ObjectiveIL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervical cancer cells and study its related mechanisms.MethodsWound healing and matrigel transwell assays were used to examine the effect of IL-17A on cervical cancer cell migration and invasion by a panel of cervical cancer cell lines. The levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were investigated using western blotting. The activity of p38 and nuclear factor-kappa B (NF-κB) signal pathway was detected too.ResultsHere, we showed that IL-17A could promote the migration and invasion of cervical cancer cells. Further molecular analysis showed that IL-17A could up-regulate the expressions and activities of MMP2 and MMP9, and down-regulate the expressions of TIMP-1 and TIMP-2. Furthermore, IL-17A also activates p38 signal pathway and increased p50 and p65 nuclear expression. In addition, treatment of cervical cancer cells with the pharmacological p38/NF-κB signal pathway inhibitors, SB203580 and PDTC, potently restored the roles of invasion and upregulation of MMPs induced by IL-17A.ConclusionIL-17A could promote the migration and invasion of cervical cancer cell via up-regulating MMP2 and MMP9 expression, and down-regulating TIMP-1 and TIMP-2 expression via p38/NF-κB signal pathway. IL-17A may be a potential target to improve the prognosis for patients with cervical cancer.

Hiwi, also named PiwiL1, is a human homologue of the Piwi family which is associated with stem cells and is overexpressed in several types of cancers. In the present study, we aimed to investigate the role of Hiwi in cervical carcinogenesis. Immunochemical analysis showed a significantly higher frequency of Hiwi staining in high-grade squamous intraepithelial lesions (HSILs) and cervical cancer tissues when comparing with the frequency in normal cervices. Particularly, Hiwi staining was restricted to basal cells of the normal cervix and was associated with the progression of cervical cancer and chemotherapy resistance. We further found that ectopic Hiwi increased the chemical resistance in SiHa cells, and silencing of Hiwi in HeLa cells decreased the cell viability. In addition, as a cancer stem cell marker, Hiwi promoted the tumorsphere formation in vitro and tumorigenicity in vivo and elevated the expression of several stem cell self-renewal-associated transcription factors, in spite of inhibited the proliferation. These results suggest that Hiwi may participate in the carcinogenesis of cervical cancer and may be a potential therapeutic target molecule for cervical cancers.

Abstract. Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signalregulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC.

Based on the increasing pressure on the water environment, this study aims to clarify the overall status of wastewater discharge in China, including the spatio-temporal distribution characteristics of wastewater discharge and its driving factors, so as to provide reference for developing “emission reduction” strategies in China and discuss regional sustainable development and resources environment policies. We utilized the Exploratory Spatial Data Analysis (ESDA) method to analyze the characteristics of the spatio-temporal distribution of the total wastewater discharge among 31 provinces in China from 2002 to 2013. Then, we discussed about the driving factors, affected the wastewater discharge through the Logarithmic Mean Divisia Index (LMDI) method and classified those driving factors. Results indicate that: (1) the total wastewater discharge steadily increased, based on the social economic development, with an average growth rate of 5.3% per year; the domestic wastewater discharge is the main source of total wastewater discharge, and the amount of domestic wastewater discharge is larger than the industrial wastewater discharge. There are many spatial differences of wastewater discharge among provinces via the ESDA method. For example, provinces with high wastewater discharge are mainly the developed coastal provinces such as Jiangsu Province and Guangdong Province. Provinces and their surrounding areas with low wastewater discharge are mainly the undeveloped ones in Northwest China; (2) The dominant factors affecting wastewater discharge are the economy and technological advance; The secondary one is the efficiency of resource utilization, which brings about the unstable effect; population plays a less important role in wastewater discharge. The dominant driving factors affecting wastewater discharge among 31 provinces are divided into three types, including two-factor dominant type, three-factor leading type and four-factor antagonistic type. In addition, the proposals aimed at reducing the wastewater discharge are provided on the basis of these three types.

The unique tumor microenvironment (TME) characteristics such as immunosuppression impeded traditional cancer treatments. In contrast, developing cascade catalytic nanoplatforms by fully making use of substances in TME for cancer therapy may deserve full credit. Herein, a cascade catalytic nanoplatform based on glucose oxidase (GOD) modified mesoporous iron oxide nanoparticles (IONP) loaded with Artemisinin (ART) is developed, which is designed as IONP-GOD@ART. GOD can catalyze the oxidization of glucose into gluconic acid and H 2 O 2 , which not only realizes tumor starvation therapy, but also provides H 2 O 2 for IONP mediated Fenton reaction. Simultaneously, mesoporous IONP releases Fe 2+ and Fe 3+ ions in acidic TME. On the one hand, iron ions undergo Fenton reaction to generate hydroxyl radicals for chemodynamic therapy. On the other hand, the endoperoxide bridge in ART is broken in presence of Fe 2+ and further generates reactive oxygen species (ROS) to achieve therapeutic purpose. In this sense, IONP-GOD@ART manipulates TME characteristics and leads to "butterfly effect", which brings out a large amount of ROS for eliciting immunogenic cell death, inducing M1-TAMs polarization, and further reprogramming immunosuppressive TME for enhanced immunotherapy. By this delicate design, the cascade catalytic nanoplatform of IONP-GOD@ART realizes potent cancer immunotherapy for tumor regression and metastasis prevention.