Sinomenine Inhibits Migration and Invasion of Human Lung Cancer Cell through Downregulating Expression of miR-21 and MMPs.

Sinomenine is an alkaloid derived from Sinomenium acutum. Recent studies have found that sinomenine can inhibit various cancers by inhibiting the proliferation, migration and invasion of tumors and inducing apoptosis. This study aims to investigate the effect and mechanism of sinomenine on inhibiting the migration and invasion of human lung adenocarcinoma cells in vitro. The results demonstrate that viabilities of A549 and H1299 cells were inhibited by sinomenine in a dose-dependent manner. When treated with sub-toxic doses of sinomenine, cell migration and invasion are markedly suppressed. Sinomenine decreases the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9, and the extracellular inducer of matrix metalloproteinase (EMMPRIN/CD147), but elevates the expression of reversion-inducing cysteine-rich proteins with kazal motifs (RECK) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. In addition, sinomenine significantly increases the expression of the epithelial marker E-cadherin but concomitantly decreases the expression of the mesenchymal marker vimentin, suggesting that it suppresses epithelial-mesenchymal transition (EMT). Moreover, sinomenine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. The downregulation of miR-21 decreases cell invasion, while the upregulation of miR-21 increases cell invasion. Furthermore, the downregulation of miR-21 stimulates the expression of RECK, TIMP-1/-2, and E-cadherin, but reduces the expression of MMP-2/-9, EMMPRIN/CD147, and vimentin. Taken together, the results reveal that the inhibition of A549 cell invasion by sinomenine may, at least in part, be through the downregulating expression of MMPs and miR-21. These findings demonstrate an attractive therapeutic potential for sinomenine in lung cancer anti-metastatic therapy.

Proteomic Identification of the Galectin-1-Involved Molecular Pathways in Urinary Bladder Urothelial Carcinoma.

Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP⁺), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival.

Role of galectin-1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway.

Human galectin-1 is a member of the galectin family, proteins with conserved carbohydrate-recognition domains that bind galactoside. Galectin-1 is highly expressed in various tumors and participates in various oncogenic processes. However, detailed descriptions of the function of galectin-1 in urinary bladder urothelial carcinoma have not been reported. Our previous cohort investigation showed that galectin-1 is associated with tumor invasiveness and is a possible independent prognostic marker of urinary bladder urothelial carcinoma. The present study aimed to clarify the relevance of galectin-1 expression level to tumor progression and invasion. In order to decipher a mechanism for the contribution of galectin-1 to the malignant behavior of urinary bladder urothelial carcinoma, two bladder cancer cell lines (T24 and J82) were established with knockdown of galectin-1 expression by shRNA. Bladder cancer cells with LGALS1 gene silencing showed reduced cell proliferation, lower invasive capability, and lower clonogenicity. Extensive signaling pathway studies indicated that galectin-1 participated in bladder cancer cell invasion by mediating the activity of MMP9 through the Ras-Rac1-MEKK4-JNK-AP1 signaling pathway. Our functional analyses of galectin-1 in urinary bladder urothelial carcinoma provided novel insights into the critical role of galectin-1 in tumor progression and invasion. These results revealed that silencing the galectin-1-mediated MAPK signaling pathway presented a novel strategy for bladder cancer therapy.

Galectin-1 dysregulation independently predicts disease specific survival in bladder urothelial carcinoma.

