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Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 85% of all malignant pancreatic exocrine tumors and is one of the main causes of cancer-related fatalities. PDAC is characterized by a high glycolytic rate to ensure its survival as a result of hypovascularization and the desmoplastic reaction. In this study, microRNA 323a (miR-323a) was shown to be downregulated within pancreatic cancer tissues and cells, and enriched in the glucose metabolism pathway. In vitro, overexpression of miR-323a suppressed cell viability, DNA synthesis, and colony formation; in vivo, miR-323a overexpression suppressed the tumor growth within a xenograft mouse model. Regarding cellular glycolysis, miR-323a overexpression decreased glucose-6-phosphate levels, inhibited glucose uptake, and reduced lactate and adenosine triphosphate production. miR-323a was found to directly target hexokinase 2 (HK-2) and negatively regulated HK-2 expression. HK-2 overexpression exerted oncogenic effects on pancreatic cancer cells and promoted cellular glycolysis; more importantly, HK-2 overexpression partially eliminated the effects of miR-323a overexpression. In conclusion, miR-323a is downregulated within pancreatic cancer and serves as a tumor-suppressive miRNA through inhibiting cancer cell proliferation and glycolysis. miR-323a exerts its tumor-suppressive effects through targeting HK-2.

This study aimed to identify differentially expressed genes (DEGs) and pathways in benign prostatic hyperplasia (BPH) by comprehensive bioinformatics analysis. Data of the gene expression microarray (GSE6099) were downloaded from GEO database. DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein–protein interaction network was constructed through STRING. Anterior gradient 2 (ARG2) and lumican (LUM) staining in paraffin-embedded specimens from BPH and normal prostate (NP) were detected by immunohistochemistry (IHC). Differences between groups were analyzed by the Student’s t test. A total of 24 epithelial DEGs and 39 stromal DEGs were determined. The GO analysis results showed that epithelial DEGs between BPH and NP were enriched in biological processes of glucose metabolic process, glucose homeostasis and negative regulation of Rho protein signal transduction. For DEGs in stroma, enriched biological processes included response to ischemia, antigen processing and presentation, cartilage development, T cell costimulation and energy reserve metabolic process. ARG2, as one of the epithelial DEGs, was mainly located in epithelial cells of prostate. In addition, LUM is primarily expressed in the stroma. We further confirmed that compared with NP, the BPH have the lower ARG2 protein level (p = 0.029) and higher LUM protein level (p = 0.003) using IHC. Our study indicated that there are possible differentially expressed genes in epithelial and stromal cells, such as ARG2 and LUM, which may provide a novel insight for the pathogenesis of BPH.

The dysregulation of androgen receptor (AR) signaling is a critical event in the progression of prostate cancer (PCa) and hormone therapy consisting of androgen deprivation (ADT) or AR inhibition is therefore used to treat advanced cases. It is known that N-cadherin becomes upregulated following ADT and can directly induce PCa transformation to the castration-resistant stage (CRPC). However, the relationship between AR and N-cadherin is unclear and may promote better understanding of CRPC pathogenesis and progression. Here, we demonstrate a new axis of N-cadherin/c-Jun/N-myc downstream regulated gene 1 (NDRG1) that N-cadherin promotes c-Jun expression and suppresses NDRG1 to promote invasion and migration of PCa cells through epithelial to mesenchymal transition (EMT). Targeting N-cadherin in combination with enzalutamide (ENZ) treatment synergistically suppressed PC3 cell proliferation in vivo and in vitro. Further studies showed that compared to lower Gleason score (GS) (GS < 7) cases, high GS (GS > 7) cases exhibited elevated N-cadherin expression and reduced NDRG1 expression, corroborating our in vitro observations. We further demonstrate that c-Jun, AR, and DNA methyltransferase-1 (DNMT1) form a complex in the 12-O-tetradecanoyl phorbol-13-acetate (TPA) response elements (TREs) region of the NDRG1 promoter, which suppresses NDRG1 transcription through DNA hypermethylation. In conclusion, we demonstrate an underlying mechanism for how N-cadherin collaborates with AR and NDRG1 to promote CRPC progression. Controlling N-cadherin/c-Jun/NDRG1 axis may help to overcome resistance to commonly used hormone therapy to improve long-term patient outcomes.

Background The main purpose of this study was to compare the postoperative complications caused by surgical reconstruction via either retrosternal (RS) or prevertebral (PV) routes in thoracoscopic and laparoscopic esophagectomy patients. Materials and Methods We retrospectively screened the perioperative data in total 59 patients who underwent minimally invasive esophagectomy in time period from January 2016 to January 2018. All the patients were subgrouped into two cohorts according to the surgical routes being taken: the RS route group (28 patients) and the PV route group (31 patients). The perioperative data including operation and hospitalization time and surgical complications were comparatively analyzed. Results The surgical procedure in all patients was successful and no case of death occurred during perioperative stage in both groups. Notably, patients in the RS group had significantly lower propensity of pneumonia than patients in the PV group (p 0.05). Conclusion RS and PV paths are both safe and effective routes that yielded similar postoperative complications. Reconstruction after thoracoscopic and laparoscopic esophagectomy via the RS route had lower propensity of pneumonia than PV route.

