中药治疗小儿呼吸道合胞病毒性肺炎疗效观察

目的:评价中药清肺口服液治疗小儿呼吸道合胞病毒性肺炎痰热闭肺证的有效性和安全性。方法:选取小儿呼吸道合胞病毒性肺炎痰热闭肺证62例,随机入组。试验组27例,使用清肺口服液加用不含抗病毒药物的液体,对照组35例,使用利巴韦林加用清肺口服液安慰剂。结果:试验组痊愈率76.19%,显效率23.81%,对照组痊愈率48.15%,显效率29.63%,试验组综合疗效显著优于对照组。安全性评价方面,试验组未见不良反应。结论:清肺口服液治疗小儿呼吸道合胞病毒性肺炎痰热闭肺证综合疗效明显优于利巴韦林注射液,且安全性良好。

DC-CTL免疫细胞对卵巢上皮癌细胞的靶向性治疗研究

目的探讨经树突状细胞(DC)诱导的细胞毒性T淋巴细胞(CTL)免疫细胞靶向性的抑制卵巢上皮癌细胞的机制,为临床上DC-CTL治疗卵巢癌提供理论基础。方法无胸腺BALB/C/nu/nu裸小鼠48只,分为4组,每组12只,裸鼠人卵巢癌SKOV3移植瘤模型成功后用未经DC诱导的CTL免疫细胞和经DC诱导的CTL免疫细胞进行治疗,比较各组裸鼠移植瘤体积和重量、抑瘤率、移植瘤miRNAlet-7表达和HMGA2蛋白表达的差异。结果 DC-CTL组和CTL组裸鼠的移植瘤体积和移植瘤重量低于模型对照组(F值分别为8.175、6.823,均P<0.05),DC-CTL组裸鼠的移植瘤体积和移植瘤重量低于CTL组,且差异具有统计学意义(t=13.244,P<0.05);DC-CTL组裸鼠的抑瘤率(69.57±10.81)%高于CTL组(42.35±8.15)%,且差异具有统计学意义(t=6.965,P<0.05);DC-CTL组和CTL组裸鼠的移植瘤miRNAlet-7表达均高于模型对照组(F=7.528,P<0.05),DC-CTL组裸鼠的移植瘤miRNAlet-7表达(1.69±0.40)高于CTL组(1.17±0.39),且差异具有统计学意义(t=2.964,P<0.05);DC-CTL组和CTL组裸鼠的HM GA2蛋白表达的ISH评分均低于模型对照组(F=6.419,P<0.05),DC-CTL组裸鼠的HM GA2蛋白表达的ISH评分(15.31±1.72)低于CTL组(17.18±1.86),且差异具有统计学意义(t=3.143,P<0.05)。结论经DC诱导的CTL免疫细胞能够明显抑制裸鼠卵巢癌移植瘤的生长,其机制可能为促进let-7表达和抑制HMGA2蛋白表达有关。

反式构型铂配合物抗癌药物研究进展

人们一直认为反式构型铂配合物无抗癌活性 .但是 ,近来研究发现 ,一些反式构型的铂配合物显示了良好的抗癌活性 .本文综述了这些配合物的结构。

沙蟾毒精抗肿瘤作用研究进展

沙蟾毒精是从中华大蟾蜍的分泌物蟾酥或干燥表皮蟾皮中提取的一种单体成分。沙蟾毒精可通过促进肿瘤细胞凋亡、抑制肿瘤细胞侵袭和转移、抑制肿瘤血管生成等途径发挥抗肿瘤作用,在肺癌、肝癌、乳腺癌、前列腺癌等多种恶性肿瘤中均具有很好的抗肿瘤活性,但应用于临床还需要解决毒性作用及不良反应等问题。

Constituents from Ranunculus sieboldii Miq.

Aim To investigate the chemical composition of Ranunculus sieboldii Miq..Methods Repeated column chromatography over silica gel, polyamide and RP-18 followed by gelfiltration on sephadex LH-20 were used to isolate chemical constituents, and their structures wereelucidated by extensive spectroscopic methods (UV, IR, MS, ~1H NMR, ^(13)C NMR) including 2D NMR(COSY, HMQC, HMBC, NOESY) techniques and by direct comparing spectral data with those reported inliterature. Results Five flavonoid glycosides named apigenin-4'-O-α-L-rhamnopyranoside (1),apigenin-7-O-β-D-glucopyranosyl-4'-O-α-L-rhamnopyranoside (2), apigenin-8-C-α-L-arabinopyranoside(3), apigenin-8-C-β-D-ga-lactopyranoside (4) , tricin-7-O-β-D-glucopyranoside (5), together withtricin (6), luteolin (7), scopoletin (8), esculetin (9), scoparone (10), ferulic acid (11),protocatechuic acid (12) , and tematolide (13) were isolated from the 95% etha-nolic extract of itswhole plant, and their cytotoxic activities were preliminarily tested. Conclusion Compounds 1-12were obtained from this genus and compound 13 from this species for the first time. Furthermore,compound 1 was for the first time isolated from nature while the ^(13)C NMR data of compounds 2 and3 are reported for the first time. The bioassay revealed that compound 1 was active against BEL-7407and A549 cell lines (IC_(45) 43, 77 μg·mL^(-1)), 8 and 10 showed inhibitory activities on KB celllines (IC_(50) 78, 44 μg·mL^(-1)) and HL-60 cell lines (Ic_(50) 85, 85 μg·mL^(-1)), while 7exerted moderate cytotoxic activities on KB, BFL-7407, A549 and HL-60 cell lines with their IC_(50)being 51, 55, 44 and 10 μg·mL^(-1) , respectively.