PURPOSE: Galectin-1 is highly expressed in various tumors and participates in various oncogenic processes. Our previous proteomics investigation demonstrated that galectin-1 is up-regulated in high compared to nonhigh grade lesions. Thus, in the current cohort study we clarified the correlation of galectin-1 over expression with various clinicopathological features and prognosis. MATERIALS AND METHODS: We selected 185 cases of consecutively treated primary localized bladder urothelial carcinoma for study. Transurethral resection of bladder tumor was performed in all patients followed by radical cystectomy in those with T2 to T4 tumors. Pathological slides were examined to determine cytoplasmic galectin-1 immuno-expression and correlate galectin-1 dysregulation with various clinicopathological factors and disease specific survival. RESULTS: Positive galectin-1 immuno-expression in tumors was significantly linked to pT status (p = 0.0295), histological grade (p = 0.037), vascular invasion (p = 0.0287) and nodal status (p = 0.0012). Galectin-1 over expression in tumors significantly predicted disease specific survival at the univariate (p = 0.0002) and multivariate levels (p = 0.03, HR 2.438, 95% CI 1.090-5.451). In situ hybridization indicated that the LGALS1 gene was amplified in 43 specimens in an independent cohort of 56 snap frozen tumor specimens. Association analysis showed that an increased LGALS1 mRNA level was linked to bladder urothelial carcinoma invasiveness (p = 0.016) and LGALS1 gene amplification was significantly associated the amount of GAL-1 protein in tumors (p <0.0001). On the univariate level gene amplification was also closely linked to disease specific survival (p = 0.0006). CONCLUSIONS: These results reveal that galectin-1 over expression is a possible independent factor for bladder cancer prognosis.

Mesoporous Europium-Doped Titania Nanoparticles (Eu-MTNs) for Luminescence-Based Intracellular Bio-Imaging.

Monodisperse and mesoporous europium (Eu)-doped titania nanoparticles (denoted as Eu-MTNs) were prepared by a co-synthesis method with the presence of a cationic surfactant (i.e., CTAB). A maximum loading amount of 8 mol% of Eu could be successfully incorporated into the framework of MTNs. The synthesized Eu-MTNs samples were characterized with X-ray diffraction (XRD) and scanning electron microscopy (SEM), with their luminescent property examined by photoluminescence (PL). Under ultraviolet irradiation, the Eu-MTNs samples exhibit several characteristic luminescence corresponding to 5D0-7F(j) for Eu+3 ions, which can be attributed to the energy transfer from titania nanocrystallite to Eu3+ ions dispersed in amorphous mesoporous titania region. The potential intracellular bio-imaging application of the synthesized Eu-MTN nanoparticles was demonstrated with a breast cancer cell line (i.e., BT-20). High biocompatibility and strong luminescence of the Eu-MTNs show great potential in biomedical applications.

Benign prostatic hyperplasia complicated with T1DM can be alleviated by treadmill exercise-evidences revealed by the rat model.

BACKGROUND: Both benign prostatic hyperplasia (BPH) and Type-1 diabetes mellitus (T1DM) share similar epidemiologic features and are all associated with the insulin-like growth factor (IGF)-mediated hormonal imbalance. The purpose of this study is to understand whether exercise (EX) could alleviate DM and DM + BPH. METHODS: Sprague-Dawley rats were divided into eight groups: normal control, EX, BPH, BPH + EX, DM, DM + EX, BPH + DM, and BPH + DM + EX. T1DM was induced by intraperitoneal (ip) injection of streptozotocin (65 mg/kg) in Week 2, and BPH was induced by successive ip injections of Sustanon® (testosterone, 3.5 mg/head) plus estradiol (0.1 mg/head) from Week 3 to Week 9. Treadmill exercise training (20 m/min, 60 min per time) was performed three times per week for 6 weeks. RESULTS: In BPH + EX, EX maintained at a constant body weight (BW); and suppressed stromal layer thickening, collagen deposition, blood glucose (BG), levels of testosterone (Ts), 5α-reductase(5αRd), dihydrotestosterone (DHT), androgen receptor (AR), serum hydrogen peroxide, TBARs, and interleukin-6 (IL-6). EX recovered testes size and substantially increased nitric oxide (NO) levels. In DM + EX group, EX decreased BW, PW, nuclear proliferation, inflammatory cell aggregation, collagen deposition, and BG. As contrast, EX upregulated insulin, IGF, Ts, NO, 5αRd, AR, and DHT, and substantially reduced PSA. In BPH + DM + EX, EX maintained BW at a subnormal level, slightly suppressed prostate stromal inflammation, collagen deposition, and BG, moderately restored sIn and IGF. Although failed to suppress Ts, EX highly upregulated 5αRd and suppressed DHT and AR, together with highly upregulated NO resulting in substantially reduced PSA. CONCLUSION: EX, by remodeling androgen and NO expressions, can effectively alleviate BPH, DM, and BPH + DM.

