Inhibitory effect of beta-adrenergic stimulants on the histamine reaction in human skin. I. Studies with fenoterol.

In 20 volunteers histamine inhibition by fenoterol (Th 1165 a) was studied. The wheal and erythema reaction caused by intracutaneous application of 5 mug histamine can be inhibited by applying fenoterol in doses from 100--400 mug in form of a metered aerosol on the skin 5 min before the injection of histamine. In this study the dose-reaction effect yielded on ED50 of 140 mug fenoterol.     

Regulation of human basophil function by phosphatase inhibitors.

1. Okadaic acid, a cell permeant inhibitor of protein serine/threonine phosphatases (PPs), attenuated the IgE-mediated release of the pre-formed mediator, histamine from human basophils in a time- and dose-dependent manner. Optimal inhibition (77 +/- 4%, P < 0.0001) of histamine release was observed following a 2 h incubation with 1 microM okadaic acid. 2. Okadaic acid and two analogues of okadaic acid were also studied and were found to inhibit the IgE-dependent release of histamine. Concentrations required to inhibit release by 50% (IC50) were 0.6 microM for okadaic acid and 7.5 microM for okadaol, whereas okadaone was inactive. 3. The structurally-unrelated PP inhibitor, calyculin A, also inhibited IgE-dependent histamine release from basophils dose-dependently and was approximately six fold more potent than okadaic acid. 4. The IgE-mediated generation of sulphopeptidoleukotrienes (sLT) from basophils was inhibited by okadaic acid and related analogues with the following rank order of potency; okadaic acid (approx. IC50 0.3 microM) > okadaol (3 microM) > okadaone (inactive). 5. Okadaic acid, okadaol and okadaone (all at 3 microM) inhibited the IgE-mediated generation of the cytokine interleukin 4 (IL4) from human basophils by 67 +/- 9% (P < 0.002), 48 +/- 14% (P < 0.05) and 8 +/- 7% (P = 0.31), respectively. 6. Extracts of purified human basophils liberated 32P from radiolabelled glycogen phosphorylase and this PP activity was inhibited by 17 +/- 3% (P < 0.0005) by a low (2 nM) concentration of okadaic acid and was inhibited by 96 +/- 1% (P < 0.0001) by a higher (5 microM) concentration of okadaic acid. Because a low (2 nM) concentration of okadaic acid inhibits PP2A selectively whereas a higher (5 microM) concentration inhibits both PP1 and PP2A, these findings suggest that both PP1 and PP2A are present in basophils. 7. In total these data suggest that PPs are resident in human basophils and that PPs may be important in the regulation of basophil function.     

Inhibitory effect of bestatin on the growth of human lymphocytes.

Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM-induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes. These growth inhibitory (human) and stimulatory (mouse) effect of bestatin was found to be independent of adherent cells (macrophage and dendritic cell), indicatory directly working to T or B lymphocytes.     

Inhibitory effect of povidone-iodine for the antigen expression of human cytomegalovirus.

Anti-human cytomegalovirus (HCMV) properties of povidone-iodine (PVP-I) were evaluated in vitro. The effect of PVP-I was evaluated by indirect immunofluorescence assay on HCMV-infected MRC-5 cells. Percentages of fluorescent cells positive for HCMV immediate early and early antigens in cultures inoculated with AD 169 treated with PVP-I at various concentrations and reaction times were compared with the number of fluorescent cells in the controls inoculated with the virus alone. PVP-I was found to exert some inhibitory effect at a concentration of 0.5% and complete inhibition at a concentration of 7.5% on the infection of MRC-5 cells by HCMV AD 169 strain. Entirely new approaches to the prevention of HCMV infections in infants are necessary. The adequate use of PVP-I as a disinfectant may reduce the transmission of HCMV.     

Inhibitory effect of glyburide on human cytochrome p450 isoforms in human liver microsomes.

