(4Z)-4-[(2,6-Diisopropyl­anilino)(phen­yl)methyl­idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one

In the title compound, C29H31N3O, the three terminal benzene rings are oriented at dihedral angles of 20.7 (3), 65.8 (3) and 72.6 (3)° with respect to the central pyrazolone ring. Intra­molecular N—H⋯O hydrogen bonding occurs between the imine and carbonyl groups. Inter­molecular C—H⋯π inter­actions are present in the crystal structure

Histone deacetylase 3 binds to and regulates the GCMa transcription factor

Human GCMa transcription factor regulates expression of syncytin, a placental fusogenic protein mediating trophoblastic fusion. Recently, we have demonstrated that CBP-mediated GCMa acetylation underlies the activated cAMP/PKA signaling pathway that stimulates trophoblastic fusion. Because protein acetylation is a reversible modification governed by histone acetyltransferases (HATs) and histone deacetylase (HDACs), in this study we investigated the key HDACs responsible for deacetylation of GCMa and thus the reduction in GCMa activity to avoid unwanted fusion events that may have adverse effects on placental morphogenesis. We herein demonstrate that the HDAC inhibitor, trichostatin A (TSA), increases the level of acetylated GCMa and that HDAC1, 3, 4 and 5 interact with and deacetylate GCMa. Glutathione S-transferase (GST) pull-down assays further verified direct interaction between GCMa and HDAC3 or CBP and HDAC3. HDAC3 counteracts the transcriptional coactivator activity of CBP and the enhancement effect of CBP on GCMa-mediated transcriptional activation. Correlatively, we found in placental cells that HDAC3 associates with the proximal GCMa-binding site (pGBS) in the syncytin promoter and dissociates from pGBS in the presence of forskolin, which stimulates the association of CBP and GCMa with pGBS. Our studies support that trophoblastic fusion in placental morphogenesis depends on the regulation of GCMa activity by HAT and HDAC

Efficient total syntheses of louisianins C and D

[[abstract]]An efficient synthetic route for the preparation of louisianins C and D was developed starting with the commercially available 4-cyanopyridine. Louisianins C and D were synthesized in seven steps and with overall yields 22% and 20%, respectively, following a novel cyclization-decarboxylation sequence involving 4-bromo-6,7-dihydrocyclopenta[c]pyridin-5-one as the key intermediate. (C) 2008 Elsevier Ltd. All rights reserved

Effectiveness of influenza vaccination in patients with end-stage renal disease receiving hemodialysis: a population-based study.

BackgroundLittle is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.MethodsWe used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.ResultsThe age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72-0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75-0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64-1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12-0.33) and mortality (adjusted HR 0.50, 95% CI 0.41-0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26-0.35) after counting vaccination for multi-years.ConclusionsESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly

The morphology of diaphragmatic defects in hepatic hydrothorax: Thoracoscopic finding

BackgroundUntil now, the pathophysiology of hepatic hydrothorax has been moot. We discuss (on the basis of gross videothoracoscopy findings in 11 cases and the literature) the pathogenesis and clinical presentation of this complex condition.MethodsWe prospectively studied 11 patients (age, 31–73 years; 6 men and 5 women) with refractory hepatic hydrothorax (Child-Pugh class B-C) who underwent thoracoscopic repair of diaphragmatic defects. The diaphragmatic defects were examined intraoperatively.ResultsThe diaphragmatic defects stemming from hepatic hydrothorax were classified into 4 morphologic types: type I, no obvious defect (1 patient); type II, blebs lying on the diaphragm (4 patients); type III, broken defects (fenestrations) in the diaphragm (8 patients); and type IV, multiple gaps in the diaphragm (1 patient). The type of diaphragmatic defect did not correlate with the volume occupied by the pleural effusion in the preoperative chest radiograms.ConclusionsThe finding of this study allowed hepatic hydrothorax pathophysiology to be directly visualized, and further studies concerning the treatment of hepatic hydrothorax might be based on these mechanisms

Functional Effects of let-7g Expression in Colon Cancer Metastasis.

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment

Baicalein, Ethyl Acetate, and Chloroform Extracts of Scutellaria baicalensis

This study rated antiviral activity of Scutellaria baicalensis Georgi (S. baicalensis) extracts against influenza A virus subtypes, for example, pandemic 2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC50 values ranging from 73.16 to 487.40 μg/mL and plaque reduction IC50 values ranging from 23.7 to 27.4 μg/mL. Chloroform extract showed antiviral activities with plaque reduction IC50 values ranging from 14.16 to 41.49 μg/mL Time-of-addition assay indicated that EtOAc and chloroform extracts also significantly inhibited virus yields after infection. HPLC analysis demonstrated that baicalin was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222, Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in vitro replication of influenza A viruses pandemic 2009 H1N1 (IC50 = 0.018 μM) and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose baicalein with other anti-influenza agents could be applicable for development of alternative remedies treating influenza A virus infection