microRNA-489 Plays an Anti-Metastatic Role in Human Hepatocellular Carcinoma by Targeting Matrix Metalloproteinase-7

Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of hepatocellular carcinoma (HCC). miR-489 was found to play either oncogenic or tumor suppressive roles in human cancers. Recent study reported that the levels of miR-489 in late recurrent HCC patients were evidently higher than that in early recurrent cases, suggesting that miR-489 may function as a tumor suppressive miRNA in HCC. Yet, the clinical value and biological function of miR-489 remain rarely known in HCC. Here, we presented that miR-489 level in HCC tissues was notably reduced compared to matched non-cancerous specimens. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of HCC patients. Accordingly, the levels of miR-489 were obviously down-regulated in HCC cells. Ectopic expression of miR-489 in HCCLM3 and MHCC97H cells prominently inhibits the migration and invasion of tumor cells and reduced lung metastases in vivo, while miR-489 knockdown increased these behaviors of HepG2 and MHCC97L cells. Mechanically, miR-489 negatively regulated matrix metalloproteinase-7 (MMP7) abundance in HCC cells. Herein, MMP7 was found to be a downstream molecule of miR-489 in HCC. An inversely correlation between miR-489 and MMP7 was confirmed in HCC specimens. MMP7 knockdown prohibited cell migration and invasion while MMP7 overexpression showed opposite effects on HCC cells. Furthermore, restoration of MMP7 expression could abrogate the anti-metastatic effects of miR-489 on HCCLM3 cells with enhanced cell migration and invasion. Altogether, miR-489 potentially acts as a prognostic predictor and a drug-target for HCC patients.     

抗菌肽改良设计及抗炎作用的研究进展

抗菌肽因其具有广谱抗菌活性、不容易引起抵抗性,被认为是先天免疫系统对抗微生物感染的多功能工具。然而,天然抗菌肽存在抗菌活性低、稳定性低、溶血性高等问题,使其较难应用于临床,所以研究人员对抗菌肽进行改良设计以期获得更高抗菌活性、更低溶血活性的新型抗菌肽。另外,天然抗菌肽作为一类免疫效应因子而被发现,其表现出的抑菌、免疫调节、内毒素中和等作用,使得研究人员对抗菌肽在抗炎作用的研究表现出极大的兴趣。就抗菌肽的药物设计方法及抗炎作用机制进行综述。     

三江源区生态系统和土壤保持服务对未来气候变化的响应特征

气候变化条件下的生态系统响应特征对生态系统服务的提升和生态环境保护具有重要意义。现有气候变化评估多以全球或区域大尺度研究为主,不适合局地小尺度。以2015年为基准,根据局地特征改进了综合顺序分类系统（CSCS）,模拟了未来不同温室气体排放模式下三江源地区自然植被分布,同时分析了植被覆盖度及土壤保持功能的时空变化。研究结果表明：①在2080年的不同排放情境下,三江源地区的降水和气温增长主要发生在生长季（5—9月）和半湿润地区,其中,高排放情境的增幅最大（42.21 mm和4.93℃）;②三江源地区潜在自然植被主要由草地转化为森林,植被覆盖度和土壤保持服务在不同排放情境下均呈现由西北向东南增加的趋势,与水热规律一致,其中高排放情境的增幅最大,低排放最小;③ 利用三江源地区原生裸地演替特点和多年NPP改进的CSCS模型,模拟精度提高了24%。研究成果为局地小尺度生态系统气候响应特征提供了必要的手段和规律认识。     

Different responses of CR(−) and CR(+) B cells to LPS stimulation

Proliferative response of B cells with or without CR [CR(+) or CR(?) B cells] was compared in their polyclonal response when they were stimulated with lipopolysaccharide (LPS). CR(+) B cells responded better in proliferation and more poorly in polyclonal antibody formation than did CR(?) B cells. The dissociation between proliferation and antibody formation in LPS response was not due to the shift of the time kinetics nor the exhaustion of the culture medium. T cells and macrophages did not take part in the dissociation, since macrophage depletion from nu/nu mouse spleen cells could not modify the dissociation. The polyclonal antibody response of CR(?) B cells was more resistant to irradiation than that of CR(+) B cells. These results suggest that among LPS-responsive B cells there are CR(?) B-cell subset(s) more mature than CR(+) B cells.     

The carbohydrate of human thrombin: Structural analysis of glycoprotein oligosaccharides by mass spectrometry

The carbohydrate structure of human thrombin has been determined by direct probe mass spectrometry of the oligosaccharides released by trifluoroacetolysis from the asialo glycoprotein. The free oligosaccharides were studied as permethylated and N-trifluoroacetylated oligosaccharide alditols. The structure was confirmed by sequential exoglycosidase digestion of intact thrombin and sugar and methylation analysis of the oligosaccharides by gas-liquid chromatography-mass spectrometry. The results indicate the following structure:

with Fuc present on only about 50% of the oligosaccharides.     

Lymphokine and phorbol (PMA) regulation of complement (C2) synthesis using U937

Human monocytes synthesize large amounts of the second complement component (C2) after incubation with a T-lymphocyte product called monocyte complement stimulator (MCS). The human monocyte-like cell line, U937, also synthesizes C2 and can be stimulated to increase this synthesis by lymphokine-rich culture supernates. Additionally, phorbol myristate acetate (PMA), an agent which induces maturational changes in other macrophage-like cell lines, also stimulates C2 synthesis by U937 cells. Lymphokine and PMA stimulation of C2 secretion by U937 are both reversibly inhibitable by cycloheximide. At optimal concentrations for stimulation of C2 synthesis, PMA inhibits [³H]thymidine incorporation by U937 indicating that increased C2 is not due to increased numbers of U937 cells.     

