and the consequence on wound healing. Normal human fibroblasts were seeded on heparin-bioactivated PPy/PLLA conductive membranes, cultured for 24 h, and then exposed to ES of 50 or 200 mV/mm for 2, 4, or 6 h. Following ES, the cells were either subjected to various analyses or re-seeded to investigate their healing capacity. Our findings show that ES had no cytotoxic effect on the fibroblasts, as demonstrated by the similar LDH activity levels in the ES-exposed and non-exposed cultures, and by the comparable cell viability under both conditions. Furthermore, the number of viable fibroblasts was higher following exposure to 6 h of ES than in the non-exposed culture. This enhanced cell growth was likely due to the ES up-regulated secretion of FGF-1 and FGF-2. In an in vitro scratch-wound assay where cell monolayer was used as a healing model, the electrically stimulated dermal fibroblasts migrated faster following exposure to ES and recorded a high contractile behaviour toward the collagen gel matrix. This enhanced contraction was supported by the high level of α-smooth muscle actin expressed by the fibroblasts following exposure to ES, indicating the characteristics of myofibroblasts. Remarkably, the modulation of fibroblast growth continued long after ES. In conclusion, this work demonstrates for the first time that exposure to ES promoted skin fibroblast growth and migration, increased growth factor secretion, and promoted fibroblast to myofibroblast transdifferentiation, thus promoting wound healing.  相似文献   
986.
987.
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Highlights
  • •In-depth proteomes of 4 SARS-CoV-2 cell line models (Vero E6, Calu-3, Caco-2, A549).
  • •Proteomic evidence for thousands of Chlorocebus sabaeus proteins.
  • •Proteomic response of Vero E6 cells to SARS-CoV-2 infection.
  • •Synthetic peptides, spectral libraries, and targeted assays for SARS-CoV-2 proteins.
  相似文献   
988.
989.
The roles of α5-nicotinic acetylcholine receptors (α5-nAChRs) in various types of solid cancer have been reported; however, its role in melanoma remains unknown. We knocked down α5-nAChR expression in melanoma cells to investigate the role of α5-nAChR in the proliferation, migration, and invasion of melanoma cells, and its effect on downstream signaling pathways. Using immunohistochemical analysis, we determined that α5-nAChR expression is significantly increased in human melanoma tissues and cell lines compared with normal human skin tissues. Knocking down α5-nAChR expression in melanoma cells in culture significantly inhibited the proliferation, migration, and invasiveness of melanoma cell lines. Specifically, knockdown of α5-nAChR inhibited PI3K-AKT and ERK1/2 signaling activity. Moreover, we confirmed that the Notch1 signaling pathway is the downstream target of α5-nAChR in melanoma. Our findings suggest that α5-nAChR plays a critical role in melanoma development and progression, and that targeting α5-nAChR may be a strategy for melanoma treatment.  相似文献   
990.
Zhang  Zhen  Zhang  Yu  Zhang  Shanying  Wang  Lifeng  Liang  Xiaoyu  Wang  Xinquan  Wu  Huiyi  Zou  Haotian  Zhang  Chenghui  Wang  Meng 《Journal of Plant Growth Regulation》2022,41(6):2232-2245
Journal of Plant Growth Regulation - Mulberry (Morus alba L.) leaf, a “source of both medicine and food”, contains antioxidant ingredients such as flavonoids, alkaloids and polyphenols....  相似文献   
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