Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.
Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs) through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM) extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR) to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1) were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.
In this study, we selected four different color fleshed sweet potatoes, purple-(Jizi 01), red-(Xinong 431), yellow-(Beijing 553) and white-(Shangshu 19) fleshed cultivars as test materials, analyzed nutrient composition, dietary fiber content, anthocyanins quantification, and total phenolics content, and also measured their total antioxidant activity in four different types of sweet potato. In view of differences in flesh color, the nutrient contents of different cultivars appeared to be significantly different. Starch contents of Beijing 553 and Shangshu 19 were higher, but fat contents were lower than others. Protein content of Shangshu 19 was the highest followed by Jizi 01 and Xinong 431. In addition, our analysis results confirmed that purple fleshed sweet potato possesses much higher anthocyanins content than others, even up to 6.23 mg/g dry matter. Also, dietary fiber, total phenolics content, and total antioxidant capacity of Jizi 01 were significantly higher.
Commercial catches of the 'major carps' (grass carp Ctenopharyngodon idella, silver carp Hypophthalmichthys molitrix, black carp Mylopharyngodon piceus and bighead carp Aristichthys nobilis) in the middle and lower reaches of the Yangtze River have declined precipitously since construction of the Three Gorges Dam (TGD). To assess specific environmental effects, young-of-the-year major carps were collected below TGD in the Yangtze River at Jianli (larvae) and E'zhou (juveniles) and in the Dongting Lake (juveniles) during June-August 2007. Lapillar otoliths were analyzed to determine early growth. There were no discernible growth increments in otoliths for a majority of the larvae (38 of 63 grass carp and 40 of 47 silver carp), while increments were evident in otoliths formed in the larval stage for all the juveniles, indicating that larvae without discernible increments failed to recruit to the juvenile stage. Back-calculated hatch dates of major carps were between 31 May and 24 July. The initiation of the spawning season was delayed about 1 month compared to pre-TGD records. Larval growth rates, as reflected by otolith-increment width, were lower at Dongting Lake (closer to TGD) than at E'zhou (farther from TGD), indicating that TGDmoderated effects on early growth and development of carps are more apparent for fishes hatched nearer to the dam. The delay in spawning and decreased early growth may partly explain the recent decline of the major carp resources in the middle and lower Yangtze River.
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