HIF-1α induces immune escape of prostate cancer by regulating NCR1/NKp46 signaling through miR-224.

BACKGROUND: Metastasis of prostate cancer (PCa) is largely affected by natural killer (NK) cells. This study aimed to clarify the mechanisms underlying tumor cells escaping from NK cells mediated by HIF-1α. METHODS: MiR-224 expression in lymphocytes and HIF-1α protein level in NK cells were determined by qRT-PCR and western blot, respectively. The amount of NKp46+ NK cells was detected with flow cytometry. The IFN-γ level was examined by enzyme linked immunosorbent assay (ELISA). NK cells were tested for cytolytic activity with a Non-Radioactive Cytotoxicity Assay, and treated with oxygenglucose deprivation (OGD) for hypoxia simulation. Interaction between miR-224 and NCR1 was evaluated with dual luciferase reporter assay. RESULTS: MiR-224 was down-regulated in lymphocytes isolated from prostate cancer tissues (n = 10). Overexpression of miR-224 protected prostate cancer from NK cells. HIF-1α increased miR-224 to inhibit the killing capability of NK cells on prostate cancer. MiR-224 controlled the expression of NCR1. Overexpression of miR-224 protected prostate cancer from NK cells through NCR1/NKp46 signaling. Suppression of HIF-1α enhanced the cytotoxicity of NK cells on prostate cancer via miR-224/NCR1 pathway. CONCLUSION: HIF-1α inhibits NCR1/NKp46 pathway through up-regulating miR-224, which affects the killing capability of NK cells on prostate cancer, thus inducing immune escape of tumor cells.

[Effects of elevated Cd, Zn and their combined effects on antioxidant system of tobacco]. / é«˜æµ“åº¦é•‰ã€é”ŒåŠå ¶å¤åˆä½œç”¨å¯¹çƒŸè‰æŠ—æ°§åŒ–ç³»ç»Ÿçš„å½±å“.

A solution culture was conducted to study the effects of elevated Cd and/or Zn ions (0.1 mmol·L-1 Cd2+, 0.15 mmol·L-1 Zn2+, 0.1 mmol·L-1 Cd2++0.15 mmol·L-1Zn2+) on seed germination rate and reactive oxygen species (ROS) level, antioxidants contents, antioxidant enzyme activities and product of membrane lipid peroxidation in tobacco seedling leaves. The results showed that compared to control, the seed germination rate decreased under elevated level of Cd2+or Zn2+, the superoxide radical (O2-· ) generation rate and hydrogen peroxide (H2O2) content in tobacco seedlings increased, the activities of catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDAR), and glutathione reductase (GR) increased, content of glutathione (GSH) and GSH/GSSG (oxidized glutathione) ratio decreased, and malondialdehyde (MDA) content increased. Compared to elevation of the level of only Cd2+ or Zn2+, the seed germination rate under elevation of both Cd2+ and Zn2+ levels was enhanced significantly; O2-· generation rate, contents of H2O2 and MDA decreased; CAT, APX and MDAR activities increased in the last stage of Cd2+ and Zn2+ exposure. Heavy metal Cd2+ or Zn2+ could induce the physiological injury to tobacco seedlings, and the toxic effects increased with prolonged stress time. The combined treatment of Cd and Zn could alleviate the toxicity of single stress on tobacco seedlings.

Effects of Evodiamine on the Pharmacokinetics of Dapoxetine and Its Metabolite Desmethyl Dapoxetine in Rats.

The objective of this work was to investigate the effect of orally administered evodiamine on the pharmacokinetics of dapoxetine and its active metabolite desmethyl dapoxetine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 10 mg/kg dapoxetine alone) and the combination group (10 mg/kg dapoxetine orally co-administered with 100 mg/kg evodiamine). The plasma concentration of dapoxetine and desmethyl dapoxetine were estimated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and different pharmacokinetic parameters were calculated using the Drug and Statistics 2.0 software. Compared to the control group, the pharmacokinetic parameter of t1/2, AUC(0-∞) and Tmax of dapoxetine in combination group was significantly increased by 63.3% (p < 0.01), 44.8% (p < 0.01) and 50.4% (p < 0.01), respectively. Moreover, evodiamine had significantly decreased the pharmacokinetic parameter of t1/2 and AUC(0-∞) of desmethyl dapoxetine. This study demonstrated that evodiamine inhibits the metabolism of dapoxetine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing dapoxetine to the patients already taking evodiamine.

[Transabdominal ultrasound measurement of intravesical prostatic protrusion helps diagnosis of benign prostatic obstruction].

