Artificial Intelligence in Pancreatic Image Analysis: A Review.

Pancreatic cancer is a highly lethal disease with a poor prognosis. Its early diagnosis and accurate treatment mainly rely on medical imaging, so accurate medical image analysis is especially vital for pancreatic cancer patients. However, medical image analysis of pancreatic cancer is facing challenges due to ambiguous symptoms, high misdiagnosis rates, and significant financial costs. Artificial intelligence (AI) offers a promising solution by relieving medical personnel's workload, improving clinical decision-making, and reducing patient costs. This study focuses on AI applications such as segmentation, classification, object detection, and prognosis prediction across five types of medical imaging: CT, MRI, EUS, PET, and pathological images, as well as integrating these imaging modalities to boost diagnostic accuracy and treatment efficiency. In addition, this study discusses current hot topics and future directions aimed at overcoming the challenges in AI-enabled automated pancreatic cancer diagnosis algorithms.

Di-n-butyl phthalate induces oversecretion of vascular endothelium-derived NAP-2 and promotes epithelial-mesenchymal transition of urothelial cells in newborn hypospadias rats.

Di-n-butyl phthalate (DBP) is a plasticizer commonly used in industrial production and is present in our daily life. It has been confirmed that DBP causes genitourinary malformations, especially hypospadias. However, the research of hypospadias mainly focusses on the genital tubercle in previous studies. In this study, we found DBP could affect the exocrine function of the vascular endothelium which disturb the development of genital nodules and induced hypospadias. We used cytokine array to find that vascular endothelium-derived NAP-2 may be a major abnormal secreted cytokine with biological functions. The transcriptomic sequencing analysis showed that abnormal activation of the RhoA/ROCK signaling pathway was the main reason for increased NAP-2 secretion. The expression levels of epithelial-mesenchymal transition (EMT) biomarkers and NAP-2 in hypospadias animal models were detected with Immunohistochemistry, Western blot, Immunofluorescence, and ELISA methods. The expression levels of NAP-2, RhoA/ROCK signaling pathway related proteins, reactive oxygen species (ROS) levels in HUVEC cells, EMT biomarkers and migration capacity of urothelial cells cocultured with HUVEC were measured with ELISA, flow cytometry, Western blot or Transwell assay for further cell experiments. The results showed that DBP leaded to NAP-2 oversecretion from vascular endothelium mainly rely on the activation of RhoA/ROCK signaling pathway and ROS accumulation. The RhoA/ROCK inhibitor fasudil could partially decrease ROS production, and both fasudil and N-acetyl-L-cysteine (NAC) could decrease NAP-2 secretion. Meanwhile, the oversecretion of NAP-2 from HUVEC in coculture system promoted EMT and migration capacity of urothelial cells, and TGF-ß inhibitor LY219761 could block the aberrant activation of EMT process. Therefore, it could be concluded that DBP increase NAP-2 secretion from vascular endothelium by RhoA/ROCK/ROS pathway, and further promote EMT in urothelial cells through TGF-ß pathway. This study provided a novel direction for studying the occurrence of hypospadias and may provide a hypospadias predictive marker in the future.

Effects of microplastic type on growth and physiology of soil crops: Implications for farmland yield and food quality.

