The Constituents of Euchresta Formosana

A new flavanone, euchrenone a₁₇ ( 1 ), along with eighteen known compounds, glabrol ( 2 ), euchrenone a₂ ( 3 ), formononetin ( 4 ), 7‐methoxy‐2′,4′‐dihydroxyisoflavone ( 5 ), 3‐(3,4‐dimethoxy‐phenyl)‐7,8‐dihydroxy‐chromon‐4‐one ( 6 ), 5,7,2′‐trihydroxy‐4′‐methoxyisoflavone ( 7 ), 2′‐hydroxygenistein ( 8 ), euchrenone b₁ ( 9 ), euchrenone b₂ ( 10 ), euchrenone b₁₆ ( 11 ), vanillin ( 12 ), p‐hydroxybenzoic acid ( 13 ), medicagol ( 14 ), octadecyl ferulate ( 15 ), (+)‐syringaresinol ( 16 ), β‐sitosteryl‐D‐glucoside ( 17 ), and a mixture of β‐sitosterol ( 18 ) and stigmasterol ( 19 ), were isolated from the methanolic extracts of the roots of Euchresta formosana. The structures of these compounds were established by means of spectral analysis.     

Total synthesis of (±)-17-norcamptothecin, a novel E-ring modified camptothecin

The first total synthesis of (±)-17-norcamptothecin, a novel camptothecin analog possessing an α-hydroxy-γ-lactone E-ring, has been accomplished by using a short and flexible route. The stability of this new compound in aqueous medium has been evaluated through fluorescence spectroscopy.     

大鼠去势后肾上腺与前列腺中Cyp17a1基因的表达

通过定量检测大鼠去势前后肾上腺和前列腺中Cyp17a1基因的表达, 试图从分子水平解释去势手术后大鼠机体内雄性激素水平的变化.     

A novel derivative of geldanamycin and its antitumor activity

A new derivative of geldanamycin was synthesized by introducing the 6-cinnamamido-hexyl-amino group into the 17-site of geldanamycin,a heat shock protein 90(Hsp90)inhibitor,to obtain 17-(6-cinnamamido-hexylamino)-17-demethoxygel-danamycin (CNDG).Its in vitro and in vivo anfitumor effects were evaluated by MTT assay and xenografl in nude mice.     

Sm2Fe17N3晶体的价电子结构分析和结合能、最强键能计算

由EET理论直接建立了Sm2Fe17N3晶体的价电子结构,同时计算并筛选了晶体的结合能和最强键能,分别为EC^0=14716.8±13.7kJ·mol^-1和Eα=110.1311 kJ·mol^-1。分析计算结果表明:Sm2Fe17N3晶体内共价电子数主要分布在12对由Fe(c1),Fe(c2)和Fe(c3)参与形成的最强键能的键上,由这3种Fe晶位原子形成的共价键键距普遍小于0.3 nm,共价键较强对晶体结合能作主要贡献;并且其结合能相比Sm2Fe17晶体的小得多,解释了Sm2Fe17合金在低温和非真空状态条件下易氧化而经过渗氮后得到的Sm2Fe17N3则表现出常温下结构稳定、化学性能好的特性;计算出N原子参与形成的成键原子对的理论键能值普遍在1 kJ·mol^-1左右,反映出Sm2Fe17N3化合物内在渗氮特性,分析了制备钐铁氮永磁材料过程中Sm2Fe17合金较低温渗氮难、渗氮不稳定和渗氮不均匀的缺陷。     

Acetyl salicylic acid inhibits Th17 airway inflammation via blockade of IL-6 and IL-17 positive feedback

T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.     

静电纺丝方法制备a2-K8 P2W17 MnO61纳米纤维

运用高压静电纺丝和程序升温焙烧的方法制备了a2-K8P2W17MnO61纳米纤维．通过红外光谱（FT-IR）和X射线粉末衍射（XRD）对纤维进行了表征．结果表明，制备的纳米纤维为纯杂多酸盐a2—K8P2W17MnO61,扫描电子显微镜（SEM）图形显示焙烧后获得纳米纤维的平均直径大约为140nm。     

Sensitive Determination of 17β-Estradiol using a Magneto Sensor Based on Magnetic Molecularly Imprinted Polymer

The analysis of 17β-estradiol with high sensitivity and selectivity is extremely relevant to control the impacts that this compound can cause on health and the environment. Thus, we describe the development and application of a magneto carbon paste electrode based on magnetic molecularly imprinted polymer (MCPE-MMIP) for determination of 17β-estradiol. The analyte adsorbed on the MMIP was immobilized on the electrode surface by magnetic capture. The morphological and structural characterization of the obtained MMIP suggests that the material was effectively synthesized. MCPE-MMIP showed an improvement in the sensitivity for 17β-estradiol detection when compared to electrode configurations in the absence of this material. The optimum conditions (0.10 mol L⁻¹ phosphate buffer pH 7.0) were reached by differential pulse adsorptive stripping voltammetry (DPAdSV), in which the method presented linearity ranged from 0.06 to 175 μmol L⁻¹ with limits of detection and quantification of 0.02 and 0.06 μmol L⁻¹, respectively. The proposed sensor was applied effectively in the analysis of 17β-estradiol in river water and raw milk samples, exhibiting excellent recovery values (between 96.20 and 104 %), which were confirmed by HPLC analysis.     