NGAL can alternately mediate sunitinib resistance in renal cell carcinoma.

PURPOSE: Serum NGAL is highly expressed in patients with advanced renal cancer treated with sunitinib. We investigated the role of NGAL in sunitinib resistance in renal cell carcinoma to identify potential tactics to overcome it. MATERIALS AND METHODS: NGAL expression was correlated with sunitinib sensitivity. Vascular endothelial growth factor related upstream Ras, Erk1/2 and STAT1 phosphorylation activity in Caki-1 and NGAL transfected Caki-1 cells after sunitinib treatment was analyzed using Western blot. NGAL and vascular endothelial growth factor-A interaction with sunitinib therapeutic efficacy was monitored in renal cell carcinoma tumor xenografted mice by tumor growth inhibition, serum NGAL and vascular endothelial growth factor-a levels, and microscopic examination of tumor microvascular density. RESULTS: Sunitinib cytotoxicity in various renal cell carcinoma cell lines was reversibly related to NGAL expression. Sunitinib showed the lowest 50% inhibitory concentration (5.53 µM) in Caki-1 cells, which had the lowest NGAL expression of these renal cell carcinoma cell lines. After sunitinib treatment adding NGAL inhibited Ras and Erk1/2 phosphorylation but activated STAT1α phosphorylation in Caki-1 cells and Caki-1 cells transfected with NGAL. In a xenograft mouse model sunitinib significantly inhibited tumor growth in Caki-1 mice. NGAL transfected Caki-1 mice had higher serum NGAL and lower vascular endothelial growth factor-A than Caki-1 mice. Microvascular density was decreased in Caki-1 mice with sunitinib treatment. CONCLUSIONS: NGAL in tumor cells may show crosstalk with vascular endothelial growth factor-a and alternative activation in stimulating tumor growth during sunitinib treatment. It may become a therapeutic target to reverse sunitinib resistance in renal cell carcinoma.

Association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer: a meta-analysis.

Several previous studies have investigated the association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer in various populations. However, these results remain inconsistent. Therefore, we performed this meta-analysis to evaluate the relationship between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer. An extensive literature search was performed to identify all eligible studies regarding this association. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to estimate the strength of risk under fixed and random effects models. We identified and included eight case-control studies including 2,036 cases and 2,273 controls. No significant association was found between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer under the dominant model; however, those with the SULT1A1 Arg/Arg genotype had a significantly increased risk (OR = 1.218, 95 % CI = 1.067-1.392, P = 0.0044) under the recessive model. In the subgroup analysis of ethnicity, a significant association was observed in Caucasians under the recessive model (OR = 1.269, 95 % CI = 1.069-1.506, P = 0.007). Furthermore, an increased risk of bladder cancer was observed between the Arg213His polymorphism and never smokers in the recessive model (OR = 1.428, 95 % CI = 1.079-1.890, P = 0.013). The results of this meta-analysis indicate that the SULT1A1 Arg213His polymorphism is associated with the risk bladder cancer under a recessive model; however, a possibly higher risk for Caucasians with the Arg/Arg genotype and never smokers needs further investigation.

α-Solanine inhibits invasion of human prostate cancer cell by suppressing epithelial-mesenchymal transition and MMPs expression.

α-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by α-solanine remains unclear. This study investigates the suppression mechanism of α-solanine on motility of the human prostate cancer cell PC-3. Results show that α-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of α-solanine, cell invasion is markedly suppressed by α-solanine. α-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT). α-Solanine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), and tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate α-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K), Akt and ERK. Moreover, α-solanine downregulates oncogenic microRNA-21 (miR-21) and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by α-solanine may be, at least in part, through blocking EMT and MMPs expression. α-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of α-solanine for suppressing invasion of prostate cancer cell.

Epigenetic regulation of vascular endothelial growth factor a dynamic expression in transitional cell carcinoma.

Vascular endothelial growth factor A (VEGF-A) is a key mediator in the neovascularization of cancers. We have found that VEGF-A was expressed at significantly higher levels in high-grade transitional cell carcinoma (TCC) cells than low-grade TCC cells in our previous study. In the present study, promoter methylation pattern was assessed and quantified by bisulfite genomic sequencing (BGS) and specific VEGF-A CpG sites in low-grade, but not in high-grade, TCC cells were observed. Reporter assays indicated that hypermethylation of nine CpG sites can inhibit the transcriptional activity of the VEGF-A gene. Subsequent chromatin immunoprecipitation (ChIP) assay revealed down-regulation of transcription activity of VEGF-A with increasing binding of methyl-CpG-binding protein 2 (MBD2) and trimethyl-histone H3 (Lys9) proteins to these CpG sites in low-grade TCC cells during hypermethylation. Furthermore, treatment of low-grade TCC cells with DNA methyltransferase inhibitor and histone deacetylase inhibitor can restore the expression of VEGF-A and promote the invasive ability of low-grade TCC cells. Hypermethylation with lower expression levels of VEGF-A in low-grade TCC tumors than high-grade TCC tumors was also confirmed in clinical specimens by reverse transcriptase-PCR and pyrosequencing analyses. Our findings are the first results indicating that VEGF-A expression is suppressed in low-grade TCC tumors by promoter hypermethylation. This offers a new perspective on the role of VEGF-A in TCC tumor behavior.

CXCL1/GROα increases cell migration and invasion of prostate cancer by decreasing fibulin-1 expression through NF-κB/HDAC1 epigenetic regulation.

Inflammatory tumor microenvironments play pivotal roles in the development of cancer. Inflammatory cytokines such as CXCL1/GROα exert cancer-promoting activities by increasing tumor angiogenesis. However, whether CXCL1/GROα also plays a role in the progression of prostate cancer, particularly in highly invasive castration-resistant prostate cancer (CRPC), has not been investigated. We explored whether CXCL1/GROα enhances cell migration and invasion in PC-3 and DU145 CRPC. Induction of PC-3 and DU145 cancer progression by CXCL1/GROα is associated with increased AKT activation and IκB kinase α (IKKα) phosphorylation, resulting in nuclear factor-kappaB (NF-κB) activation. Activated NF-κB interacts with histone deacetylase 1 (HDAC1) to form a gene-silencing complex, which represses the expression of fibulin-1D by decreasing the acetylation of histone H3 and H4 on the NF-κB-binding site of the fibulin-1D promoter. Blockade of AKT2 by small hairpin RNA (shRNA) decreases IKKα phosphorylation, NF-κB nuclear translocation and cell migration, indicating that AKT is required in CXCL1/GROα-mediated NF-κB activation and cell migration. In addition, NF-κB and HDAC1 shRNA decrease the effect of CXCL1/GROα on fibulin-1D downregulation, migration and invasion, suggesting that the NF-κB/HDAC1 complex is also involved in CXCL1/GROα-mediated cancer progression. Our findings provide the first evidence that CXCL1/GROα decreases fibulin-1D expression in prostate cancer cells and also reveals novel insights into the mechanism by which CXCL1/GROα regulates NF-κB activation through the AKT pathway. Our results also clearly establish that co-operation of NF-κB and HDAC1 regulates fibulin-1D expression by epigenetic modification. Our study suggests that inhibition of CXCL1/GROα-mediated AKT/NF-κB signaling may be an attractive therapeutic target for CRPC.

HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma.

BACKGROUND: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs). METHODS: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors. RESULTS: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p < 0.0001), MeFS (p < 0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015). CONCLUSIONS: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy.

CXCL5/ENA78 increased cell migration and epithelial-to-mesenchymal transition of hormone-independent prostate cancer by early growth response-1/snail signaling pathway.

