AcSDKP的生物学活性研究进展

AcSDKP是从胎牛骨髓中提取的一种生理性造血细胞生长抑制因子。作为一种负性调控因子，AcSDKP具有抑制造血干细胞生长的生物学功能，并且对其他细胞有生长抑制作用，具有多种生物学功能，并且有望在癌症治疗中发挥重要作用。本文就其生物学活性的研究进展作一综述。     

丹参注射液对体外培养成纤维细胞的增殖和形态的影响

目的研究丹参注射液对体外培养成纤维细胞的增殖和形态的影响。方法用含有浓度为0～200mg/mL丹参注射液的培养液作用于成纤维细胞,培养72h后,MTT检测细胞活性,显微镜下观察细胞形态变化。结果与对照组相比,丹参注射液在体外培养条件下对成纤维细胞的生长具有明显的抑制作用,并且随着药物浓度的增加,抑制作用也逐渐增强。结论丹参注射液对成纤维细胞有抑制作用并且呈剂量依赖性。提示其可能有预防或延缓肺纤维化疾病进程的作用。     

体外培养创面成纤维细胞的生物学特性及其意义

目的 研究创面成纤维细胞的生物学特性有利于揭示创面愈合过程中瘢痕形成的机理。方法 采用体外成纤维细胞培养技术，开展创面成纤维细胞的分离培养，建立细胞库；细胞的生长动力学和增殖型、合成型、收缩型等表型变化；细胞因子对不同时期来源创面成纤维细胞增殖活怀、蛋白合成及其收缩功能的影响。结果 体外培养的创面成纤维细胞保持其在体内的生物学特性；春增殖、合成、收缩等表型间转化存在着一定的规律性；不同时期来源的创面成纤维细胞对细胞因子的反应性不同。结论 体外控制条件下创面成纤维细胞的生物学活动及其影响因素在细胞水平上揭示了瘢痕形成的理论基础与调控机理，为指导临床防治烧伤后瘢痕增生或／和瘢痕挛缩提供了依据。     

海蟑螂提取物的抗肿瘤作用

目的考察海蟑螂提取物的抗肿瘤作用。方法采用温浸、减压浓缩、冷冻干燥制备海蟑螂提取物；MTT法检测其对人子宫颈癌细胞（HeLa）、人胃癌细胞（7901）、人非大细胞肺癌细胞（NCI）和正常人体成纤维细胞（929）的生长抑制作用；考察对小鼠移植性肉瘤（S180）生长的影响。结果海蟑螂提取物对HeLa，7901,NCI细胞的生长均有明显的抑制作用；对正常的人成纤维细胞的生长无明显抑制效应。海蟑螂提取物腹腔注射0．25，0．50，1.00g·kg^-1共7d，对S180的抑瘤率分别为26．9％，45．3％和64．6％。结论海蟑螂提取物在体内外均有显著的抗肿瘤作用，且毒性较低。     

从成纤维细胞生长现象探讨毛乳头细胞凝集性生长的成因

成纤维细胞和毛乳头细胞同属于真皮成分，有学者认为，毛乳头细胞是一种特殊化的成纤维细胞，但这种细胞缺乏特异的细胞标志，要将毛乳头细胞与成纤维细胞区别开，主要依赖于毛乳头细胞的一个特异性生长特征，即凝集性生长现象.然而，复习文献发现。这两种细胞分离培养的方法是不同的。推测凝集性生长现象的出现有可能与这种接种方式有关。因此。我们培养了通常认为不具有凝集性生长特性的真皮成纤维细胞，模拟毛乳头细胞的接种方式，以观察是否出现与毛乳头细胞凝集性生长现象类似的现象，现将结果报告如下。     

复方木鸡冲剂对多种肿瘤细胞体外生长抑制作用的观察

目的研究复方木鸡冲剂在体外对不同组织来源肿瘤细胞的生长抑制作用。方法应用MTT法观察复方木鸡冲剂对多种肿瘤细胞的生长抑制作用，倒置显微镜观察细胞形态的变化，流式细胞术分析细胞凋亡。结果复方木鸡冲剂对不同组织来源的多种肿瘤细胞有明显的生长抑制作用，并能使HL-60和HepG2细胞的凋亡率增加。结论复方木鸡冲剂在体外对多种肿瘤细胞的生长有抑制作用，初步认为是通过诱导细胞凋亡实现的。     

