Active components with inhibitory activities on IFN-γ/STAT1 and IL-6/STAT3 signaling pathways from Caulis Trachelospermi.

Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1) with IC50 value of 2.43 µg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3) with IC50 value of 1.38 µg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1) and nortrachelogenin 4-O-ß-D-glucopyranoside (2), together with six known compounds. The lignan compounds 1-4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 µM and 9.46 µM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 µM, 6.47 µM and 2.92 µM, respectively.

Transforming growth factor-ß-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2.

In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-ß (TGF-ß)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of human ASM cells after incubation with TGF-ß (100 pM) and/or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and collagen remodeling. FGF-2 inhibited TGF-ß-stimulated increases in transgelin (SM22) and calponin gene expression (n = 15, P < 0.01) in an extracellular signal-regulated kinase 1/2 (ERK1/2) signal transduction-dependent manner. The abundance of ordered α-smooth muscle actin (α-SMA) filaments formed in the presence of TGF-ß were also reduced by FGF-2, as was the ratio of F-actin to G-actin (n = 8, P < 0.01). Furthermore, FGF-2 attenuated TGF-ß-stimulated increases in ASM cell stiffness and the ASM-mediated contraction of lattices, composed of collagen fibrils (n = 5, P < 0.01). However, the TGF-ß-stimulated production of IL-6 was not influenced by FGF-2 (n = 4, P > 0.05), suggesting that FGF-2 antagonism is selective for the regulation of ASM cell contractile protein expression, organization, and function. Another mitogen, thrombin (0.3 U ml(-1)), exerted no effect on TGF-ß-regulated contractile protein expression (n = 8, P > 0.05), α-SMA organization, or the ratio of F-actin to G-actin (n = 4, P > 0.05), suggesting that the inhibitory effect of FGF-2 is dissociated from its mitogenic actions. The addition of FGF-2, 24 hours after TGF-ß treatment, still reduced contractile protein expression, even when the TGF-ß-receptor kinase inhibitor, SB431542 (10 µM), was added 1 hour before FGF-2. We conclude that the ASM cell differentiation promoted by TGF-ß is antagonized by FGF-2. A better understanding of the mechanism of action for FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma.

Graphene oxide affects bacteriophage infection of bacteria by promoting the formation of biofilms.

Graphene oxide (GO) is increasingly used in a range of fields, such as electronics, biosensors, drug delivery, and water treatment, and the likelihood of its release into the environment is increasing correspondingly. GO is involved in the formation of biofilms and leads bacteria to over proliferate, but the effects of GO on bacteriophage infection remain unexplored. We noted bacterial overgrowth in experiments when GO was used to treat the bacterial culture medium, leading us to question whether bacterial proliferation caused by GO affects phage infection of target bacteria. Treating Pseudomonas aeruginosa with GO at a low dosage (0.02 mg/mL) led to biofilm expansion in LB medium. Biofilm formation in the presence of GO affected the ability of bacteriophages to kill bacteria and reproduce. Similarly, the presence of GO deposits increased the ratio of bacteria to phage, providing a favorable environment for bacterial growth. Additionally, increasing the positive electrical charge in the culture environment inhibited the rejection of bacteriophages by negatively charged GO, improving phage reproduction. Finally, adding GO to sewage in imitation field experiments significantly increased the bacterial diversity and richness in the sewage, stimulating a significant increase in the variety and number of bacteria. Collectively, these results indicate that GO hinders phage infection by providing a bacterial refuge. The results of this study provide valuable insights into how GO interacts with bacteriophages to explore the effects on bacterial growth.

The long non-coding RNA SNHG5 regulates gefitinib resistance in lung adenocarcinoma cells by targetting miR-377/CASP1 axis.

Gefitinib resistance is one of the major obstacles for the treatment of lung adenocarcinoma (LAD). The present study aimed to investigate the effects of the long non-coding RNA (lncRNA), small nucleolar RNA host gene 5SNHG5 on gefitinib resistance in LAD and explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) results showed that SNHG5 expression was significantly down-regulated in LAD patients with acquired gefitinib resistance and gefitinib resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib sensitive LAD cells to gefitinib treatment. Bioinformatics analysis showed that SNHG5 exerted its function through interaction with miR-377, which was further confirmed by luciferase reporter assay in 293T cells. Overexpression of SNHG5 suppressed the expression of miR-377, while the knockdown of SNHG5 increased the miR-377 expression. MiR-377 expression was significantly up-regulated in LAD specimens with acquired gefitinib resistance and was negatively correlated with SNHG5 expression. In addition, CASP1 was predicted as a downstream target of miR-377 Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells and knockdown of miR-377 increased the CASP1 expression in PC9GR cells. In vitro functional assay showed that knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance. Overall, the present study demonstrated, for the first time, that the SNHG5/miR-377/CASP1 axis functions as an important role in LAD cells gefitinib resistance and potentially contributes to the improvement of LAD diagnosis and therapy.