细胞凋亡与癌变的相生相克——肿瘤的发育生物学根源

早期癌变（prooncogenesis）是肿瘤诊断和防治的最关键时期,却是癌学研究领域中最薄弱的环节.因此,将从发育生物学视角来探索此时期的基本特征.细胞凋亡和癌变两种相互拮抗的功能均源自失控增殖细胞,不过前者是必然本能,而后者是致癌条件下的或然事件.在早期癌变中,它们之间存在复杂的＂相生相克＂关系：一方面,开始癌变的细胞尚未累积出足够的致癌基因变异,原发癌的出现尚需不断阻止凋亡功能的监控;另一方面,凋亡功能虽遭到促癌变因子的阻遏,但促凋亡基因,特别是p53尚未发生突变,逆转的可能性仍然存在,因此在防治上有很大的空间.为了给深入探索早期癌变问题提供理论依据,提出了一个＂细胞凋亡转向癌变＂的假说,初步进行了分子和线粒体生理水平的论证,并强调在癌学研究上如欲获得重大突破,就应以早期癌变为重中之重,同时建议把弄清楚Ca^2＋以及H^＋,ROS等荷电粒子的代谢动态作为切入点.     

Shared Genetic Pathways Contribute to the Tolerance of Endogenous and Low-Dose Exogenous DNA Damage in Yeast

DNA damage that escapes repair and blocks replicative DNA polymerases is tolerated by bypass mechanisms that fall into two general categories: error-free template switching and error-prone translesion synthesis. Prior studies of DNA damage responses in Saccharomyces cerevisiae have demonstrated that repair mechanisms are critical for survival when a single, high dose of DNA damage is delivered, while bypass/tolerance mechanisms are more important for survival when the damage level is low and continuous (acute and chronic damage, respectively). In the current study, epistatic interactions between DNA-damage tolerance genes were examined and compared when haploid yeast cells were exposed to either chronic ultraviolet light or chronic methyl methanesulfonate. Results demonstrate that genes assigned to error-free and error-prone bypass pathways similarly promote survival in the presence of each type of chronic damage. In addition to using defined sources of chronic damage, rates of spontaneous mutations generated by the Pol ζ translesion synthesis DNA polymerase (complex insertions in a frameshift-reversion assay) were used to infer epistatic interactions between the same genes. Similar epistatic interactions were observed in analyses of spontaneous mutation rates, suggesting that chronic DNA-damage responses accurately reflect those used to tolerate spontaneous lesions. These results have important implications when considering what constitutes a safe and acceptable level of exogenous DNA damage.     

Effect of a Photo-synthetic Inhibitor on Tryptamine Pathway-mediated Sekiguchi Lesion Formation in Lesion Mimic Mutant of Rice Infected with Magnaporthe grisea

A lesion-mimic mutant of rice (cv. Sekiguchi-asahi) showed enhanced resistance to Magnaporthe grisea infection, thereby inducing Sekiguchi lesion ( sl ) formation and tryptamine accumulation under light. Both Sekiguchi lesion formation and tryptamine accumulation in leaves infected with M. grisea were inhibited by pretreatment with the photosynthetic inhibitor, 3-(3, 4-Dichlorophenyl)-1,1-dimethylurea (DCMU), which suppressed the gene expression of tryptophan decarboxylase ( TDC ), monoamine oxidase activity, H₂O₂ generation and DNA fragmentation. Catalase activity was inhibited by M. grisea infection under light, but magnitude of the inhibition was reduced in leaves pretreated with DCMU. Furthermore, tryptophan accumulated in M. grisea- infected leaves under light but not in DCMU-pretreated ones. Interestingly, such DCMU inhibition was reduced in the presence of tryptophan. Our studies suggest that chloroplasts function as the inhibitor of anti-oxidant system such as catalase activity and the supplier of a precursor of tryptamine and tryptophan in the sl mutant infected with M. grisea .     

Mechanisms of mutagenesis induced by DNA lesions: multiple factors affect mutations in translesion DNA synthesis

Abstract

Environmental mutagens lead to mutagenesis. However, the mechanisms are very complicated and not fully understood. Environmental mutagens produce various DNA lesions, including base-damaged or sugar-modified DNA lesions, as well as epigenetically modified DNA. DNA polymerases produce mutation spectra in translesion DNA synthesis (TLS) through misincorporation of incorrect nucleotides, frameshift deletions, blockage of DNA replication, imbalance of leading- and lagging-strand DNA synthesis, and genome instability. Motif or subunit in DNA polymerases further affects the mutations in TLS. Moreover, protein interactions and accessory proteins in DNA replisome also alter mutations in TLS, demonstrated by several representative DNA replisomes. Finally, in cells, multiple DNA polymerases or cellular proteins collaborate in TLS and reduce in vivo mutagenesis. Summaries and perspectives were listed. This review shows mechanisms of mutagenesis induced by DNA lesions and the effects of multiple factors on mutations in TLS in vitro and in vivo.     

Ginkgolide B promotes oligodendrocyte precursor cell differentiation and survival via Akt/CREB/bcl-2 signaling pathway after white matter lesion

White matter lesion (WML) is caused by chronic cerebral hypoperfusion, which are usually associated with cognitive impairment. Evidence from recent studies has shown that ginkgolide B has a neuroprotective effect that could be beneficial for the treatment of ischemia; however, it is not clear whether ginkgolide B has a protective effect on WML. Our data show that ginkgolide B can promote the differentiation of oligodendrocyte precursor cell (OPC) into oligodendrocytes and promote oligodendrocyte survival following a WML. Ginkgolide B (5, 10, 20 mg/kg) or saline is administered intraperitoneally every day after WML. After 4 weeks, the data of Morris water maze suggested that rats’ memory and learning abilities were impaired, and the administration of ginkgolide B enhanced behavioral achievement. Also, treatment with ginkgolide B significantly attenuated this loss of myelin. Our result suggests that ginkgolide B promotes the differentiation of OPC into oligodendrocytes. We also found that ginkgolide B ameliorates oligodendrocytes apoptosis. Furthermore, ginkgolide B enhanced the expression of phosphorylated Akt and CREB. In conclusion, our data firstly show that ginkgolide B promotes oligodendrocyte genesis and oligodendrocyte myelin following a WML, possibly involving the Akt and CREB pathways.     

