Search

Oxidative stress is one of the main pathogenesis for many human diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays a key role in regulating intracellular antioxidant responses, and thus activation of Nrf2/ARE signaling pathway is a potential chemopreventive or therapeutic strategy to treat diseases caused by oxidative damage. In the present study, we have found that treatment of Beas-2B cells with botrysphins D (BD) attenuated sodium arsenite [As (III)]-induced cell death and apoptosis. Meanwhile, BD was able to upregulate protein levels of Nrf2 and its downstream genes NQO1 and γ-GCS through inducing Nrf2 nuclear translocation, enhancing protein stability, and inhibiting ubiquitination. It was also found that BD-induced activation of the Nrf2/ARE pathway was regulated by PI3K, MEK1/2, PKC, and PERK kinases. Collectively, BD is a novel activator of Nrf2/ARE pathway, and is verified to be a potential preventive agent against oxidative stress-induced damage in human lung tissues.

Exogenous toxicants (e.g. arsenic, cigarette smoke), trigger oxidative stress, and initiate the pathogenesis of many human diseases. Induction of nuclear factor E2-related factor 2 (Nrf2) counteracts exogenous toxicant-induced oxidative insults. Using a high-throughput screen, we firstly identified a citrus polymethoxyflavone, (2S)-5,6,7,3′,4′-pentamethoxyflavanone (PMF), to be an Nrf2 activator, and an investigation targeting Nrf2 pathway was performed. Our study indicated that: (i) PMF activated Nrf2 and its downstream genes, NQO1 and γ-GCS, and enhanced the stabilization of Nrf2 through inhibiting Nrf2 ubiquitination. (ii) Inhibition of PI3K, p38 MAPK, PKC and PERK by specific kinase inhibitors suppressed PMF-induced activation of Nrf2. (iii) PMF conferred Nrf2-dependent protection against sodium arsenite- and cigarette smoke extract- induced cytotoxicity in lung epithelial cells. Collectively, our data demonstrate that PMF is a novel Nrf2 activator with potential prevention against oxidative insults. The diverse pharmacological functions of citrus polymethoxyflavone might be related to their ability of activating Nrf2 pathway.

Continuous overproduction of reactive oxygen species (ROS), termed as oxidative stress, plays a crucial role in the onset and progression of many human diseases. Activation of nuclear transcription factor erythroid 2-related factor (Nrf2) by small molecules could eliminate ROS, and thus block the pathogenesis of oxidative stress-induced diseases. In this study, a natural flavonoid library was established and tested for their potential Nrf2 inducing effects. Based on QR inducing effect of flavonoids, their structure-activity relationship (SAR) on Nrf2 induction was summarized, and twenty flavonoids were firstly identified to be potential activators of Nrf2-mediated defensive response. Then, 7-O-methylbiochanin A (7-MBA) was further investigated for its capability on the Nrf2 activation and prevention against oxidative insults in human lung epithelial cells. Further studies indicated that 7-MBA activated Nrf2 signaling pathway and protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]-induced cytotoxicity in an Nrf2-dependent manner. Activation of Nrf2 by 7-MBA upregulated intracellular antioxidant capacity, which was produced by enhancement of Nrf2 stabilization, blockage of Nrf2 ubiquitination, as well as Nrf2 phosphorylation by mitogen-activated protein kinase (MAPK), protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Taken together, 7-MBA is a novel isoflavone-type Nrf2 activator displaying potential preventive effect against oxidative damages in human lung epithelial cells.

Rebar steel is used in the construction of various buildings. Vanadium (V), one of microalloying elements, is often added in the rebar steel to improve mechanical property. In order to analyse the effect of V on the microstructure and property of rebar steel, 0.043 wt.% V was added in a 20MnSi rebar steel. The base steel and V added steel were refined in a 50 kg vacuum induction furnace and rolled to plates of 14 mm thick. The mechanical properties of two steels were compared by tensile tests on a Wan-10000 tensile testing machine. The microstructure and precipitation of two steels were analysed by SEM and TEM observations. The microstructures of two steels consist of ferrite and pearlite. However, the grains of V bearing steel are finer. Moreover, fine nanoscale precipitates of V can be observed in V bearing steel. Therefore, the mechanical property of V addition rebar steel is improved by gain refinement strengthening and precipitation strengthening.

