Whether dietary β-carotene and vitamin A intake protect against lung cancer risk is not clear. Therefore, we performed this meta-analysis to investigate the association between them. The related articles were searched using the databases PubMed and the Web of Knowledge up to May 2015. We used the random-effect model to estimate the relative risk (RR) and their 95% CI. Small-study effect was assessed using Egger’s test. In total, 19 studies comprising 10,261 lung cancer cases met the inclusion criteria. The pooled RR and their 95% CI was 0.855 (0.739–0.989) for higher category of dietary vitamin A intake and lung cancer risk, especially among Asian populations and in the cohort studies. Evidence from 18 studies suggested that higher category of dietary β-carotene intake could reduce lung cancer risk (0.768 (0.675–0.874)).The associations were also significant in American and Asian populations. In conclusions, higher category of dietary β-carotene and vitamin A intakes could reduce the risk of lung cancer. However, the dose-response analysis was not performed due to the limited data in each individual study. Due to this limitation, further studies with detailed dose, cases and person-years for β-carotene and vitamin A of each category are wanted to assess this dose-response association.

Objective and design To investigate the therapeutic effects of various HDAC inhibitors on the development of chronic allergic airway disease in mice with airway inflammation, airway remodeling, and airway hyperresponsiveness. Subjects Wild-type BALB/C mice (N = 72). Treatment Tubastatin A HCl [TSA, a selective histone deacetylase 6 (HDAC6) inhibitor], PCI-34051 (a selective HDAC8 inhibitor), and givinostat (a broad-spectrum HDAC inhibitor that inhibits class I and class II HDACs and several pro-inflammatory cytokines). Methods Mice were divided into six groups: control, asthma, dexamethasone (positive control), TSA, PCI-34051, and givinostat (n = 12 per group). Twenty-four hours after OVA nebulization, airway hyperresponsiveness, inflammation, and remodeling were assessed. Results The chronic asthma mouse model produced typical airway inflammation, airway remodeling, and airway hyperresponsiveness. Administration of PCI-34051 and dexamethasone reduced the eosinophilic inflammation and airway hyperresponsiveness in asthma to reduce the airway remodeling. Treatment with Tubastatin A HCl reduced airway inflammation and was associated with decreased IL-4, IL-5 and total inflammatory cell count, as well as goblet cell metaplasia and subepithelial fibrosis; however, this outcome was not as effective as that with dexamethasone. TGF-β1 expression in the cytoplasm of airway epithelium of mice in the Tubastatin A HCl group was reduced and expression of α-SMA in the airway smooth muscle was also decreased. Conclusions The results suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice.

Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) is a ligand-activated transcription factor that exerts multiple biological effects. Growing evidence suggests that PPARγ plays an important role in inflammation; however, the effects of this transcription factor on the inflammation caused by smoking are unclear. Methods: We measured the expression of inflammatory cytokines (leukotriene B4, LTB4 and interleukin 8, IL-8), PPARγ and toll-like receptors (TLR2 and TLR4) in alveolar macrophages (AMs) harvested from rats exposed to cigarette smoke (CS) for 3 months in vivo. Some of the rats were pre-treated with rosiglitazone (PPARγ agonist, 3 mg/kg/day, ip), rosiglitazone (3 mg/kg/day, ip) + BADGE (bisphenol A diglycidyl ether, a PPARγ antagonist, 30 mg/kg/day, ig), or BADGE alone (30 mg/kg/day, ig). We also measured the expression of PPARγ, TLR2, TLR4 and nuclear factor-kappaB (NF-κB) in AMs gained from normal rats, which exposed to 5% CSE (cigarette smoke extract) for 12hrs, respectively pretreated with PBS, rosiglitazone (30 uM), rosiglitazone (30 uM) + BADGE (100 uM), 15d-PGJ2 (PPARγ agonist, 5 uM), 15d-PGJ2 (5 uM) + BADGE (100 uM), or BADGE (100 uM) alone for 30 min in vitro. Results: In vivo, rosiglitazone counteracted CS-induced LTB4 and IL-8 release and PPARγ downregulation, markedly lowering the expression of TLR4 and TLR2. In vitro, both rosiglitazone and 15d-PGJ2 inhibited CS-induced inflammation through the TLR4 signaling pathway. Conclusions: These results suggest that PPARγ agonists regulate inflammation in alveolar macrophages and may play a role in inflammatory diseases such as COPD.

