MicroRNA-362 induces cell proliferation and apoptosis resistance in gastric cancer by activation of NF-κB signaling.

BACKGROUND: According to cancer-related microRNA (miRNA) expression microarray research available in public databases, miR-362 expression is elevated in gastric cancer. However, the expression and biological role of miR-362 in gastric progression remain unclear. METHODS: miR-362 expression levels in gastric cancer tissues and cell lines were determined using real-time PCR. The roles of miR-362, in promoting gastric cancer cell proliferation and apoptosis resistance, were assessed by different biological assays, such as colony assay, flow cytometry and TUNEL assay. The effect of miR-362 on NF-κB activation was investigated using the luciferase reporter assay, fluorescent immunostaining. RESULTS: MiR-362 overexpression induced cell proliferation, colony formation, and resistance to cisplatin-induced apoptosis in BGC-823 and SGC-7901 gastric cancer cells. MiR-362 increased NF-κB activity and relative mRNA expression of NF-κB-regulated genes, and induced nuclear translocation of p65. Expression of the tumor suppressor CYLD was inhibited by miR-362 in gastric cancer cells; miR-362 levels were inversely correlated with CYLD expression in gastric cancer tissue. MiR-362 downregulated CYLD expression by binding its 3' untranslated region. NF-κB activation was mechanistically associated with siRNA-mediated downregulation of CYLD. MiR-362 inhibitor reversed all the effects of miR-362. CONCLUSION: The results suggest that miR-362 plays an important role in repressing the tumor suppressor CYLD and present a novel mechanism of miRNA-mediated NF-κB activation in gastric cancer.

Overexpression of GOLPH3 is associated with poor prognosis and clinical progression in pancreatic ductal adenocarcinoma.

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) has been identified as an oncoprotein in various human cancers; however, its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. We examined GOLPH3 expression levels and relationship with survival in patients with PDAC to establish the significance of GOLPH3 in the development and progression of PDAC. METHODS: Real-time qPCR and Western blotting were performed to analyze the expression levels of GOLPH3 mRNA and protein in paired PDAC tumor and adjacent non-tumor tissues. Immunohistochemistry was used to analyze the expression levels of GOLPH3 protein in paraffin-embedded tissues from 109 cases of PDAC. Univariate and multivariate analyses were performed to identify correlations between the immunohistochemical data for GOLPH3 expression and the clinicopathologic characteristics in PDAC. RESULTS: Expression levels of GOLPH3 mRNA and protein were upregulated in PDAC lesions compared to paired adjacent noncancerous tissues. Expression of GOLPH3 was significantly correlated with clinical stage (P = 0.006), T classification (P = 0.021), N classification (P = 0.049) and liver metastasis (P = 0.035). Patients with high GOLPH3 expression had shorter overall survival times compared to those with low GOLPH3 expression (P = 0.007). Multivariate analysis revealed that GOLPH3 overexpression was an independent prognostic factor in PDAC. CONCLUSIONS: Our findings suggest that GOLPH3 expression status may be a potential prognostic biomarker and therapeutic target in PCAC.

Urinary incontinence as a main clinical manifestation of early stage Wernicke's encephalopathy: a case report.

Wernicke's encephalopathy (WE) is a condition caused by a deficiency of vitamin B1. While there have been many reported cases of WE in the literature, there are few reports on the early stages of the disorder. In this report, we present a case of WE with urinary incontinence as the main clinical manifestation. A 62-year-old female patient was admitted to the hospital due to intestinal obstruction and did not receive vitamin B1 supplements for 10 days. Three days after her operation, she developed urinary incontinence. She also had mild mental symptoms, such as a little indifference. After consultation with a urologist and neurologist, the patient was immediately given intramuscular vitamin B1 at a dosage of 200 mg/day. After 3 days of supplementing with vitamin B1, her urinary incontinence and mental symptoms improved and were completely resolved after 7 days of treatment. Surgeons should be aware that when long-term fasting patients have urinary incontinence, it may be a symptom of WE, and they should be supplied with vitamin B1 in a timely manner without extensive examination.

Transcriptome Data Reveal Geographic Heterogeneity in Gene Expression in Patients with Prostate Cancer.

Background: The incidence of prostate cancer (PC) exhibits geographical heterogeneity. However, the metabolic mechanisms underlying this geographic heterogeneity remain unclear. This study aimed to reveal the metabolic mechanism of the geographic heterogeneity in the incidence of PC.This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell. Methods: Transcriptomic data from public databases were obtained and analyzed to screen geographic-differentially expressed genes and metabolic pathways. Associations between these differentially expressed genes and the incidence of PC were determined to identify genes that were highly associated with PC incidence. A co-expression network analysis was performed to identify geographic-specific regulatory pathways. Results: A total of 175 differentially expressed genes were identified in four countries and were associated with the regulation of DNA replication and the metabolism of pyrimidine, nucleotides, purines, and galactose.Additionally, the expression of the genes CLVS2, SCGB1A1, KCNK3, HHIPL2, MMP26, KCNJ15, and PNMT was highly correlated with the incidence of PC. Geographic-specific differentially expressed genes in low-incidence areas were highly correlated with KCNJ15, MMP26, KCNK3, and SCCB1A1, which play a major role in ion channel-related functions. Conclusions: This study suggests that geographic heterogeneity in PC incidence is associated with the expression levels of genes associated with amino acid metabolism, lipid metabolism, and ion channels.

The Flow-Induced Degradation and Vascular Cellular Response Study of Magnesium-Based Materials.

Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.

Adhesive and Self-Healing Polyurethanes with Tunable Multifunctionality.

Many polyurethanes (PUs) are blood-contacting materials due to their good mechanical properties, fatigue resistance, cytocompatibility, biosafety, and relatively good hemocompatibility. Further functionalization of the PUs using chemical synthetic methods is especially attractive for expanding their applications. Herein, a series of catechol functionalized PU (C-PU-PTMEG) elastomers containing variable molecular weight of polytetramethylene ether glycol (PTMEG) soft segment are reported by stepwise polymerization and further introduction of catechol. Tailoring the molecular weight of PTMEG fragment enables a regulable catechol content, mobility of the chain segment, hydrogen bond and microphase separation of the C-PU-PTMEG elastomers, thus offering tunability of mechanical strength (such as breaking strength from 1.3 MPa to 5.7 MPa), adhesion, self-healing efficiency (from 14.9% to 96.7% within 2 hours), anticoagulant, antioxidation, anti-inflammatory properties and cellular growth behavior. As cardiovascular stent coatings, the C-PU-PTMEGs demonstrate enough flexibility to withstand deformation during the balloon dilation procedure. Of special importance is that the C-PU-PTMEG-coated surfaces show the ability to rapidly scavenge free radicals to maintain normal growth of endothelial cells, inhibit smooth muscle cell proliferation, mediate inflammatory response, and reduce thrombus formation. With the universality of surface adhesion and tunable multifunctionality, these novel C-PU-PTMEG elastomers should find potential usage in artificial heart valves and surface engineering of stents.

Application of a Reactive Oxygen Species-Responsive Drug-Eluting Coating for Surface Modification of Vascular Stents.

Stent implantation is the primary method used to treat coronary heart disease. However, it is associated with complications such as restenosis and late thrombosis. Despite surface modification being an effective way to improve the biocompatibility of stents, the current research studies are not focused on changes in the vascular microenvironment at the implantation site. In the present study, an adaptive drug-loaded coating was constructed on the surface of vascular stent materials that can respond to oxidative stress at the site of vascular lesions. Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium. EGCG has antioxidant activity, and pitavastatin calcium can inhibit smooth muscle cell proliferation. Therefore, EGCG and pitavastatin calcium provided a synergistic anti-inflammatory effect. Moreover, the coating was cross-linked using disulfide bonds, which accelerated the release of the drug in response to reactive oxygen species. A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo.

Inflammation as a risk factor for stroke in atrial fibrillation: data from a microarray data analysis.

OBJECTIVE: Stroke is a severe complication of atrial fibrillation (AF). We aimed to discover key genes and microRNAs related to stroke risk in patients with AF using bioinformatics analysis. METHODS: GSE66724 microarray data, including peripheral blood samples from eight patients with AF and stroke and eight patients with AF without stroke, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between AF patients with and without stroke were identified using the GEO2R online tool. Functional enrichment analysis was performed using the DAVID database. A protein-protein interaction (PPI) network was obtained using the STRING database. MicroRNAs (miRs) targeting these DEGs were obtained from the miRNet database. A miR-DEG network was constructed using Cytoscape software. RESULTS: We identified 165 DEGs (141 upregulated and 24 downregulated). Enrichment analysis showed enrichment of certain inflammatory processes. The miR-DEG network revealed key genes, including MEF2A, CAND1, PELI1, and PDCD4, and microRNAs, including miR-1, miR-1-3p, miR-21, miR-21-5p, miR-192, miR-192-5p, miR-155, and miR-155-5p. CONCLUSION: Dysregulation of certain genes and microRNAs involved in inflammation may be associated with a higher risk of stroke in patients with AF. Evaluating these biomarkers could improve prediction, prevention, and treatment of stroke in patients with AF.

Cu∥-loaded polydopamine coatings with in situ nitric oxide generation function for improved hemocompatibility.

NO is the earliest discovered gas signal molecule which is produced by normal healthy endothelial cells, and it has many functions, such as maintaining cardiovascular homeostasis, regulating vasodilation, inhibiting intimal hyperplasia and preventing atherosclerosis in the blood system. Insufficient NO release is often observed in the pathological environment, for instance atherosclerosis. It was discovered that NO could be released from the human endogenous NO donor by many compounds, and these methods can be used for the treatment of certain diseases in the blood system. In this work, a series of copper-loaded polydopamine (PDA) coatings were produced through self-polymerization time for 24, 48 and 72 h. The chemical composition and structure, coating thickness and hydrophilicity of the different copper-loaded PDA coatings surfaces were characterized by phenol hydroxyl quantitative, X-ray photoelectron spectroscopy, ellipsometry atomic force microscopy and water contact angles. The results indicate that the thickness and the surface phenolic hydroxyl density of the PDA coatings increased with the polymerization time.This copper-loaded coating has glutathione peroxidase-like activity, and it has the capability of catalyzing NO releasing from GSNO. The surface of the coating showed desirable hemocompatibility, the adhesion and activation of platelets were inhibited on the copper-loaded coatings. At the same time, the formation of the thrombosis was also suppressed. These copper-loaded PDA coatings could provide a promising platform for the development of blood contact materials.

GOLPH3 Promotes Cancer Growth by Interacting With STIP1 and Regulating Telomerase Activity in Pancreatic Ductal Adenocarcinoma.

Overexpression of Golgi phosphoprotein 3 (GOLPH3) predicts poor prognosis and is a potential therapeutic target in pancreatic ductal adenocarcinoma (PDAC). However, its role and underlying molecular mechanisms in the progression of PDAC remain unknown. In the present study, using high-throughput bimolecular fluorescence complementation (BiFC) analysis, we identified that stress-inducible protein-1 (STIP1) interacts with GOLPH3 and confirmed the interaction using co-localization and co-immunoprecipitation. The levels of GOLPH3 and STIP1 in PDAC tissues and adjacent non-cancerous pancreatic tissues were determined using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR. Real-time Quantitative-telomere repeat amplification (Q-TRAP) was applied to detect relative telomerase activity, and cell proliferation was measured when small interfering RNAs targeting GOLPH3 or STIP1 were transfected into PDAC cell lines. BALB/c nude mice were used to assess tumor growth inhibition of BXPC3 cells stably transfected with GOLPH3 short hairpin RNA. In summary, GOLPH3 was found to interact with STIP1 and both proteins were overexpressed and co-localized in PDAC tissues and cell lines. Moreover, suppression of GOLPH3 expression using shRNAs in PANC1 and BXPC3 cells inhibited tumor cell proliferation both in vitro and in vivo. Mechanistically, GOLPH3 interacts with STIP1 to activate telomerase reverse transcriptase (hTERT) and telomerase activity by c-Myc, and then upregulates cell cycle-related signaling proteins, including cyclin D1, to promote tumor cell growth, suggesting that disrupting the interaction between STIP1 and GOLPH3 would be a promising new strategy to treat PDAC.

Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants.

Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress-strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.

Dendritic cells transduced with a PSMA-encoding adenovirus and cocultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against prostate cancer cells.

