视黄素诱导的癌细胞凋亡及其对癌细胞生长抑制的相关性

以不同的受体选择性视黄素处理乳腺癌细胞，通过荧光显微术、ＴｄＴ测定和细胞生长测定，分析视黄素诱导的癌细胞凋亡及其对癌细胞生长抑制的相互关系；将受体ＲＡＲα基因转染乳腺癌ＭＢ－２３１细胞，发现受体转染与细胞凋亡诱导有关；ＲＡＲ和ＲＸＲ受体选择性视黄素联合使用，对诱导癌细胞凋亡和抑制癌细胞生长具有加强作用．结果证实，视黄素能够诱导乳腺癌细胞的细胞凋亡，并与抑制癌细胞的恶性生长相一致，这可能是视黄素抗癌作用的机制之一．     

家蝇蛹血淋巴抗菌活性的诱导及相关蛋白/多肽的表达规律

对家蝇蛹血淋巴的抗菌活性进行了诱导，并用统计学逐步回归的方法和多项式回归的方法确定了抗菌相关蛋白／多肽，研究了其表达规律。结果表明，针刺、带菌针刺和超声波均能诱导家蝇蛹产生抗G^ 球菌的物质，而对G^-杆菌无效。在分子量低于18000的蛋白／多肽中，有两种物质（R5、R6）对抑菌活性有显著影响，它们的表观分子量分别在12000和7650左右，这两种蛋白／多肽均在诱导下表达。其中，R6对抑菌活性有极显著正贡献，而R5对抑菌活性有显著负贡献，推测R5为细胞生长促进因子。     

可溶性人TRAIL蛋白诱导肝癌细胞的凋亡

为研究可溶性人TRAIL蛋白（sTRAIL）对肝癌细胞株SMMC7721的生长抑制效应及凋亡诱导作用．采用显微镜、台盼蓝排斥试验、MTT比色试验、TUNEL法和DNA断裂实验等方法检测细胞增殖和细胞凋亡．通过显微镜观察到核染色质凝集等凋亡的形态学变化,台盼蓝排斥试验、MTT比色试验结果显示,sTRAIL蛋白可显著抑制SMMC7721细胞的生长和增殖,并且TUNEL法检测到经sTRAIL处理后的细胞凋亡指数与对照比较有显著差异,DNA断裂实验亦观察到典型的DNA梯形条带,这些结果提示sTRAIL可诱导肝癌细胞株SMMC7721发生凋亡,具有抗肝癌的作用．     

茶氯香酰胺脂质体对人肝癌细胞生长和迁移的抑制作用

以茶氯香酰胺脂质体(TClC-L)为研究对象,研究其对人肝癌细胞(SMMC7721)生长和迁移的影响,并且探索其作用的分子机制,为研发抗肝癌新药提供科学依据.应用MTT法检测TClC-L对SMMC7721细胞生长的影响;应用划痕法和细胞流式分别检测TClC-L对SMMC7721细胞迁移和死亡的影响;应用Hoechst 33258染色检测SMMC7721细胞凋亡形态学变化;应用Western blotting技术检测TClC-L对SMMC7721细胞生长、凋亡和迁移密切相关蛋白表达的影响和其可能作用的分子机制.结果显示,TClC-L对SMMC7721细胞生长有显著的抑制作用,显示出剂量和时间的依赖性关系; TClC-L能够显著地降低SMMC7721细胞的迁移能力,促进其凋亡; TClC-L显著上调抑制肝癌细胞生长和诱导癌细胞凋亡的相关蛋白因子Bax、Caspase-3、PARP和迁移抑制因子E-cadherin蛋白的表达水平,下调促进细胞生长和迁移以及抗凋亡的相关蛋白因子Bcl-2、HGF、cMet、NF-κB、MMP9、VEGFR2、c-Myc蛋白的表达水平. TClC-L抑制人肝癌细胞SMMC7721的生长和迁移作用的分子机制涉及到HGF/c-Met/VEGFR-NF-κB信号通路.     

一氧化氮供体的合成及其抗菌性能研究

一氧化氮供体S-亚硝基-N-乙酰基-DL-青霉胺（SNAP）对微生物生长具有显著的抑制效果. 为了进一步验证SNAP对微生物抗抑作用，本文通过亚硝化反应制备得到SNAP固体，并基于不同SNAP浓度验证其抗菌性能. 结果表明：（1）通过核磁和紫外表征, 我们成功制备得到SNAP；（2）SNAP对大肠杆菌、金黄色葡萄球菌（耐药/非耐药）和淋球菌均表现出明显的抑制作用且具有浓度依赖性，表明SNAP具有广谱抗菌特性. SNAP优良的抗菌特性使其及一氧化氮供体在抗抑菌领域有着广阔的应用前景.     

