Prognostic value of inflammation and immune-related gene NOD2 in clear cell renal cell carcinoma.

Inflammation and immune responses play important roles in cancer development and prognosis. We identified 59 upregulated inflammation- and immune-related genes (IIRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. Among the upregulated IIRGs, nucleotide binding oligomerization domain 2 (NOD2), PYD and CARD domain (PYCARD) were also confirmed to be upregulated in the Oncomine database and in three independent GEO data sets. Tumor immune infiltration resource database analysis revealed that NOD2 and PYCARD levels were significantly positively correlated with infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells. Multivariate Cox hazards regression analysis indicated that based on clinical variables (age, gender, tumor grade, pathological TNM stage), NOD2, but not PYCARD, was an independent, unfavorable ccRCC prognostic biomarker. Functional enrichment analyses (GSEA) showed that NOD2 was involved in innate immune responses, inflammatory responses, and regulation of cytokine secretion. Meanwhile, mRNA and protein levels of NOD2 were elevated in four ccRCC cell lines (786-O, ACHN, A498 and Caki-1), and its knockdown significantly inhibited IL-8 secretion, thereby inhibiting ccRCC cell proliferation and invasion. Furthermore, results showed that miR-20b-5p targeted NOD2 to alleviate NOD2-mediated IL-8 secretion. In conclusion, NOD2 is a potential prognostic biomarker for ccRCC and the miR-20b-5p/NOD2/IL-8 axis may regulate inflammation- and immune-mediated tumorigenesis in ccRCC.

Two highly stable isoreticular M8-pyrazolate (M = Co, Ni) metal-organic frameworks for CO2 conversion.

Two isoreticular metal-organic frameworks (MOFs) constructed from M8(OH)4(H2O)2(pyz)12 (M = Co, Ni; pyz = pyrazolate) secondary building units (SBUs) and Ni(salen)-derived metalloligands were synthesized. The two MOFs were found to be highly stable in a wide pH and temperature range. Together with the tetrabutylammonium bromide (TBAB) co-catalyst, they catalysed the cycloaddition of CO2 to epoxides with near-quantitative yields and easy recyclability for at least 11 cycles.

Understanding the role of pathways in a deep neural network.

Deep neural networks have demonstrated superior performance in artificial intelligence applications, but the opaqueness of their inner working mechanism is one major drawback in their application. The prevailing unit-based interpretation is a statistical observation of stimulus-response data, which fails to show a detailed internal process of inherent mechanisms of neural networks. In this work, we analyze a convolutional neural network (CNN) trained in the classification task and present an algorithm to extract the diffusion pathways of individual pixels to identify the locations of pixels in an input image associated with object classes. The pathways allow us to test the causal components which are important for classification and the pathway-based representations are clearly distinguishable between categories. We find that the few largest pathways of an individual pixel from an image tend to cross the feature maps in each layer that is important for classification. And the large pathways of images of the same category are more consistent in their trends than those of different categories. We also apply the pathways to understanding adversarial attacks, object completion, and movement perception. Further, the total number of pathways on feature maps in all layers can clearly discriminate the original, deformed, and target samples.

Self-Adaptive Graph With Nonlocal Attention Network for Skeleton-Based Action Recognition.

Graph convolutional networks (GCNs) have achieved encouraging progress in modeling human body skeletons as spatial-temporal graphs. However, existing methods still suffer from two inherent drawbacks. Firstly, these models process the input data based on the physical structure of the human body, which leads to some latent correlations among joints being ignored. Furthermore, the key temporal relationships between nonadjacent frames are overlooked, preventing to fully learn the changes of the body joints along the temporal dimension. To address these issues, we propose an innovative spatial-temporal model by introducing a self-adaptive GCN (SAGCN) with global attention network, collectively termed SAGGAN. Specifically, the SAGCN module is proposed to construct two additional dynamic topological graphs to learn the common characteristics of all data and represent a unique pattern for each sample, respectively. Meanwhile, the global attention module (spatial attention (SA) and temporal attention (TA) modules) is designed to extract the global connections between different joints in a single frame and model temporal relationships between adjacent and nonadjacent frames in temporal sequences. In this manner, our network can capture richer features of actions for accurate action recognition and overcome the defect of the standard graph convolution. Extensive experiments on three benchmark datasets (NTU-60, NTU-120, and Kinetics) have demonstrated the superiority of our proposed method.

Towards artefact-free AFM image presentation and interpretation.