The inhibitory effect of glyburide [International Nonproprietary Name (INN), glibenclamide] on CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 activities was evaluated using pooled human liver microsomes. Glyburide strongly inhibited CYP2C9-catalyzed S-warfarin and phenytoin metabolism in a competitive manner, with Ki (IC50) values of 2.4 (11.3) microM and 3.1 (9.4) microM, respectively. CYP3A4-catalyzed midazolam 1-hydroxylation was inhibited by glyburide with a Ki (IC50) value of 42.5 (90.0) microM. However, glyburide showed no appreciable inhibitory effect on CYP1A2, CYP2C8, CYP2C19, CYP2E1, or CYP2D6. In summary, glyburide showed potent inhibition on CYP2C9 and weak inhibition on CYP3A4, whereas it had minimal or no inhibitory effect on the other cytochromes p450 examined. It is anticipated that clinically significant drug-drug interactions will ensue when glyburide is coadministered with agents that are cleared primarily by the CYP2C9-mediated pathway and those with narrow therapeutic ranges.     

尖吻蝮蛇毒抑瘤组分I对人肺癌 A549细胞增殖抑制作用

目的：研究尖吻蝮蛇毒抑瘤组分I（ AAVC-I） 对人肺癌A549细胞增殖抑制及凋亡的作用。方法： 采用MTT法检测不同浓度的AAVC-I对A549细胞的24 h 与48 h 抑制率;应用HE染色、Hoechst33258荧光染色,从形态学观察细胞凋亡;采用免疫组化的方法,检测bax蛋白表达的变化。结果： MTT显示,AAVC-I能抑制A549细胞增殖,呈时间和剂量依赖性;AAVC-I处理24 h 后,镜下可见细胞核固缩,核深染及凋亡小体;免疫组化显示,随药物浓度增加,平均光密度值呈递增趋势,表明bax蛋白表达相应上调。结论：尖吻蝮蛇毒抑瘤组分I对人肺癌A549细胞具有抑制作用,并诱导其凋亡,可能与bax表达上调有关。     

Effects of silybin on histamine release from human basophil leucocytes.

1. Effects of a naturally occurring flavonoid, silybin, on histamine release from human basophils were examined, in order to assess the potential utility in the treatment of allergic disorders. 2. The f-met peptide and anti-IgE-induced histamine release was significantly (P less than 0.05) inhibited in a concentration-dependent fashion. Conversely, no significant (P greater than 0.05) effect on calcium ionophore A23187-induced histamine secretion was documented. The inhibitory activity was significantly (P less than 0.05) reversed by elevating extracellular calcium concentrations. 3. The anti-allergic properties of silybin can be reasonably ascribed to a membrane-stabilizing activity, possibly related to an interference in calcium influx. These results indicate that an in vivo evaluation of the anti-allergic activity of silybin would be worthwhile.     

蜂毒素对人胚肺成纤维细胞生长的抑制作用及其机制探讨

目的研究蜂毒素(melittin)对人胚肺成纤维细胞(MRC-5)生长的抑制作用及其机制。方法采用MTT法检测蜂毒素对MRC-5细胞的增殖抑制作用;流式细胞仪检测细胞周期;RT-PCR法检测细胞中Cyclin D1、CDK4及E2F-1mRNA的表达变化;Western blot法检测Cyclin D1、CDK4、p21及E2F-1蛋白表达。结果与对照组比较,蜂毒素处理组细胞增殖明显受到抑制,并呈剂量和时间依赖性(P<0.05);流式细胞仪检测结果发现,随着浓度的增大,G0/G1期细胞百分比逐渐上升,S期细胞百分比逐渐下降;同时Western blot结果提示蜂毒素(1,2,4 mg.L-1)可以明显降低Cyclin D1、CDK4及E2F-1表达,而上调p21表达。结论蜂毒素能抑制MRC-5细胞增殖,其机制可能与干扰该细胞G0/G1期相关基因的转录相关且抑制Cyclin D1/E2F信号转导。     

Inhibitory effect of aminoethyl-chitooligosaccharides on invasion of human fibrosarcoma cells

Chitooligosaccharides (COS) have been reported to show a variety of biological efficacies such as anti-bacterial activity, anti-tumor activity and immune activity. The purpose of this study is to investigate the inhibitory effect of aminoethyl-chitooligosaccharides (AE-COS) synthesized from COS that were substituted hydroxyl groups with aminoethyl group at C-6 position on cell invasion of human fibrosarcoma cells. First of all, the effect of AE-COS on cell viability was observed using MTT assay. The cytotoxicity of AE-COS was increased in a dose dependent manner. The inhibitory effects of AE-COS on the activity and expression level of MMP-2 and MMP-9 related to invasion of cancer cells were examined using gelatin zymography and western blot. It was found that AE-COS above 20 μg/ml showed the inhibitory effect on the activity and expression of MMP-9. Furthermore, AE-COS at 20 μg/ml reduced the expression level of p50, a part of NF-κB, compared with phorbol-12- myristate-13- acetate (PMA) group. The available data let us hypothesize that AE-COS could provide chemoprevention as an inhibitor against cell invasion associated with metastasis.     