Microplastic residues pose one of the most serious environmental problems in areas where plastic mulch is used extensively. Microplastic pollution has potentially serious consequences for ecosystems and human health. Several studies have analyzed microplastics in greenhouses or laboratory climate-controlled chambers; however, field studies evaluating the effects of different microplastics on different crops in extensive farming are limited. Therefore, we selected three major crops, Zea mays (ZM, monocotyledon), Glycine max (GM, dicotyledon, aboveground-bearing), and Arachis hypogaea (AH, dicotyledon, belowground-bearing) and investigated the effect of adding polyester microplastics (PES-MPs) and polypropylene microplastics (PP-MPs). Our results demonstrate that PP-MPs and PES-MPs decreased the soil bulk density of ZM, GM, and AH. Regarding soil pH, PES-MPs increased the soil pH of AH and ZM, whereas PP-MPs decreased the soil pH of ZM, GM, and AH compared to controls. Intriguingly, different coordinated trait responses to PP-MPs and PES-MPs were observed in all crops. In general, commonly measured parameters of AH, such as plant height, culm diameter, total biomass, root biomass, PSII maximum photochemical quantum yield (Fv/Fm), hundred-gain weight, and soluble sugar tended to decrease under PP-MPs exposure; however, some indicators of ZM and GM increased under PP-MPs exposure. PES-MPs had no obviously adverse influence on the three crops, except for the biomass of GM, and even significantly increased the chlorophyll content of AH, specific leaf area, and soluble sugar of GM. Compared with PES-MPs, PP-MPs have serious negative effects on crop growth and quality, especially AH. The findings of the present study provides evidence for evaluating the impact of soil microplastic pollution on crop yield and quality in farmland and lay a foundation for future investigations on the exploration of MP toxicity mechanisms and adaptability of different crops to microplastics.

Upregulation of FGF7 Induced Intravesical Prostatic Protrusion of Benign Prostatic Hyperplasia via the ERK1/2 Signaling Pathway.

INTRODUCTION: Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. METHODS: Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. RESULTS: First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. CONCLUSIONS: Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression.

Transformation of dissolved organic matter at a full-scale petrochemical wastewater treatment plant.

Transformation of dissolved organic matter (DOM) in petrochemical wastewater (PCW) treatment has rarely been studied. In this work, low- and high-salinity PCW were collected from a treatment plant and the transformations of DOM at molecular level along the treatment processes of both PCW were comparatively investigated. By using Orbitrap MS, the polar DOM constituents were categorized into five molecular classes namely saturated compounds, aliphatics, highly unsaturated and phenolic compounds (Huph), polyphenols and condensed polycyclic aromatics (Cpla). Aliphatics (58.62%) with low molecular weight (150-250 Da) and O/C (0-0.2) were dominant in raw low-salinity PCW; while Huph (65.03%) with O/C at 0.2-0.8 were rich in raw high-salinity PCW. After full-scale treatment, differentiated DOM constituents in both raw PCWs were transformed into aliphatics and Huph with O/C at 0.3-0.5. Anoxic/Oxic treatment of low-salinity system (L-A/O) removed a high fraction of aliphatics (53.05%); while Huph with low O/C (0.1-0.3) (65.68%) in the effluent of L-A/O were further mineralized by ozonation of low-salinity system (L-ozonation). In comparison, anoxic/oxic treatment of high-salinity system (H-A/O) mainly removed unsaturated Huph (34.10%) and aliphatics (30.86%). This resulted in a decrease of dissolved organic carbon as indicated via Spearman correlation. Different from L-ozonation, ozonation of high-salinity system (H-ozonation) degraded aliphatics (26.09%) and Huph (41.85%) with a relatively high O/C (0.2-1.2). After L-A/O and L-ozonation treatments, remaining saturated compounds that were originated from raw low-salinity PCW, were removed by subsequent biological aerated filter. Comparatively, after H-A/O and H-ozonation treatments, residual Huph and aliphatics which were mainly bio-derivates and ozonated intermediates, were further removed by air flotation filter. Hence, DOM transformation of different PCWs along similar treatments varied significantly. This study provides in-depth insights on DOM transformation along a full-scale PCW treatment process.

Identification and validation of an immune-related gene prognostic signature for clear cell renal carcinoma.