Mycologie medicale dans l'ouest de la France: Contribution du service de Parasitologie de l'Universite de NANTES (1963–1973)

Résumé Le service de Parasitologie de l'Université de NANTES s'est intéressé aux problèmes de Mycologie hospitalière, d'épidémiologie des mycoses ainsi que d'expérimentation sur les affinités fongiques, à l'échelon régional, et de 1963 à 1973.La contribution clinique a porté essentiellement sur les levuroses étudiées soit au niveau des cavités buccales irradiées, soit chez les malades des services de Réanimation où l'interprétation du rôle pathogène de Candida parapsilosis nécessite des épreuves immunologiques.Nous avons décrit une forme de Blastomycose chéloïdienne à Aureobasidium pullulans.Nos études morphologiques ont surtout porté sur l'observation au microscope électronique à balayage des ultrasculptures présentées par les champignons kératinophiles, ce qui nous a permis de distinguer les différentes espèces du complexe Microsporum gypseum. Il ne semble pourtant pas que cette technique d'observation permette de résoudre tous les problèmes. La conservation des Dermatophytes en eaudistillée par la méthode de Castellani s'est révélée particulièrement remarquable: une souche de M. gypseum a été récupérée après 6 ans de conservation par ce procédé.Notons, en matière d'épidémiologie la prédominance de Trichophyton rubrum sur T. mentagrophytes, survenue récemment: la recrudescence passagère d'Epidermophyton floccosum; la présence d'Arthroderma simii sur une plage. Une étude des champignons kératinophiles telluriques du massif armoricain a porté sur près de 3000 échantillons de terre, ce qui a permis de retrouver, assez rarement d'ailleurs, Arthroderma benhamiae.Nos expérimentations ont porté sur les réponses sérologiques et histologiques de lapins à une imprégnation aspergillaire par instillation intra-trachéale: les résultats obtenus ont été comparés aux examens sérologiques obtenus chez l'homme atteint d'aspergillose. Enfin, nous avons remarqué que le contact levures-cellules sarcomateuses opéré in vitro permet aux levures d'acquérir un pouvoir immunisant antitumoral par emprunt antigénique. La création d'un service de Parasitologie, Mycologie et Immunologie Parasitaire à l'Unité d'Enseignement et de Recherche des Techniques Médicales de NANTES nous a permis non seulement d'aborder les problèmes du diagnostic biologique des mycoses humaines, mais aussi d'entreprendre des enquêtes épidémiologiques dans la région nantaise ainsi que des expériences sur les affinités fongiques.

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Studies on non-H-2-linked lymphocyte-activating determinants. IV. Ontogeny of the Mls product on murine B cells.

The minor lymphocyte stimulating (Mls) locus codes for lymphocyte activating determinants (LADs) on murine B lymphocytes, but not T lymphocytes. This observation was strengthened by a series of techniques which allow deletion and addition of T and B cells. These included the use of cytotoxic antisera such as anti-Thy 1.2, anti-MTLA, anti-MBLA, and complement, and the use of a goat anti-μ antisera, and finally the use of a fluorescence activated cell sorter (FACS).The studies in this report document the organ distribution and the ontogenetic appearance of the surface LADs on the surface of B lymphocytes from DBA/2N (H-2^d, Mls^a) and CBA/J (H-2^k, Mls^d) mice. Adult-like ability to stimulate H-2 identical BALB/c (H-2^d, Mls^b) and C3H/He (H-2^k, Mls^c) responder cells appeared at about 4–5 weeks of age. Inability of neonatal cells to induce an Mls-defined MLC was found not to be due to a low frequency of B lymphocytes or to the presence of suppressor cells, but due to the absence of the Mls-coded LADs on their surface. These data support the concept that the Mls-coded LADs are present on adult B lymphocytes and are specific markers of B-cell differentiation, which is preceded by membrane IgM and the δ homologue of human IgD, Ia, and the receptor for the third component of complement.     

Isolation of synaptonemal complexes from hamster spermatocytes

Nuclei from Chinese hamster testicular cells in suspension were prepared in a sucrose gradient. Following the basic procedure of Blobel and co-workers for separating a fibrous lamina-nuclear pore complex, synaptonemal complexes (SCs) from spermatocytes were isolated free of other nuclear structures, except for fibrillar tufts at the attachment plaques in which annuli were observed. All the major morphological components of the SC appeared to be intact, showing that the structure could survive the procedure and was not dispersed by the removal of DNA with DNase and solubilization of membranes and some proteins with Triton X-100. Isolated sex bodies were also well preserved, as were various structures from other cell types in the mixed cell suspension, such as spermatid manchettes, acrosomal ‘ghosts’, axonemes, etc. While no nuclear matrix was found associated with autosomal SCs, a residual material was present in the sex body, in which the X and Y axes were embedded. The results indicate the feasibility of isolating and fractionating SCs from testicular cell suspensions enriched for pachytene spermatocytes. The association between SC attachment plaques and annuli that is seen in spreads of whole nuclei persists through the isolation procedure and implies an integrated structural relationship.