虫草素对人肝癌Bel-7402细胞抑制及作用机制的研究

<正>虫草素是虫草的主要活性成分,具有抗肿瘤、抑菌、抑制病毒、抑制蛋白质激酶活性等作用[1-2]。研究证明虫草素能抑制mRNA的合成,诱导细胞凋亡,促进细胞分化,对多种肿瘤细胞的生长具有抑制作用[1-2]。诱导肿瘤细胞凋亡以及作用靶点已成研究的焦点。为探讨虫草素诱导肿瘤细胞凋亡的新靶点,对虫草素作用人肝癌Bel-7402细胞后的抑制     

Inhibitory effect of chalcone derivatives on recombinant human aldose reductase

More than fifty chalcone derivatives were synthesized to examine structure-activity relationships against human aldose reductase. Certain 2',4'-dihydroxychalcone derivatives inhibited human aldose reductase activities, and 2',4',2, 4-tetrahydroxychalcone and 2',4',2-trihydroxychalcone showed potent inhibitory activity with IC50 values of 7.4x10(-9) M and 1.6x10(-7) M, respectively. On the other hand, cis-form chalcones, which were isomerized from the original trans-forms by irradiation of daylight in methanol solution, promoted the activity of human aldose reductase.     

基于雌激素代谢调控的白藜芦醇对MNNG诱导子宫内膜癌变的抑制作用

目的考察白藜芦醇(Res)是否可能通过调控雌激素内稳态,进而抑制MNNG诱导小鼠子宫内膜的癌变。方法采用MNNG诱导EC小鼠模型,将小鼠随机分为Control组、Res组、MNNG组、MNNG+Res组。HE染色观察组织病理情况;q PCR检测Ccnd1、CK-19、Erbb2 mRNA的表达;LC-MS/MS检测小鼠血清和子宫中E_1、E_2、2-MeOE_1、4-MeOE_1、2-MeOE_2、4-MeOE_2、16α-OHE_1、2-OHE_1、4-OHE_1、2-OHE_2和4-OHE_2的含量。结果 MNNG组小鼠子宫内膜腺体增多、拥挤,局灶形成筛孔;MNNG+Res组小鼠子宫内膜腺体减少,趋于正常。与Control组相比,MNNG组Ccnd1、Erbb2mRNA表达明显升高,MNNG+Res组明显降低。MNNG组小鼠的血清和子宫组织中,2-MeOE_2、2-MeOE_1和4-MeOE_1含量明显下降,4-OHE_2含量明显增加,给予Res治疗后,血清中4-MeOE_1含量明显升高,子宫组织中2-MeOE_2和2-MeOE_1含量明显升高,4-OHE_2在血清和子宫组织中含量均明显降低。结论 EC小鼠体内雌激素内稳态失衡,Res可以上调雌激素代谢产物2-MeOE_2的含量,降低4-OHE_2的含量,抑制EC的发生发展。     

Role of calcineurin in the regulation of human lung mast cell and basophil function by cyclosporine and FK506

BACKGROUND AND PURPOSE: Cyclosporine and FK506 are thought to act by targeting the Ca2+-dependent protein phosphatase, calcineurin. The aim of the present study was to determine whether cyclosporine and FK506 stabilize mast cells and basophils by interacting with calcineurin. EXPERIMENTAL APPROACH: The effects of cyclosporine and FK506 on the IgE-mediated release of histamine from mast cells and basophils were evaluated. The presence of calcineurin in cells was determined by Western blotting. Ca2+-dependent protein phosphatase activities were assessed in cell extracts using a synthetic phosphorylated peptide that is known to serve as a substrate for calcineurin. KEY RESULTS: FK506 was about 100-fold more potent than cyclosporine as an inhibitor of IgE-dependent histamine release from mast cells and basophils. Immunoblotting of solubilized preparations of purified cells demonstrated the presence of calcineurin in mast cells and basophils. In enzyme assays, mast cells expressed approximately 7-fold higher Ca2+-dependent protein phosphatase activity than basophils. Whereas cyclosporine effectively inhibited Ca2+-dependent protein phosphatase activity in cell extracts, FK506 was considerably less effective. CONCLUSIONS AND IMPLICATIONS: FK506 and cyclosporine inhibit the stimulated release of histamine from mast cells and basophils. However, the ability of cyclosporine, but not FK506, to inhibit Ca2+-dependent protein phosphatase activity questions whether FK506 stabilizes mast cells and basophils by interacting with calcineurin.     