Clear Cell Renal Carcinoma (ccRCC) accounts for nearly 80% of renal carcinoma cases, and immunotherapy plays an important role in ccRCC therapy. However, the responses to immunotherapy and overall survival for ccRCC patients are still hard to predict. Here, we constructed an immune-related predictive signature using 19 genes based on TCGA datasets. We also analyzed its relationships between disease prognosis, infiltrating immune cells, immune subtypes, mutation load, immune dysfunction, immune escape, etc. We found that our signature can distinguish immune characteristics and predict immunotherapeutic response for ccRCC patients with better prognostic prediction value than other immune scores. The expression levels of prognostic genes were determined by RT-qPCR assay. This signature may help to predict overall survival and guide the treatment for patients with ccRCC.

Identification of Feature Genes of a Novel Neural Network Model for Bladder Cancer.

Background: The combination of deep learning methods and oncogenomics can provide an effective diagnostic method for malignant tumors; thus, we attempted to construct a reliable artificial neural network model as a novel diagnostic tool for Bladder cancer (BLCA). Methods: Three expression profiling datasets (GSE61615, GSE65635, and GSE100926) were downloaded from the Gene Expression Omnibus (GEO) database. GSE61615 and GSE65635 were taken as the train group, while GSE100926 was set as the test group. Differentially expressed genes (DEGs) were filtered out based on the logFC and FDR values. We also performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the biological functions of the DEGs. Consequently, we utilized a random forest algorithm to identify feature genes and further constructed a neural network model. The test group was given the same procedures to validate the reliability of the model. We also explored immune cells' infiltration degree and correlation coefficients through the CiberSort algorithm and corrplot R package. The qRT-PCR assay was implemented to examine the expression level of the feature genes in vitro. Results: A total of 265 DEGs were filtered out and significantly enriched in muscle system processes, collagen-containing and focal adhesion signaling pathways. Based on the random forest algorithm, we selected 14 feature genes to construct the neural network model. The area under the curve (AUC) of the training group was 0.950 (95% CI: 0.850-1.000), and the AUC of the test group was 0.667 (95% CI: 0.333-1.000). Besides, we observed significant differences in the content of immune infiltrating cells and the expression levels of the feature genes. Conclusion: After repeated verification, our neural network model had clinical feasibility to identify bladder cancer patients and provided a potential target to improve the management of BLCA.

Preconception exposure to dibutyl phthalate (DBP) impairs spermatogenesis by activating NF-κB/COX-2/RANKL signaling in Sertoli cells.

Dibutyl phthalate (DBP) is an endocrine disruptor, which causes male reproductive dysfunction in rodents. Previous researches demonstrated that DBP exposure impaired spermatogenesis, however, the molecular mechanism is largely uncovered. In this study, we demonstrated that prenatal exposure to DBP increased receptor activator of nuclear factor-κB ligand (RANKL) expression in seminiferous tubules, especially in Sertoli cells. Western blot and immunofluorescence assays showed that DBP induced up-regulation of RANKL expression in Sertoli cells. Furthermore, experimental data showed that DBP increased COX-2 and p-p65 expression in Sertoli cells and depleting COX-2 and p-p65 by specific inhibitor NS3-98 and BAY117082 could partially abolish DBP induced up-regulation of RANKL. Moreover, the content of RANKL in Sertoli cells was significantly increased after DBP exposure by conducting enzyme linked immunosorbent assay (ELISA), which promoted spermatogonial stem cells (C18-4 cells) apoptosis in a paracrine manner. Together, our data demonstrated that a novel mechanism for DBP induced impairment of spermatogenesis by activating NF-κB/COX-2/RANKL signaling in Sertoli cells, and provided a diagnostic and therapeutic target.

Tumour microenvironment landscape and immunotherapy response in bladder cancer decoded by stromal MOXD1 based on copper-related genes signature.