异硫氰酸异丁酯抑制肝癌细胞HepG2生长的效应与机理

为了探究异硫氰酸异丁酯(isobutyl isothiocyanate)对肝癌细胞HepG2的生长抑制效应及其分子机制，该研究通过MTT实验检测化合物对细胞的生长抑制率，计算出IC50值为3.5 μg·mL－1；通过流式细胞技术检测发现0.437 μg·mL－1以上浓度的化合物能诱导HepG2细胞凋亡；通过划痕实验检测发现0.875 μg·mL－1以上浓度的化合物能抑制细胞迁移；进一步通过生物信息学分析表明异硫氰酸异丁酯的靶蛋白可能为巨噬细胞迁移抑制因子(MIF)，且HepG2细胞中MIF表达量高于低敏感株.免疫印迹实验也进一步发现化合物不仅能够抑制蛋白酪氨酸激酶2/信号转导子和转录激活子3(JAK2/STAT3)信号通路的激活，还能下调p53蛋白表达.研究结果表明，异硫氰酸异丁酯可能通过靶向HepG2细胞中的MIF蛋白，影响MIF与其受体CD74相互作用，从而下调p53蛋白表达，阻滞细胞周期的正常进行，诱导细胞凋亡，对肝癌具有特异性的抑癌潜力.     

石榴鞣花酸提取物对人肺癌细胞A549凋亡的诱导

为了探讨石榴鞣花酸提取物(EAEFP)诱导人肺癌细胞凋亡的作用及其可能的作用途径,以A549肺癌细胞为研究对象,采用四甲基偶氮唑盐(MTT)比色法评估EAEFP对A549肺癌细胞的抑制效果。通过4′,6-二脒基-2苯基吲哚(DAPI)染色法观察EAEFP对A549肺癌细胞形态的作用。利用流式细胞仪测定EAEFP对A549肺癌细胞分裂周期和细胞凋亡的影响。研究结果表明:石榴鞣花酸提取物能显著抑制A549肺癌细胞的生长。随着石榴鞣花酸提取物质量浓度的增加,A549肺癌细胞形态发生明显变化,细胞周期被阻滞在G1期,细胞凋亡率显著增加。石榴鞣花酸提取物能抑制A549肺癌细胞增殖,通过阻滞细胞周期从而诱导细胞凋亡。     

癌症的研究策略与方法

癌症是一种严重威胁人类生命与健康的恶性疾病.目前还没有找到有效的方法来治愈癌症.从癌症的发现、治疗及预防史对癌症的产生原因、研究进程和治疗方法等进行综述,并提出了癌细胞很可能是高等动物细胞回复突变成"原始真核动物细胞"的理论.治疗癌症必须找出癌细胞与正常细胞在代谢、生长、繁殖及调控上的差异,从生命机理上理解癌症,从而达到根治的目的.     

人工养殖水蛭前景诱人

在国际医学领域，水蛭的医用价值被广泛引起重视，水蛭体内含有多种药用成份。对消除手术引起的后遗症，防止血液过早凝固等都有重要作用，许多国家的药物学家纷纷利用水蛭开发各种药物，取得了良好的效果。目前我国不少地方已开展了水蛭的人工养殖。水蛭生命力强，繁殖极快，易于饲养管理，且人工养殖场地可大可小，具有投资少，见效快，效益高的特点，是一项新兴的养殖项目。水蛭生活于坑塘里，雌雄同体，异体受精，一次产卵上千粒。水娃易饲养，食性广，主食水中微生物和浮藻，人工养殖可用畜禽血拌饲料、草粉等，而且生长快无病害。每平…     

TGF-β1对不同肺癌细胞生物学行为的影响

用重组人转化生长因子β1（TGF－β1）处理不同的肺癌细胞95C、95D，研究TGF－β1对不同肺癌细胞迁移、粘附等生物学行为的影响，从而揭示肿瘤细胞的恶性行为机制。按Dean Sheppard方法测定细胞迁移能力；用划痕法和琼脂滴法测定细胞迁移能力；同时还测定了各肺癌细胞的铺展。结果表明：95C的迁移能力、细胞铺展率和增殖率最高，95D次之；用TGF－β1处理后，95C、95D与Fn的粘附率和铺展率较对照组都有显著增加，TGF－β1处理24、48h后可以明显增加两株肺癌细胞的迁移率。TGF－β1处理对两株肺癌细胞的增殖和生长无显著影响。提示不同肺癌细胞迁移和粘附能力存在差异，TGD－β1对肺癌细胞生长学行为存在显著影响。TGF－β1对所介导的信号转导通路起着重要的调控作用，从而影响肺癌细胞的若干生物学行为。     

广东省高校人才培养与区域经济协同发展研究

结合广东省高校人才培养的现状,通过对广东省高校人才培养和区域经济增长进行协整分析、误差修正模型和格兰杰因果检验,结果表明,广东高校人才培养与经济增长存在长期、短期均衡关系,经济增长是高校人才培养的Granger原因.     