Polyhydroxylated Steroidal Sapogenins from Tupistra wattii

Two novel polyhydroxylated steroidal sapogenins, wattigenin B ((25R)-spirost-1beta, 2beta, 3beta, 4beta, 5beta, 6beta, 7alpha-heptol, 1) and wattigenin C ((25S)-spirost-1beta, 2beta, 3beta, 4beta, 5beta, 7alpha-hexalrydroxyl-6-one, 2), together with two known sapogenins, kitigenin (3) and convallagenin B (4), were isolated froth the fresh rhizomes of Tupistra wattii Hook. f. The structures of the compounds were determined on the basis of spectroscopic analysis. The four sapogenins were evaluated for the cytotoxicities on the cancer cell line K562 and A2780a in vitro. Compounds 1 - 4 were obtained from the plant for the first time.

Binding tendency with oligonucleotides and cell toxicity of cetyltrimethyl ammonium bromide-coated single-walled carbon nanotubes

Functionalized carbon nanotubes （CNTs） were made for the delivery of genes and drugs and CNT-based biosensors. The basis of CNTs is for binding with biomolecules in biomedical applications. The binding tendency with small interfering RNA oligonucleotides and cytotoxicity of cetyltrimethyl ammonium bromide （CTAB）-coated single-walled carbon nanotubes （SWNTs） were studied. The field emission scanning electron microscopy and transmission electron microscopy results show that a SWNT suspension in CTAB solution was well-dispersed and stable. CTAB is the cross-linker between SWNTs and oligonucleotides. The CTAB-coated SWNTs have less cytotoxicity to human umbilical vein endothelial cells than single SWNTs and the cytotoxicity of CTAB-coated SWNTs depended on the concentration of CTAB-coated SWNTs.

Effects of chitosan coating on biocompatibility of Mg-6%Zn-10%Ca_3(PO_4)_2 implant

A Mg?6%Zn?10%Ca3(PO4)2 composite with a chitosan coating was prepared to study its in vivo biodegradation properties. The chitosan dissolved in a 0.2% acetic acid solution was applied on the surface of Mg?6%Zn?10%Ca3(PO4)2 composite specimens and solidified at 60 °C for 30 min to form the coating. The cytotoxicity evaluation of chitosan coated specimens is at level 0, which indicates that such coating is safe for cellular applications. The in vivotests of chitosan coated composite show that the concentration of metal ions from the composite measured in the venous blood of Zelanian rabbits is less than that from the uncoated composite specimens. The chitosan coating impedes the in vivo degradation of the composite after surgery. The in vivo testing also indicates that the chitosan coated composite is harmless to important visceral organs, including the heart, kidneys and liver of the rabbits. The new bone formation surrounding the chitosan coated composite implant shows that the composite improves the concrescence of the bone tissues. And the chitosan coating is an effective corrosion resistant layer that reduces the hydrogen release of the implant composite, thereby decreasing the subcutaneous gas bubbles formed.

Purification and Characterization of Cytotoxins from Agkistrodon acutus Venom and Their Anticancer Activity

Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.

Study on Flavonoids from the Methanol Extracts of Tephrosia purpurea Leaves

[Objective] The aim was to determine flavonoids from the MeOH extracts of Tephrosia purpurea leaves and their cytotoxicitives against the ovarian cells from Sprodenia litura （SL cells）.[Method] The compounds were isolated with column chromatography and their structures were established on the basis of various spectroscopic analysis （including UV,1D and 2D NMR analyses as well as HR-ESRMS）.The cytotoxicity against the SL cells was evaluated by using MTT method.[Result] Six known flavonoids,6-methoxykaempferol （1）,6-methoxykaempferol 7-O-α-rhamnopyranoside （2）,6-methoxykaempferol 3-O-α-rhamnopyranosyl（1→2）[α-rhamno-pyranosyl（1→6）]-β-galactopyranoside （3）,6-methoxykaempferol 3-O-α-rhamnopyranosyl （1 →2）[α-rhamnopyranosyl （1 →6）]-β-galactopyranoside-7-O-α-rhamnopyranoside （4）,pongachin （5）,5,7-dimethoxy-8-（3-hydroxy-3-methylbut-1Z-enyl） flavanone （6） were isolated and determined.Except compound 5,the others were isolated from T.purpurea for the first time.For the cytotoxicity compound 5 had significant activity with the IC50 value of 4.4 mg/L while compound 1 and 3,whose cytotoxicity exceeded rotenone,also showed moderate activity.[Conclusion] Of all the compounds from T.purpurea leaves,the content of 6-methoxykaempferol compounds was considerable.The profiles of these compounds against SL cells suggested that compounds 1,3 and 5,whose cytotoxicity exceeded rotenone,were worth further research.

