ABSTRACT
BACKGROUND/AIMS: LukS-PV is a component of Panton-Valentine leukocidin (PVL). We have previously demonstrated that LukS-PV potently promoted differentiation and induced apoptosis in THP-1 cells. However, the precise mechanisms of these actions remain unknown. MicroRNAs (miRs) play important roles in cellular differentiation and apoptosis. This study aimed to investigate the role of miR-125a-3p in LukS-PV-regulated differentiation and apoptosis and its underlying mechanism in THP-1 cells. METHODS: MicroRNA profiling analyses were conducted to determine differential miRNA expression levels in THP-1 cells treated with LukS-PV. Cell differentiation and apoptosis were measured in THP-1 cells by gain-of-function and loss-of-function experiments. Bioinformatics analysis and luciferase reporter assays were used to confirm the targets of miR-125a-3p. The effects of the miR-125a-3p targets on cellular differentiation were determined by knocking them down. RESULTS: MiR-125a-3p was up-regulated after treating the human monocytic leukaemia cell line THP-1 with LukS-PV. In addition, miR-125a-3p positively regulated apoptosis and differentiation in THP-1 cells treated with LukS-PV. Concordantly, luciferase reporter assays confirmed that neurofibromatosis type 1 (NF1) and B-cell lymphoma 2 (Bcl-2) were direct target genes of miR-125a-3p. Moreover, NF1 knockdown in THP-1 cells significantly promoted differentiation in vitro. Finally, the extracellular signal-regulated kinase (ERK) pathway, a downstream target of NF1, was activated after NF1 knockdown. CONCLUSIONS: These findings confirm that miR-125a-3p is involved in LukS-PV-mediated cell differentiation and apoptosis in THP-1 cells.
Subject(s)
Apoptosis/drug effects , Bacterial Toxins/pharmacology , Cell Differentiation/drug effects , Exotoxins/pharmacology , Leukocidins/pharmacology , MicroRNAs/metabolism , Neurofibromin 1/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , 3' Untranslated Regions , Antagomirs/metabolism , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Base Sequence , Caspase 3/metabolism , Cell Line , Down-Regulation/drug effects , Exotoxins/genetics , Exotoxins/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Leukocidins/genetics , Leukocidins/metabolism , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Neurofibromin 1/antagonists & inhibitors , Neurofibromin 1/genetics , Phosphorylation/drug effects , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Sequence Alignment , Signal Transduction/drug effects , Transcriptome/drug effects , bcl-2-Associated X Protein/metabolismABSTRACT
Water-promoted ortho-selective monohydroxymethylation of phenols in the NaBO2 system generates salicyl alcohols in 65-97% yields. A remarkable rate-enhancement by water was observed, and NaBO2 appeared to serve the dual role of a suitable base and an efficient chelating reagent. This protocol possesses many advantages such as short reaction times, expanded substrate scope, and high mono- and regio-selectivities. The experimental results were explained by the calculations based on local ionisation energy minima, leading to a possible reaction mechanism.
Subject(s)
Borates/chemistry , Phenols/chemistry , Water/chemistry , Formaldehyde/chemistry , Methylation , StereoisomerismABSTRACT
OBJECTIVE: To observe the influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy, and provide evidence for clinical application of auricular point sticking. METHODS: One hundred and twenty cases of selective gynecological laparoscopy under general anesthesia were randomly divided into an auricular point sticking group and a placebo group, 60 cases in each group. In the auricular point sticking group, the auricular point sticking with vaccaria seeds was applied at Shenmen (TF 4), Wei (CO 4) and Jiaogan (AH 6a) before the operation and 1, 5, 9, 23 h after the operation, which were pressed 5 min each point each time. The two ears were proceeded at the same time. In the placebo group, the same point selection, sticking paste was used as the auricular point sticking group, but no sticking or pressing with vaccaria seeds was adopted. The incidence of nausea and vomiting, the usage rate of tropisetron and morphine within 24 hours of the operation, as well as the score of visual analogue scale (VAS) and other adverse reactions at 2, 6, 10, 24 h after the operation were observed respectively. RESULTS: Compared with the placebo group, the incidence of nausea and vomiting [31.7% (19/60), 16.7% (10/60) vs 58.3% (35/60), 35.0% (21/60)], the usage rate of tropisetron [21.7% (13/60) vs 48.3% (29/60)] and morphine [18.3% (11/60) vs 38.3% (23/60)], the VAS scores at all different time points in the auricular point sticking group were all decreased (all P < 0.05), and no adverse reaction was observed. CONCLUSION: The auricular point sticking could significantly decrease the incidence of nausea and vomiting in patients of gynecological laparoscopy and has positive analgesic effect.
