Pyrrole and furan oligoglycosides from the starfish Asterina batheri and their inhibitory effect on the production of pro-inflammatory cytokines in lipopolysaccharide-stimulated bone marrow-derived dendritic cells

Three new pyrrole oligoglycosides, astebatheriosides A–C (1–3), and a new furan oligoglycoside, astebatherioside D (4), were isolated from the starfish Asterina batheri by various chromatographic methods. Their structures were elucidated by spectroscopic and chemical methods. Compounds 2, 3, and 4 moderately inhibited IL-12 p40 production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) with IC₅₀ values of 36.4, 31.6, and 22.8 μM, respectively.     

Comparison of population genetic patterns in two widespread freshwater mussels with contrasting life histories in western North America

We investigate population genetic structuring in Margaritifera falcata, a freshwater mussel native to western North America, across the majority of its geographical range. We find shallow rangewide genetic structure, strong population‐level structuring and very low population diversity in this species, using both mitochondrial sequence and nuclear microsatellite data. We contrast these patterns with previous findings in another freshwater mussel species group (Anodonta californiensis/A. nuttalliana) occupying the same continental region and many of the same watersheds. We conclude that differences are likely caused by contrasting life history attributes between genera, particularly host fish requirements and hermaphroditism. Further, we demonstrate the occurrence of a ‘hotspot’ for genetic diversity in both groups of mussels, occurring in the vicinity of the lower Columbia River drainage. We suggest that stream hierarchy may be responsible for this pattern and may produce similar patterns in other widespread freshwater species.     

Functional consequences of retro-inverso isomerization of a miniature protein inhibitor of the p53–MDM2 interaction

Peptide retro-inverso isomerization is thought to be functionally neutral and has been widely used as a tool for designing proteolytically stable d-isomers to recapitulate biological activities of their parent l-peptides. Despite success in a wide range of applications, exceptions amply exist that clearly defy this rule of thumb when parent l-peptides adopt an α-helical conformation in their bound state. The detrimental energetic effect of retro-inverso isomerization of an α-helical l-peptide on its target protein binding has been estimated to be 3.0–3.4 kcal/mol. To better understand how the retro-inverso isomer of a structured protein works at the molecular level, we chemically synthesized and functionally characterized the retro-inverso isomer of a rationally designed miniature protein termed stingin of 18 amino acid residues, which adopts an N-terminal loop and a C-terminal α-helix stabilized by two intra-molecular disulfide bridges. Stingin emulated the transactivation peptide of the p53 tumor suppressor protein and bound with high affinity and via its C-terminal α-helix to MDM2 and MDMX—the two negative regulators of p53. We also prepared the retro isomer and d-enantiomer of stingin for comparative functional studies using fluorescence polarization and surface plasmon resonance techniques. We found that retro-inverso isomerization of l-stingin weakened its MDM2 binding by 720 fold (3.9 kcal/mol); while enantiomerization of l-stingin drastically reduced its binding to MDM2 by three orders of magnitude, sequence reversal completely abolished it. Our findings demonstrate the limitation of peptide retro-inverso isomerization in molecular mimicry and reinforce the notion that the strategy works poorly with biologically active α-helical peptides due to inherent differences at the secondary and tertiary structural levels between an l-peptide and its retro-inverso isomer despite their similar side chain topologies at the primary structural level.¹     

Synthesis and biological evaluation of new chlorin derivatives as potential photosensitizers for photodynamic therapy

Three new water-soluble chlorin derivatives 3, 5 and 8 for potential use as photosensitizers in photodynamic therapy (PDT) for cancer were synthesized from photoprotoporphyrin IX dimethyl ester (1). The in vivo biodistribution and clearance of chlorin derivatives 3, 5 and 8 were investigated in tumor-bearing mice. Iminodiacetic acid derivative 8 showed the greatest tumor-selective accumulation among the new chlorin derivatives with maximum accumulation in tumor tissue at 3 h after intravenous injection and rapid clearance from normal tissues within 24 h after injection. The in vivo therapeutic efficacy of PDT using 8 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3 h after injection of 8. Tumor growth was significantly inhibited by PDT using 8. These results indicate that iminodiacetic acid derivative 8 is useful as a new photosensitizer to overcome the disadvantages of photosensitizers that are currently in clinical use.     

