Nickel-Catalyzed, Aminoquinoline-Directed Chemo- and Regioselective Carboamination of Unactivated Olefins with Organoboronic Acids and Anthranils.

A nickel-catalyzed three-component carboamination of unactivated alkenes with organoboronic acids and anthranils has been achieved for the expedient synthesis of δ-aryl and γ-amino acid derivatives. The 8-aminoquinoline (AQ) directing group is crucial for the success of the reaction, and anthranil serves as an arylnitrene precursor in this conversion. This method features mild reaction conditions, good chemo- and regioselectivity, and a broad substrate scope with good functional group tolerance.

Combined effects of cadmium and simulated acid rain on soil microbial communities in the early cultivation of Populus beijingensis seedlings.

The combined cadmium (Cd) and acid rain pollution poses a significant threat to the global ecological environment. Previous studies on the combined adverse effects have predominantly focused on the aboveground plant physiological responses, with limited reports on the microbial response in the rhizosphere soil. This study employed Populus beijingensis seedlings and potting experiments to simulate the impacts of combined mild acid rain (pH=4.5, MA) or highly strong acid rain (pH=3.0, HA), and soil Cd pollution on the composition and diversity of microbial communities, as well as the physiochemical properties in the rhizosphere soil. The results showed that Cd decreased the content of inorganic nitrogen, resulting in an overall decrease of 49.10 % and 46.67 % in ammonium nitrogen and nitrate nitrogen, respectively. Conversely, acid rain was found to elevate the content of total potassium and soil organic carbon by 4.68 %-6.18 % and 8.64-19.16 %, respectively. Additionally, simulated acid rain was observed to decrease the pH level by 0.29-0.35, while Cd increased the pH level by 0.11. Moreover, Cd alone reduced the rhizosphere bacterial diversity, however, when combined with acid rain, regardless of its intensity, Cd was observed to increase the diversity. Fungal diversity was not influenced by the acid rain, but Cd increased fungal diversity to some extend under HA as observed in bacterial diversity. In addition, composition of the rhizosphere bacterial community was primarily influenced by the inorganic nitrogen components, while the fungal community was driven mainly by soil pH. Furthermore, "Metabolism" was emerged as the most significant bacterial function, which was markedly affected by the combined pollution, while Cd pollution led to a shift from symbiotroph to other trophic types for fungi. These findings suggest that simulated acid rain has a mitigating effect on the diversity of rhizosphere bacteria affected by Cd pollution, and also alters the trophic type of these microorganisms. This can be attributed to the acid rain-induced direct acidic environment, as well as the indirect changes in the availability or sources of carbon, nitrogen, or potassium.

Selective removal of thiosulfate from coke oven gas desulfurization wastewater by catalytic wet air oxidation with manganese-based oxide from spent ternary lithium-ion batteries.

Selective and efficient removal of thiosulfates (S2O32-) to recover high-purity and value-added thiocyanate products by fractional crystallization process is a promising route for the resource treatment of coke oven gas desulfurization wastewater. Herein, catalytic wet air oxidation (CWAO), with manganese-based oxide synthesized from spent ternary lithium-ion batteries (MnOx-LIBs), was proposed to selectively remove S2O32- from desulfurization wastewater. 98.0 % of S2O32- is selectively removed by the MnOx-LIBs CWAO system, which was 4.1 times that of the MnOx CWAO system. The synergistic effect among multiple metals from spent LIBs induces the enlarged specific surface area, increased reactive sites and formation of oxygen vacancy, promoting the adsorption and activation of O2, thereby realizing high-efficiency removal of S2O32-. The satisfactory selective removal efficiency can be maintained in the proposed system under complex environmental conditions. Notably, the proposed system is cost-effective and applicable to actual wastewater, in which 81.2 % of S2O32- is selectively removed from coke oven gas desulfurization wastewater. More importantly, compared with the typical processes, the proposed process is simpler and more environmentally-friendly. This work provides an alternative route to selectively remove S2O32- from coke oven gas desulfurization wastewater, expecting to drive the development of resource utilization of coke oven gas desulfurization wastewater.