Potential of combining of liquid membranes and molecularly imprinted polymers in extraction of 17β‐estradiol from aqueous samples

The potential of combination of liquid membranes (microporous membrane liquid–liquid extraction) and molecularly imprinted polymers (MIPs) was performed using 17β‐estradiol (E2) as model compound. The model compound was extracted from aqueous sample through a hydrophobic porous membrane that was impregnated with hexane/ethyl acetate (3:2), which also formed part of the acceptor phase. In the acceptor phase, the compound was bound onto MIP particles that were also part of the organic phase. The potential of such combination was optimised for the type and amount of MIP particles in the organic acceptor phase, the extraction time, and the type of organic acceptor solvent. Ultrasound assisted binding of E2 onto MIP particles was also investigated. MIPs prepared by precipitation polymerization were found to be superior to those prepared by bulk polymerization. Increase in the extraction time and the amount of MIP particles in the acceptor phase led to more E2 binding onto the MIP particles. Hexane/ethyl acetate (3:2) as an organic acceptor was found to give higher E2 binding onto MIP particles compared to toluene, diethyl ether, and hexane. Ultrasound was furthermore found to increase the binding of E2 onto MIP particles. The selectivity of the technique was demonstrated by extracting wastewater and where clean chromatograms were obtained compared to liquid membrane extractions (SLMs) alone.     

3-羟基雌甾-1,3,5(10),15-四烯-17-酮的高效合成

以雌酚酮为原料,以取代的苯甲酰作为雌酚酮酚羟基的保护基,乙二醇为雌酚酮羰基的保护基,经过溴代、脱溴和水解等5步反应,通过优化反应路线、反应试剂及反应条件,以65%的高收率制得3-羟基雌甾-1,3,5(10),15-四烯-17-酮.中间体及目标产物的结构经过元素分析、核磁共振波谱(NMR)和电喷雾电离-质谱(ESI-MS)确证.     

一锅法合成16－咪唑甲基甾酮

去氢表雄酮或３－甲氧基雌酮与聚甲醛、咪唑一锅反应，直接而简便地合成了１６－咪唑甲基或１６－羟甲基－１６－咪唑甲基甾酮。     

IL-17-deficient allogeneic bone marrow transplantation prevents the induction of collagen-induced arthritis in DBA/1J mice

IL-17-producing CD4⁺ T cells (Th17) play important functions in autoimmune diseases and allograft rejection of solid organs. We examined the effects of IL 17 and its mechanism of action on arthritis in a murine collagen-induced arthritis (CIA) model using bone marrow transplantation (BMT) system. DBA/1J mice were administered a lethal radiation dose and then rescued with bone marrow derived from either wild-type (WT) or IL-17^-/- mice on C57BL/6 background mice. CIA was induced after the bone marrow transplant, and disease progression was characterized. DBA/1J mice with CIA that received IL-17^-/- donor bone marrow showed potently inhibited development and severity of clinical arthritis as compared with CIA mice that received WT bone marrow. Reduced secretion of the pro-inflammatory cytokines tumor necrosis factor-α, IL-1β, and IL-6, and collagen-specific T cell responses were observed in mice that received IL-17^-/- bone marrow. IL-17 blockade also inhibited effector T cell proliferation by reciprocally regulating the Treg/Th17 ratio. IL-17 blockade prevented joint destruction in mice with CIA. These findings suggest that CIA with BMT is a viable method of immunological manipulation and that IL-17 deficiency suppresses severe joint destruction and inflammation in CIA mice. There may be clinical benefits in blocking IL-17 and BMT in the treatment of rheumatoid arthritis.     

