Effects of 101BHG-D01, a novel M receptor antagonism, on allergic rhinitis in animal models and its mechanism.

Allergic rhinitis (AR) is a nasal mucosal disease with sneezing and nasal itching as the main symptoms. Although AR treatment continues to improve, there remains a lack of effective drugs. There are still controversies regarding whether anticholinergic drugs can effectively and safely relieve the symptoms of AR and reduce inflammation in the nasal mucosa.

Cadmium induced cardiac toxicology in developing Japanese quail (Coturnix japonica): Histopathological damages, oxidative stress and myocardial muscle fiber formation disorder.

The anthropogenic-induced cadmium (Cd) pollution poses great threats to human health and wildlife survival. Birds also suffer from Cd contamination and Cd exerts negative impacts on multiple organs in birds. However, its toxic effects on cardiac organ of birds are still unclear.

Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs.

ZDHXB-101 (3',5-Diallyl-2, 4'-dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde) protects against airway remodeling and hyperresponsiveness via inhibiting both the activation of the mitogen-activated protein kinase and the signal transducer and activator of transcription-3 signaling pathways.

Airway remodeling consists of the structural changes of airway walls, which is often considered the result of longstanding airway inflammation, but it may be present to an equivalent degree in the airways of children with asthma, raising the need for early and specific therapeutic interventions. The arachidonic acid cytochrome P-450 (CYP) pathway has thus far received relatively little attention in its relation to asthma. In this study, we studied the inhibition of soluble epoxide hydrolase (sEH) on airway remodeling and hyperresponsiveness (AHR) in a chronic asthmatic model which long-term exposure to antigen over a period of 12 weeks.

Inhibition of soluble epoxide hydrolase attenuates airway remodeling in a chronic asthma model.

Airway remodeling in asthma is difficult to treat because of its complex pathophysiology that involves proinflammatory cytokines, as well as the arachidonic acid cytochrome P-450 (CYP) pathway; however, it has received little attention. In this study, we assessed the efficacy of a soluble epoxide hydrolase (sEH) on airway remodeling in a mouse model of chronic asthma. The expression of sEH and CYP2J2 and the level of 14,15-epoxyeicosatrienoic acid (14,15-EET), airway remodeling and hyperresponsiveness (AHR) were analyzed to determine the level of sEH inhibition.

Chronic lead exposure induces histopathological damage, microbiota dysbiosis and immune disorder in the cecum of female Japanese quails (Coturnix japonica).

Lead (Pb) is one of the most hazardous metals to human and wildlife and it also has multiple negative impacts on birds. However, its influences on bird gut morphology and intestinal microbiota were still unclear. We used female Japanese quails (Coturnix japonica) to examine the effects of chronic lead exposure (0, 50 ppm and 1000 ppm) on cecal histology, microbial communities and immune function.

Akt/PKB signaling regulates cigarette smoke-induced pulmonary epithelial-mesenchymal transition.

Objectives: Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) is found in invasive or metastatic phenotypes in lung cancer and COPD. MK-2206, a pan Akt inhibitor, has failed in clinical trials for solid tumors when administered alone at tolerated doses, but it has been shown to have synergistic effects when applied with certain molecular targeted agents.

Daily, circadian and seasonal changes of rhodopsin-like encephalic photoreceptor and its involvement in mediating photoperiodic responses of Gambel's white-crowned Sparrow, Zonotrichia leucophrys gambelii.

Extra-retinal, non-pineal, encephalic photoreceptors (EP) play important roles in mediating development of the reproductive system by the annual change in day length (photoperiodic gonadal response - PGR) in birds. However, the distribution of rhodopsin-like EPs and their functional daily, circadian and seasonal changes are still unclear in the avian brain. This study identifies two novel groups of rhodopsin-immunoreactive cells in the nucleus paraventricularis magnocellularis (PVN) of the hypothalamus and in the medial basal hypothalamus (MBH) in a seasonally breeding species, Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii).

Soluble epoxide hydrolase inhibitor AUDA decreases bleomycin-induced pulmonary toxicity in mice by inhibiting the p38/Smad3 pathways.

Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-β-induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways.

Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways.

Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease (COPD). Our previous studies have indicated that Rac1 is involved in lipopolysaccharide-induced pulmonary injury and CS-mediated epithelial-mesenchymal transition. However, the contribution of Rac1 activity to CS-induced lung inflammation remains not fully clear.

Grape seed extract ameliorates bleomycin-induced mouse pulmonary fibrosis.

Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity.

EETs Attenuate Ox-LDL-Induced LTB4 Production and Activity by Inhibiting p38 MAPK Phosphorylation and 5-LO/BLT1 Receptor Expression in Rat Pulmonary Arterial Endothelial Cells.

Cytochrome P-450 epoxygenase (EPOX)-derived epoxyeicosatrienoic acids (EETs), 5-lipoxygenase (5-LO), and leukotriene B4 (LTB4), the product of 5-LO, all play a pivotal role in the vascular inflammatory process. We have previously shown that EETs can alleviate oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation in primary rat pulmonary artery endothelial cells (RPAECs). Here, we investigated whether ox-LDL can promote LTB4 production through the 5-LO pathway.

Formoterol synergy with des-ciclesonide inhibits IL-4 expression in IgE/antigen-induced mast cells by inhibiting JNK activation.

Inhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists (LABA) is the most important treatment for allergic asthma, although the mechanism still remains unclear. However, mast cells play a central role in the pathogenesis of asthma. In this study, we explored the sole or synergetic effects of des-ciclesonide (ICS) and formoterol (LABA) on the cytokines IL-4 and IL-13 and on histamine release from mast cells (RBL-2H3 cells).

Effects of the inhalation of the m3 receptor antagonist bencycloquidium bromide in a mouse cigarette smoke-induced airway inflammation model.

Bencycloquidium bromide (BCQB), a novel M3 receptor antagonist, alleviates airway hyperresponsiveness, inflammation, and airway remodeling in a murine model of asthma. The aim of this study was to investigate the anti-inflammatory activity of inhaled BCQB in a cigarette smoke (CS)-induced model of acute lung inflammation. Mice exposed to CS developed chronic obstructive pulmonary disease (COPD).

Comparing single-agent with doublet chemotherapy in first-line treatment of advanced non-small cell lung cancer with performance status 2: a meta-analysis.

Aim: This systematic review and meta-analysis was performed to assess the efficacy and side effects between single-agent and doublet chemotherapy in first-line treatment of advanced non-small cell lung cancer with performance status 2 (PS2).

Methods: We searched for randomized controlled trials in online electronic databases and extracted data from eligible studies for meta-analysis. Pooled hazard ratio (HR) for overall survival (OS), pooled risk difference (RD) for 1-year survival, pooled risk ratio (RR) for objective response rate (ORR) and adverse effects were calculated using a fixed-effect model.

Epoxyeicosatrienoic acids attenuate cigarette smoke extract-induced interleukin-8 production in bronchial epithelial cells.

In response to endothelial cell activation, arachidonic acid can be converted by cytochrome P450 (CYP) epoxygenases to epoxyeicosatrienoic acids (EETs), which have potent vasodilator and anti-inflammatory properties. In this study, we investigated the effects of exogenous EETs on cigarette smoke extract (CSE)-induced inflammation in human bronchial epithelial cells (NCI-H292). We found that CSE inhibited the expression of CYP2C8 and mildly stimulated the expression of epoxide hydrolase 2 (EPHX2) but did not change the expression of CYP2J2.

Cigarette smoke extract-induced BEAS-2B cell apoptosis and anti-oxidative Nrf-2 up-regulation are mediated by ROS-stimulated p38 activation.

Cigarette smoke contains reactive oxygen (ROS) that can cause oxidative stress. It increases the number of apoptotic and necrotic lung cells and further induces the development of chronic airway disease. In this study, we investigated the effects of cigarette smoke extract (CSE) on apoptosis in human bronchial epithelial cells (BEAS-2B).

Cigarette smoke-induced alveolar epithelial-mesenchymal transition is mediated by Rac1 activation.

Background: Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT.

EETs alleviate ox-LDL-induced inflammation by inhibiting LOX-1 receptor expression in rat pulmonary arterial endothelial cells.

Oxidized low-density lipoprotein (Ox-LDL) is associated with atherosclerotic events through the modulation of arachidonic acid (AA) metabolism and activation of inflammatory signaling. Cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) mitigate inflammation through nuclear factor-κB (NF-κB). In this study, we explored the effects and mechanisms of exogenous EETs on the ox-LDL-induced inflammation of pulmonary artery endothelial cells (PAECs), which were cultured from rat pulmonary arteries.

A systematic review of gemcitabine and taxanes combination therapy randomized trials for metastatic breast cancer.

Purpose: Gemcitabine/taxanes-based combination shows anti-tumor activity for the treatment of metastatic breast cancer, but there is a debate regarding the advantages of gemcitabine and taxanes regimens as a first-line or second-line treatment for metastatic breast cancer. Here we conducted a systematic review and meta-analysis to compare the efficacy and toxicity for patients receiving chemotherapy with or without GT-based regimens.

Methods: The randomized controlled trials were performed by searching Pubmed, MEDLINE, EMBASE, and conference proceedings.

Shp2 plays an important role in acute cigarette smoke-mediated lung inflammation.

Cigarette smoke (CS), the major cause of chronic obstructive pulmonary disease, contains a variety of oxidative components that were implicated in the regulation of Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) activity. However, the contribution of Shp2 enzyme to chronic obstructive pulmonary disease pathogenesis remains unclear. We investigated the role of Shp2 enzyme in blockading CS-induced pulmonary inflammation.

Simvastatin delivery via inhalation attenuates airway inflammation in a murine model of asthma.

The dose-response of the pleiotropic effects of statins on airway inflammation has not yet been established and may differ from that of their cholesterol-lowering effects. High oral doses of statins may have adverse effects, and it may be possible to overcome the side effects and low clinical efficacy by administering statins via inhalation. In this study, we hypothesize that simvastatin is a potential anti-inflammatory drug with biological and pharmacokinetic properties suitable for delivery by the inhaled route.

M(3) muscarinic receptor antagonist bencycloquidium bromide attenuates allergic airway inflammation, hyperresponsiveness and remodeling in mice.

M(3) muscarinic receptors are localized on inflammatory cells, airway smooth muscle, and submucosal glands, known to mediate bronchoconstriction, mucus secretion, and airway remodeling. It is hypothesized bencycloquidium bromide (BCQB), a novel M(3) receptor antagonist, might have potential effects on airway hyperresponsiveness, inflammation and airway remodeling in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation.