眼镜蛇毒组分C的抗瘤活性及其对肿瘤细胞存活率的影响

目的观察眼镜蛇毒组分Ｃ对ＢＡＬＢ／Ｃ型小鼠腹水型肝癌Ｈ２２的抑瘤作用及其体外对肝癌Ｈ２２细胞存活率的直接影响。方法通过半体内实验,观察眼镜蛇毒组分Ｃ对小鼠腹水型肝癌Ｈ２２的抑瘤率;通过细胞培养,以细胞存活率为指标观察中华眼镜蛇毒组分Ｃ对ＢＡＬＢ／Ｃ型小鼠腹水型肝癌Ｈ２２细胞在体外的直接杀伤作用。结果眼镜蛇毒组分Ｃ能明显抑制ＢＡＬＢ／Ｃ型小鼠腹水型肝癌Ｈ２２细胞的生长,其抑瘤作用随剂量增大而增强,ＩＣ５０为９５ｍｇ／Ｌ。在体外,眼镜蛇毒组分Ｃ的浓度对ＢＡＬＢ／Ｃ型小鼠腹水型肝癌Ｈ２２细胞存活率的影响随其作用剂量的增大而增强,ＩＣ５０为９ｍｇ／Ｌ;同时,这种影响还随其作用时间的延长而增强。结论眼镜蛇毒组分Ｃ对ＢＡＬＢ／Ｃ型小鼠腹水型肝癌Ｈ２２有显著的抑瘤作用。     

Glycoproteomic analysis of two mouse mammary cell lines during transforming growth factor (TGF)-β induced epithelial to mesenchymal transition

Background  

TGF-β acts as an antiproliferative factor in normal epithelial cells and at early stages of oncogenesis. However, later in tumor development TGF-β can become tumor promoting through mechanisms including the induction of epithelial-to-mesenchymal transition (EMT), a process that is thought to contribute to tumor progression, invasion and metastasis. To identify EMT-related breast cancer therapeutic targets and biomarkers, we have used two proteomic approaches to find proteins that change in abundance upon the induction of EMT by TGF-β in two mouse mammary epithelial cell lines, NMuMG and BRI-JM01.     

Exogenous and endogenous TLR ligands activate anti-chromatin and polyreactive B cells

Autoreactive B cells may become activated in a T-independent manner via synergistic engagement of the BCR and TLRs. Using the VH3H9 Ig H chain transgene to track anti-chromatin B cells, we demonstrate that VH3H9/Vlambda1 anti-chromatin B cells proliferate in response to stimulatory oligodeoxynucleotides containing CpG motifs, suggesting that these autoreactive B cells are responsive to TLR9 signaling. Strikingly, some VH3H9 B cells, but not the well-characterized VH3H9/Vlambda1 B cells, proliferate spontaneously in culture medium. This proliferation is blocked by inhibitory CpG oligodeoxynucleotides, implicating the TLR9 (or possibly TLR7) pathway. Most hybridomas generated from the proliferating cells are polyreactive, and one exhibits binding to nuclear Ags but not to the other Ags tested. Thus, B cells carrying autoreactive and/or polyreactive specificities may be susceptible to T cell-independent activation via dual engagement of the BCR and TLRs.     

Degradation of polycyclic aromatic hydrocarbons dissolved in Tween 80 surfactant solutions by Sphingomonas paucimobilis EPA 505

The degradation rates of mixtures of pyrene (PYR), fluoranthene (FLA), and phenanthrene (PHE) by Sphingomonas paucimobilis EPA 505 were measured in the presence of the nonionic surfactant Tween 80. For strain EPA 505, FLA and PHE are growth substrates, while PYR is not. Linear degradation rates ranging from 0.05 to 2.2 mg x L(-1) x h(-1) were observed for FLA, PYR, and PHE at approximately 10(7) colony-forming units (CFU)/mL. At lower biomass, PYR degradation exhibited lognormal degradation. The degradation rates of PYR, FLA, and PHE increased with increasing biomass and substrate concentration. At high FLA concentrations, FLA degradation rates were faster in the presence of surfactant than in the absence of surfactant, suggesting that some of the FLA was transported directly into the cell from the micellar phase. In mixtures, PHE was the preferred substrate and was utilized first, followed by FLA and then PYR. Once the competing substrates were degraded, the remaining substrate was degraded at the same rate or faster than the rate found in the single-substrate system. Based on the results with Tween 80, it appears that PHE, PYR, and FLA are competing for the same enzymatic sites.     