Isoquinoline alkaloids possess a wide range of structural features and pharmaceutical activities and are promising drug candidates. Ten water-soluble catecholic isoquinolines were isolated from the medicinal plant Portulaca oleracea, including three new (1–3) and seven known compounds (4–10), along with the known catecholamines 11 and 12 and four other known compounds (13–16). A method of polyamide column chromatography using EtOAc–MeOH as the mobile phase was developed for the isolation of catecholic isoquinolines. Alkaloids 1–12 exhibited anti-inflammatory activities (EC50 = 18.0–497.7 μM) through inhibition of NO production in lipopolysaccharide-induced murine macrophage RAW 264.7 cells. Among these compounds, 11, 2, 5, 4, and 8 were more potent than was the positive control, 3,4-dihydroxybenzohydroxamic acid (EC50 = 82.4 μM), with EC50 values of 18.0, 18.1, 35.4, 36.3, and 58.7 μM, respectively. Additionally, at 100 μM, compounds 1–12 showed different degrees of β2-adrenergic receptor (β2-AR) agonist ...

Oxidative stress is involved in the onset and progression of many human diseases. Activators of the Keap1/Nrf2/ARE pathway effectively inhibit the progression of oxidative stress-induced diseases. Herein, a small library of diterpenoids was established by means of phytochemical isolation, and chemical modification on naturally occurring molecules. The diterpenoids were subjected to a NAD(P)H: quinone reductase (QR) assay to evaluate its potential inhibition against oxidative stress. Sixteen diterpenoids were found to be novel potential activators of Nrf2-mediated defensive response. Of which, an isopimarane-type diterpenoid, sphaeropsidin A (SA), was identified as a potent activator of the Keap1/Nrf2/ARE pathway, and displayed approximately 5-folds potency than that of sulforaphane (SF). SA activated Nrf2 and its downstream cytoprotective genes through enhancing the stabilization of Nrf2 in a process involving PI3K, PKC, and PERK, as well as potentially interrupting Nrf2-Keap1 protein-protein interaction. In addition, SA conferred protection against sodium arsenite [As(III)]- and cigarette smoke extract (CSE)-induced redox imbalance and cytotoxicity in human lung epithelial cells, as wells as inhibited metronidazole (MTZ)-induced oxidative insult in Tg (krt4: NTR-hKikGR)cy17 transgenic zebrafish and lipopolysaccharide (LPS)-induced oxidative damage in wild-type AB zebrafish. These results imply that SA is a lead compound for therapeutic agent against oxidative stress-induced diseases, and diterpenoid is a good resource for discovering drug candidates and leads of antioxidant therapy.

The nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in regulating the intracellular oxidative stress, and thus activation of Nrf2 by nature-derived molecules effectively alleviates the pathological process of oxidative stress-induced chronic diseases. The isopentenyl-substituted flavonoid norartocarpin (NOR) induced the activity of NAD(P)H: quinone reductase (QR), implying that it might be a potential Nrf2 activator. Further studies indicated that NOR upregulated the protein levels of Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (GCLM) through facilitating the nuclear translocation of Nrf2 and enhancing Nrf2 protein stability. NOR-induced activation of Nrf2 pathway was associated with multiple upstream kinases, including mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), protein kinase C (PKC), and protein kinase R-like endoplasmic reticulum kinase (PERK). Moreover, NOR protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]-induced cytotoxicity in an Nrf2-dependent manner. Collectively, NOR was firstly identified to be an Nrf2 activator, which demonstrated the capability of preventing oxidative insults in human lung epithelial cells.

