3'-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels.

Isoflavones are widely consumed by people around the world in the form of soy products, dietary supplements and drugs. Many isoflavones or related crude extracts have been reported to exert pain-relief activities, but the mechanism remains unclear. Voltage-gated sodium channels (VGSCs) play important roles in excitability of pain sensing neurons and many of them are important nociceptors. Here, we report that several isoflavones including 3'-methoxydaidzein (3MOD), genistein (GEN) and daidzein (DAI) show abilities to block VGSCs and thus to attenuate chemicals and heat induced acute pain or chronic constriction injury (CCI) induced pain hypersensitivity in mice. Especially, 3MOD shows strong analgesic potential without inducing addiction through inhibiting subtypes NaV1.7, NaV1.8 and NaV1.3 with the IC50 of 181 ± 14, 397 ± 26, and 505 ± 46 nmol·L-1, respectively, providing a promising compound or parent structure for the treatment of pain pathologies. This study reveals a pain-alleviating mechanism of dietary isoflavones and may provide a convenient avenue to alleviate pain.

miR-150 exerts antileukemia activity in vitro and in vivo through regulating genes in multiple pathways.

MicroRNAs, a class of small noncoding RNAs, have been implicated to regulate gene expression in virtually all important biological processes. Although accumulating evidence demonstrates that miR-150, an important regulator in hematopoiesis, is deregulated in various types of hematopoietic malignancies, the precise mechanisms of miR-150 action are largely unknown. In this study, we found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission. Restoration of miR-150 markedly inhibited growth and induced apoptosis of leukemia cells, and reduced tumorigenicity in a xenograft leukemia murine model. Microarray analysis identified multiple novel targets of miR-150, which were validated by quantitative real-time PCR and luciferase reporter assay. Gene ontology and pathway analysis illustrated potential roles of these targets in small-molecule metabolism, transcriptional regulation, RNA metabolism, proteoglycan synthesis in cancer, mTOR signaling pathway, or Wnt signaling pathway. Interestingly, knockdown one of four miR-150 targets (EIF4B, FOXO4B, PRKCA, and TET3) showed an antileukemia activity similar to that of miR-150 restoration. Collectively, our study demonstrates that miR-150 functions as a tumor suppressor through multiple mechanisms in human leukemia and provides a rationale for utilizing miR-150 as a novel therapeutic agent for leukemia treatment.

Comparison of transvenous versus transthoracic catheter-based device closure of patent ductus arteriosus with amplatzer duct occluder.

OBJECTIVE: This study compared the clinical outcome of the transvenous versus transthoracic approach for closure of patent ductus arteriosus (PDA). BACKGROUND: There are no data regarding the results of transvenous versus transthoracic catheter-based device closure of PDA with Amplatzer duct occluder (ADO) despite their increasing use as alternatives to conventional surgery. METHODS: In this observational study, a total of 150 consecutive patients with PDA were allocated either to the transvenous approach (group A, n = 108) and the transthoracic approach (group B, n = 42) by using ADO between January 2010 and April 2012. Echocardiography was performed to evaluate the prespecified initial and 6-month success of PDA closure. The technical indices and procedure-related major acute and chronic complications were documented. RESULTS: There were similar initial success rates (98.2% vs 100%; P>.05) and 6-month success rates (99.1% vs 100%; P>.05) between groups, and group A had fewer major acute complications (3.7% vs 85.7%; P<.001), shorter operating time (1.3 hours vs 2.1 hours; P<.001), Intensive Care Unit stay (0 hours vs 23.0 hours; P<.001), and recovery time (3.8 days vs 9.5 days; P<.001), and lower rates of general anesthesia (36.1% vs 100%; P<.001), blood transfusion (0.9% vs 71.4%; P<.001), and extra use of antibiotics (27.8% vs 78.6%; P<.001), and lower total cost of hospitalization ($3815.78 vs $5730.21; P<.001). CONCLUSIONS: Despite similar efficacy for duct closure with ADO, transvenous approach was associated with fewer acute complications, more periprocedural comfort, and lower cost; thus, transthoracic approach should not be a reasonable choice for duct closure except for particular indications.

Molluscicidal activity of Aglaia duperreana and the constituents of its twigs and leaves.

The methanol (MeOH) extract of the twigs and leaves of Aglaia duperreana was investigated for its molluscicidal activity against Pomacea canaliculata. The extract was found to exhibit significant molluscicidal activity. The ethyl acetate soluble fraction of the extract showed the most potent molluscicidal activity among different solvent fractions. The bioactivity-guided chemical investigation of the ethyl acetate soluble fraction led to a new triterpenoid along with 15 known compounds. Their structures were elucidated by spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance techniques as well as mass spectroscopic analysis. The molluscicidal activities of compounds 2-16 against P. canaliculata were also investigated. Naringenin trimethyl ether showed significant molluscicidal activity with a median lethal concentration (LC(50)) of 3.9 µg/mL, which was indicated higher potency than the positive control, tea saponin (LC(50)=4.5 µg/mL).