ERK介导的炎性反应参与肾缺血再灌注损伤

目的研究小鼠肾缺血再灌注损伤的发病机制。方法建立小鼠肾缺血再灌注损伤模型。12只雄性C57BL／6随机分为2个组（n=6）,分别为假手术组（Sham）,肾缺血再灌注损伤模型组（IRI）。IRI组血管夹夹闭左肾动脉,置于32℃温箱后1h松开血管夹,去除右肾。Sham组操作同上,但不夹闭左肾动脉。再灌注24h后处死小鼠,收集血清和肾脏标本。测定血清肌酐（Cr）和血尿素氮（BUN）。PAS染色后显微镜下观察肾脏形态学变化,Western印迹分析ERK、p-ERK的表达,PCR检测MCP-1、IFN-γ。结果与假手术组（Sham）相比,IRI组血清肌酐、血尿素氮明显升高,病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显,还可观察到炎性细胞浸润明显增加。ERK、p-ERKWestern印迹结果PCR显示MCP-1、TNF-α也明显上调,但ERK表达不变。结论在肾缺血再灌注中,ERK激活介导的炎性后府可能参与了肾扣伤。     

A peptide receptor-based bioelectronic nose for the real-time determination of seafood quality

We herein report a peptide receptor-based bioelectronic nose (PRBN) that can determine the quality of seafood in real-time through measuring the amount of trimethylamine (TMA) generated from spoiled seafood. The PRBN was developed using single walled-carbon nanotube field-effect transistors (SWNT-FETs) functionalized with olfactory receptor-derived peptides (ORPs) which can recognize TMA and it allowed us to sensitively and selectively detect TMA in real-time at concentrations as low as 10fM. Utilizing these properties, we were able to not only determine the quality of three kinds of seafood (oyster, shrimp, and lobster), but were also able to distinguish spoiled seafood from other types of spoiled foods without any pretreatment processes. Especially, the use of small synthetic peptide rather than the whole protein allowed PRBNs to be simply manufactured through a single-step process and to be reused with high reproducibility due to no requirement of lipid bilayers. Furthermore, the PRBN was produced on a portable scale making it effectively useful for the food industry where the on-site measurement of seafood quality is required.     

Purification and Properties of Allothreonine Aldolase from Maise Seedlings

In order to elucidate the structure-activity relationship of griseofulvin (1), (±)-6′-demethyl analog (3), 2′-demethoxy-6′-demethyldihydro analog (4), (±)-dechloro-6′-ethyl analog (5), (±)-dechloro-6′-epi-ethyl analog (6), (±)-6′-ethyl analog (7) and (±)-6′-epi-ethyl analog (8) were synthesized by a Diels-Alder cycloaddition of alkylidene ketones (16, 17, 18, 19 and 20) with modified 1,3-butadienes (21 or 22). Their biological activities were examined against fungi.     

EZH2在乳腺癌中的表达及其临床意义

目的 探讨EZH2在乳腺癌中的表达及其临床意义.方法 用免疫组化的方法研究105例乳腺癌中EZH2蛋白表达情况,并进一步探讨其与乳腺癌临床病理因素及其预后的关系.结果 EZH2蛋白在乳腺癌组织中表达明显高于乳腺良性疾病,其表达与患者年龄、肿瘤大小、TNM分期、PR和c-erbB-2表达无关(P＞0.05),与淋巴结转移、病理组织学分级、ER表达及乳腺癌预后相关(P＜0.05).EZH2蛋白表达在三阴性乳腺癌中表达明显高于非三阴性乳腺癌(P＜0.05).结论 EZH2在乳腺癌淋巴结转移及侵袭中扮演一定的角色,其与乳腺癌预后相关,与ER阴性的乳腺癌发生发展有关.     

食用菌加工产业研究现状与前景

食用菌加工是利用物理、化学和生物方法处理食用菌子实体或菌丝体,生产食用菌制品。它可以解决食用菌从生产到商品出售所存在的时间矛盾,提高食用菌的商品价值。详细介绍了食用菌的干制加工、盐渍加工及罐藏加工技术,概括了食用菌深加工产业的发展现状及研究进展,提出了对食用菌加工的展望。