Three new nor-clerodane-type furanoditerpenoids, tinocapillins A–C ( 1 – 3 ), and three known diterpenoids were isolated from the rhizomes of Tinospora capillipes . Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configuration of compound 4 was established by single-crystal X-ray diffraction analysis using Cu Kα radiation. Compounds 1 , 2 , and 5 exhibited moderate inhibitory activity on the proliferation of the A549, Hep G2, Hela, and OS-RC-2 human cancer cell lines.

The combination of near-infrared spectroscopy and pattern recognition methods, including soft independent modeling of class analogy, least squares support machine, and extreme learning machine, was employed for textile fabrics classification. The fabrics of cotton, viscose, acrylic, polyamide, polyester, and blend fabric of cotton-viscose were divided into training and prediction sets (60:60) for developing models and evaluating the classification abilities of the models. The classification accuracy and speed of soft independent modeling of class analogy, least squares support machine, and extreme learning machine were compared. Both least squares support machine and extreme learning machine achieved the classification accuracy of 100% for the prediction set. However, extreme learning machine performed much faster than least squares support machine, which suggested that extreme learning machine may be a promising method for real-time textile fabrics classification with a comparable accuracy based ...

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, β-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3′, 4, 4′-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 protein–protein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue., Graphical abstract fx1, Highlights • The chemical compositions of Cinnamomum chartophyllum are firstly identified. • The active ingredients supporting the biological functions of C. chartophyllum are verified. • NLD and THD are identified to be Nrf2 activators for the first time. • NLD and THD protect human lung epithelial cells against As(III)-induced cytotoxicity.

High-strength steels are usually microalloyed with niobium (Nb), titanium (Ti) and vanadium (V), individually or in combination. The reheating temperature during austenization has a significant influence on the precipitation of microalloyed steels. The purpose of the study is to investigate the effect of reheating temperature on precipitates of microalloying elements. The research results show that reheating temperature should be high enough to ensure the dissolution of carbide and nitride precipitates in order to improve the precipitation strengthening of microalloying elements during rolling and cooling. The results provide the theoretical reference for the determination of reheating technology of microalloyed steels.

In this paper, the Urea-SCR system is first introduced; then change of the urea solution concentration under different temperatures with time lapsing is given. Meanwhile, conditions for the urea crystallization are analyzed and SCR converter adaptability is tested under high sulfur environment on engine test bench. As the efficiency of NOx conversion is not significantly reduced after aging and the activity of the catalyst is very little damaged by dense sulfur content in fuel, SCR catalyst is able to adapt to the application of high-sulfur-contained fuel environment in our country.

In order to fulfill future emission standards for middle and heavy-duty vehicles like state Ⅳ and Ⅴ, advanced measures on exhaust gas and engine functionality are required. Selective Catalytic Reduction (SCR) technology is the unique technology currently which can improve the emission and reduce fuel consumption simultaneously. Firstly the reductants and its chemical reactions, SCR system configurations and its working principle and urea dosing control strategy are introduced. Then tests are conducted on a diesel engine with SCR system at bench. The results of ESC cycle show that NOx emission is decreased by more than 67% with the open-loop control strategy. Additionally, the urea and fuel consumption and ammonia leakage have been compared and analyzed respectively, the experiment data indicates that the urea water solution consumption ratio is only 5.7% of fuel for this SCR system, while its average ammonia slip is below 5 ppm.

This study investigated the influence of various organically modified montmorillonites (organoclays) on the structure and properties of rigid polyurethane foam (RPUF) nanocomposites. The organoclays were modified with cetyltrimethyl ammonium bromide (CTAB), methyl tallow bis(2-hydroxyethyl) quaternary ammonium chloride (MT2ETOH) and tris(hydroxymethyl)aminomethane (THMA) and denoted as CMMT, Cloisite 30B and OMMT, respectively. MT2ETOH and THMA contain hydroxyl groups, while THMA does not have long aliphatic tail in its molecule. X-ray diffraction and transmission electron microscopy show that OMMT and Cloisite 30B can be partially exfoliated in the RPUF nanocomposites because their intercalating agents MT2ETOH and THMA can react with isocyanate. However, CMMT modified with nonreactive CTAB is mainly intercalated in the RPUF matrices. At a relatively low filler content, the RPUF/CMMT composite foam has a higher specific compressive strength (the ratio of compressive strength against the apparent density of the foams), while at relatively high filler contents, RPUF/Cloisite 30B and RPUF/OMMT composites have higher specific compressive strengths, higher modulus and more uniform pore size than the RPUF/CMMT composite.

