3,3′Diindolylmethane Suppresses Vascular Smooth Muscle Cell Phenotypic Modulation and Inhibits Neointima Formation after Carotid Injury

3,3'Diindolylmethane (DIM), a natural phytochemical, has shown inhibitory effects on the growth and migration of a variety of cancer cells; however, whether DIM has similar effects on vascular smooth muscle cells (VSMCs) remains unknown. The purpose of this study was to assess the effects of DIM on the proliferation and migration of cultured VSMCs and neointima formation in a carotid injury model, as well as the related cell signaling mechanisms.DIM dose-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs without cell cytotoxicity. This inhibition was caused by a G0/G1 phase cell cycle arrest demonstrated by fluorescence-activated cell-sorting analysis. We also showed that DIM-induced growth inhibition was associated with the inhibition of the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4/6 as well as an increase in p27(Kip1) levels in PDGF-stimulated VSMCs. Moreover, DIM was also found to modulate migration of VSMCs and smooth muscle-specific contractile marker expression. Mechanistically, DIM negatively modulated PDGF-BB-induced phosphorylation of PDGF-recptorβ (PDGF-Rβ) and the activities of downstream signaling molecules including Akt/glycogen synthase kinase(GSK)3β, extracellular signal-regulated kinase1/2 (ERK1/2), and signal transducers and activators of transcription 3 (STAT3). Our in vivo studies using a mouse carotid arterial injury model revealed that treatment with 150 mg/kg DIM resulted in significant reduction of the neointima/media ratio and proliferating cell nuclear antigen (PCNA)-positive cells, without affecting apoptosis of vascular cells and reendothelialization. Infiltration of inflammatory cells was also inhibited by DIM administration.These results demonstrate that DIM can suppress the phenotypic modulation of VSMCs and neointima hyperplasia after vascular injury. These beneficial effects on VSMCs were at least partly mediated by the inhibition of PDGF-Rβ and the activities of downstream signaling pathways. The results suggest that DIM has the potential to be a candidate for the prevention of restenosis

Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis.

Nuclear factor erythroid 2-related factor 2 (NRF2) functions as a transcription factor and regulates a wide array of antioxidant and stress-responsive genes. NRF2 has been widely implicated in different types of cancers, but only limited studies concerning the relationship between NRF2 expression and tumour invasion or prognosis in lung cancer. Therefore, we conducted a meta-analysis to determine the prognostic value of NRF2 in patients with non-small cell lung cancer (NSCLC). The relationship between NRF2 expression in NSCLC patients and clinicopathological features was also investigated. Overall survival (OS) and treatment response rate were evaluated using STATA software. Twenty eligible articles with 2530 lung cancer patients were included in this meta-analysis. The results revealed that high expression level of NRF2 was associated with pathologic distant metastasis (odds ratio (OR) = 2.64, 95% confidence interval (CI) 1.62-4.31; P < 0.001), lymph node metastasis (OR = 2.14, 95% CI: 1.53-3.00; P < 0.001), and tumour node metastasis (TNM) stage (OR = 1.95, 95% CI: 1.52-2.49, P < 0.001). High NRF2 expression was associated with low treatment response rate in platinum-based chemotherapy (HR = 0.11, 95% CI 0.02-0.51; P = 0.005). High expression level of NRF2 is predictive for poor overall survival rate (HR = 1.86, 95% CI 1.44-2.41, P < 0.001) and poor progression-free survival (PFS) (HR = 2.27, 95% CI 1.26-4.09, P = 0.006). Compared to patients with a low level of NRF2 expression, patients with high NRF2 expression levels were associated with worse OS and PFS when given the chemotherapy or EGFR-TKI. Together, our meta-analysis results suggest that NRF2 can act as a potential indicator of NSCLC tumour aggressiveness and help the prognosis and design of a better treatment strategy for NSCLC patients

Surface Defect-Extended BIM Generation Leveraging UAV Images and Deep Learning

Defect inspection of existing buildings is receiving increasing attention for digitalization transfer in the construction industry. The development of drone technology and artificial intelligence has provided powerful tools for defect inspection of buildings. However, integrating defect inspection information detected from UAV images into semantically rich building information modeling (BIM) is still challenging work due to the low defect detection accuracy and the coordinate difference between UAV images and BIM models. In this paper, a deep learning-based method coupled with transfer learning is used to detect defects accurately; and a texture mapping-based defect parameter extraction method is proposed to achieve the mapping from the image U-V coordinate system to the BIM project coordinate system. The defects are projected onto the surface of the BIM model to enrich a surface defect-extended BIM (SDE-BIM). The proposed method was validated in a defect information modeling experiment involving the No. 36 teaching building of Nantong University. The results demonstrate that the methods are widely applicable to various building inspection tasks