Introduction: We aimed to develop a copper-related gene (CRG) signature that can be used to evaluate prognosis and guide therapeutic management in bladder cancer patients. Methods: The raw transcriptome profiles and clinical data of 405 bladder samples were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed copper-related genes were identifified using the Molecular Signatures Database (MSigDB) database and univariate and multivariate Cox regression analysis. A multigene prognostic signature based on 14 CRGs was developed by least absolute shrinkage and selection operation (LASSO) analysis in the TCGA cohort and validated in the Gene Expression Omnibus (GEO) cohort. Multiple analyses were then conducted in which the nomograms, clinicopathological features, immune-related cell infifiltration characteristics, and therapy responses of the high- and low-risk score groups were compared. Results: A 14 CRGs signature was constructed and used to classify patients into high-risk and low-risk groups. Compared to patients classifified as high-risk, low-risk patients in both the TCGA cohort and the GEO cohort had better overall survival. Patients in high-risk groups had more aggressive clinical features, immunologically "cold" infifiltrating characteristics, and experienced lower therapeutic effificacy. We identifified a CRG signature of bladder cancer and validated it using unsupervised clustering analysis. Monooxygenase DBH-like 1 (MOXD1) was further identifified, and its potential for evaluating the tumor immune microenvironment and predicting the immunotherapy response was explored. Discussion: These results suggest a novel research direction for precision therapy of bladder cancer and demonstrate that copper-related genes can play a promising role in predicting prognosis and may serve as therapeutic targets for bladder cancer.

Development and Validation of Prognostic Model in Transitional Bladder Cancer Based on Inflammatory Response-Associated Genes.

BACKGROUND: Bladder cancer is a common malignant type in the world, and over 90% are transitional cell carcinoma. While the impact of inflammatory response on cancer progression has been reported, the role of inflammatory response-associated genes (IRAGs) in transitional bladder cancer still needs to be understood. METHODS: In this study, IRAGs were download from Molecular Signature Database (MSigDB). The transcriptional expression and matched clinicopathological data were separately obtained from public databases. The TCGA-BLCA cohort was used to identify the differentially expressed IRAGs, and prognostic IRAGs were filtrated by univariate survival analysis. The intersection between them was displayed by Venn diagram. Based on least absolute shrinkage and selection operator (LASSO) regression analysis method, the TCGA-BLCA cohort was used to construct a risk signature. Survival analysis was conducted to calculate the overall survival (OS) in TCGA and GSE13507 cohort between two groups. We then conducted univariate and multivariate survival analyses to identify independently significant indicators for prognosis. Relationships between the risk scores and age, grade, stage, immune cell infiltration, immune function, and drug sensitivity were demonstrated by correlation analysis. The expression level of prognostic genes in vivo and in vitro were determined by qRT-PCR assay. RESULTS: Comparing with normal tissues, there were 49 differentially expressed IRAGs in cancer tissues, and 12 of them were markedly related to the prognosis in TCGA cohort for transitional bladder cancer patients. Based on LASSO regression analysis, a risk model consists of 10 IRAGs was established. Comparing with high-risk groups, survival analysis showed that patients in low-risk groups were more likely to have a better survival time in TCGA and GSE13507 cohorts. Besides, the accuracy of the model in predicting prognosis is acceptable, which is demonstrated by receiver operating characteristic curve (ROC) analysis. Age, stage, and risk scores variables were identified as the independently significant indicators for survival in transitional bladder cancer. Correlation analysis represented that the risk score was identified to be significantly related to the above variables except gender variable. Moreover, the expression level of prognostic genes in vivo and in vitro was markedly upregulated for transitional bladder cancer. CONCLUSIONS: A novel model based on the 10 IRAGs that can be used to predict survival time for transitional bladder cancer. In addition, this study may provide treatment strategies according to the drug sensitivity in the future.

Identification and Validation of a Novel Immune-Related lncRNA Signature for Bladder Cancer.