Atomic force microscopy (AFM) is based upon a simple operational principle. However, the presentation and interpretation of AFM images can easily suffer from consequential artefacts that are easily overlooked. Here we discuss results from AFM and its companion variations AFM-IR (AFM combined with infrared spectroscopy) and PF-QNM (an AFM mode called peak-force quantitative nano-mechanical mapping) by imaging 'bee' structures in asphalt binder (bitumen) as examples. We show how common problems manifest themselves and provide solutions, with the intent that authors can present their results clearly and avoid interpreting artefacts as true physical properties, thereby raising the quality of AFM research.

Cascaded parallel crowd counting network with multi-resolution collaborative representation.

Accurately estimating the size and density distribution of a crowd from images is of great importance to public safety and crowd management during the COVID-19 pandemic, but it is very challenging as it is affected by many complex factors, including perspective distortion and background noise information. In this paper, we propose a novel multi-resolution collaborative representation framework called the cascaded parallel network (CP-Net), consisting of three parallel scale-specific branches connected in a cascading mode. In the framework, the three cascaded multi-resolution branches efficiently capture multi-scale features through their specific receptive fields. Additionally, multi-level feature fusion and information filtering are performed continuously on each branch to resist noise interference and perspective distortion. Moreover, we design an information exchange module across independent branches to refine the features extracted by each specific branch and deal with perspective distortion by using complementary information of multiple resolutions. To further improve the robustness of the network to scale variance and generate high-quality density maps, we construct a multi-receptive field fusion module to aggregate multi-scale features more comprehensively. The performance of our proposed CP-Net is verified on the challenging counting datasets (UCF_CC_50, UCF-QNRF, Shanghai Tech A&B, and WorldExpo'10), and the experimental results demonstrate the superiority of the proposed method.

Identification of CeRNA Regulatory Networks in Atrial Fibrillation Using Nanodelivery.

The initiation and maintenance of AF is a complex biological process that is the ultimate manifestation of many cardiovascular diseases. And the pathogenesis of atrial fibrillation (AF) is unclear. Therefore, this study aimed to find the potential competing endogenous RNAs (ceRNAs) network and molecular dysregulation mechanism associated with AF. GSE135445, GSE2240, and GSE68475 were obtained from the Gene Expression Omnibus (GEO). Differential analysis was utilized to identify the differentially expressed mRNAs, miRNAs, and lncRNAs between AF and sinus rhythms (SR). AF-associated mRNAs and nanomaterials were screened and their biological functions and KEGG signaling pathways were identified. Nanomaterials for targeted delivery are uniquely capable of localizing the delivery of therapeutics and diagnostics to diseased tissues. The target mRNAs and target lncRNAs of differentially expressed miRNAs were identified using TargetScan and LncBase databases. Finally, we constructed the ceRNAs network and its potential molecular regulatory mechanism. We obtained 643 AF-associated mRNAs. They were significantly involved in focal adhesion and the PI3K-Akt signaling pathway. Among the 16 differentially expressed miRNAs identified, 31 differentially expressed target mRNAs, as well as 5 differentially expressed target lncRNAs were identified. Among them, we obtained 2 ceRNAs networks (hsa-miR-125a-5p and hsa-let-7a-3p). The aberrant expression of network target genes in AF mainly activated the HIF-1 signaling pathway. We speculated that the interaction pairs of miR-125a-5p and let-7a-3p with target mRNAs and target lncRNAs may be involved in AF. Our findings have a positive influence on investigating the pathogenesis of AF and identifying potential therapeutic targets.

A Study of Urodynamic Parameters at Different Bladder Filling Stages for Predicting Upper Urinary Tract Dilatation.

PURPOSE: To identify more accurate predictors of upper urinary tract dilatation (UUTD) in neurogenic bladder (NB) children, we studied the relationship among urodynamic parameters at different bladder filling stages, detrusor leak point pressure (DLPP) and UUTD. METHODS: A total of 158 children (3-16 years) with NB were included and then divided into 2 groups according to whether their NB diagnosis was complicated with UUTD: the UUTD group (39 patients) and those without UUTD group (control group, 119 patients). The bladder filling phase was divided into 3 equal parts: the early, middle, and end filling stages. The bladder compliance (BC) and detrusor pressure (△Pdet) at each phase and DLPP at the end filling stage were recorded. RESULTS: A BC<8 mL/cm H2O both in the middle and end stages is more specific than a BC<9 mL/cm H2O in the end stage (72%, 73%, vs. 66%), and △Pdet >8 cm H2O in the early stage, 20 cm H2O in the middle stage and 25 cm H2O in the end stage are more sensitive than △Pdet >40 cm H2O in the end stage (82%, 85%, 85%, vs. 49%). A DLPP cutoff value of 20 cm H2O showed higher sensitivity for predicting UUTD than 40 cm H2O. CONCLUSION: Low BC and a high △Pdet in the middle and end filling stages are more accurate factors than classic indicators for predicting UUTD. In addition, a DLPP value of >20 cm H2O in the end bladder filling stage shows high sensitivity.