Analysis of the Fungal Community in Apple Replanted Soil Around Bohai Gulf

Apple replant disease (ARD) is a frequently occurring plant disease in replanted orchards around Bohai Gulf, which causes growth inhibition and even death of plants. The aim of this study was to investigate the etiology of ARD around Bohai Gulf. In this study, the primary growth inhibition of apple seedlings was evaluated in ten replanted soils, sampled around Bohai Gulf. A fungal clone library was used to identify changes in the structure and composition of the soil fungal community. The results revealed that the Simpson diversity indices of Laizhou and Pulandian orchards were higher than others, presenting severe ARD. Ascomycota dominated around Bohai Gulf at the phyla level. Fusarium and Saccharomyces were abundant in all replanted soils. In addition, correlations between the relative abundance of fungal genera in soils and the severity of ARD were analyzed. The results showed that Fusarium was correlated positively with the severity of ARD, but Mortierella was negatively correlated. Furthermore, the quantitative PCR of Fusarium oxysporum, which was regarded as a factor of ARD, was performed. Overall, this study demonstrated that ARD was strongly associated with an unbalanced microbial ecosystem with more pathogenic fungi, while Fusarium in the apple replanted soil was the key factor for ARD around Bohai Gulf. Keywords: apple, replanted disease, Fungi clone library, fusarium, fungal communit

Lag effect of ambient temperature on respiratory emergency department visits in Beijing: a time series and pooled analysis

Abstract Background Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. Methods Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. Results The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0–21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. Conclusions Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases

Utilization of CO2 and biomass char derived from pyrolysis of Dunaliella salina: The effects of steam and catalyst on CO and H2 gas production

Biomass char, by-product of Dunaliella salina pyrolysis at a final pyrolysis temperature of 500掳C, was used as feedstock material in this study. The reactions of biomass char with CO2 were performed in a fixed-bed reactor to evaluate the effect of temperature and steam on the CO2 conversion, CO yield and gas composition. The CO2 conversion and CO yield without steam and catalyst reached about 61.84% and 0.99mol/(mol CO2) at 800掳C, respectively. Steam and high temperature led to high CO2 conversion. A new approach for improving H2 was carried out by using biomass char and Au/Al2O3 catalyst, which combined steam gasification of biomass char and water gas shift reaction, and the H2 concentration was 1.8 times higher than without catalyst. The process not only mitigated CO2 emission and made use of residual biomass char, but also created renewable source. 漏 2012 Elsevier Ltd

DIM prevents cell cycle progression in VSMCs.

<p>VSMCs were grown with DIM (25 µM) in the absence or presence of PDGF-BB (20 ng/ml) for 24 h, and cell cycle distribution was evaluated with flow cytometric analysis. A. Representative cell cycle profiles are shown. B. Quantification of VSMCs in the G0/G1, S, and G2/M phases, as determined by flow cytometric evaluation, is shown (#<i>P</i><0.01 versus control group; *<i>P</i><0.01 versus PDGF alone; n = 3). C. Cell cycle protein expression was measured with western blot analysis. GAPDH detection served as a loading control.</p

Inhibitory effects of DIM on PDGF-Rβ, Akt, GSK-3β, ERK1/2, and STAT3 activation in the PDGF-BB-stimulated VSMCs.

<p>Serum-starved VSMCs were stimulated with PDGF-BB for an indicated time in the absence or presence of DIM (25 µM). The protein levels of phospho-PDGF-Rβ, PDGF-Rβ, phospho-Akt, Akt, phospho-GSK-3β, GSK-3β, phospho-ERK1/2, ERK1/2, phospho-STAT3, and STAT3 were determined with western blot analysis. One representative image out of 3 independently performed experiments is shown.</p

Effect of DIM on reendothelialization, inflammation, apoptosis, and extracellular matrix deposition in vivo.

<p>A. Representative immunohistochemical staining for CD31 at day 7 and day 28 after injury. B, Quantitative analysis showed no difference in the extent of reendothelialization between the 2 groups (n = 6, <i>P</i> = NS versus injured control, *<i>P</i><0.05 versus day 7). C. Infiltration of inflammatory cells at 7days after vascular injury. Inflammatory cells were immunostained with anti-CD45 antibody. Arrows indicate positive cells (n = 6, *<i>P</i><0.05 versus injured control). D. Apoptotic cells were assessed by TUNEL method at 7 days after injury. Arrows indicate TUNEL-positive cells. E. Sirius red staining of injured vessels (28 days). Collagen fibers were stained in red.</p

DIM prevents neointima formation induced by guidewire injury.

<p>A–B. Representative sections of the injured carotid artery of either an animal from the control group or the DIM-treated group are shown. C–D. Quantification of the intimal area and I/M ratios of carotid arteries of mice from either the control group or the DIM-treated group (n = 6, *<i>P</i><0.01 versus injured control). E. Quantification of PCNA-positive cells of carotid arteries of mice from either the control group or the DIM-treated group (n = 9; *<i>P</i><0.01 versus injured control).</p