Prostate cancers that are resistant to hormone therapy are more invasive and have greater ability to spread to other organs than androgen-dependent prostate cancers. Furthermore, this type of prostate cancer is also highly resistant to current forms of chemotherapy. This study analyzed CXCL5/ENA78, which is highly expressed in androgen-independent prostate cancers, and is responsible for cell migration and epithelial-to-mesenchymal transition in two androgen-independent prostate cancer cell lines. Inducement of PC-3 and DU145 cancer progression by CXCL5/ENA78 is associated with increased Raf/MEK/ERK activation, and the upregulation of early growth response-1 (Egr-1) and Snail. Blockade of Egr-1 decreased Snail upregulation and cell migration, indicating that Egr-1 is required in CXCL5/ENA78-mediated Snail enhancement and cell migration. In addition, Egr-1 siRNA also decreased the effect of CXCL5/ENA78 on p27 inhibition, Cdk4 induction and cell proliferation, suggesting Egr-1 is also involved in CXCL5/ENA78-mediated cell growth. Moreover, blocking ERK1/2 by siRNA suppressed CXCL5/ENA78-induced Egr-1 enhancement, cell migration, and proliferation. Our study suggests that inhibition of CXCL5/ENA78-mediated ERK/Egr-1/Snail signaling is an attractive therapeutic target for androgen-independent prostate cancer.

Effects of electroacupuncture on benign prostate hyperplasia patients with lower urinary tract symptoms: a single-blinded, randomized controlled trial.

We tested the effect of electroacupuncture (EA) on lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH) patients. A total of 42 BPH patients with LUTS were randomly assigned to either the EA group (EG), received 2 Hz EA for 20 min twice/week for a total of twelve treatments, or a sham EA group (CG), received sham EA. The increase of voiding volume, average flow rate, and maximal flow rate in the EG were 32.2 ± 104.4 mL, 1.2 ± 1.6 mL/sec, and 2.3 ± 3.7 mL/sec, respectively, from baseline value (before EA) using the measurement of an uroflowmetry. These increases were greater than -37.9 ± 120.4, -0.22 ± 2.7, and -0.3 ± 4.3, respectively, in the CG (P = .038, .026, and .030, resp.). The changes of prostate special antigen and international prostatic symptom score were not significantly different between two groups (P = .573, .175, resp.), suggesting the clinical improvement of 2 Hz EA was quite limited to the LUTS of patients with BPH.

A multivariable logistic regression equation to evaluate prostate cancer.

BACKGROUND/PURPOSE: A possible means of decreasing prostate cancer mortality is through improved early detection. We attempted to create an equation to predict the likelihood of having prostate cancer. METHODS: Between January 2005 and May 2008, patients who received prostate biopsies were retrospective evaluated. The relationship between the possibility of prostate cancer and the following variables were evaluated: age; serum prostate specific antigen (PSA) level, prostate volume, numbers of prostatic biopsies, digital rectal examination (DRE) findings, and the presence of hypoechoic nodule under transrectal ultrasonography. RESULTS: A multivariate regression model was created to predict the possibility of having prostate cancer, and a receiver-operating characteristic (ROC) curve was drawn based on the predictive scoring equation. Using a predictive equation, P=1/(1-e(-x)), where X=-4.88,+1.11 (if DRE positive),+0.75 (if hypoechoic nodule of prostate present),+1.27 (when 7

Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway.

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-kappaB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-kappaB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.

Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells.

Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to possess some anti-cancer and anti-inflammation capabilities. In this study, fisetin has exhibited inhibitory effects on the adhesion, migration, and invasion ability of a highly metastatic PC-3 cells under non-cytotoxic concentrations. Gelatin zymography assay showed that fisetin inhibited the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. Our result also showed that fisetin could inhibit the phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2) and Akt. Moreover, fisetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun, and the binding abilities of NF-kappaB and activator protein-1 (AP-1). Also, the results showed that the protein and mRNA levels of MMP-2 and MMP-9 were significantly reduced by Western blot and semi-quantitative RT-PCR. Further, treating specific inhibitors for PI3K (Wortmannin) or JNK (SP600125) to PC-3 cells could reduce the protein expressions of MMP-2 and MMP-9. These results showed fisetin could inhibit the metastatic ability of PC-3 by reducing MMP-2 and MMP-9 expressions through suppressing phosphoinositide 3-kinase/Akt (PI3K/Akt) and JNK signaling pathways. This suggested fisetin can serve as a potential candidate for treating cancer metastasis.