HRANet: Hierarchical region-aware network for crowd counting.

Aiming to tackle the most intractable problems of scale variation and complex backgrounds in crowd counting, we present an innovative framework called Hierarchical Region-Aware Network (HRANet) for crowd counting in this paper, which can better focus on crowd regions to accurately predict crowd density. In our implementation, first, we design a Region-Aware Module (RAM) to capture the internal differences within different regions of the feature map, thus adaptively extracting contextual features within different regions. Furthermore, we propose a Region Recalibration Module (RRM) which adopts a novel region-aware attention mechanism (RAAM) to further recalibrate the feature weights of different regions. By the integration of the above two modules, the influence of background regions can be effectively suppressed. Besides, considering the local correlations within different regions of the crowd density map, a Region Awareness Loss (RAL) is designed to reduce false identification while producing the locally consistent density map. Extensive experiments on five challenging datasets demonstrate that the proposed method significantly outperforms existing methods in terms of counting accuracy and quality of the generated density map. In addition, a series of specific experiments in crowd gathering scenes indicate that our method can be practically applied to crowd localization.

Investigating the aging mechanism of asphaltene and its dependence on environmental factors through AIMD simulations and DFT calculations.

To understand the complex aging mechanism of asphalt and its dependence on environmental factors, the chemical reactivity of asphaltene during aging under different environmental conditions was studied through first-principles molecular simulations and density functional theory calculations. The aging of asphaltene was demonstrated to involve a series of subreactions along different pathways on the asphaltene molecules, including hydrogen abstraction from carbon, formation of polar groups, aromatization of cycloalkanes, and homolysis of side chains. These subreactions occurred with different free-energy barriers and, therefore, had different kinetic rates. Asphaltene aging was found to be slightly accelerated in the presence of water owing to the improved electron transfer ability of the asphaltene molecule in an aqueous solvent. Under ultraviolet radiation, the asphaltene molecule transitioned to an excited state with an excitation energy of 348.7 kJ/mol, significantly increasing its aging rate. This work bridges the gap between electronic-scale modeling and diversified experimental observations related to asphalt aging and is expected to provide theoretical guidance for strategies to prevent or delay the aging-induced failure of asphalt pavements.

MD-UNET: Multi-input dilated U-shape neural network for segmentation of bladder cancer.

Accurate segmentation of the tumour area is crucial for the treatment and prognosis of patients with bladder cancer. However, the complex information from the MRI image poses an important challenge for us to accurately segment the lesion, for example, the high distinction among people, size of bladder variation and noise interference. Based on the above issues, we propose an MD-Unet network structure, which uses multi-scale images as the input of the network, and combines max-pooling with dilated convolution to increase the receptive field of the convolutional network. The results show that the proposed network can obtain higher precision than the existing models for the bladder cancer dataset. The MD-Unet can achieve state-of-art performance compared with other methods.

Significant Prognostic Value of the Autophagy-Related Gene P4HB in Bladder Urothelial Carcinoma.

While hundreds of consistently altered autophagy-related genes (ARGs) have been identified in cancers, their prognostic value in bladder urothelial carcinoma (BUC) remains unclear. In the present study, we collected 232 ARGs from the Human Autophagy Database (HADb), and identified 37 differentially expressed ARGs in BUC based on The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that among the 37 differentially expressed ARGs, prolyl 4-hydroxylase, beta polypeptide (P4HB), and regulator of G protein signaling 19 (RGS19) were significantly negatively correlated with overall survival (OS) and disease-free survival (DFS). Overexpression of P4HB and RGS19 in BUC was further validated using independent data sets, including those from the Oncomine and Gene Expression Omnibus (GEO) databases. cBioPortal and UALCAN analyses indicated that altered P4HB and RGS19 mRNA expression was significantly associated with mutations and clinical characteristics (nodal metastasis and cancer stage). Moreover, co-expression network analysis and gene set enrichment analysis (GSEA) predicted that the potential functions of P4HB and RGS19 are involved in the endoplasmic reticulum (ER) stress response, cytokine-mediated signaling pathway and inflammatory response. More importantly, multivariate Cox proportional hazards regression analysis demonstrated that P4HB, but not RGS19, is an independent and unfavorable BUC biomarker based on clinical characteristics (age, gender, cancer stage, and pathological TNM stage). Finally, we validated that the mRNA and protein expression levels of P4HB were upregulated in four bladder cancer cell lines (T24, J82, EJ, and SW780) and found that knockdown of P4HB dramatically inhibited the invasion and proliferation of bladder cancer cells. In summary, our study screened ARGs and identified P4HB as a biomarker that can predict the progression and prognosis of BUC and may provide a better understanding of the autophagy regulatory mechanisms involved in BUC.