PURPOSE: We aimed to construct an immune-related long noncoding ribonucleic acids (irlncRNA) signature to evaluate the prognosis of patients without specific expression level of these irlncRNA. METHODS: The raw transcriptome data were downloaded from The Cancer Genome Atlas (TCGA), irlncRNAs were filtered out using an online immune related gene database and coexpression analysis, differently expressed irlncRNA (DEirlncRNA) pairs were identified by univariate analysis. The areas under curve (AUC) were compared and the Akaike information criterion (AIC) values of receiver operating curve (ROC) was counted, the most optimal model was constructed to divide bladder cancer patients into high- and low-risk groups usingõ the cut-off point of ROC. Then, we evaluated them from multiple perspectives, such as survival time, clinic-pathological characteristics, immune-related cells infiltrating, chemotherapeutics efficacy and immune checkpoint inhibitors. RESULTS: 14 DEirlncRNA pairs were included in this signature. Patients in high-risk groups demonstrated apparent shorter survival time, more aggressive clinic-pathological characteristics, different immune-related cells infiltrating status, lower chemotherapeutics efficacy. CONCLUSION: The irlncRNA signature demonstrated a promising prediction value for bladder cancer patients and was important in guiding clinical treatment.

Targeting ADT-Induced Activation of the E3 Ubiquitin Ligase Siah2 to Delay the Occurrence of Castration-Resistant Prostate Cancer.

Siah2 is an E3 ubiquitin ligase that targets androgen receptor (AR) and plays an important role in the development of castration-resistant prostate cancer (CRPC). However, the regulation of Siah2 in prostate cancer (PCa) is largely unknown. In this study, we used AR-dependent and -independent cells lines to investigate the cellular roles of AR and androgen deprivation therapy (ADT) on Siah2 protein levels and E3 ligase activity using Western blotting and co-immunoprecipitation. We also validated our findings using patient samples taken before and after ADT. Finally, we used xenograft tumor models to test the effects of ADT combined with vitamin K3 (Vit K3) on tumor growth in vivo. Our results showed that AR stabilizes Siah2 protein by attenuating its self-ubiquitination and auto-degradation, likely by blocking its E3 ubiquitin ligase activity. Conversely, ADT decreased Siah2 protein expression but enhanced its E3 ligase activity in PCa cells. Notably, the findings that ADT decreasing Siah2 protein expression were verified in a series of paired PCa samples from the same patient. Additionally, we found that ADT-induced Siah2 activation could be abolished by Vit K3. Strikingly, ADT combined with Vit K3 treatment delayed the occurrence of CRPC and dramatically inhibited the growth of tumor xenografts compared with ADT treatment alone. AR is an inhibitor of Siah2 in PCa, and ADT leads to the continuous activation of Siah2, which may contribute to CRPC. Finally, ADT+Vit K3 may be a potential approach to delay the occurrence of CRPC.

Nomogram for preoperative estimation of prognosis after retropubic tension free vaginal tape in female patients with stress urinary incontinence.

BACKGROUND: To identify risk factors by developing a nomogram for predicting surgical outcomes for female patients who underwent tension free vaginal tape (TVT) for stress urinary incontinence (SUI). METHODS: Data on 365 patients with pure SUI who underwent TVT at the Shanghai General Hospital between February, 2017 and July, 2018, were retrospectively collected. Within this group, symptoms of patients who were found to have disappeared or have been improved (subjective success group) were compared with symptoms of those patients who were found to have no change or recurrence (subjective failure group). We evaluated the effect of treatment after TVT surgery on SUI patients based upon patient prognosis. RESULTS: During the study period, 327 women underwent TVT surgery and met the qualifications for inclusion in six-month follow-up consultations and 38 patients were lost. Multivariable logistic regression analysis of risk factors that were important in relation to the failure of surgery indicated two independent predictors: total cholesterol (TC) (P=0.005) and maximal urethral closure pressure (MUCP) (P=0.028). We developed a nomogram to predict prognosis after TVT in female patients with SUI using these parameters. CONCLUSIONS: We developed a predictive model for preoperative estimation of prognosis in female patients who underwent TVT based treatment for SUI. This model could select patients who were found to have successful postoperative outcomes, which can lead to a rational therapeutic choice.

External Validation of the Prognostic Value of an Immune-Associated Gene Panel for Clear Cell Renal Cell Carcinomas.