Coccomyxa Gloeobotrydiformis Improves Learning and Memory in Intrinsic Aging Rats

Declining in learning and memory is one of the most common and prominent problems during the aging process. Neurotransmitter changes, oxidative stress, mitochondrial dysfunction and abnormal signal transduction were considered to participate in this process. In the present study, we examined the effects of Coccomyxa gloeobotrydiformis (CGD) on learning and memory ability of intrinsic aging rats. As a result, CGD treated (50 mg/kg·d or 100 mg/kg ·d for a duration of 8 weeks) 22-month-old male rats, which have shown significant improvement on learning and spatial memory ability compared with control, which was evidently revealed in both the hidden platform tasks and probe trials. The following immunohistochemistry and Western blot experiments suggested that CGD could increase the content of Ach and thereby improve the function of the cholinergic neurons in the hippocampus, and therefore also improving learning and memory ability of the aged rats by acting as an anti-inflammatory agent. The effects of CGD on learning and memory might also have an association with the ERK/CREB signalling. The results above suggest that the naturally made drug CGD may have several great benefit as a multi-target drug in the process of prevention and/or treatment of age-dependent cognitive decline and aging process.     

Three novel α-L-iduronidase mutations in 10 unrelated Chinese mucopolysaccharidosis type I families

Mucopolysaccharidosis type I (MPS I) arises from a deficiency in the α-L-iduronidase (IDUA) enzyme. Although the clinical spectrum in MPS I patients is continuous, it was possible to recognize 3 phenotypes reflecting the severity of symptoms, viz., the Hurler, Scheie and Hurler/Scheie syndromes. In this study, 10 unrelated Chinese MPS I families (nine Hurler and one Hurler/Scheie) were investigated, and 16 mutant alleles were identified. Three novel mutations in IDUA genes, one missense p.R363H (c.1088G > A) and two splice-site mutations (c.1190-1G > A and c.792+1G > T), were found. Notably, 45% (nine out of 20) and 30% (six out of 20) of the mutant alleles in the 10 families studied were c.1190-1G > A and c.792+1G > T, respectively. The novel missense mutation p.R363H was transiently expressed in CHO cells, and showed retention of 2.3% IDUA activity. Neither p.W402X nor p.Q70X associated with the Hurler phenotype, or even p.R89Q associated with the Scheie phenotype, was found in this group. Finally, it was noted that the Chinese MPS I patients proved to be characterized with a unique set of IDUA gene mutations, not only entirely different from those encountered among Europeans and Americans, but also apparently not even the same as those found in other Asian countries.     

Expressional and functional studies of CKLF1 during dendritic cell maturation

Chemokine-like factor 1 (CKLF1) was the first member of the CKLF-like MARVEL transmembrane domain containing member (CMTM) family to be discovered. Its expression level is increased clearly in peripheral blood lymphocytes upon phytohemagglutinin stimulation, but little is known about the expression and function of CKLF1 in dendritic cells (DCs), which are the most potent antigen-presenting cells. In the present study, we showed that CKLF1 was highly expressed in monocytes. During differentiation from monocytes to immature DCs, CKLF1 was increased dramatically on day 2 and then decreased from day 3 to 5. Upon maturation with different stimuli, CKLF1 was down-regulated. Two peptides of CKLF1, C19 and C27, stimulated the effect of immature DCs (imDCs) on T-cell proliferation and IFN-γ production. Further study on DC maturation showed that C19 and C27 up-regulated HLA-DR expression and IL-12 secretion, with no obvious effects on CD80, CD83 or CD86. Thus, CKLF1-C19 and -C27 can stimulate antigen-presenting capability of imDCs.