Prevention of distal stent graft-induced new entry after endovascular repair for type B aortic dissection: A retrospective cohort study.

OBJECTIVES: Distal stent graft-induced new entry (dSINE) can occur after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). In this study we aimed to compare the effectiveness of restrictive bare stent (RBS), tapered stent graft (TSG), and non-TSG in TEVAR in preventing dSINE after a midterm follow-up. METHODS: This retrospective cohort study included patients with TBAD who underwent TEVAR (June 2010 to December 2018). The occurrence of dSINE during follow-up was examined. Predictors of dSINE were determined using Fine-Gray regression with death as the competing event. Survival was evaluated using Cox proportional hazards regression. RESULTS: Finally, 364 patients were included: 111 with non-TSG TEVAR, 125 with TSG TEVAR, and 128 with TEVAR with RBS. After 54.5 months, incidences of dSINE in the 3 groups were 12.61%, 4.80%, and 1.56%, respectively (P = .002). On Fine-Gray regression adjusted for clinically relevant covariates, the expansion mismatch ratio (subdistribution hazard ratio, 1.09; 95% CI, 1.07-1.12; P < .001) and complete false lumen thrombosis (subdistribution hazard ratio, 0.35; 95% CI, 0.13-0.94; P = .037) were identified as predictors of dSINE. The Cox proportional hazards regression analysis revealed that dSINE was not only a risk factor for aortic-related mortality (hazard ratio, 17.90; 95% CI, 3.27-98.12; P = .001), but also a predominant risk factor for all-cause mortality (hazard ratio, 4.91; 95% CI, 1.66-14.52; P = .004). CONCLUSIONS: dSINE can happen in TBAD patients who undergo TEVAR. Thus, long-term surveillance is crucial. TSG and RBS had lower expansion mismatch ratios, which might help prevent dSINE.

Highly Dispersed FeAg-MCM41 Catalyst for Medium-Temperature Hydrogen Sulfide Oxidation in Coke Oven Gas.

The traditional hydrolysis-cooling-adsorption process for coke oven gas (COG) desulfurization urgently needs to be improved because of its complex nature and high energy consumption. One promising alternative for replacing the last two steps is selective catalytic oxidation. However, most catalysts used in selective catalytic oxidation require a high temperature to achieve effective desulfurization. Herein, a robust 30Fe-MCM41 catalyst is developed for direct desulfurization at medium temperatures after hydrolysis. This catalyst exhibits excellent stability for over 300 h and a high breakthrough sulfur capacity (2327.6 mgS gcat-1). Introducing Ag into the 30Fe-MCM41 (30Fe5Ag-MCM41) catalyst further enhances the H2S removal efficiency and sulfur selectivity at 120 °C. Its outstanding performance can be attributed to the synergistic effect of Fe-Ag clusters. During H2S selective oxidation, Fe serves as the active site for H2S adsorption and dissociation, while Ag functions as the catalyst promoter, increasing Fe dispersion, reducing the oxidation capacity of the catalyst, improving the desorption capacity of sulfur, and facilitating the reaction between active oxygen species and [HS]. This process provides a potential route for enhancing COG desulfurization.

Effect of AR gene-specific knockout on the process of radiation-induced pulmonary fibrosis and its mechanism.

Numerous studies have proved that epithelial-mesenchymal transition (EMT) of lung epithelial cells is one of the important causes of radiation-induced pulmonary fibrosis (RIPF). Aldose reductase (AR) is a monomer enzyme in the polyglycolic metabolic pathway and belongs to the aldo-keno reductase protein superfamily. Our previous studies have found that AR as one of the most significantly up-regulated genes was associated with the development of bleomycin-induced PF in rats. It is not clear whether aldose reductase is related to the regulation of radiation-induced EMT and mediates RIPF. AR-knockout mice, wild-type mice and lung epithelial cells were induced by radiation to establish a RIPF animal model and EMT system, to explore whether AR is mediation to RIPF through the EMT pathway. In vivo, AR deficiency significantly alleviated radiation-induced histopathological changes, reduced collagen deposition and inhibited collagen I, matrix metalloproteinase 2 (MMP2) and Twist1 expression. In addition, AR knockout up-regulated E-cadherin expression and up-regulated α-SMA and Vimentin expression. In vitro, AR, collagen I and MMP2 expression were increased in lung epithelial cells after radiation, which was accompanied by Twist1 expression up-regulation and EMT changes evidenced by decreased E-cadherin expression and increased α-SMA and Vimentin expression. Knockdown or inhibition of AR inhibited the expressions of Twist1, MMP2 and collagen I, and reduced cell migration and reversed radiation-induced EMT. These results indicated that aldose reductase may be related to radiation-induced lung epithelial cells EMT, and that inhibition of aldose reductase might be a promising treatment for RIPF.