论韩江流域的鳄鱼分布问题

本文提出:1.鳄鱼曾经在韩江河谷地带生存.2.韩江鳄鱼有两种,一种为湾鳄,生活在南海海岸地带;另一种是马来鳄,栖息在河谷内部.3.韩江流域的鳄鱼杀绝的年代在明朝初期,即550年之前.     

A mutant protein kinase C that can transform fibroblasts

Expression of normal protein kinase C (PKC) isoenzymes in fibroblasts has been shown to alter growth regulation but has failed to induce complete transformation of the recipient cells. Here we report on a murine ultraviolet-induced fibrosarcoma cell line which has an unusual PKC subcellular distribution with 87% of the PKC activity associated with the membrane. We have cloned and sequenced the alpha-PKC complementary DNA from ultraviolet-induced-fibrosarcoma cells and from mouse Balb/c brain and found four point mutations in the fibrosarcoma PKC, of which three are in the highly conserved regulatory domain and one is in the conserved region of the catalytic domain. Expression of this mutant alpha-PKC gene in normal Balb/c 3T3 fibroblasts results in a fibrosarcoma-like PKC membrane localization and in cell transformation, as judged by their formation of dense foci, anchorage-independent growth and ability to induce solid tumours when inoculated into nude mice. By contast, transfectants expressing the normal alpha-PKC cDNA do not display a morphology typical of malignant transformed cells and fail to induce tumours in vivo. These findings demonstrate that point mutations in the primary structure of PKC modulate enzyme function and are responsible for inducing oncogenicity.     

芳樟醇对莓实假单胞菌的抑菌活性及机制

食品在生产、运输和贮藏过程中易受致病菌污染而引起食源性疾病。芳樟醇具有抗菌作用,但其作用机制尚不明确。研究芳樟醇对莓实假单胞菌的抑菌活性及作用机制,可为其作为天然食品防腐剂的开发提供理论依据。通过测定最小抑菌浓度、绘制细菌生长曲线评价芳樟醇的抑菌活性；通过扫描电子显微镜观察、结晶紫染色实验、二乙酸荧光素染色实验以及测定电导率、核酸泄漏、呼吸代谢活力和呼吸链脱氢酶活性的变化探究芳樟醇的抑菌机制。结果表明:芳樟醇对莓实假单胞菌具有较强的抑制作用,最小抑菌浓度为1.5mL/L；芳樟醇能破坏莓实假单胞菌细胞的结构形态和细胞膜的完整性,增加细胞膜的通透性,导致胞内物质泄漏、膜外电导率升高；能抑制呼吸代谢活力和呼吸链脱氢酶活性,破坏呼吸链,导致胞内代谢紊乱。研究认为,芳樟醇可通过破坏莓实假单胞菌的细胞结构和抑制其呼吸代谢而发挥抑菌作用,有望作为天然防腐剂应用于食品的防腐保鲜。     

Template-directed synthesis of a genetic polymer in a model protocell

Contemporary phospholipid-based cell membranes are formidable barriers to the uptake of polar and charged molecules ranging from metal ions to complex nutrients. Modern cells therefore require sophisticated protein channels and pumps to mediate the exchange of molecules with their environment. The strong barrier function of membranes has made it difficult to understand the origin of cellular life and has been thought to preclude a heterotrophic lifestyle for primitive cells. Although nucleotides can cross dimyristoyl phosphatidylcholine membranes through defects formed at the gel-to-liquid transition temperature, phospholipid membranes lack the dynamic properties required for membrane growth. Fatty acids and their corresponding alcohols and glycerol monoesters are attractive candidates for the components of protocell membranes because they are simple amphiphiles that form bilayer membrane vesicles that retain encapsulated oligonucleotides and are capable of growth and division. Here we show that such membranes allow the passage of charged molecules such as nucleotides, so that activated nucleotides added to the outside of a model protocell spontaneously cross the membrane and take part in efficient template copying in the protocell interior. The permeability properties of prebiotically plausible membranes suggest that primitive protocells could have acquired complex nutrients from their environment in the absence of any macromolecular transport machinery; that is, they could have been obligate heterotrophs.     