成纤维细胞生长因子安全性研究进展

成纤维细胞生长因（Fibroblast growth factor,FGF）是广泛存在于多种组织中的一类多肽因子,能影响多种细胞的生长、分化及功能,具有广泛的临床研究价值。为确保研制的新药的安全性,并提供新药对人类健康危害程度的科学依据,需对新药进行临床前安全性评价,其主要有急性毒性试验、长期毒性试验（反复给药毒性试验）、特殊毒性试验、皮肤用药及腔道用药毒性试验、药物依赖性试验及抗生育药及细胞毒性抗肿瘤药的毒性评价。本文综述了成纤维细胞生长因子的毒性试验的研究。     

青蒿琥酯对成纤维细胞和内皮细胞的选择性研究

目的:探讨青蒿琥酯(Art)是否对成纤维细胞增殖有特异的细胞选择作用.方法:选用人胚肺成纤维细胞株(HLF)、人皮肤瘢痕成纤维细胞(HSF)和人脐静脉内皮细胞(HUVEC),用免疫组化法鉴别细胞;MTT法检测青蒿琥酯对上述3种细胞存活与增殖的影响;光镜观察青蒿琥酯作用下细胞形态学的改变;琼脂糖凝胶电泳观察细胞DNA的变化.结果:青蒿琥酯在30～240 mg·L-1浓度范围内作用细胞 24 h 对两种来源的成纤维细胞的增殖都具有明显的抑制作用(P＜0.05),对血管内皮细胞增殖抑制作用不明显(P＞0.05).药物作用 24 h 后,HLF、HSF、HUVEC细胞的IC50分别为:64、60、600 mg·L-1.光镜下见两种成纤维细胞用药组细胞变圆,突起变短变少,胞浆颗粒增多;而内皮细胞在形态上无明显的变化.琼脂糖凝胶电泳结果显示在240 mg·L-1浓度作用 24 h,两种成纤维细胞的DNA出现梯带状的电泳图谱,而内皮细胞的DNA无梯状条带.结论:青蒿琥酯对来源于肺和皮肤的成纤维细胞的增殖具有抑制作用,而对血管内皮细胞生长增殖无明显的影响.该药还能诱导两种成纤维细胞凋亡,而对脐静脉内皮细胞无明显诱导凋亡的作用.     

ERK1/2及JNK通路在AcSDKP抑制PDGF诱导的大鼠心脏成纤维细胞增殖和胶原蛋白表达中的作用

目的探讨细胞外信号调节激酶1/2(ERK1/2)及C-Jun氨基末端激酶(JNK)通路在N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)抑制血小板源性生长因子(PDGF)诱导的大鼠心脏成纤维细胞增殖和胶原蛋白表达中的作用。方法将新生Wistar大鼠心脏成纤维细胞分为对照组(A组)、10ng/ml PDGF刺激组(B组)、10-9 mol/L AcSDKP+10ng/ml PDGF干预组(C组)、25μmol/L PD98059+10ng/ml PDGF干预组(D组)和10nmol/L SP600125+10ng/ml PDGF干预组(E组)。MTT法检测心脏成纤维细胞代谢活性的变化,Western blot法检测大鼠心脏成纤维细胞中ERK1/2、JNK及磷酸化-ERK1/2、磷酸化-JNK蛋白表达和Ⅰ型、Ⅲ型胶原蛋白的表达。结果与A组相比,B组心脏成纤维细胞代谢活性、Ⅰ型及Ⅲ型胶原蛋白表达、磷酸化-ERK1/2及磷酸化-JNK蛋白表达均增强(P<0.05);而C、D、E组能明显逆转B组上述各观察指标的增加过程(P<0.05)。结论 AcSDKP能够通过阻断PDGF介导的ERK1/2及JNK通路的激活,进而抑制大鼠心脏成纤维细胞增殖和胶原蛋白表达。     

白血病抑制因子的药理毒理学作用与临床应用前景

白血病抑制因子是一种能抑制小鼠Ｍ１白血病细胞克隆生长和促进其分化的多功能细胞因子。它主要产生于单核细胞、淋巴细胞、成纤维细胞和一些肿瘤细胞。其生物学作用广泛，它可抑制造血祖细胞增殖，升高外周血血小板和巨核细胞数，抑制胚胎干细胞分化，参与胚胎的生长和发育，对血小板减少性疾病和某些白血病将有较好的治疗作用。     

Styryl lactones and their derivatives: biological activities, mechanisms of action and potential leads for drug design

Nature is an inexhaustible source of natural compounds with interesting biological activities. In general, natural products are an important source of new compounds with a variety of structural arrangements and singular properties. Styryl lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess interesting biological properties, in particular antiproliferative activity against cancer cells. In general, the cytotoxicity of styryl lactones appears to be specific against cancer cells since insignificant effects of these compounds on normal cells are reported. A large body of evidence suggests that the antiproliferative activity of styryl lactones is associated with the induction of apoptosis in target cells. In the first part of this review we discuss the biological activities of styryl lactones focusing on cancer cells, the causal agent of Chagas' disease and the vectors for yellow fever and human lymphatic filariasis. Stru described in detail for ninety styryl lactones. The last part describes the molecular targets of styryl lactones for inducing apoptosis, as well as immunosuppressive and inflammatory processes. Overall, understanding how these compounds exert their activities in biological system is essential for future development and application of styryl lactones for human health.     