Mechanistic Insights into the Mechanism of Inhibitor Selectivity toward the Dark Kinase STK17B against Its High Homology STK17A

As a member of the death-associated protein kinase (DAPK) family, STK17B plays an important role in the regulation of cellular apoptosis and has been considered as a promising drug target for hepatocellular carcinoma. However, the highly conserved ATP-binding site of protein kinases represents a challenge to design selective inhibitors for a specific DAPK isoform. In this study, molecular docking, multiple large-scale molecular dynamics (MD) simulations, and binding free energy calculations were performed to decipher the molecular mechanism of the binding selectivity of PKIS43 toward STK17B against its high homology STK17A. MD simulations revealed that STK17A underwent a significant conformational arrangement of the activation loop compared to STK17B. The binding free energy predictions suggested that the driving force to control the binding selectivity of PKIS43 was derived from the difference in the protein–ligand electrostatic interactions. Furthermore, the per-residue free energy decomposition unveiled that the energy contribution from Arg41 at the phosphate-binding loop of STK17B was the determinant factor responsible for the binding specificity of PKIS43. This study may provide useful information for the rational design of novel and potent selective inhibitors toward STK17B.     

Ion-pair high-performance liquid chromatography separation of β-endorphin-(6–17) from fourteen fragments

Summary In order to support metabolism studies of the proposed antipsychotic compound β-endorphin-(6–17), (Org 5878), the HPLC separation of this parent compound from fourteen peptide fragments was studied. The addition to the mobile phase of hydrophobic ion-pairing agents proved to be necessary to obtain adequate separation. The influence of the chromatographic parameters pH, type and concentration of the pairing agent, buffer concentration and temperature were investigated systematically. As a result the complete separation of Org 5878 and its fourteen fragments is reported.     

不同类型探针对免疫层析方法的分析灵敏度影响研究

为研究不同类型探针对免疫层析方法的分析灵敏度影响,该研究以17β-雌二醇(17f3-E2)为检测对象,采用磁性纳米材料标记7 μg/mL的17β-E2单克隆抗体(检测抗体)制备了传统探针,采用磁性纳米材料分别标记5 μg/mL的17P-E2单克隆抗体和5 μg/mL的羊抗鼠IgG多克隆抗体(第二抗体)制备了配对探针,采...     

Enzymatic Determination of Urinary Total 17β-Hydroxysteroids

Abstract

An enzymatic determination of urinary total 17β-hydroxysteroids is described. The principle of the method is as follows: after hydrolysis with β-glucuronidase and solvolysis, the ethyl acetate layer, which is washed with alkaline solution and water, is transferred to two test tubes, then each of them is evaporated. To one test tube is added 3β,17β-hydroxysteroid dehydrogenase (EC 1.1.1.51, from P. testosteroni), NAD⁺, 2-ρ-iodophenyl-3-ρ-nitrophenyl-5-phenyltetrazolium chloride (INT), and diaphorase (EC 1.6.99.2, from C. kluyveri) for determination of total 3β,17β-hydroxysteroids. To another test tube is added 3β-hydroxysteroid oxidase (EC 1.1.3.6, from B. sterolicum) for determination of total 3β-hydroxysteroids. The value of 17β-hydroxysteroids is calculated by subtracting the value for 3β-hydroxysteroids from the value for the 3β,17β-hydroxysteroids.     

A stereochemical examination of the equine metabolism of 17alpha-methyltestosterone

An investigation was conducted into the stereochemistry of the equine urinary metabolites of 17α-methyltestosterone observed after oral administration. Standards of the complete range of C3/C5/C16 stereoisomeric 17α-methylandrostane-3,17β-diols, 17α-methylandrostane-3,16,17β-triols and 17α-hydroxymethylandrostane-3,17β-diols were purchased or synthesised, and were used to unequivocally identify the absolute structures of the metabolites. Phase I metabolism was found to involve combinations of Δ⁴-3-ketone reduction with both 5α,3β- and 5β,3α-stereochemistry, hydroxylation at C16 with both 16α- and 16β-stereochemistry and hydroxylation of the 17α-methyl substituent. Phase II metabolism involved mainly sulfation with a lesser degree of β-glucuronidation.     

Synthesis of Cardioactive Steroids III Modified Synthetic Route to Isocardenolide

A modified synthetic route to isocardenolide (I) via furan intermediate (6) was studied. The diene (4) could easily be synthesized from carbinol (1) or acetate (2). Dissolving metal reduction of diene (4) to Δ¹, 17β-furyl compound (6) was successfully achieved.     

Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 ± 12.2 cells/mm2 and 5.6 ± 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 ± 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.     

2-羟基脱氧雌酚酮的合成

2-羟基雌甾化合物是人体内对生理机能有重要意义的雌激素代谢产物,其在生物体内的含量极少,需用化学方法合成来满足研究、应用的需要。迄今为止,已报道了较多合成2-羟基和4-羟基雌甾化合物的方法[1-3],但选择性和产率并不十分理想。我们在文献报道的合成路线[1]的基础上,合成了