CO2 sequestration and CaCO3 recovery with steel slag by a novel two-step leaching and carbonation method.

The steel smelting process produces extensive CO2 and Ca-containing steel slag (SS). Meanwhile, the low value utilization of steel slag results in the loss of Ca resources. CO2 sequestration utilizing SS can reduce carbon emissions while achieving Ca circulation. However, conventional SS carbon sequestration methods suffer from slow reaction rates, finite Ca usage efficiency, and difficulty separating the CaCO3 product from SS. Herein, an innovative two-step leaching (TSL) and carbonation method was presented based on the variations in leaching efficiency of activated Ca under different conditions, aiming at efficient leaching, carbon sequestration, and high-value reuse of SS. This method employed two NH4Cl solutions in sequence for two leaching operations on SS, allowing the Ca leaching rate to be effectively increased. According to the findings, TSL could increase the activated Ca leaching rate by 26.9 % and achieve 223.15 kg CO2/t SS sequestration compared to the conventional one-step leaching (CSL) method. If part of the CaCO3 is recovered as a slagging agent, about 34.1 % of the exogenous Ca introduction could be saved. In addition, the CO2 sequestration of TSL did not significantly decrease after 8 cycles. This work proposes a strategy that has the potential for recycling SS and reducing carbon emissions.

Identification of Key Biomarkers and Candidate Molecules in Non-Small-Cell Lung Cancer by Integrated Bioinformatics Analysis.

Background: Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods: From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal, String and Cytoscape, and Timer tools. Results: We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis (P < 0.05). We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis (P < 0.05). On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients (P < 0.05). Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions: The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.

Nickel-Catalyzed Hydroamination of Olefins with Anthranils.

A nickel-catalyzed polarity-reversed hydroamination of olefins has been achieved with anthranils as the electrophilic aminating agents and hydrosilane as the reductant. This protocol provides a facile access to N-alkyl-2-aminobenzophenones that are versatile intermediates in organic synthesis. A wide range of olefins and anthranils are compatible in this transformation, delivering the desired amines in useful to excellent yields (38 examples, up to 92% yield). The utility of this protocol is exhibited in the late-stage functionalization of drug molecules and the valuable derivatives of the obtained amination products.

lncRNA CASC9 regulates cell migration and invasion in hemangioma endothelial cells by targeting miR-125a-3p/Nrg1.

BACKGROUND: Despite being one of the most common benign tumors, the prevalence and pathogenesis of hemangiomas (HAs) are poorly understood. We aimed to identify the biological role of the long non-coding RNA (lncRNA) CASC9 in the HA-derived endothelial cell (HDECs) phenotype as well as elucidate the mechanism involved. METHODS: The expression of CASC9 was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). the effect of CASC9 on cell proliferation, migration and invasion of HDECs were examined by CCK8, wound healing, and transwell assay, respectively. Bioinformatics analysis and a luciferase reporter assay were utilized to investigated the mechanisms involved. The in vivo tumorigenesis capability of CASC9 on HA was also evaluated. RESULTS: The expression of CASC9 was significantly elevated in HA tissue compared to normal tissue. Down-regulation of CASC9 inhibited proliferation, migration, and invasion of HDECs. The translation of cyclinD1, N-cadherin, Twist, and MMP2 was also decreased by CASC9 knockdown treatment. Furthermore, CASC9 over-expression exerted the opposite effect of proliferation, migration, and invasion of HDECs. We also found that CASC9 interacts with miR-125a-3p/Nrg1 to regulate cellular functions. Interestingly, miR-125a-3p can reverse the effect of CASC9 on proliferation, migration, and invasion of HDECs. Together, the clinical data showed that CASC9 expression is negatively correlated with miR-125a-3p expression and positively correlated with Nrg1 expression. CASC9 also exerted anti-tumorigenesis capability in vivo. CONCLUSION: Our study indicates that CASC9 accelerates cell growth and invasion of HDECs and provides new insights for the diagnosis and molecular therapy of HA.