Clear cell renal cell carcinomas (ccRCCs) are highly immune infiltrates, and many of them respond to immunotherapy with checkpoint inhibitors including anti-PD-L1 or anti-PD1 agents. However, the effect of immune genes on clinical outcomes in ccRCCs has not been fully studied. Here, we show in this study that an immune-associated gene panel has a prognostic value for clear cell renal cell carcinomas. We performed single-sample gene set enrichment analysis (ssGSEA) and cell type identification by estimating subsets of RNA transcripts (CIBERSORT) algorithms on patient-matched normal renal and RCC tissues to characterize two immunophenotypes and immunological characteristic subpopulations. Furthermore, LASSO Cox regression was applied to develop a novel prognosis-associated model for ccRCC patients based on an immune-gene panel. The results were verified by the Gene Expression Omnibus (GEO) dataset and coordinated with the clinicopathological characteristics of ccRCCs, along with genomic signatures. Finally, based on the above perspectives, we generated a nomogram with a high prognostic efficiency for ccRCC patients. Overall, this study offers a unique perspective that can contribute to improving the accuracy of prognosis prediction and treatment with immunotherapy.

Activation of the RhoA/ROCK pathway contributes to renal fibrosis in offspring rats induced by maternal exposure to di-n-butyl phthalate.

Maternal exposure to di-n-butyl phthalate (DBP) can cause renal fibrosis in adult offspring rats. However, its underlying mechanisms have not yet been fully understood. In this study, we investigated whether the RhoA/ROCK pathway plays an important role in offspring renal fibrosis induced by maternal exposure to DBP. Our results showed that maternal exposure to DBP (850 mg/kg/day orally feeding during gestational days 14-18) activated the RhoA/ROCK pathway and induced epithelial-mesenchymal transition (EMT) in kidneys of offspring rats. Compared with the control group treated with normal saline, EMT in the kidneys of offspring rats undergoing 8 weeks of ROCK inhibitor Y-27632 treatment (at a dose of 30 mg/kg) was significantly inhibited, the degree of renal fibrosis was significantly reduced, and the renal function was significantly improved. DBP (10 µmol/L) activated the RhoA/ROCK pathway and induced EMT in NRK-52E cells in vitro. Both 5 µM and 10 µM Y-27632, a ROCK inhibitor, significantly reduced the EMT of NRK-52E cells. Taken together, our findings suggest that the RhoA/ROCK pathway plays an important role in the pathogenesis of renal fibrosis in offspring rats induced by maternal exposure to DBP via promoting EMT of renal tubular epithelial cells.

Di-n-butyl phthalate (DBP) reduces epithelial-mesenchymal transition via IP3R in hypospadias during maternal exposure.

OBJECTIVE: This study focused on the oxidative stress effect of di-n-butyl phthalate (DBP) on development of the urinary system. METHODS: We examined the mRNA expression of genital tubercle (GT) in control and DBP induced hypospadias group by Affymetrix Rat 230 2.0 Array. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of inositol-1,4,5-triphate-receptor (IP3R) and epithelial-mesenchymal-transition (EMT)-related molecular markers, such as E-cadherin, ß-Catenin, Snail, N-cadherin, in the GT of hypospadiac male rats and controls. The results of array were further confirmed in vitro. The changes of intracellular calcium concentration in urethral epithelial cells were detected by Fluo-3-AM before and after DBP treatment. The levels of reactive oxygen species (ROS) in urethral epithelial cells were measured by DCFH-DA with different concentrations of DBP (0, 1, 10, 100 µmol/L) treatment. RESULTS: The mRNA expression profiles of GT in control and DBP induced hypospadias group showed high expression of IP3R and the abnormalities of EMT. Compared to the control group, the expression levels of IP3R, E-cadherin and ß-Catenin increased at both the protein and mRNA levels. However the expression levels of Snail and N-cadherin decreased. The intracellular calcium concentration increased significantly after DBP treatment. The effect of DBP on urethral epithelial cells was linked to the generation of oxidative stress. CONCLUSION: DBP can influence the development of GT through its oxidative stress effect, which significantly increases the concentration of calcium and inhibits EMT in urethral epithelial cells, and block the fusion process of urethral groove, causing the occurrence of hypospadias. This study provides a new understanding of DBP's molecular mechanisms on hypospadias and may lead to new treatment strategies for the disease.

