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Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.
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Objective:To develop the UPLC-MS/MS method for the determination of amygdalin, cinnamic acid, rhein, emodin and glycyrrhizic acid in Taohe-Chengqi Decoction simutaneously. Methods:The separation was performed on Supelco Discovery C18, and isocratic elution was carried out with mobile phase consisting of acetonitrile - 4 mmol/L ammonium formate. The mass spectrometer was operated in the positive and negative ionization electrospray (ESI) mode using multiple monitoring (MRM) to analize of five ingredients. The precursor to product ion transitions monitored for amygdalin, cinnamic acid, rhein, emodin and glycyrrhizic acid were m/z 458.2→296.0, 146.8→103.1, 283.7→239.9, 269.7→226.1 and 821.4→350.9, respectively. Results:Amygdalin, cinnamic acid, rhein, emodin and glycyrrhizic acid were analyzed, the linear ranges were 0.001 6-0.102 4, 0.001 6-0.102 4, 0.001 6-0.102 4, 0.000 8-0.051 2 and 0.000 4-0.256 0 ng, respectively. The r were 0.998 7, 0.999 1, 0.999 5, 0.998 9 and 0.998 6, respectively. The recovery of five analytes ranges from 97.33% to 105.33% and the Relative Standard Deviations were all below 2.69%. Conclusion:This UPLC-MS/MS method is exclusive, rapid and sensitivewhich could be applied for the determination of amygdalin, cinnamic acid, rhein, emodin and glycyrrhizic acid in Taohe-Chengqi Decoction.
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Objective:To investigate the potential mechanism by which Brucella suis vaccine strain S2 induces the apoptosis of BV-2 microglia cells, and to discover new protein targets for neurobrucellosis treatment. Methods:BV-2 microglia cells were treated with Brucella suis vaccine strain S2 for 0, 3, 6, 12 and 24 h. Western blot assay and RT-qPCR were performed to detect the expression of p-JNK and p53 at protein and mRNA levels in BV-2 microglia cells. Cell apoptosis was measured by flow cytometry. Immunofluorescence was used to analyze nuclear p-JNK. Results:Brucella suis vaccine strain S2 could promote the expression of p-JNK and p53 at both protein and mRNA levels and increase nuclear p-JNK in BV-2 microglia cells. Moreover, it could also induce the apoptosis of BV-2 microglia cells. Conclusions:Brucella suis vaccine strain S2 could promote the apoptosis of BV-2 microglia cells through activating JNK and promoting p53 expression.
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OBJECTIVE:To study the pharmacokinetics and brain targeting of Toutongning nasal spray in rats in vivo. METH-ODS:84 SD rats were divided into nasal administration group and vein administration group,42 in each group,with dose of 1.2 mL/kg. 5 mL sample blood was taken in abdominal aorta after 5,10,15,30,60,90,120 min of administration,and brain tissue was taken (6 rats in each time point). HPLC-MS was adopted to determine the concentration of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma and brain tissue of rats in each group,and DAS 2.0 software was used to calculate the pharma-cokinetic parameters and brain targeting indexes. RESULTS:The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in plasma of rats in nasal administration group were(0.2024±0.0158),(0.3738±0.0857)μg/mL;tmax were(10.0000±0.0000) min;and AUC0-∞ were (16.5429 ± 2.1103),(27.4527 ± 5.5721)μg·h/mL,respectively. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were (0.1802 ± 0.0384),(0.3204 ± 0.0277)μg/g;tmax were (10.0000 ± 0.0000)min;and AUC0-∞ were(17.1053±2.4329),(24.5416±3.7534)μg·h/g,respectively. The cmax of prim-o-glucosylcimi-fugin and 5-O-methylvisammioside in plasma of rats in vein administration group were (0.3002 ± 0.0161),(0.5267 ± 0.0441)μg/mL;tmax were(10.0000±0.0000)min;and AUC0-∞ were(28.0105±4.1128),(60.2941±11.2902)μg·h/mL,respective-ly. The cmax of prim-o-glucosylcimifugin and 5-O-methylvisammioside in brain tissue of rats were(0.1498±0.0315),(0.1998± 0.0401)μg/g;tmax were(15.0000±0.0000)min;and AUC0-∞were(22.6434±2.8831),(36.7218±14.8856)μg·h/g,respec-tively. The brain targeting indexes of prim-o-glucosylcimifugin and 5-O-methylvisammioside were 2.3870 and 2.1761,respective-ly. CONCLUSIONS:After nasal administration of Toutongning nasal spray,parts of drugs can directly transport to the brian by na-sal absorption. It is scientific and reasonable to make nasal spray.
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The basic theory of high power green laser equipment for prostate hyperplasia therapy and the components of the system developed are introduced. Considering the requirements of the clinical therapy, the working process of the high power green laser apparatus are designed and the laser with stable output at 120 W is achieved. The controlling hardware and application software are developed, and the safety step is designed. The high power green laser apparatus manufactured with characteristics of stable output, multifunctional and friendly interface provides a choices of prostate hyperplasia therapy for using nationalization instrument.
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Humans , Laser Therapy , Lasers , Male , Patient Safety , Prostatic Hyperplasia , Therapeutics , SoftwareABSTRACT
Objective To examine the white matter microstructure alternations in the patients with generalized anxiety disorder (GAD) with diffusion weighted imaging.Methods 19 patients with GAD and 20 matched healthy controls were assessed using apparent diffusion coefficient (ADC) and exponential apparent diffusion coefficient (eADC) in the regions of interests (ROIs) approach.The ROIs were the white matter of bilateral cingulate and bilateral hippocampus.Results Significantly increased ADC values were found in GAD patients (0.78±0.02,0.79±0.03) with respect to normal controls in the right and left anterior cingulate white matter.Significantly decreased eADC values were found in GAD patients (0.46±0.01,0.45±0.01) in the right and left anterior cingulate white matter.Conclusion Diffuse cingulate white matter alterations on DWI in GAD denote the disruption of white matter integrity.