Influenza A virus enhances IgE-mediated histamine release from human basophil leukocytes. Examination of the effect of viral neuraminidase and haemagglutinin

Histamine release caused by anti-IgE was examined in leukocyte suspensions from 10 healthy individuals. Influenza A virus was found to enhance the histamine release but did not release histamine per se. When monoclonal antibodies directed against the viral neuraminidase were included in the samples, the potentiating effect of the virus was completely abolished. The same occurred using a neuraminidase inhibitor. However, monoclonal antibodies directed against the viral haemagglutinin also abolished the potentiation. A binding of virus to the basophil cell surface by haemagglutinin therefore seems to be necessary for the viral neuraminidase to cause potentiation of mediator release.     

川楝素对乳腺癌MDA-MB-231细胞增殖的抑制作用

目的 探讨川楝素对人三阴性乳腺癌MDA-MB-231细胞生长的抑制作用及其机制.方法 取对数生长期的MDA-MB-231细胞,采用0、6.25、12.50、25.00、50.00和100.00 nmol/L川楝素处理,绘制生长曲线.川楝素0、12.5和50 nmol/L处理72 h后,采用MTS法检测川楝素对MDA-MB-231细胞增殖,流式细胞仪检测乳腺癌细胞凋亡和周期,Western blot检测凋亡相关蛋白半胱氨酶蛋白酶3(Caspase-3)、聚腺苷酸二磷酸核糖转移酶(PARP)和cleave-PARP表达.结果 川楝素呈时间和剂量依赖性抑制MDA-MB-231乳腺癌细胞增殖(P＜0.01).川楝素作用48、72和96 h的半数抑制浓度(IG0)分别为9.32、16.96和122.37nmol/L.川楝素能呈浓度依赖性诱导乳腺癌细胞凋亡(P＜0.01),阻滞细胞在S期(P＜0.01).以0、12.50和50.00 nmol/L川楝素处理MDA-MB-231细胞72 h,其早期凋亡率分别为8.12％、20.85％和67.21％,处于细胞周期S期的细胞占32.69％、47.90％和61.23％,凋亡相关蛋白Caspase-3和PARP减少,cleaved-PARP增多.结论 川楝素对人乳腺癌MDA-MB-231细胞增殖具有抑制作用;其机制可能与诱导细胞凋亡和引起细胞S期阻滞有关.     

Notes on the peroxidase activity of human basophil leukocytes

In recent years, basophils have been described as peroxidase-positive in some textbooks (6, 8). However, as far as basophils in the peripheral blood from healthy persons are concerned, they must be considered as peroxidase-negative. This discrepancy is thought to be based on the following points: 1) fixation of human basophils is more difficult than that of the other leukocytes; 2) counterstaining with a certain basic dye causes misinterpretation of the enzyme reaction; 3) diaminobenzidine which has been most frequently used as hydrogen donor in the peroxidase reaction is so sensitive to non-enzymatic substances that substrate-minus experiments as well as inhibition experiments for peroxidase are absolutely necessary; and 4) basophils in the peripheral blood from healthy persons are originally peroxidase-negative. On the other hand, basophils in the peripheral blood from patients with myeloid leukemia are frequently peroxidase-positive, and yet, the peroxidase demonstrated in such basophils is not true myeloperoxidase since peroxidase from the above patients is resistant to heating, methanol and other chemicals known as inhibitors of myeloperoxidase. These data are illustrated by many color photographs.     

澳洲茄胺对人骨肉瘤移植瘤的抑制作用及其机制

目的 探讨澳洲茄胺对人骨肉瘤移植瘤的抑制作用及其机制.方法 该研究于2018年1月至2019年3月完成.MG63细胞株购于中科院上海细胞库.将0.2 mL人骨肉瘤MG63细胞悬液(共2×106个细胞)注射于裸鼠右侧腋窝皮下,建立人骨肉瘤移植瘤模型,实验分为4组,即对照组和澳洲茄胺组(10 mg/kg、20 mg/kg、...