In vitro hepatotoxicity of the cyanobacterial alkaloid cylindrospermopsin and related synthetic analogues.

Cylindrospermopsin (CY), a sulfate ester of a tricyclic guanidine substituted with a hydroxymethyluracil, is a cyanobacterial toxin of increasing environmental import as it frequently occurs in drinking water reservoirs. As a toxin, CY mainly targets the liver but also involves other organs. In hepatocytes CY inhibits the synthesis of protein and of glutathione, leading to cell death. The total chemical synthesis of CY has recently been reported (Xie et al., 2000, J. Am. Chem. Soc. 22, 5017-5024). The synthesis has provided analogues of CY to study aspects of the relationship between chemical structure and activity that contribute to toxicity. Protein synthesis inhibition was measured in vitro using a rabbit reticulocyte system. Primary cultures of rat hepatocytes were used to determine the biological activity of CY and analogues in intact cells. Protein synthesis and cell glutathione levels were measured. We could distinguish between CY transport and biological activity by comparing the results in vitro to those in intact cells. The role of the sulfate group in CY toxicity was examined by comparing biological effects of CY with that of CY-DIOL (synthetic CY lacking the sulfate group). The sulfate group was found not to play a role in CY activity or in its uptake into cells, since there was no significant difference in biological activity in vitro or in cells between natural CY and CY-DIOL. The orientation of the hydroxyl group at C7 also had no impact on biological activity or transport of CY, since the C7 epimer of CY (EPI-CY) and the corresponding diol (EPI-DIOL) had activity similar to RAC-CY in vitro and in intact cells. AB-MODEL, the analogue lacking an intact C ring, and the methyl and hydroxyl groups of ring A could inhibit protein synthesis (but at concentrations 500-1000-fold higher than natural CY). Other structurally simpler synthetic analogues lacked biological activity.     

None of the four tyrosine residues is essential for the biological activity of erythropoietin

Erythropoietin (EPO), a glycoprotein hormone, regulates the proliferation and differentiation of erythroid progenitor cells. Many attempts have been made to identify the functionally important amino acids of the hormone. One of those early studies has found that heavy radioiodination of EPO caused the loss of its biological activity, suggesting some important role of one of the four tyrosine residues (Goldwasser, 1981). Thus, in this study, we have generated and tested four Tyr→Phe substitution mutants to clarify the possible role of the tyrosine residue(s) in the hormone’s biological activity. When the mutant and wild type EPO cDNAs were transfected into COS-7 cells and the biological activities of the muteins were assayed using the primary murine erythroid spleen cells, no mutation tested was found to affect the biological activity of the hormone. Thus we conclude that, contrary to the previous observation, none of the four tyrosine residues in erythropoietin is critically involved in the binding of the hormone to its receptor.     

Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment

The complex tumor microenvironment is a most important factor in cancer development. The biological microenvironment is composed of a variety of barriers including the extracellular matrix and associated cells such as endothelia cells, pericytes, and cancer-associated fibroblasts. Different strategies can be utilized to enhance nanoparticle-based drug delivery and distribution into tumor tissues addressing the extracellular matrix or cellular components. In addition to the biological microenvironment, the immunological conditions around the tumor tissue can be very complicated and cancer cells have various ways of evading immune surveillance. Nanoparticle drug delivery systems can enhance cancer immunotherapy by tuning the immunological response and memory of various immune cells such as T cells, B cells, macrophages, and dendritic cells. In this review, the main components in the tumor biological and immunological environment are discussed. The focus is on recent advances in nanoparticle-based drug delivery systems towards targets within the tumor microenvironment to improve cancer chemotherapy and immunotherapy.     

Interaction of Gc (vitamin-D binding protein) with membrane of activated natural cytolytic cells

Gc (a vitamin D binding protein) has been speculated to play a role in the function of immune response, yet, it has not been examined for its biological response properties. Therefore, we tried to (a) characterize the appearance of membrane bound Gc (mGc) on non-activated and mitogen activated lymphocytes as well as on Interleukin-2 activated killer cells and (b) examine the role of serum isolated human Gc on human blastogenesis and cytotoxicity (natural killing and lymphokine-activated killing). Our data suggests that activated cells possess a greater number of cells with mGc than non-activated cells and that as a biological response modified we find modulation of blastogenesis and cytotoxicity to be consistently but not very significantly down-regulated. Anti-Gc antibody was observed to significantly inhibit NK activity.     

