OBJECTIVENaringenin has been reported to attenuate Mucin (MUC) 5AC secretion in many pathological models. Many stimuli activate MUC5AC expression through JNK/AP-1 signaling pathways. We hypothesized that naringenin may have inhibitory effects on mucous hypersecretion by modulating MUC5AC production and inhibiting JNK/AP-1 signaling pathways.

METHODThe cell model of mucous hypersecretion was made by human lung adenocarcinoma epithelial (A549) cells stimulated by RSV. A549 cells were subcultured and then randomly divided into 7 groups, which were designated as group C (cell control group), groups R1-3 (cells were infected with RSV at the multiplication of infection (MOI) of 0. 5, 1. 0, 5. 0), groups N1-2 (cells infected with viruses in presence of Nar 30 - 100 mol/L), groups N3-4 (uninfected cells treated with Nar 30 - 100 µmol/L), group D (DMSO), group S (cells infected with viruses in presence of SP600125). After incubating for 24 hrs, the expression of MUC5AC at mRNA and protein level in the groups were determined by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). The protein expression changes of JNK, p-JNK and AP-1 were measured by Western blotting.

RESULTThe expressions of MUC5AC protein and mRNA in all RSV infected groups were significantly higher than that in group C in a dose-dependent manner (all P <0. 05). Nar of 30 and 100 µmol/L significantly and dose-dependently decreased RSV-induced secretion of MUC5AC protein in cell supernatant and expression of MUC5AC mRNA (P <0. 05). The relative content of p-JNK, AP-l in R2 groups were 3. 31 ± 0. 34 and 1. 94 ± 0. 05. Theyfrweremtgnificanty increased as compared with group C (both 1. 00 ± 0. 00) (all P <0. 05). The levels of p-JNK in N2 and S groups were 2. 10 ± 0. 20. 27 and 1.±97 ± 0. 16. The levels of AP-1 in N2 and S groups were 1. 40 ± 0. 03, 1. 36 ± 0. 05. Nar and SP600125 led to a largest decrease in levels of p-JNK and AP-1 when compared with group R2 (P <0. 05). The MUC5AC protein in group R2 was (48. 19 ± 0. 47) µg/L. The protein expression of MUC5AC in group R2 was significantly higher than that in group C [(36. 67 ± 1. 50) g/L] with a statistically significant difference (P <0. 05). The protein expression of MUC5AC in groups N2 and S were(43. 17 ± 1. 06) µg/L, (44.±02 ± 0. 99) µg/L, Nar and SP600125 remarkably inhibited RSV-induced secretion of MUC5AC in supernatant of A549 cells (P < 0. 05).

CONCLUSIONSNaringenin might be able to block RSV-induced mucous

Adenocarcinoma ; Blotting, Western ; Cell Line, Tumor ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Flavanones ; pharmacology ; Humans ; Lung Neoplasms ; Mucin 5AC ; secretion ; Mucus ; secretion ; Random Allocation ; Signal Transduction ; Transcription Factor AP-1 ; drug effects

Objective To explore the clinical application of DKK-1,TFF3 and CA72-4 detection in the diagnosis and treatment of gastric cancer.Methods Seventy-five cases(gastric cancer group) of gastric cancer admitted to our hospital from January 2013 to May 2015 were selected.Seventy cases of benign gastric disease(benign gastric disease group) and 70 persons undergoing the physical examination(healthy control group) were selected as the research subjects.The concentration of CA72-4 in each group was detected by the electrochemiluminescence analyzer.The serum DKK-1 and TFF3 levels in each group were detected by enzyme linked immunosorbent assay(ELISA).The receiver operating characteristic(ROC) curve was drawn for evaluating the diagnostic efficiency of each index in each group.The sensitivity,specificity,positive predictive rate and negative predictive rate of 3 indicators for diagnosing gastric cancer before operation were compared.The concentration change of various indexes after gastric cancer radical resection were compared..Results The concentrations of DKK-1,TFF3 and CA72-4 in the gastric cancer group were significantly higher than those in the benign gastric disease group and healthy control group,the difference was statistically significant(P<0.05).The area under ROC curve of DKK-1,TFF3 and CA72-4 were 0.876(95%CI 0.803-0.950),0.944 4(95%CI 0.894-0.975) and 0.818(95%CI 0.726-0.884) respectively.The sensitivity of CA72-4 was 78.6% and the specificity was 84.3%,the sensitivity of DKK-1 was 93.6% and the specificity was 87.1%,the sensitivity and specificity of TFF3 was 92.4% and 90.1% respectively.The concentrations of DKK-1,TFF3 and CA72-4 after radical resection in the gastric cancer group were significantly reduced,the difference was statistically significant compared with before treatment(P<0.05).Conclusion The detection of DKK-1,TFF3 and CA72-4 has a certain clinical value for the diagnosis of gastric cancer.The combined detection of these 3 indicators is conducive to improve the specificity and sensitivity of gastric cancer diagnosis.