The ignored emission of volatile organic compounds from iron ore sinter process.

Iron ore sintering is a major source of gaseous and particulate pollutants emission in iron smelt plant. The aim of present study is to characterize the volatile organic compounds (VOCs) emission profiles from iron ore sintering process. Both sinter pot test and sinter simulation experiment were conducted and compared. Out results showed that sinter process produced large quantity of VOCs together with NOx and SO2. VOCs and NO were produced simultaneously in sinter pot test from 3 to 24 min after ignition, flowed by SO2 production from 15 min to the end of sintering. Total VOCs (TVOC) concentration in sinter flue gas was affected by the coal and coke ratio in sinter raw material. The maximum TVOC concentration was 34.5 ppm when using 100% coal as fuel. Sinter simulation experiments found that the number of VOCs species and their concentrations were found by sinter temperature. The largest VOCs species varieties were obtained at 500 °C. Benzene, toluene, xylene and ethylbenzene were major VOCs in sinter flue gas based on the results from both simulation test and sinter pot. It thus demonstrated that in addition to NOx, SO2 and metal oxide particles, sinter flue gas also contained significant amount of VOCs whose environmental impact cannot be ignored. Based on our work, it is timely needed to establish a new VOC emission standard for sinter flue gas and develop advanced techniques to simultaneously eliminate multi-pollutants in iron ore sinter process.

Iron-Catalyzed Synthesis of 2H-Imidazoles from Oxime Acetates and Vinyl Azides under Redox-Neutral Conditions.

A novel and versatile method for the synthesis of 2H-imidazoles via iron-catalyzed [3 + 2] annulation from readily available oxime acetates with vinyl azides has been developed. This denitrogenative process involved N-O/N-N bond cleavages and two C-N bond formations to furnish 2,4-substituted 2H-imidazoles. This protocol was performed under mild reaction conditions and needed no additives or ligands. Furthermore, this is a green reaction involving oxime acetate as internal oxidant, acetic acid, and nitrogen as byproducts.

Calcitonin gene-related peptide down-regulates bleomycin-induced pulmonary fibrosis.

We have found that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis, and up-regulation of eIF3a induced by TGF-ß1 is mediated via the ERK1/2 pathway. Whether ERK1/2 - eIF3a signal pathway is involved in calcitonin gene-related peptide (CGRP)-mediated pathogenesis of bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in rats. Primary pulmonary fibroblasts were cultured to investigate the proliferation by BrdU incorporation method and flow cytometry. Sensory CGRP depletion by capsaicin exacerbated bleomycin-induced pulmonary fibrosis in rats, as shown by a significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, accompanied with increased expression of TGF-ß1, eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. Exogenous application of CGRP significantly inhibited TGF-ß1-induced proliferation and differentiation of pulmonary fibroblasts concomitantly with decreased expression of eIF3a, phosphorylated ERK1/2, α-SMA, collagen I, and collagen III. These effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that endogenous CGRP is related to the development of pulmonary fibrosis induced by bleomycin, and the inhibitory effect of CGRP on proliferation of lung fibroblasts involves the ERK1/2 - eIF3a signaling pathway.

[Effect of sesamin on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary hypertension].

OBJECTIVE: To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH). METHOD: Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot. RESULT: After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC. CONCLUSION: Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.

Role of eukaryotic translation initiation factor 3a in bleomycin-induced pulmonary fibrosis.