OBJECTIVE: The lack of curative therapies for advanced prostate cancer (PCa) has prompted a search for novel treatments such as immunotherapy. In this study, we analyzed whether dendritic cells (DCs) from healthy donors transduced with a PSMA-encoding adenovirus (Ad-PSMA) and cocultured with autologous cytokine-induced killer cells (CIKs) can induce a strong specific immune response against PCa cells in vitro. MATERIALS AND METHODS: Ad-PSMA was constructed by DNA recombination. DCs and CIKs were prepared by cytokines induction from peripheral blood mononuclear cells, and flow cytometry was used to measure the phenotypes of DCs and CIKs. DCs were transduced with Ad-PSMA and then cocultured with autologous CIKs. The cytotoxicity of the cocultured cells against specific target LNCaP cells and control targets DU145 and PC3 cells was analyzed by a 4-h LDH release assay. RESULTS: DCs were transduced with Ad-PSMA with transfection efficiency of 70% and the transduction did not alter typical morphology of mature DCs. The PSMA protein was effectively expressed in DCs, which were transfected with Ad-PSMA. Ad-PSMA-transduced DCs stimulated CIKs strongly to lyse about 75% of PSMA-expressing PCa cells. Furthermore, the cocultivation of Ad-PSMA-transduced DCs with CIKs could significantly increase the production of interferon-gamma after restimulated with PSMA peptide mixtures. CONCLUSIONS: The data demonstrate that DCs, which were transduced with a PSMA-expressing adenovirus and cocultured with autologous CIKs, induce a PSMA-specific, strong immune response against PCa cells. Therefore, this approach may have a potential for an adoptive immunotherapy for patients with advanced PCa.

High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma.

BACKGROUND: Phosphodiesterase 4D (PDE4D) has recently been reported as an oncogene in various types of human cancers. However, the expression and significance of PDE4D in pancreatic ductal adenocarcinoma (PDAC) have not been elucidated. Methods: Immunohistochemistry (IHC) was used to examine the expression of PDE4D in 104 clinicopathologically characterized PDAC cases. PDE4D expression in paired tumor tissues and adjacent noncancerous tissues were detected by western blotting and real time qRT-PCR. The correlation of PDE4D expression levels with clinicopathological features and prognosis in patients were analyzed by univariate and multivariate methods. Effect of PDE4D on pancreatic cancer cells was detected by cell migration and invasion assays. Results: We found that PDE4D was significantly up-regulated in PDAC tumor tissues compared to those paired adjacent noncancerous tissues at both protein and mRNA levels. High level of PDE4D was significantly associated with clinical stage (P = 0.004), T classification (P = 0.003), lymph node metastasis (P = 0.022) and liver metastasis (P = 0.038). Patients with higher levels of PDE4D had shorter overall survival time contrast with those with lower PDE4D expression (P = 0.002). Multivariate analysis indicated that PDE4D may be an independent prognostic factor for PDAC. PDE4D depletion significantly suppressed ß-catenin and Snail expression as well as the migration and invasion abilities of pancreatic cancer cells. Conclusions: Our study reveals that PDE4D up-regulated in PDAC was closely associated with poor prognosis of PDAC patients and multiple aggressive clinicopathological characteristics. PDE4D could be a useful prognostic biomarker and therapeutic target for PDAC.

An Albumin Biopassive Polyallylamine Film with Improved Blood Compatibility for Metal Devices.

Nowadays, a variety of materials are employed to make numerous medical devices, including metals, polymers, ceramics, and others. Blood-contact devices are one of the major classes of these medical devices, and they have been widely applied in clinical settings. Blood-contact devices usually need to have good mechanical properties to maintain clinical performance. Metal materials are one desirable candidate to fabricate blood-contact devices due to their excellent mechanical properties and machinability, although the blood compatibility of existing blood-contact devices is better than other medical devices, such as artificial joints and artificial crystals. However, blood coagulation still occurs when these devices are used in clinical settings. Therefore, it is necessary to develop a new generation of blood-contact devices with fewer complications, and the key factor is to develop novel biomaterials with good blood compatibility. In this work, one albumin biopassive polyallylamine film was successfully established onto the 316L stainless steel (SS) surface. The polyallylamine film was prepared by plasma polymerization in the vacuum chamber, and then polyallylamine film was annealed at 150 °C for 1 h. The chemical compositions of the plasma polymerized polyallylamine film (PPAa) and the annealed polyallylamine film (HT-PPAa) were characterized by Fourier transform infrared spectrum (FTIR). Then, the wettability, surface topography, and thickness of the PPAa and HT-PPAa were also evaluated. HT-PPAa showed increased stability when compared with PPAa film. The major amino groups remained on the surface of HT-PPAa after annealing, indicating that this could be a good platform for numerous molecules' immobilization. Subsequently, the bovine serum albumin (BSA) was immobilized onto the HT-PPAa surface. The successful introduction of the BSA was confirmed by the FTIR and XPS detections. The blood compatibility of these modified films was evaluated by platelets adhesion and activation assays. The number of the platelets that adhered on BSA-modified HT-PPAa film was significantly decreased, and the activation degree of the adhered platelets was also decreased. These data revealed that the blood compatibility of the polyallylamine film was improved after BSA immobilized. This work provides a facile and effective approach to develop novel surface treatment for new-generation blood-contact devices with improved hemocompatibility.

Golgi Phosphoprotein 3 Promotes Malignant Phenotypes via FAK/Raf/MEK and Wnt/ß-Catenin Signaling Pathways in Human Renal Cell Carcinoma.

Golgi phosphoprotein 3 (GOLPH3), a proto-oncogene product, is significantly increased during the progression of several types of cancer. However, its biological role and underlying mechanism in the development of renal cell carcinoma (RCC) remain poorly understood. In this study, GOLPH3 was found to be highly expressed in RCC specimens compared to the corresponding non-tumor tissues. In vitro, ectopic overexpression of GOLPH3 substantially promoted the proliferative and invasive capacity of RCC cells, while the depletion of GOLPH3 significantly inhibited proliferation and invasion of RCC cells. Furthermore, the average tumor volume was significantly increased in mice injected with 769-P cells highly expressing GOLPH3, whereas GOLPH3 knockdown reduced the tumor growth rate. Mechanistically, using a high-throughput phospho-proteome array verified by Western blotting, we have identified that phosphorylated proteins (FAK, Raf1, MEK, and GSK3ß) were upregulated, activating, in turn, FAK/Raf1/MEK and Wnt/ß-catenin signaling pathways in RCC cells. Taken together, our findings demonstrate that GOLPH3, whose expression is related to enhanced cell proliferation and invasion via activation of GOLPH3-FAK/Raf1/MEK axis or Wnt/ß-catenin signaling pathways, may provide a new therapeutic target to treat renal cell carcinoma.

Endothelial mimetic multifunctional surfaces fabricated via polydopamine mediated copper immobilization.

Nitric oxide (NO), which is continuously released from the normal healthy endodermis cell layer of the vascular system, plays a crucial role in the stability and health maintenance of blood vessels. It is one of the most important gaseous signaling molecules and regulates cardiovascular homeostasis, inhibits blood clotting and intimal hyperplasia, and prevents atherosclerosis. Insufficient NO production is often observed in atherosclerosis lesions. In this work, a NO-generating bioactive coating built by a polydopamine film (PDA) and a copper ion was fabricated. The coating (Cu/PDA) had glutathione peroxidase (GPx)-like activity and was able to catalyze NO release from S-nitrosothiols (RSNOs) due to the catalytic activity of the copper ion. It was also capable of catalyzing RSNO decomposition and NO production. The copper ion was embedded in the PDA coating to ensure the effectiveness of long-term NO-catalytic activity. The surface exhibited a favorable suppression of vascular smooth muscle cell (VSMC) proliferation and also efficiently reduced thrombosis formation. Additionally, the NO catalytic surface had a positive influence on endothelial cell (EC) growth behavior. The in vivo study verified that the modified surface promoted healthy endothelium formation and suppressed intimal hyperplasia, which is conducive to re-endothelialization and for reducing restenosis of vascular stents. This work provides a potential strategy for the development of novel cardiovascular implants.

Upregulation of Oxytocin Receptor in the Hyperplastic Prostate.

Background: The etiology of benign prostatic hyperplasia (BPH) is complex, both age and androgen are thought to be important. However, the failure of androgen blockade treatments suggests other paracrine/autocrine factors involved in BPH. Oxytocin was found to have a paracrine/autocrine role in prostate in recent years. The influence of BPH on prostatic oxytocin receptor (OTR) expression has never been studied. Material and methods: A testosterone-estradiol induced rat model of BPH was employed and human hyperplastic prostate specimens were harvested. Expressions of OTR, α1-adrenoreceptor subtypes and nitric oxide synthase isoforms were determined via real-time RT-PCR. OTR was further analyzed with Western-Blotting and histological examination. Subsequently, rat epithelial cells, human stromal cells and epithelial cells were cultured in vitro and treated with gradient concentrations of OT from 1 to 5 days. Cell proliferation was tested by Cell Counting Kit-8 and Flow Cytometry. Results: The rat BPH model was validated with significant increased prostate weight. H-E stain revealed a different histopathology between human and rat BPH. Masson's trichrome staining demonstrated that smooth muscle (SM) cells, epithelium cells and collagen fibers were simultaneously augmented in this rat BPH model and human BPH samples. OTR mainly localized in epithelium in rat prostate whereas it mainly localized in stroma in human prostate. OTR gene was upregulated 3.3-fold in rat BPH and 3.0-fold in human BPH, along with increased expression of 2.0-fold α1aARs and 3.0-fold eNOS for rat BPH and 5.0-fold α1aARs for human BPH. The expression of OTR protein was upregulated 1.4-fold in rat BPH and 3.9-fold in human BPH, respectively. Increased concentrations of exogenous OT can accelerate proliferation of rat epithelial cells and human stromal cells but has no impact on human epithelial cells in vitro. Flow Cytometry showed oxytocin could significantly increase G2/M period cell number. Conclusions: Our novel data demonstrates a significant and previously undocumented upregulation of OTR in both rat and human BPH. Moreover, exogenous OT accelerates proliferation of rat prostate epithelial cells and human prostate stromal cells. It is suggested OTR is involved in the development of BPH and OT regulatory system could be a potential new target for the BPH treatment.

Upregulation of macrophage migration inhibitory factor promotes tumor metastasis and correlates with poor prognosis of pancreatic ductal adenocarcinoma.

Macrophage migration inhibitory factor (MIF) is a pro­inflammatory cytokine that serves important roles in cancer. MIF overexpression is frequently observed in numerous human cancer types, including pancreatic carcinoma. However, the prognostic value and function of MIF in pancreatic ductal adenocarcinoma (PDAC) have not been fully elucidated. In the present study, upregulation of MIF expression in PDAC tissue compared with adjacent normal tissue was observed. Furthermore, MIF overexpression was identified to be significantly associated with poor survival rates in patients with PDAC. Multivariate Cox regression analysis confirmed that MIF was an independent risk factor for poor survival. Functional analyses demonstrated that MIF knockdown significantly inhibited the proliferation and invasion of pancreatic cancer cells in vitro compared with control cells. IN addition, mechanistic investigations revealed that silencing MIF leads to inhibition of AKT serine/threonine kinase and extracellular­signal­regulated kinase activation, and suppression of cyclin D1 and matrix metalloproteinase­2 expression, which may suppress tumor proliferation and invasion. These results highlight the importance of MIF overexpression in PDAC aggressiveness, and indicate that MIF may be a potential therapeutic target for pancreatic cancer.

Enhanced antitumor effects by the coculture of allotumor RNA-pulsed dendritic cells with autologous cytokine-induced killer cells on hormone-refractory prostate cancer.

In this study, we evaluated antitumor effects of allotumour RNA-transfected dendritic cells (DCs) cocultured with autologous cytokine-induced killer cells (CIKs) on hormone-refractory prostate cancer. The cocultured cells enhanced prostate cancer cytolysis from 26% (CIKs-induced cytolysis) to 80.8%. They also increased the productions of CD4(+) Th1 (IFN-γ(+)IL-4(-), 55.52%) and CD8(+) T (IFN-γ(+), 69.59%) cells determined by intracellular cytokines IFN-γ /IL-4 staining and reduced the rate of CD4(+) CD25(+) cells from 18.72% (in CIKs) to 9.72%. The cocultured cells significantly inhibited tumor growth in SCID mouse and induced cancer cells necrosis and apoptosis. Our study indicates that tumor RNA-pulsed DCs cocultured with autologous CIKs significantly enhance antitumor immunity, which can be induced by increased CD4(+) Th1 and CD8(+) T cells and decreased CD4(+)CD25(+) regulatory T (T(reg)) cells. This provides a potential immunotherapy strategy for HRPC.

Surface Modification of Cardiovascular Stent Material 316L SS with Estradiol-Loaded Poly (trimethylene carbonate) Film for Better Biocompatibility.

A delay in the endothelialization process represents a bottleneck in the application of a drug-eluting stent (DES) during cardiovascular interventional therapy, which may lead to a high risk of late restenosis. In this study, we used a novel active drug, estradiol, which may contribute to surface endothelialization of a DES, and prepared an estradiol-loaded poly (trimethylene carbonate) film (PTMC-E5) on the surface of the DES material, 316L stainless steel (316L SS), in order to evaluate its function in improving surface endothelialization. All the in vitro and in vivo experiments indicated that the PTMC-E5 film significantly improved surface hemocompatibility and anti-hyperplasia, anti-inflammation and pro-endothelialization properties. This novel drug-delivery system may provide a breakthrough for the surface endothelialization of cardiovascular DES.