Increased risk of subsequent benign prostatic hyperplasia in non-Helicobacter pylori-infected peptic ulcer patients: a population-based cohort study.

The vagus nerve plays an essential role in homeostasis and inflammation. Clinically, peptic ulcer patients without helicobacter pylori (HP) infection may provide a population for studying the effect of vagal hyperactivity. There were interests in the association of gastrointestinal disease and urogenital disorders. Herein, we try to investigate subsequent risk of benign prostatic hyperplasia (BPH) in non-HP infected peptic ulcer patients. We identified 17,672 peptic ulcer admission male patients newly diagnosed in 1998-2007 from Taiwan Health Insurance Database, and 17,672 male comparison without peptic ulcer, frequency matched by age, and index-year. We assessed subsequent incidence of BPH in each cohort by the end of 2013, and then compared the risk of developing BPH between individuals with and without peptic ulcer. In addition, peptic ulcer patients underwent surgery were also examined. There were 2954 peptic ulcer patients and 2291 comparisons noted with the occurrence of BPH (25.35 and 16.70 per 1000 person-years, respectively). Compared to comparisons, peptic ulcer patients had a 1.45- and 1.26-fold BPH risk in multivariable Cox model and Fine and Gray model (95% CI 1.37-1.54 and 1.19-1.34). In age-stratified analysis, the highest risk of BPH was in 45-59 years (interaction p < 0.05). Regarding surgery types, peptic ulcer patients who underwent simple suture surgery (i.e.: with integrated vagus nerve) had a significant higher BPH risk than comparison (HR 1.50 and 95% CI 1.33-1.74; SHR 1.26 and 95% CI 1.07-1.48), while patients underwent truncal vagotomy/pyloroplasty showed a lower incidence of BPH. In this study, non-HP-infected male peptic ulcer patients were found to have an increased risk of subsequent BPH. Indicating that there might be a role of vagus nerve. Based on the limitations of retrospective nature, further studies are required.

Manufacturing technology of banana-assorted breads: The fermentative characteristics affected by different banana cultivars.

Taiwan produces large quantities of bananas in the southern area. Recently, due to the export quantity has been greatly reduced, in order to efficiently maintain the banana agriculture and economy, the development of alternate uses of bananas has become urgently in need. Bananas contain a fair amount of nutrients with low glycemic index. Currently, as the bread consumption is increasing, we tried to manufacture banana-assorted breads. The desiccated powders of Musa sapientum var TC2-425 Linn [(genomically, called as Musa (AAA) (MA)] and Musa basjoo "Nam Wa" (MB) were separately incorporated at 15%, 20%, and 25% (denoted as MA15-MA25 and MB15-MB25). Results indicated that MA exhibited higher contents of moisture, ash, crude protein, and lutein, while with lower crude fat, crude fibers, carbohydrate, sodium, total soluble sugars, and pectin. The contents of taste compounds (name, samples in decreasing order) were as follows: 5'-CMP (MB25, MB20); 5'-GMP (MA25, MA20); 5'-AMP (MB25, MA15); 5'-XMP (MA25, MA20); 5'-IMP (MA25, MB20, MB25); and 5'-UMP (MA20, MA25, MB20). Hedonic scoring (HS) indicated MA15, MA20, MB15, and MB20 were more acceptable. Textural profile analysis (TPA; for 0-6 days, only 0-4 days are shown) revealed that "flavor," "mouthfeel," "hardness," "gumminess," and "chewiness" were the determinant key roles. Conclusively, due to different chemical constituent of banana, different recipes must be considered. The bread acceptability is affected by the fermentative profile which in turn is governed by the contents of soluble sugars, pectin, taste compounds, and the overall activity of yeast cells.