A 3-year-old Chinese boy presented with prominent clinical features of malonic aciduria, including developmental delay, short stature, brain abnormalities and massive excretion of malonic acid and methylmalonic acid. Molecular characterization by DNA sequencing analysis and multiplex ligation-dependent probe amplification of the MLYCD gene revealed a heterozygous mutation (c.920T>G, p.Leu307Arg) in the patient and his father and a heterozygous deletion comprising exon 1 in the patient and his mother. The missense mutation (c.920T>G) was not found in 100 healthy controls and has not been reported previously. Our findings expand the number of reported cases and add a novel entry to the repertoire of MLYCD mutations.

Low molecular weight polylactic acid (PLA) microparticles containing prostaglandin E2 were prepared. An average particle size of 30 micron was obtained by grinding at low temperature. These particles were further treated by heating to modify the shape and the release pattern. Microscopic studies showed that the modified particles had a smoother surface than the non-modified particles. The drug was also incorporated into PLA microcapsules using the solvent evaporation process, but the incorporation efficiency was lower. We studied the release profiles of modified particles prepared using different molecular weight PLA. The release rate depended on the molecular weight with lower molecular weights having a greater release rate. In addition, the release studies showed different matrix forms made from the same molecular weight PLA had different release patterns. For example, the microcapsules released the drug very slowly whereas the modified particles exhibited a moderate release rate. It was also noted that the matrix release model could describe the release patterns of microcapsules and modified particles very well. However, the release patterns of non-modified microparticles did not follow this model.

Prostaglandin E2 was successfully incorporated into low molecular weight polylactic acid microcapsules. The size distribution of the microcapsules ranges from 20 to 50 micron. The microcapsules released drug continuously up to three days in vitro. The galactosamine induced fulminant hepatic failure rats model was used. 36 hours after the injection of galactosamine, those rats in grade II coma were chosen and pairs were matched for comparable degree of coma. Then each of the pair was randomly selected as control or treated. Each rat in the treated group received an intraperitoneal injection of PGE2 microcapsules containing 0.55 mg of PGE2. The control received blank PLA microcapsules only. The survival rate of the treated group was 40% compared to 10% in the control group. There was a significant (P less than 0.05) increase in the survival rate in the treated group.

Background Chronic obstructive pulmonary disease (COPD) is a major public health problem and gives arise to severe chronic morbidity and mortality in the world. Inflammatory response and oxidative stress play dominant roles in the pathological mechanism of COPD, and have been regarded to be two important targets for the COPD therapy. Traditional Chinese medicines (TCMs) possess satisfying curative effects on COPD under guidance of the TCM theory in China, and merit in-depth investigations as a resource of lead compounds. Methods One hundred ninety-six of TCMs were collected, and extracted to establish a TCM extract library, and then further evaluated for their potency on inhibitions of oxidative stress and inflammatory response using NADP(H):quinone oxidoreductase (QR) assay and nitric oxide (NO) production assay, respectively. Results Our investigation observed that 38 of the tested TCM extracts induced QR activity in hepa 1c1c7 murine hepatoma cells, and 55 of them inhibited NO production in RAW 264.7 murine macrophages at the tested concentrations. Noteworthily, 20 of TCM extracts simultaneously inhibited oxidative stress and inflammatory responses. Conclusion The observed bioactive TCMs, particularly these 20 TCMs with dual inhibitory effects, might be useful for the treatment of COPD. More importantly, the results of the present research afford us an opportunity to discover new lead molecules as COPD therapeutic agents from these active TCMs. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1347-y) contains supplementary material, which is available to authorized users.