Eukaryotic translation initiation factor 3a (eIF3a) is a multifunctional protein and plays an important role in regulation of cellular function including proliferation and differentiation. In the present study, we tested the function of eIF3a in pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Primary pulmonary fibroblasts were cultured for proliferation investigation by BrdU incorporation method and flow cytometry. The expression/level of eIF3a, TGF-ß1, ERK1/2 and α-SMA were analyzed by ELISA, real-time PCR or western blot. Results showed that the expression of eIF3a was obviously increased in lungs of pulmonary fibrosis rats accompanied by up-regulation of α-SMA and collagens. In cultured pulmonary fibroblasts, application of exogenous TGF-ß1 induced cell proliferation and differentiation concomitantly with up-regulation of eIF3a expression and ERK1/2 phosphorylation. The effects of TGF-ß1-induced proliferation of fibroblasts and up-regulation of α-SMA were abolished by eIF3a siRNA. TGF-ß1-induced eIF3a expression was reversed in the presence of PD98059, an inhibitor of ERK1/2. These findings suggest that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis by regulating pulmonary fibroblasts׳ function, and up-regulation of eIF3a induced by TGF-ß1 is mediated via the ERK1/2 pathway.

Postoperative prophylaxis of venous thromboembolism (VTE) in patients undergoing high ligation and stripping of the great saphenous vein (GSV).

To analyze the necessity of venous thromboembolism (VTE) prophylaxis for patients undergoing high ligation and stripping of the great saphenous vein (GSV) and to estimate the efficacy and safety of different anticoagulant protocols in a single-center randomized controlled trial with large sample size. A total of 2196 patients undergoing high ligation and stripping of the GSV were randomized to one of the following postoperative VTE prophylaxis protocols: group A, no VTE prophylaxis (n=542); group B, subcutaneous low-dose unfractionated heparin (LDUH) hypodermic injection, 125 U/kg per day in three divided doses (n=531); group C, low-molecular-weight heparin (LMWH) 6000 IU once a day (n=573); and group D, LMWH 4000 IU twice daily (n=550). Groups were compared for the incidence of VTE and major hemorrhage within 1 month following surgery. Varicose vein severity was classified by CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic elements) score. The clinical characteristics of the patients were equally matched between groups. Postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) were significantly higher in group A (DVT 5.17%, PE 1.48%) compared to groups B (0.56%, 0%), C (0.35%, 0%) and D (0.36%, 0%) (p<0.01). The incidence of VTE did not differ between the three active chemoprophylaxis arms. Hemorrhagic complications were low for each group but higher in group B (0.75%) compared to the other groups (group A 0.18%; group C 0.17%; group D 0.18%, p<0.01). Hemorrhagic complications did not differ amongst groups A, C and D. In conclusion, postoperative VTE chemoprophylaxis following high ligation and GSV stripping effectively reduces the venous thrombosis complications of this procedure. Of the three active strategies tested, no difference in efficacy was noted; however, thrice daily LDUH did increase bleeding complications.

Operating condition influences on PCDD/Fs emissions from sinter pot tests with hot flue gas recycling.

This study was designed to clarify the influence of operating conditions on the formation and emissions of polychlorinated-p-dibenzodioxins and dibenzofurans (PCDD/Fs) from a sintering process with hot flue gas recycling. A pilot scale sinter pot with simulated flue gas recycling was developed, and four key operational parameters, including temperature, oxygen content of the simulated waste flue gas, the coke rate of the sintering mixture, and the quicklime quality, were selected for exploring PCDD/Fs formation. The results showed that the temperature of the recycled flue gas had a major affect on PCDD/Fs formation, and a high temperature could significantly increase their formation during sintering. A clear linear correlation between the temperature of recycling flue gas and PCDD/Fs emission (r = 0.93) was found. PCDD/Fs could be reduced to a certain extent by decreasing the level of oxygen in the recycled flue gas, while sintering quality was unchanged. The coke rate had no significant influence on the formation of PCDD/Fs, but the quality of quicklime used in the sintering mixture could affect not only the amount of PCDD/Fs emissions but also the sintering productivity. Compared with a benchmark sinter pot test, PCDD/Fs emissions markedly decreased with improvements to quicklime quality. However, the reduction in PCDD/Fs emissions realized by using high-quality quicklime was limited by the temperature of the inlet gas. The highest reduction achieved was 51% compared with conventional quicklime when the temperature of the inlet gas was 150 degrees C.