Interactions Among Pratylenchus penetrans,P. scribneri,and Verticillium dahliae in the Potato Early Dying Disease Complex

Microplots were infested with combinations of the fungus Verticillium dahliae and Pratylenchus penetrans and P. scribneri to test for individual and combined effects of these organisms on potato yield and nematode reproduction. Verticillium dahliae alone caused yield losses in all 3 years of the experiment, and the interaction between P. penetrans and V. dahliae was significant (P ≤ 0.05) in 2 years. Pratylenchus penetrans alone caused yield losses in 2 years and P. scribneri alone caused yield losses in 1 year. No two-way or three-way interaction was found involving P. scribneri. In 1987, reproduction for low densities of P. penetrans was 5 times higher when P. scribneri was also present than when it was absent, and 3.5 times higher in 1988. In nematode species mixtures, reproduction of P. scribneri was decreased by V. dahliae in 1987-88. The final population density of P. scribneri was negatively affected by V. dahliae and positively related to the initial proportion of P. scribneri to P. penetrans. In species mixtures with proportions of P. penetrans ranging from 0.1 to 0.5, reproduction of P. penetrans was negatively affected by V. dahliae and decreased linearly in relation to the increase in the initial proportion of P. penetrans in both years. The final population density of P. penetrans was affected only by V. dahliae.     

Seasonal changes of two biomarkers of oxidative stress (LDH,MDA) in the edible mollusc Donax trunculus (Mollusca: Bivalvia) from the Gulf of Annaba (Algeria): correlation with carbohydrate and lipid contents

The aim of the study was to determine seasonal variations of two biomarkers of oxidative stress, lactate dehydrogenase (LDH) and malondialdehyde (MDA), and their correlation with lipid-carbohydrate metabolism in the edible bivalve Donax trunculus. The samples were collected during the four seasons in 2014 at two sites in the Gulf of Annaba (northeast of Algeria): El Battah, which is some distance from any source of pollution, is considered a relatively clean site, while Sidi Salem is a site exposed to various sources of industrial, urban and harbour pollution. The results show a significant decrease in LDH activity in Sidi Salem D. trunculus compared with those at El Battah. Moreover, carbohydrate levels increased significantly in Sidi Salem. The MDA rate increased significantly in Sidi Salem relative to El Battah, while the amounts of lipid showed a significant decrease. The lipid and carbohydrate metabolism was negatively correlated with LDH and MDA. This difference between the two sites was observed for all seasons, with more effect in spring and summer. The results obtained showed that under stressful conditions due to anthropogenic factors, some physiological processes of D. trunculus can be affected. Thus, D. trunculus appears to be a suitable sentinel species for the assessment of ecotoxicological risk in the Gulf of Annaba.     

Effect of hydration on assessment of early enamel lesion using swept‐source optical coherence tomography

Establishing reproducible methodologies for assessment of early enamel lesions using optical coherence tomography (OCT) appears to be challenging. This in vitro study longitudinally evaluated the subsurface enamel lesion progression after 3, 9 and 15 days by cross‐sectional scanning using 1310 nm centered swept‐source OCT (SS‐OCT) under hydrated and dry conditions. The positive difference between the depth‐integrated OCT signals at dry and hydrated conditions were calculated and adopted as dehydration parameter (DH). A linear regression was found between DH and the square root of demineralization time (R² = 0.99). Significant differences were found in DH between sound and demineralized enamel, and between different periods of demineralization (p < 0.001). Hydration state affects the reflectivity of demineralized porous enamel, and the effect can be potentially used for assessment of early enamel lesion using OCT. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Influence of Selected Cultural Practices on Winter Survival of Pratylenchus brachyurus and Subsequent Effects on Soybean Yield

Planting date of soybean, Glycine max, influenced winter survival of Pratylenchus brachyurus in microplots at two locations in North Carolina. Delayed planting resulted in a linear decrease (P = 0.05) in the numbers of P. brachyurus at soybean harvest. Effects of planting date on nematode numbers persisted over winter, indicating that survival in the absence of a host is density independent. Compared with winter fallow, winter wheat, Triticum aestivum, reduced winter survival of P. brachyurus. Subsequent soybean yields were suppressed by the overwintering population of this nematode at one location but not at another.     

In vitro biofilm models to study dental caries: a systematic review

The aim of this systematic review is to characterize and discuss key methodological aspects of in vitro biofilm models for caries-related research and to verify the reproducibility and dose-response of models considering the response to anti-caries and/or antimicrobial substances. Inclusion criteria were divided into Part I (PI): an in vitro biofilm model that produces a cariogenic biofilm and/or caries-like lesions and allows pH fluctuations; and Part II (PII): models showing an effect of anti-caries and/or antimicrobial substances. Within PI, 72.9% consisted of dynamic biofilm models, while 27.1% consisted of batch models. Within PII, 75.5% corresponded to dynamic models, whereas 24.5% corresponded to batch models. Respectively, 20.4 and 14.3% of the studies reported dose-response validations and reproducibility, and 32.7% were classified as having a high risk of bias. Several in vitro biofilm models are available for caries-related research; however, most models lack validation by dose-response and reproducibility experiments for each proposed protocol.