This study was aimed to evaluate the quality ofYuan-Hu Zhi-Tong (YHZT) tablet from different manufacturers by high performance liquid chromatography (HPLC) fingerprint. An HPLC method was developed to establish the fingerprint of 12 batches of YHZT from 10 manufacturers. The common peaks were confirmed by mass spectrometric analysis. Similarity analysis (SA), hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to analyze the fingerprint chromatography. The results showed that there were 15 common peaks in which 12 components were from Corydalis Rhizoma and 3 from Radix Angelicae Dahuricae. The similar degrees of 12 batches of YHZT tablet were between 0.498 and 0.999. Based on the values, they could fall into three groups. The result of HCA showed that 12 batches of samples could be divided into 3 classes. The results of PCA indicated that the first three principal components (PCs) could represent the 15 common peaks. According to the scores of 3 PCs, 12 batches of samples could be divided into three categories. The classification result was mainly affected by the components of Corydalis Rhizoma. The classification results of three methods were basically the same. Based on the combination of three methods, 12 samples can be divided into three grades in the aspect of quality. It was concluded that the quality differences of YHZT tablet from different manufacturers were obvious. The combining application of three methods can be used in the evaluation on fingerprint of samples from different sources and influence factor analysis. It can be used as an effective method for quality evaluation.

Clinopodii Herba is a type of traditional folk medicine. Modern research showed that Clinopodii Herba contains triterpenes and its saponins, flavones, volatile oil, phenylpropanoids and other chemical components. It has many pharmacological activities such as hemostasis, antibiosis, hypoglycemic activity, anti-oxidation, and anti-in-flammation. The main clinical application of Clinopodii Herba is for the treatment of various types of bleeding. After searching literatures on Clinopodii Herba for the recent 20 years, this article reviewed the chemical components, pharmacological activities, clinical application and research condition of Clinopodii Herba in order to provide further references for this medicine.

This study was aimed to optimize extraction technology of Asperosaponin VI from Dipsaci Radix by re-sponse surface methodology (RSM). A single-factor test and Box-Behnken design (BBD) were employed to optimize three extraction variables, including extraction time (A), ethanol concentration (B), and the ratio of ethanol to materi-al (C). The transfer rate of Asperosaponin VI was used as the evaluation index. The results showed that the optimized conditions were A of 33.13 min, B of 51.58 %, C of 23.39 mL·g-1. Under these conditions, the transfer rate was 88.39 ± 0.212% (n = 3), which was well matched with the predicted transfer rate. It was concluded that RSM can be used for extraction optimization of ultrasonic extraction process for Asperosaponin VI. This method had certain prac-tical values.

Objective:To investigate the effect of long-term oral administration of β-blocker on septic myocardial injury and prognosis.Methods:A retrospective study was conducted. Patients who were admitted to the emergency intensive care unit (EICU) and intensive care unit (ICU) of Tongde Hospital of Zhejiang Province from January 2015 to June 2020 were enrolled. A total of 289 patients who met the criteria of myocardial injury induced by sepsis were included in the analysis. Among them, 187 patients who had never taken β-blocker within 3 months before diagnosis were divided in the non-β-blocker group, and 102 patients who took β-blocker daily for more than 3 months before diagnosis were in the β-blocker group. The physiological and biochemical characteristics were compared between the two groups, including heart rate, mean arterial pressure (MAP) at the time of diagnosis, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), MB isoenzyme of creatine kinase (CK-MB), blood lactic acid (Lac), central venous oxygen saturation (ScvO 2), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score within 24 hours of diagnosis, left ventricular ejection fraction (LVEF), early and late mitral orifice diastolic peak flow velocity ratio (E/A), utilization rate of vasoactive drugs during hospitalization and 28-day mortality. Results:The heart rate in the β-blocker group at the time of diagnosis was significantly lower than that in the non-β-blocker group (bpm: 107±8 vs. 110±7, P < 0.01), and the levels of cTnI and BNP within 24 hours of diagnosis were significantly lower than those in the non-β-blocker group [cTnI (μg/L): 0.191 (0.220) vs. 0.291 (0.300), BNP (ng/L): 627 (133) vs. 690 (201), both P < 0.05]. However, there were no significant differences in MAP, CK-MB, Lac, ScvO 2, SOFA score, APACHE Ⅱ score, LVEF, E/A, vasoactive drug utilization rate, and 28-day mortality between the β-blocker and non-β-blocker groups [MAP (mmHg, 1 mmHg = 0.133 kPa): 70.6±3.9 vs. 69.9±3.8, CK-MB (μg/L): 4.24 (3.33) vs. 4.32 (3.13), Lac (mmol/L): 3.50 (1.80) vs. 3.50 (1.90), ScvO 2: 0.729±0.032 vs. 0.735±0.041, SOFA score: 7.74±2.34 vs. 7.25±2.23, APACHE Ⅱ score: 17.19±5.13 vs. 18.27±6.12, LVEF: 0.567±0.058 vs. 0.557±0.051, E/A: 0.71 (0.20) vs. 0.69 (0.20), vasoactive drug utilization rate: 60.8% (62/102) vs. 56.7% (106/187), 28-day mortality: 23.5% (24/102) vs. 25.7% (48/187), all P > 0.05]. Conclusion:Long-term oral administration of β-blocker reduce myocardial injury in septic patients, and has no effect on disease severity and prognosis.

Purpose: Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. Materials and Methods: RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. Results: We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. Conclusion Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

Natural products (NPs) are important drug pools for human disease prevention and treatment. The great advances in synthetic biology have greatly revolutionized the strategies of NPs development and production. This review entitled with design and construction of artificial biological systems for complex NPs biosynthesis, mainly introduced the progresses in artificial design of synthetic biological parts, naturally mining novel synthetic parts of NPs, the assembly & adaption of the artificial biological modules & systems.
Biological Products ; chemistry ; metabolism ; Escherichia coli ; genetics ; metabolism ; Neural Networks (Computer) ; Recombinant Proteins ; biosynthesis ; genetics ; Synthetic Biology ; methods ; Systems Biology ; methods