Antibacterial agents specifically inhibiting lipopolysaccharide synthesis

The spread of antibiotic resistance in Gram-negative bacteria has sustained a continuing search for new agents with antibacterial activity against this important class of bacterial pathogen. Because the biosynthesis of lipopolysaccharide (LPS) is unique to Gram-negative bacteria and required by them for growth and virulence, attempts have been made to discover or design antibacterial agents acting at this site; however, no such agents have so far been developed. We now present definitive experimental data documenting design of the first member of the class of antibacterial compounds which specifically inhibit LPS synthesis. The target enzyme is 3-deoxy-D-manno-octulosonate cytidylytransferase (CMP-KDO synthetase), a cytoplasmic enzyme which activates 3-deoxy-D-manno-octulosonate (KDO) for incorporation into LPS. A specific inhibitor of CMP-KDO synthetase, alpha-C-(1,5-anhydro-7-amino-2,7-dideoxy-D-manno-heptopyranosyl)-carboxy late was designed using results of our studies of the purified enzyme. LPS synthesis ceased and lipid A precursor accumulated, causing growth stasis and perturbation of outer membrane structure and function, following delivery of the inhibitor to the intracellular target by a peptide carrier. Antibacterial action required an intact oligopeptide permease system and specific intracellular aminopeptidase activity to release inhibitor from the peptide prodrug.     

Induction of hair growth by implantation of cultured dermal papilla cells

Mammalian hairs are formed by differentiation and keratinization of cells produced in the epidermal matrix (Figs 3, 4). Using the rodent vibrissa follicle as a model, transplantation studies have shown that the dermal papilla, a discrete population of specialized fibroblasts, is of prime importance in the growth of hair. Papillae induce hair growth when implanted into follicles and can interact with skin epidermis to form new hair follicles. When grown in culture, papilla cells display singular morphological and behavioural characteristics compared with connective tissue cells from other skin sources. We report here that serially cultured adult papilla cells can induce the growth of hair when implanted into follicles which otherwise would not grow hairs. This finding presents an opportunity to characterize properties distinguishing the papilla cell population from other skin fibroblasts, and, more specifically, those which control hair growth. The eventual application of this work to human hair replacement techniques can also be envisaged.     

鳖鳃腺炎与腐皮病并发症的组织病理学研究

对鳃腺炎与腐皮病并发症的鳖的肝、脾、肾、肺、肠和精巢等6种器官进行病理组织学切片,并与健康鳖的相应器官组织进行比较。结果显示：病鳖的器官组织出血,组织细胞出现肿胀、坏死、崩解,最终造成全生组织损伤;血管腕扩大,血管壁严重受损,内皮细胞坏死脱落;血管内及血液中的大量红细胞变形、破裂、溶解。此外,还对病鳖的4种组织匀浆液初步进行了抑菌实验。     

Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions

Leprosy is a spectral disease in which immune responses to Mycobacterium leprae correlate with the clinical, bacteriological and histopathological manifestations of disease, so study of its pathology provides insights into immunoregulatory mechanisms in man. At the tuberculoid pole, patients have few lesions in the skin which contain rare organisms and are able to mount strong cell-mediated immune responses to M. leprae antigens. In contrast, at the lepromatous pole, patients have disseminated skin lesions containing large numbers of acid-fast bacilli and are selectively unresponsive to antigens of M. leprae. M. leprae-induced suppressor cells derived from peripheral blood have been reported to be active in vitro, yet their in vivo significance has remained unclear. Because the focal point of the immune response to M. leprae is the skin lesion consisting of lymphocytes and macrophages, we have recently developed methods for isolating lymphocytes from skin biopsies of leprosy patients. We report here that two T8 clones derived from lepromatous leprosy skin biopsies, in the presence of lepromin, suppress concanavalin A (Con-A) responses both of peripheral blood mononuclear cells and of T4 clones in an HLA-D (HLA, histocompatibility locus antigen)-restricted manner. Moreover, these T8 clones suppressed responses of HLA-D-matched, but not HLA-D-mismatched antigen-responsive T4 clones to M. leprae antigens, indicating that T-cell suppression is major histocompatibility complex (MHC)-restricted at some level in man.     

Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes

Evolution can follow predictable genetic trajectories, indicating that discrete environmental shifts can select for reproducible genetic changes. Conspecific individuals are an important feature of an animal's environment, and a potential source of selective pressures. Here we show that adaptation of two Caenorhabditis species to growth at high density, a feature common to domestic environments, occurs by reproducible genetic changes to pheromone receptor genes. Chemical communication through pheromones that accumulate during high-density growth causes young nematode larvae to enter the long-lived but non-reproductive dauer stage. Two strains of Caenorhabditis elegans grown at high density have independently acquired multigenic resistance to pheromone-induced dauer formation. In each strain, resistance to the pheromone ascaroside C3 results from a deletion that disrupts the adjacent chemoreceptor genes serpentine receptor class g (srg)-36 and -37. Through misexpression experiments, we show that these genes encode redundant G-protein-coupled receptors for ascaroside C3. Multigenic resistance to dauer formation has also arisen in high-density cultures of a different nematode species, Caenorhabditis briggsae, resulting in part from deletion of an srg gene paralogous to srg-36 and srg-37. These results demonstrate rapid remodelling of the chemoreceptor repertoire as an adaptation to specific environments, and indicate that parallel changes to a common genetic substrate can affect life-history traits across species.