The present study was conducted to investigate the clinical significance of Eucalyptol in treating cigarette smoke-induced lung injury with the potential mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) after they were treated with Eucalyptol (260 mg/kg) orally once a day for 12 weeks. Cell counts of bronchoalveolar lavage fluid (BALF), measurements of mean liner intercept (MLI) and mean alveolar number (MAN), and lung function test were executed in experimental animals. Contents of cytokines and intercellular adhesion molecule (ICAM)-1 in BALF and ICAM-1 protein and mRNA expression in lung tissues were determined by ELISA, immunohistochemistry (IHC), and RT-PCR, respectively. A rat model of chronic obstructive pulmonary disease (COPD) displayed declining lung function, increased cell counts and cytokine production in BALF, and emphysema-like lesions in cigarette smoke-exposed lungs compared with the controls (all P<0.01). Treatment with Eucalyptol partly reversed lung function decline with obvious decrease in inflammatory cell infiltrate, TNF-α, IL-6, and ICAM-1 expression levels in the challenged lungs (all P<0.05 and 0.01). Furthermore, oral administration of the drug not only reduced the emphysema-associated lung lesions but also suppressed ICAM-1 protein and mRNA expression in the lungs compared with the control (all P<0.05 or 0.01). Intervention of Eucalyptol mitigates the ongoing inflammatory process in airways and ameliorates the cigarette smoke-induced lung injury through suppressing ICAM-1 gene expression in the diseased lungs.

Background: This study was to investigate of the mechanism by which histone deacetylase (HDAC) 8 inhibitor ameliorated airway hyperresponsiveness (AHR) and allergic airway inflammation.Methods: Mice were sensitized and then treated with budesonide (BUD) or PCI-34051 (PCI) prior to exposing to normal saline (NS) or ovalbumin (OVA). The raw264.7 cells were treated with interleukin (IL)-4 and PCI or shRNA alone. Repetitive measurements of enhanced pause (Penh) were executed by increasing concentrations of acetyl-β-methacholine chloride (0 - 50 mg/ml). Cells in bronchoalveolar lavage fluid (BALF) and pathological changes of lungs were examined, respectively. The expression levels of HDAC8, Galecitn (Gal)-3, CD68, CD86, CD163, Arg1 and NOS2 in lungs were measured. Co-regulation of HDAC8 and Gal-3 proteins was observed by immunofluorescence staining and co-immunoprecipitation assay (Co-IP).Results: Significant increases in Penh and IL-4 level were detected with a large inflammatory infiltrate, comprised predominantly of macrophages and eosinophils, into the BALF in OVA-exposed lungs. HDAC8, Gal-3, CD68, CD86, CD163, Arg1 and NOS2 proteins were over-expressed with the significant changes in the Arg1 and NOS2 mRNA levels in the lungs and the IL-4-treated cells. PCI intervention obviously reduced the counts of CD163⁺cells. Furthermore, Gal-3 knockdown suppressed Arg1 expression in the cells. Immunofluorescence staining displayed simultaneous changes in HDAC8 and Gal-3 expression in the investigated samples. Treatment with PCI resulted in synchronous reduction of HDAC8 and Gal-3 expression in the Co-IP complexes.Conclusions: The HDAC8 inhibitor ameliorates AHR and airway inflammation in animal model of allergic asthma through reducing HDAC8-Gal-3 interaction and M2 macrophage polarization.