Background. To confirm the impact of near-infrared thoracoscopy with intravenous injection of indocyanine green (ICG) during video-assisted thoracic surgery (VATS)-based segmentectomy. Materials and Methods. We retrospectively screened the perioperative data in total 21 patients who underwent segmentectomy by VATS. The segmental arteries and bronchi were identified with the help of preoperative 3-dimensional computed tomography images. Among them, clinical effectiveness and postoperative complications were analyzed. VATS segmentectomy was performed using a 3-port approach with systemic intravenous injection of ICG. Results. A total of 21 patients underwent VATS-based segmentectomy with ICG injection. The mean operation time was 126.19 ± 15.32 minutes, and the mean bleeding volume was 158.10 ± 39.95 mL. In addition, the average drainage volume 1 day after surgery was 153.81 ± 32.19 mL, and mean duration of drainage was 1.62 ± 0.59 days. Complications occurred in 6 of the 21 patients. Two patients had pneumonia, 3 had arrhythmia, and 1 had prolonged air leak. There were no complications resulting from ICG angiography. Conclusions. Near-infrared thoracoscopy with intravenous injection of ICG is a safe, fast, simple, and highly accurate method that can be used to identify the intersegmental plane and facilitate the quality of VATS-based segmentectomy.

The lymph node ratio (LNR) is defined as the number of pathologically positive LNs divided by the number of LNs examined. Some studies reported that high LNR was significantly associated with poor survival of non-small cell lung cancer (NSCLC). However, other studies could not confirm this result. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for relevant studies published up to July 2015. Primary outcome was the relationship between LNR and disease-specific survival (DSS) and overall survival (OS). Twelve studies with 25138 NSCLC patients were included in this meta-analysis. Higher LNR was significantly associated with decreased OS (HR = 1.93; 95% CI 1.64 – 2.28; P < 0.00001) and DSS (HR = 1.82; 95% CI 1.55 – 2.14; P < 0.00001). In the subgroup analysis, N1 stage NSCLC patients with higher LNR also showed decreased OS (HR = 1.60; 95% CI 1.25 – 2.28; P = 0.0002) and DSS (HR = 1.82; 95% CI 1.55 – 2.21; P < 0.0001). This meta-analysis indicated that LNR was an independent predictor of survival in patients with NSCLC.

Objective To evaluate the association between fruit/vegetable consumption and erectile dysfunction (ED) among Canadian men with diabetes. Methods Data from the 2011 Survey on Living with Chronic Diseases in Canada – Diabetes Component were analyzed using Statistical Analysis System Enterprise Guide (SAS EG). Respondents were asked a series questions related to their sociodemographics, lifestyle, and chronic health conditions. The association between fruit/vegetable consumption and ED was examined using logistic regression after controlling for potential confounding factors. Bootstrap procedure was used to estimate sample distribution and calculate confidence intervals. Results Overall, 26.2% of respondents reported having ED. The prevalence increased with age and duration of diabetes. Compared with respondents without ED, those with ED were more likely to be obese, smokers, physically inactive, and either divorced, widowed, or separated. Diabetes complications such as nerve damage, circulation problems, and kidney failure or kidney disease were also significantly associated with ED. After controlling for potential confounding factors, a 10% risk reduction of ED was found with each additional daily serving of fruit/vegetable consumed. Conclusion ED is common among Canadian men with diabetes. ED was highly associated with age, duration of diabetes, obesity, smoking, and the presence of other diabetes-related complications. Fruit and vegetable consumption might have a protective effect against ED.

The major challenges of current drug delivery systems for combination chemotherapy focus on how to efficiently transport drugs to target sites and release multiple drugs in a programmed manner. Herein, we report a novel multidrug delivery system, MSNPs 1, based on mechanized silica nanoparticles, which were constructed through functionalization of mesoporous silica nanoparticles with the acid-cleavable intermediate linkages and the monoferrocene functionalized β-cyclodextrin (Fc-β-CD) as supramolecular nanovalves. MSNPs 1 achieved zero premature release in the physiological pH solution and realized two different release modalities. In modality 1, MSNPs 1 released the encapsulated drugs gemcitabine (GEM) and doxorubicin (DOX) in sequence when they were successively applied to voltage and acid stimuli. The release time and dosage of GEM were precisely controlled via external voltage. The subsequent acid-triggered release of DOX was attributed to breakage of the intermediate linkages containing ketal groups. Modality 2 is the concurrent release of these two drugs directly upon acid exposure. Furthermore, the cell viability experiments demonstrated that MSNPs 1 had an improved cytotoxicity to MCF7 cells in comparison with single DOX- or GEM-loaded mechanized silica nanoparticles. We envisage that MSNPs 1 will play an important role in research and development for a new generation of controlled-release drug delivery system.

The roles that gammadelta T cells play in shaping initial CD4 T cell activation, and sensitivity to development of atopic diseases, remain controversial. Using a genetic knockout model of gammadelta T-cell deficiency, we investigated the role of these cells in initiation of exogenous antigen specific murine cytokine and antibody responses. Given that the most widely distributed and clinically prominent class of allergens are soluble protein antigens, we utilized OVA to examine the role played by gammadelta T cells in shaping the induction and expression of exogenous Ag specific immune responses. Focusing on immunization conditions that stimulate in vivo induction of type 2 dominant immunity, we report that gammadelta deficient and intact C57Bl6 mice exhibit similar OVA-specific responses as indicated by the (i) intensity of initial T-cell activation (ii) the type1 vs. type 2 balance of exogenous Ag specific cytokine synthesis and the (iii) intensity and the relative balance of the resulting IgE vs. IgG(2a) responses in vivo seen in these strains. Taken together, the data are consistent with the hypothesis that gammadelta T cells do not play an essential role in shaping induction of systemic immune responses to soluble exogenous antigen in type 2 dominated responses.