骨髓基质细胞与可注射聚丙交酯多孔微载体共培养的体外实验研究

目的体外共培养骨髓基质细胞与聚丙交酯多孔微载体,研究微载体对骨髓基质细胞的增殖、凋亡等生理特性的影响,为细胞移植治疗提供一种安全可靠的载体。方法密度梯度离心法获取大鼠骨髓基质细胞,与可注射聚丙交酯多孔微载体在体外共培养,倒置显微镜及扫描电镜下观察细胞的生长及黏附在微载体的情况,并应用MTT法、流式细胞仪比较共培养、单独培养以及黏附在微载体的细胞的增殖及凋亡等生理特性。结果两者共培养时,骨髓基质细胞可长期存活、增殖,并可以黏附于微载体的表面及内部孔洞中,共培养时微载体对骨髓基质细胞的增殖、凋亡等特性无明显影响。结论可注射聚丙交酯多孔微载体是一种安全、可靠的细胞载体。     

Coptisine inhibits the malignancy of bladder carcinoma cells and regulates XPO1 expression

This work is performed to investigate the effect of coptisine (COP) on the malignant biological behaviors of bladder carcinoma cells and its underlying mechanism. Bladder carcinoma cell lines were treated with different concentrations of COP in vitro. Cell counting kit-8 (CCK-8), scratch healing assay, Transwell assay, and flow cytometry were used to detect cell growth, migration, invasion, and cell cycle progression. Bioinformatics analysis was performed to predict the molecular targets of COP. Quantitative real-time PCR and western blot were adopted to determine the expression levels of exportin 1 (XPO1) mRNA and protein, respectively. Gene set enrichment analysis was applied to predict the signaling pathways related to XPO1. This study showed that COP treatment markedly suppressed the malignant biological behaviors of bladder carcinoma cells. XPO1 was identified as a downstream molecular target of COP in bladder carcinoma, and COP treatment inhibited the expression of XPO1 in bladder carcinoma cell lines. Overexpression of XPO1 reversed the impacts of COP on the malignant biological behaviors of bladder carcinoma cells. COP treatment modulated the expression level of cyclin D1 and CYP450 via XPO1. In summary, COP represses the malignant biological behaviors of bladder carcinoma cells and regulates XPO1 expression, which is promising to be a complementary drug for bladder carcinoma treatment.     

alpha(v)beta(3) Integrin antagonists as inhibitors of bone resorption

The alpha(v)beta(3) integrin is a non-covalent, heterodimeric, cell-surface protein that is expressed with varying density on numerous cell types, including osteoclasts, vascular smooth muscle cells, endothelial cells and a variety of tumour cells. Functionally, alpha(v)beta(3) mediates a diverse range of biological events including the adhesion of osteoclasts to bone matrix, smooth muscle cell migration and angiogenesis. Specifically, there has been significant attention focused on the preparation of inhibitors of alpha(v)beta(3) for use as inhibitors of bone resorption, in recognition of the medical need for improved prevention and treatment of osteoporosis. Herein, we summarise the pertinent chemistry and biological advances in the medicinal design and biological evaluation of peptide and small molecule alpha(v)beta(3) antagonists as inhibitors of bone resorption.     

Arugomycin, a new anthracycline antibiotic. III. Biological activities of arugomycin and its analogues obtained by chemical degradation and modification

Biological activities of arugomycin and its analogues obtained by chemical degradation and modification were evaluated. Differences in the sugar moieties affected their biological activities including induction of differentiation of mouse Friend erythroleukemia cells and mouse myeloid leukemia cells, antitumor activities against sarcoma S-180, Ehrlich ascites carcinoma and P388 leukemia, and cytotoxicity against murine leukemia cells. Some relationships were found between the sugar moieties and biological activities.     

生物制剂治疗儿童风湿性疾病的进展

近十几年来,生物制剂被广泛应用于儿童风湿性疾病的治疗,并取得很好的疗效,但是在国内外获批的适应证并不相同,儿童适应证较少。根据药物作用机制不同,可以将生物制剂分为针对细胞因子类、针对B细胞类、针对T细胞类和针对细胞信号转导类。本文将生物制剂按照上述4个类型进行总结归纳,介绍作用机制和适应证。