(Z)-4-(2-Hy­droxy­benzyl­idene)-1-methyl-2-phenyl-1H-imidazol-5(4H)-one

In the title compound, C17H14N2O2, the asymmetric unit comprises two mol­ecules that are comformationally similar [the dihedral angles between the phenyl rings in each are 46.35 (2) and 48.04 (3)°], with the conformation stabilized by intra­molecular O—H⋯N hydrogen bonds, which generate S(7) rings. In the crystal, inversion-related mol­ecules are linked by pairs of weak C—H⋯O hydrogen bonds, forming dimers with an R 2 2(16) graph-set motif. Weak inter-ring π–π stacking is observed in the structure, the shortest centroid-to-centroid distance being 3.7480 (13) Å

(E)-4-[(4-Diethyl­amino-2-hy­droxy­benzyl­idene)amino]­benzonitrile

The title compound, C18H19N3O, displays an E conformation with respect to the C=N double bond. The dihedral angle between the mean planes of the two benzene rings is 24.49 (3)°. An intra­molecular O—H⋯N hydrogen bond generates an S(6) ring. In the crystal, mol­ecules are linked by nonclassical inter­molecular C—H⋯O hydrogen bonds to form an infinite one-dimensional chain along [010], generating a C(8) motif

Prevalence of obstructive sleep apnea in patients with squamous cell carcinoma of the tongue following ablation surgery

AbstractBackground/purposeThe purpose of this study was to determine the prevalence of obstructive sleep apnea (OSA) in patients with squamous cell carcinoma (SSC) of the tongue after primary surgical resection and to correlate the presence of OSA with the occurrence of obstructive apnea in this patient population.Materials and methodsThis was a retrospective study of 26 Taiwanese patients, 24 males and two females, aged 37–71 years, after surgical resection of SSC of the tongue. Patients who had a follow-up after treatment of 6 months to 11 years were eligible for inclusion. During the post-treatment period, the occurrence of OSA was determined in these patients. Overnight polysomnography (PSG) was used to determine the apnea–hypopnea index (AHI). Patients were considered to have OSA if the AHI value was >5.ResultsPatients with an AHI value of <5 showed a mean body mass index (BMI) of 22.8 kg/m2, while those with an AHI value of >5 showed a mean BMI of 28.3 kg/m2. The BMI distribution between patients with AHI value of <5 and those with AHI values of >5 was statistically significant (P = 0.018). Using the definition of clinically significant sleep apnea as AHI > 5, 14 of 26 patients (53.85%) had clinical OSA. The OSA and non-OSA groups showed no statistical significance in terms of age, tumor size, tongue ablation, neck dissection [method?], or wound reconstruction methods.ConclusionIncidence of OSA in the patient population with SSC of the tongue was found to be significantly higher than that in the general population. The limitations of this study were the relatively small patient sample size and no presurgical PSG record being obtained from the patients to compare the sleep quality before and after cancer therapy

Rho Kinases Regulate the Renewal and Neural Differentiation of Embryonic Stem Cells in a Cell Plating Density–Dependent Manner

[[abstract]]BACKGROUND: Rho kinases (ROCKs) mediate cell contraction, local adhesion, and cell motility, which are considered to be important in cell differentiation. We postulated that ROCKs are involved in controlling embryonic stem (ES) cell renewal and differentiation. METHODOLOGY/PRINCIPAL FINDINGS: CCE, a murine ES cell, was treated with Y-27632 for 48 to 96 hours and colony formation was evaluated. Y-27632 blocked CCE colony formation and induced CCE to grow as individual cells, regardless of the initial seeding cell density either at 10(4)/cm(2) ("high" seeding density) or 2x10(3)/cm(2) ("low" density). However, at high seeding density, Y-27632-treated cells exhibited reduction of alkaline phosphatase (AP) staining and Oct3/4 expression. They expressed SOX-1, nestin, and MAP2c, but not betaIII-tubulin or NG-2. They did not express endoderm or mesoderm lineage markers. After removal of Y-27632, the cells failed to form colonies or regain undifferentiated state. Silencing of ROCK-1 or ROCK-2 with selective small interference RNA induced CCE morphological changes similar to Y-27632. Silencing of ROCK-1 or ROCK-2 individually was sufficient to cause reduction of AP and Oct3/4, and expression of SOX-1, nestin, and MAP2c; and combined silencing of both ROCKs did not augment the effects exerted by individual ROCK siRNA. Y-27632-treated CCE cells seeded at 2x10(3) or 6.6x10(3) cells/cm(2) did not lose renewal factors or express differentiation markers. Furthermore, they were able to form AP-positive colonies after removal of Y-27632 and reseeding. Similar to ROCK inhibition by Y-27632, silencing of ROCK-1 or ROCK-2 in cells seeded at 2x10(3)/cm(2) did not change renewal factors. CONCLUSIONS/SIGNIFICANCE: We conclude that ROCKs promote ES cell colony formation, maintain them at undifferentiated state, and prevent them from neural differentiation at high seeding density. ROCK inhibition represents a new strategy for preparing large numbers of neural progenitor cells

Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model. Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions. Turbidity was identified as the optical density measured using spectroscopy at 405 nm. We also determined the in vivo effects of catalin on cataract severity in a selenite-induced cataract rat model. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) was applied to analyze the integrity of crystallin samples. Results: PRX at 1,000 μM significantly delayed UVC-induced turbidity formation compared to controls after 4 h of UVC exposure (p<0.05), but not in groups incubated with PRX concentrations of <1,000 μM. Results were further confirmed by SDS–PAGE. The absolute γ-crystallin turbidity induced by 4 h of UVC exposure was ameliorated in the presence of catalin equivalent to 1~100 μM PRX in a concentration-dependent manner. Samples with catalin-formulated vehicle only (CataV) and those containing PRX equivalent to 100 μM had a similar protective effect after 4 h of UVC exposure compared to the controls (p<0.05). PRX at 0.03, 0.1, and 0.3 μM significantly delayed 10 mM selenite- and calcium-induced turbidity formation compared to controls on days 0~4 (p<0.05). Catalin (equivalent to 32, 80, and 100 μM PRX) had an initial protective effect against selenite-induced lens protein turbidity on day 1 (p<0.05). Subcutaneous pretreatment with catalin (5 mg/kg) also statistically decreased the mean cataract scores in selenite-induced cataract rats on post-induction day 3 compared to the controls (1.3±0.2 versus 2.4±0.4; p<0.05). However, catalin (equivalent to up to 100 μM PRX) did not inhibit calpain-induced proteolysis activated by calcium, and neither did 100 μM PRX. Conclusions: PRX at micromolar levels ameliorated selenite- and calcium-induced lens protein turbidity but required millimolar levels to protect against UVC irradiation. The observed inhibition of UVC-induced turbidity of lens crystallins by catalin at micromolar concentrations may have been a result of the catalin-formulated vehicle. Transient protection by catalin against selenite-induced turbidity of crystallin solutions in vitro was supported by the ameliorated cataract scores in the early stage of cataractogenesis in vivo by subcutaneously administered catalin. PRX could not inhibit calpain-induced proteolysis activated by calcium or catalin itself, and may be detrimental to crystallins under UVB exposure. Further studies on formulation modifications of catalin and recommended doses of PRX to optimize clinical efficacy by cataract type are warranted

Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica

Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation. Based on a bioactivity-guided purification strategy, two anthranoids, emodin and physcion, were identified from F. japonica. Spectroscopic techniques were used to characterize its crude extract, fractions and phytochemicals. The crude extract, chloroform fraction, and anthranoids of F. japonica significantly inhibited CXCR4-mediated chemotaxis. Mechanistic studies showed that emodin and physcion inhibited chemotaxis via inactivating the MEK/ERK pathway. Moreover, the crude extract and emodin could prevent or treat type 1 diabetes in non-obese diabetic (NOD) mice. This study illustrates the applicability of a combinational approach for the study of anti-inflammatory medicine and shows the potential of F. japonica and its anthranoids for anti-inflammatory therapy

Dual Targeting of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Histone Deacetylase as a Therapy for Colorectal Cancer

AbstractStatins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) inhibitors decreasing serum cholesterol and have shown promise in cancer prevention. In this study, we demonstrated the oncogenic role of HMGR in colorectal cancer (CRC) by disclosing increased HMGR activity in CRC patients and its enhancement of anti-apoptosis and stemness. Our previous studies showed that statins containing carboxylic acid chains possessed activity against histone deacetylases (HDACs), and strengthened their anti-HDAC activity through designing HMGR-HDAC dual inhibitors, JMF compounds. These compounds exerted anti-cancer effect in CRC cells as well as in AOM-DSS and ApcMin/+ CRC mouse models. JMF mostly regulated the genes related to apoptosis and inflammation through genome-wide ChIP-on-chip analysis, and Ingenuity Pathways Analysis (IPA) predicted their respective regulation by NR3C1 and NF-κB. Furthermore, JMF inhibited metastasis, angiogenesis and cancer stemness, and potentiated the effect of oxaliplatin in CRC mouse models. Dual HMGR-HDAC inhibitor could be a potential treatment for CRC