OBJECTIVE: To evaluate the measurement of intravesical prostatic protrusion (IPP) by transabdominal ultrasonography (TAUS) in the diagnosis of benign prostatic obstruction (BPO). METHODS: We studied the clinical data of 109 BPH patients referred for lower urinary tract symptoms (LUTS) from April 2005 to December 2006. IPP was measured by TAUS, urodynamic parameters such as Qmax and PdetQmax obtained by urodynamic studies and AG values calculated. The patients were divided into an obstruction and a non-obstruction group according to their AG values. RESULTS: IPP was found statistically different between the obstruction and non-obstruction groups (P<0.001) and positively correlated with the AG value (r=0.729, P=0.001). With the cutoff at IPP > or = 10 mm for the diagnosis of BPO, the sensitivity, specificity and accuracy of the diagnosis were 89.9%, 97.5% and 92.7%, respectively. CONCLUSION: The measurement of IPP by TAUS offers a valuable help for the diagnosis of BPO.

[Aike mixture has good anti-inflammatory and analgesic effects on mice].

OBJECTIVE: To study the anti-inflammatory and analgesic actions of Aike Mixture (AKM). METHODS: A total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed. RESULTS: AKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01). CONCLUSION: AKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.

[Quantitative detection of DD3 mRNA in prostate cancer tissues by real-time fluorescent quantitative reverse transcription polymerase chain reaction].

OBJECTIVE: To analyze the expression of DD3 mRNA in the prostate tissues. METHODS: DD3 mRNA was detected by realtime fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) based on the Taqman technique in the tissues of 27 patients with non-prostate cancer( NPCa), 21 prostate cancer( PCa), 39 benign prostatic hyperplasia (BPH) and 15 normal prostate (NP). The ROC curve was used to evaluate the diagnostic value of DD3 mRNA. RESULTS: DD3 mRNA expression was not detected in the NPCa tissues. The median expressions of DD3 mRNA in PCa, BPH and NP tissues were 7. 2 x 10(6), 2. 5 x 10(4) and 1.5 x 10(4) copies/mg tissue, respectively. The DD3 mRNA expression levels were significantly different between nonmalignant and malignant tissues (P < 0.01). No significant differences in DD3 mRNA expression were detected between the NP and BPH tissues and no significant correlation was found between the DD3 mRNA expression and clinical pathological parameters. The AUC-ROC was 0.937 (95% CI: 0.879 - 0.995) at cutoff value 1.4 x 10(5) copies/mg tissue. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for DD3 were 90.5%, 85.0%, 86.7%, 76.0%, 94.3%, 6.03 and 0.11 respectively. CONCLUSION: The DD3 mRNA expression is confined to prostate tissues and highly upregulated in PCa tissues. It has a potential application value in the early diagnosis of prostate cancer and the follow-up of the patient.

[Quantitative detection of differential display code 3 mRNA in peripheral blood of patients with prostate cancer].

OBJECTIVE: To investigate the expression of DD3 mRNA in the peripheral blood and its value in diagnostic of prostate cancer (Pca). METHODS: Thirty-five untreated Pca patients, aged 72 (53 - 83), 58 Pca patients treated with endocrinotherapy, aged 74 (53 - 86), and 59 patients with benign prostatic hyperplasia, aged 71 (48 - 85), underwent peripheral blood sample collection one week before or after digital examination. RT-PCR was used to examine the level of DD3 mRNA. The level of prostate specific antigen (PSA) was detected too. Ten healthy male frontiers, aged 33 (21 - 38), were used as controls. Receiver operating curve (ROC) was drawn to evaluate the diagnostic performance of DD3 mRNA. RESULTS: The DD3 mRNA level of the untreated Pca patients was 2741 copies/ml, significantly higher than those of the Pca patients treated with endocrinotherapy, patients with benign hyperplasia, and healthy persons (all < 24 copies, all P < 0.001). The DD3 mRNA level of the endocrinotherapy-treated Pca patients was significantly higher than those of the patients with benign hyperplasia, and healthy persons (both P < 0.001). ROC analysis showed that when the critical value was 846 copies/ml the area under curve of ROC (AUC-ROC) was 0.8233 (95% CI: 0.725 - 0.910). and the sensitivity was 74.34%, the specificity was 89.8%. The DD3 mRNA in the peripheral blood increased along with the increase of clinical staging (P < 0.01). CONCLUSION: The level of DD3 mRNA in the peripheral blood is an excellent marker for diagnosis pf Pca, and may help in monitoring of the curative effects of endocrinotherapy.