The long non-coding RNA SNHG1 promotes bladder cancer progression by interacting with miR-143-3p and EZH2.

The long non-coding RNA (lncRNA) SNHG1 has been shown to be implicated in the progression of multiple human carcinomas. Nevertheless, the biological functions and potential mechanism of SNHG1 in bladder cancer (BC) are uncharacterized. In the present study, SNHG1 was found to be substantially up-regulated in BC tissues and cells and was intimately correlated with the TNM stage, lymphatic invasion, metastasis and recurrence-free survival in BC patients. Down-regulation of SNHG1 dramatically attenuated the proliferation, migration and invasion of BC cells, whereas the ectopic overexpression of SNHG1 had the opposite effects in vitro. The in vivo experimental results also indicated that SNHG1 down-regulation hampered the tumour growth and metastasis of BC cells. Mechanistic investigations revealed that SNHG1 enhances HK2 expression by serving as an endogenous sponge to regulate miR-143-3p in the cytoplasm of BC cells. In the nucleus, SNHG1 could interact with EZH2 and regulate the histone methylation of the CDH1 promoter, altering the biological behaviours of BC cells. Overall, these findings elucidate an oncologic role of SNHG1 in BC and provide a new therapeutic strategy against BC.

Use of high-fidelity 3-dimensional-printed models for training novice residents in basic nasal endoscopic skills.

BACKGROUND: The use of 3-dimensional (3D)-printed models is promising in nasal endoscopic technique training. Here, we aimed to develop postsurgical simulants for use in conjunction with 3D-printed nasal models and to assess their usefulness in helping residents transfer basic endoscopic skills acquired during simulation training to clinical situations. METHODS: The secretion simulant was prepared via a crosslinked reaction between sodium alginate and acrylamide, whereas the packing simulant was prepared using a superabsorbent polymer. After the simulants' fidelity and utility were evaluated by 5 rhinologists using a 5-point Likert scale, 46 novice residents were trained using the 3D-printed nasal models and postsurgical simulants for 2 weeks. A checklist and Global Rating Scale (GRS) were used to assess their performances before and after training, and the time to finish each task was also recorded. Following training, the qualified trainees operated on real patients and were reevaluated. RESULTS: The simulants' similarity and usefulness scored ≥4.0, and the training cost was 28 CNY ($4 USD) per session. Following training, the checklist and GRS scores increased, and the operation time decreased (all p < 0.05). There were no statistical differences between the trainees' performances on the models with the simulants and on patients (all p > 0.05). CONCLUSION: The low-cost simulated secretion and dressing are safe to use. The application of the simulants in conjunction with that of 3D-printed nasal models in a simulated task setting can help residents in transferring endoscopic skills acquired during simulation teaching to real patients.

[Regulatory effect of Di'ao Xinxuekang on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats].

The aim of this paper was to observe the effect of Di'ao Xinxuekang(DXXK) on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats, and to explore its anti-atherosclerotic mechanism. Sixty SD rats were randomly divided into normal group, model group, atorvastatin group(4.0 mg·kg~(-1)), and DXXK groups(100, 30, 10 mg·kg~(-1)), with 10 rats in each group. The atherosclerosis model was induced by high fat diet plus vitamin D_2. Experimental drugs were administered intragastrically once daily for 8 weeks starting from the 9 th week. Biochemical analyzers were used to detect levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in blood lipid. The levels of serum tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1ß were detected by ELISA. Pathological changes of aortic tissues were observed by using Sudan Ⅳ and HE staining. The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in aortic tissues were detected by RT-PCR and Western blot, respectively. As compared with the model group, TC, TG, and LDL-C levels in serum were significantly decreased, HDL-C content was significantly increased, and levels of TNF-α, IL-6, and IL-1ß in serum were significantly decreased in atorvastatin group and DXXK high and middle dose groups. Aortic lesions in atorvastatin group and DXXK group were significantly improved, and the mRNA and protein expressions of TLR4, MyD88, NF-κB p65 in the aorta were decreased. DXXK has a preventive and therapeutic effect on atherosclerosis in rats, and its mechanism may be related to inhibiting inflammatory reaction by regulating TLR4/MyD88/NF-κB signal transduction, thereby inhibiting the progression of atherosclerosis.