STAT3 repressed USP7 expression is crucial for colon cancer development.

Interleukin-6 (IL-6) induced STAT3 activation is viewed as crucial for multiple tumor growth and metastasis, including colon cancer. However, the molecular mechanisms remain largely unexplored. Here, we show that expression of ubiquitin-specific protease 7 (USP7), a deubiquitylating enzyme, is decreased in STAT3-positive tumors. IL-6 administration or transfection of a constitutively activated STAT3 in SW480 cells also repressed USP mRNA expression. Using luciferase reporter and ChIP assay, we found that STAT3 bound to the promoter region of USP7 and inhibited its activity through recruiting HDAC1. As a result of the decline of USP7 expression, endogenous P53 protein level was decreased. Thus, our results suggest a previously unknown STAT3-USP7-P53 molecular network controlling colon cancer development.

[Effects of secoisolariciresinol diglucoside combined with bortezomib on induction of apoptosis in lung cancer cell line A549].

OBJECTIVE: To study the influence of Secoisolariciresinol Diglucoside (SDG) combined with Bortezomib on induction of apoptosis in lung cancer cell line A549 and its relative mechanisms. METHODS: The effect on proliferation was evaluated by MTT assay. The cell apoptosis was studied by flow cytometry and Hoechst 33342 staining. Colorimetric method was used to detect the activity of Caspase-3. Real time PCR was used to detect the expression of Caspase-3, BCL-2 and BAX mRNA. Western blot was used to determine the change of p-JNK, BCL-2 and BAX protein expression in A549 cells. RESULTS: The cell growth was significantly slowed down and the cell apoptosis was induced after the combined treatment. Meanwhile the Caspase-3 activity and the expression of Caspase-3 mRNA were obviously increased, the expression of BCL-2 mRNA and protein were significantly down regulated and the expression of BAX. p-JNK mRNA and protein were significantly up regulated after the combined treatment. CONCLUSION: The results demonstrate that SDG combined with Bortezomib can significantly induce apoptosis of A549 cells, its mechanisms may be involved in activation of the JNK pathway.

Inhibitory effect of calcitonin gene-related peptide on hypoxia-induced rat pulmonary artery smooth muscle cells proliferation: role of ERK1/2 and p27.

Calcitonin gene-related peptide (CGRP) inhibits angiotensin II-induced proliferation of aortic smooth muscle cells via inactivation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). ERK1/2 is necessary for the degradation or down-regulation of the cell cycle inhibitor p27, and is also crucial in mediating proliferation of pulmonary artery smooth muscle cells (PASMCs). Whether ERK1/2/p27 signal pathway is involved in CGRP-mediated pathogenesis of pulmonary hypertension and vascular remodeling remains unknown. Pulmonary hypertension was induced by hypoxia in rats, and capsaicin (50 mg/kg, s.c.) was used to deplete endogenous CGRP. Proliferation of cultured PASMCs was determined by BrdU incorporation method and flow cytometry. The expression/level of CGRP, p27, ERK1/2, c-fos and c-myc was analyzed by radioimmunoassay, immunohistochemistry, real-time PCR or Western blot. Sensory CGRP depletion by capsaicin exacerbated hypoxia-induced pulmonary hypertension in rats, as shown by an increase in right ventricle systolic pressure, mean pulmonary artery pressure and vascular hypertrophy, accompanied with decreased p27 expression and increased expression of phosphorylated ERK1/2, c-fos and c-myc. Exogenous application of CGRP significantly inhibited hypoxia-induced proliferation of PASMCs concomitantly with increased p27 expression and decreased expression of phosphorylated ERK1/2, c-fos and c-myc. These effects of CGRP were abolished in the presence of CGRP(8-37). Knockdown of p27 also reversed the inhibitory effect of CGRP on proliferation of PASMCs and expression of c-fos and c-myc, but not on ERK1/2 phosphorylation. These results suggest that CGRP inhibits hypoxia-induced proliferation of PASMCs via ERK1/2/p27/c-fos/c-myc pathway. Down-regulation of CGRP may contribute to remodeling of pulmonary arteries in hypoxia-induced pulmonary hypertension.