Fixed-Tumor Vaccine: A Practical Formulation with Cytokine-Microspheres for Protective and Therapeutic Antitumor Immunity

Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells. Key words cancer vaccine - cytotoxic T lymphocyte - immunotherapy - hepatoma

Reversal of Multidrug Resistance by Neferine in Adriamycin Resistant Human Breast Cancer Cell Line MCF-7/ADM

Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

Objective： To observe the recurrence and prognosis of hepatocellular carcinoma （HCC） patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 （Tα1） postoperatively. Methods： From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups： control group （n=35） received hepatectomy only; treatment group （n=35） received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results： In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% （P=0.0000）; HBeAg seroconverted rate was 73.0% vs. 7.5% （P〈0.05）; the recurrent rate was 10.0 vs 6.5 months （P=0.0032）; the median survival time was 12.5 vs. 6.0 months （P=0.0023）, respectively. Conclusion： Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.

Ascorbic Acid Promotes Arsenic-induced Cytotoxicity in Human Hepatocarcinoma Cells and Their Underlying Mechanisms

Objective: To study synergistic effect with Ascorbic acid(AA) on arsenic trioxide inducing human Hepatocarcinoma cell apoptosis, and provide theoretical basis for promoting human Hepatocarcinoma cell apoptosis induced by arsenic trioxide(AT). Methods: Human Hepatocarcinoma cell line BEL-7402 being cultured in vitro, the effect of AT and (or) AA on its growth inhibition and its two intracellular signal molecules was evaluated separately using MTT and Western blot. Results: AT at a few μmol/L concentration could suppress abnormal proliferation of human hepatocarcinoma cells, and initiate their apoptosis by activation of caspase-3, and activate extracellular-signal regulated kinases (ERKs), which were dependent on the dosage of AT conspicuously. The effect of AA on BEL-7402 was not significant; However, AA could effectively enhance AT-induced hepatocarcinoma cell apoptosis and lesion severity through activation of caspase-3 but not ERKs. Conclusion: Caspase-3 and ERKs proteins could involve in arsenic-induced hepatocarcinoma cell apoptosis and differentiation respectively as intracellular signaling molecules; The effect between AT and AA on hepatocarcinoma is synergistic, which further inhibits cell growth and induces apoptosis in human hepatocarcinoma cells through activation of caspase-3 but not ERKs.

Corrosion degradation behavior of Mg-Ca alloy with high Ca content in SBF

The corrosion degradation behavior of a Mg-Ca alloy with high Ca content aiming for a potential bone repair material in the simulated body fluid（SBF） was investigated.The microstructure and phase constitution of the pristine Mg-30%Ca（mass fraction） alloy were characterized with scanning electron microscopy（SEM） and X-ray diffraction（XRD）.The Mg-30%Ca alloy samples were immersed in the SBF for 90 d,and the morphology,composition and cytotoxicity of the final corrosion product were examined.It is found that Mg-30%Ca alloy is composed of α-Mg and Mg2 Ca phases.During the corrosion process in the SBF,the Mg2 Ca phase acts as an anode and the α-Mg phase acts as a cathode.The final corrosion product of the Mg-30%Ca alloy in SBF includes a small amount of black precipitates and white suspended particles.The white suspended particles are Mg（OH）2 and the black particles are believed to have a core-shell structure.The cytotoxicity experiments indicate that these black precipitates do not induce toxicity to cells.

Advances in Toxicology of Nε-(carboxymethyl)-lysine(CML)

Advanced glycation end-products （AGEs） are products of non-enzymatic glycation of proteins, lipids or nucleic acids and other macromolecules. To be spe- cific, Nε-（carboxymethyl）-Iysine （CML） is one of the most important components of AGEs, which is wildly distributed in the body and can be formed in vivo or in food processing and heating processes. Previous studies have shown that CML is a ma- jor immunological epitope in AGEs and plays an important role in diabetes and its complications, as well as in the development and progression of aging. This review summarized recent advances in major source, toxicological hazard and control mea- sures of CML.

Bile-acid-induced cell injury and protection

Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective

Alterations of red blood cell immunoadherence function in hepatitis B patients

AIMS To investigate the alterations of RBC immunoadherence function in patients with various hepatitis B. METHODS RBCC3bRR,RBCICRR and serum CIC levels were measured in 42 patients with acute and chronic hepatitis B at ac- tive and convalescence stages. RESULTS RBCC3bRRs at the active/acute stage of various hepatitis were decreased.They were 13,54%±5,23% in AH, 7.61%±4.12% in AFH,and 16.18%±6.10% in CH, respectively,all of which were lower than those in normal persons (18.12%±3.91% ).At the quiescent/recovery stage of various hepatitis,the RBCC3bRRs were increased significantly.The changes of RBCICRR and serum CIC level were contrary to those of RBCC3bRR. CONCLUSIONS RBC immunoadherence function is decreased in acute and chronic hepatitis.The decrease is in direct proportion to the severity of the diseases.