Preoperative CD4+CD25+/CD4+ and tumor diameter predict prognosis in male patients with bladder cancer.

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

Di-n-butyl phthalate induced autophagy of uroepithelial cells via inhibition of hedgehog signaling in newborn male hypospadias rats.

Maternal exposure to di-n-butyl phthalate (DBP) induces hypospadias via regulation of autophagy in uroepithelial cells. Here, we use gene express analysis to explore the underlying molecular mechanisms. Pregnant rats received DBP orally at a dose of 750 mg/kg/day during gestational days 14-18. Gene expression analysis showed an increased expression of the hedgehog interacting protein (HhIP) gene. In DBP-induced hypospadiac male offspring, immunohistochemistry (IHC) staining and Western blot analysis confirmed increased expression of the HhIP protein and inhibited hedgehog signaling. in vitro experiments suggest the involvement of the reactive oxygen species (ROS)-HhIP-Gli1-autophagy axis in DBP-treated primary rat urethral epithelial cells. Taken together, our findings show that prenatal exposure to DBP induces abnormal hedgehog signaling and autophagy in uroepithelial cells that may play important roles in the development of hypospadias.

RS 504393 inhibits M-MDSCs recruiting in immune microenvironment of bladder cancer after gemcitabine treatment.

Bladder cancer (BC) is a malignant tumor of urinary epithelium. Gemcitabine is an introduced treatment for BC and also has immunomodulatory function, but the immunoregulation mechanism is not clear. In this study, we found that gemcitabine-treated BC cell recruited more monocyte-myeloid-derived suppressed cells (M-MDSCs), which played a significant role in immune suppression and contributed to cancer progression. We found that this phenomenon was induced by Chemokine (C-C motif) ligand 2 (CCL2), an M-MDSCs recruitment related monomeric polypeptide. Gemcitabine treatment promotes the generation of CCL2 and CCL2 could attach to C-C chemokine receptor type 2 (CCR2) to recruit M-MDSCs. We used RS 504393, a selective CCR2 antagonist, to inhibit the recruitment of M-MDSCs. RS 504393 improved the prognosis by blocking chemotaxis of M-MDSCs, and this finding sheds lights on how to prevent and alleviate the side effects occurred on the gemcitabine-treated BC patients.

Maternal exposure to di-n-butyl phthalate promotes Snail1-mediated epithelial-mesenchymal transition of renal tubular epithelial cells via upregulation of TGF-ß1 during renal fibrosis in rat offspring.

We previously demonstrated that maternal exposure to di-n-butyl phthalate (DBP) resulted in renal fibrosis in male offspring; however, the underlying mechanism governing this effect has not been thoroughly elucidated to date. We hypothesized that DBP exposure induces TGF-ß expression and abnormal activation of epithelial-mesenchymal transition (EMT) in fibrotic kidneys. Pregnant rats received DBP orally at a dose of 850 mg/kg BW/day during gestational days 14-18. In the DBP-exposed group, immunohistochemistry (IHC) staining showed increased expression of TGF-ß1 and EMT markers. In rat kidney tubular epithelial cells (NRK52E), ROS production increased expression levels of TGF-ß1 and subsequently contributed to the induction of Snail1-mediated EMT. Notably, DBP exposure also promoted autophagy that downregulated TGF-ß1. Taken together, our findings suggest that maternal exposure to DBP promotes EMT in tubular epithelial cells via upregulation of TGF-ß1.