The Improvement of Moisture Resistance and Organic Compatibility of SrAl2O4: Eu2+, Dy3+ Persistent Phosphors Coated with Silica-Polymer Hybrid Shell.

The existing road surface marking with poor visibility at night results in traffic safety hazards in insufficient lighting roads. This study aims to prepare the dedicated aluminate-based persistent phosphors considering the integrated pavement environment, as the first step to achieve the durable luminescent road surface marking. SrAl2O4: Eu2+, Dy3+ persistent phosphors coated with silica-polymer hybrid shell were prepared by chemical precipitation and sol-gel method to improve moisture resistance and organic compatibility. The optimum silane coupling agent type and dosage, the surfactant dosage, the optimum sodium silicate dosage, and the coating reaction time in silica shell and polymer shell coating were studied based on the moisture resistance test. The silica-polymer hybrid shell coating balances the organic compatibility and thermal stability as compared to the silica or polymer shell coating in the oil absorption test and thermogravimetric analysis. Ex-Em Spectra, XRD, and SEM method were used to characterize the persistent phosphors, indicating the preparation does not destroy the persistent phosphors. The outstanding durable properties of SrAl2O4: Eu2+, Dy3+ persistent phosphors coated with silica-polymer hybrid shell as shown in this research is crucial for its potential application in waterborne luminescent coatings of road surface marking.

Integrative analysis of the lncRNA-associated ceRNA network reveals lncRNAs as potential prognostic biomarkers in human muscle-invasive bladder cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in competing endogenous RNA (ceRNA) networks involved in the development and progression of various cancers, including muscle-invasive bladder cancer (MIBC). PURPOSE: This study aims to construct the lncRNA-associated ceRNA network and identify lncRNA signatures correlated with the clinical features of MIBC tissue samples from The Cancer Genome Atlas (TGCA) database. METHODS: The differential expression profiles of MIBC associated lncRNAs, miRNAs and mRNAs were obtained from TCGA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the principal functions of significantly dysregulated mRNAs. The dysregulated lncRNA-associated ceRNA network of MIBC was constructed based on the bioinformatics data, and the correlations between lncRNA expression and clinical features were analyzed using a weighted gene coexpression network analysis (WGCNA). Six cancer specific lncRNAs from the ceRNA network were randomly selected to detect their expression in 32 paired MIBC tissue samples and 5 bladder cancer cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The ceRNA network was constructed with 30 lncRNAs, 13 miRNAs and 32 mRNAs. Seventeen lncRNAs in the ceRNA network correlated with certain clinical features, and only 1 lncRNA (MIR137HG) correlated with the overall survival (OS) of patients with MIBC (log-rank test P<0.05). GO and KEGG analyses revealed roles for the potential mRNA targets of MIR137HG in epithelial cell differentiation and the peroxisome proliferator-activated receptor (PPAR) and tumor necrosis factor (TNF) signaling pathways. The expression data from TCGA were highly consistent with the verification results of the MIBC tissue samples and bladder cancer cell lines. CONCLUSION: These findings improve our understanding of the regulatory mechanism of the lncRNA-miRNA-mRNA ceRNA network and reveal potential lncRNAs as prognostic biomarkers of MIBC.

Systemic treatment with resveratrol alleviates adjuvant arthritis-interstitial lung disease in rats via modulation of JAK/STAT/RANKL signaling pathway.

Interstitial lung disease (ILD) is the most common pulmonary manifestation of Rheumatoid arthritis (RA) lung disease. The mechanism of RA-ILD remains obscure and more effective treatments are still needed. Resveratrol (RSV) a phytoalexin found with anti-inflammation and antioxidant activity. RSV has been reported to protect against RA. In current study, we evaluated the effects of RSV on RA-ILD and further explored the underlying mechanisms. We established the RA-ILD rat model by injecting Freund's complete adjuvant (FCA). After administration of RSV into RA-ILD rats, the disease parameters were assessed, inflammatory cytokines productions were analyzed, and the effects of RSV on JAK/STAT/RANKL were evaluated. Injection of FCA caused RA-ILD in rats, which had clear lung damage, fibrosis, and elevated pro-inflammatory cytokines in both serum and lung. RSV treatment significantly ameliorated the lung disease and prevented pro-inflammatory cytokines production. In addition, RSV inhibited JAK/STAT/RANKL signaling pathway in RA-ILD rats. RSV treatment alleviates RA-ILD in rats by inhibiting JAK/STAT/RANKL signaling pathway.

Cell-penetrating peptide conjugates of gambogic acid enhance the antitumor effect on human bladder cancer EJ cells through ROS-mediated apoptosis.

BACKGROUND: Gambogic acid (GA) is the main active ingredient of resin gamboges and possesses anti-cancer activity toward various human cancer cells. However, clinical application of GA has been limited by its poor aqueous solubility and dose-limiting toxicities. Cell-penetrating peptides (CPPs) are widely used to deliver anti-cancer drugs into cancer cells and to enhance the water solubility of drugs. PURPOSE: The object of this study was to synthesize peptide-drug conjugates in which the cell-penetrating peptide TAT (trans-activator of transcription) was conjugated to GA and evaluated the anti-cancer activity of this GA-CPP conjugate (GA-TAT) in EJ bladder cancer cells. METHODS: GA is built onto the TAT, and the GA-TAT conjugates are cleaved from the solid support and purified via HPLC. The equilibrium solubility of GA-TAT was measured using the shake-flask method. The effects of GA-TAT on EJ cell viability and proliferation were determined by MTT assay, Edu assay and colony formation assay, respectively. After treated with 1.0 µM GA-TAT for 24 h, the apoptosis rate of EJ cells were detected by Acridine orange/ethidium bromide (AO/EB) assay and flow cytometry assay. The proteins of caspase-3 (processing), caspase-9 (processing), Bcl-2 and Bax were analyzed by Western blotting, and the intracellular reactive oxygen species (ROS) production was evaluated by a reactive oxygen species assay. RESULTS: In contrast to free GA, the solubility of GA-TAT in water was significantly improved. Meanwhile, GA-TAT significantly increased EJ cellular uptake, toxicity and apoptosis. Mechanistic analysis revealed that GA-TAT enhanced the anti-cancer effect of GA against EJ cells through ROS-mediated apoptosis. The results were demonstrated that GA-TAT increased the ROS level in EJ cells, and N-acetyl-L-cysteine (NAC; a well-known ROS scavenger) inhibited GA-TAT-induced ROS generation and apoptosis. Additionally, GA-TAT activated caspase-3 and caspase-9 and down-regulated the Bcl-2/Bax ratio, but these effects were largely rescued by NAC. CONCLUSION: GA-TAT has outstanding potential for promoting tumor apoptosis and exhibits promise for use in bladder cancer therapy.

rSjP40 protein promotes PPARγ expression in LX-2 cells through microRNA-27b.

miR-27b is reported to participate in the proliferation and differentiation of hepatic stellate cells (HSCs) and to regulate fat metabolism of rat HSCs by targeting retinoid X receptor α. Our previous study also indicated that the recombinant P40 protein from Schistosoma japonicum (rSjP40) inhibited the activation of HSCs. In this study, we observed the expression of miR-27b in rSjP40-treated LX-2 cells and explored its potential mechanisms. Quantitative real-time PCR showed that rSjP40 inhibits the expression of miR-27b in LX-2 cells. Further results obtained by Western blot and dual-luciferase reporter assay confirmed that miR-27b regulates peroxisome proliferator-activated receptor γ (PPARγ) expression in rSjP40-treated LX-2 cells by targeting the 3'-UTR of PPARγ. 5-AZA-2'-deoxycytidine (5-AZA-dC), which inhibits methylation of HSCs, partially reversed rSjP40-induced down-regulation expression of miR-27b in LX-2 cells. 5-AZA-dC also partially reversed rSjP40-induced up-regulation expression of PPARγ in LX-2 cells. The increased expression of PPARγ in rSjP40-treated LX-2 cells may be partially due to miR-27b methylation. Therefore, our study provides further insight into the mechanism by which rSjP40 inhibits HSC activation and provides a basis for future study of the blocking effect of rSjP40 in liver fibrosis.-Zhu, D., Lyu, L., Shen, P., Wang, J., Chen, J., Sun, X., Chen, L., Zhang, L., Zhou, Q., Duan, Y. rSjP40 protein promotes PPARγ expression in LX-2 cells through microRNA-27b.