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DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong (S. hainanensis), a Li nationality plant that has abundant aporphine alkaloids, can inhibit Topo.

To identify a dual Topo inhibitor, a deep and systematic study of active aporphine alkaloids in S. hainanensis and their mechanisms of inhibiting breast cancer proliferation and Topo activity are essential.

This study aimed to assess the anti-breast cancer and Topo inhibitory activities of oxocrebanine and explore the underlying mechanisms.

The growth inhibitory activities of 12 compounds in S. hainanensis were screened by MTT assay in MCF-7, SGC-7901, HepG-2 cells, and compared with the effects on human normal mammary epithelial MCF-10A cells as non cancer control cells. The Topo inhibitory activity was assessed by DNA relaxation and unwinding assays, kDNA decatenation assay and western blot. Cell cycle and autophagy analyses were carried out with flow cytometry and staining. Acridinrphine alkaloid in S. hainanensis. G Protein agonist Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator. Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.
Oxocrebanine was the anti-breast cancer active aporphine alkaloid in S. hainanensis. Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator. Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.
Ulcerative colitis (UC) is a chronic relapsing inflammatory disease that markedly elevates the risk of colon cancers and results in disability. The disrupted immune homeostasis has been recognized as a predominant player in the pathogenesis of UC. However, the overall remission rate of current therapies based on immunoregulation is still unsatisfactory. Si-Ni-San (SNS) has been found effective in relieving UC through thousands of years of clinical practice, yet the specific mechanisms of the protective effect of SNS were not fully elucidated.

We aim to investigate the therapeutic effects of SNS against the development of chronic colitis and the underlying mechanisms.

We established a DSS-induced chronic experimental colitis mouse model to evaluate the effect of SNS. RNA-sequencing, bioinformatic analysis, and in vitro studies were performed to investigate the underlying mechanisms.

Our data demonstrated that SNS significantly ameliorated chronic experimental colitis via inhibiting the expression of ge treatment of UC via interfering type I IFN-mediated inflammation.Sediment quality guidelines (SQGs) are a fundamental component of sediment quality assessment framework, frequently used in the first tier of assessment to predict the potential risks of contaminants in sediment. A recognized weakness of SQGs concerns the bioavailability of sediment contaminants, which may vary considerably with different physical-chemical properties. To better evaluate the ecological risks and predict the toxicity of the heavy metals (Cd, Cu, Ni, Pb, Zn) in the sediments of Haihe River of China, the risk quotients derived from total metal concentrations and SQG values were modified using multiple linear regressions with sediment properties, i.e. total organic carbon (TOC), acid-volatile sulfide (AVS), and particle size distribution (PSD). Then, the sediment toxicity was tested with the benthic organisms of chironomids and tubificids, and the relationships between the observed toxicity with the modified risk quotients were investigated. We found that the risk quotient modified with TOC and AVS displayed significantly improved relationship with the toxicity (p 0.05). Risk assessment indicated that although the heavy metals in the sediments of Haihe River of China are at a relatively low level, potential ecological risks caused by Ni and Zn still exist in some area, especially in the lower reaches along the estuary. The results indicated that the risk quotient and SQG values modified with sediment properties are promising for risk assessment of the metal contaminants in sediments.Chemical pollutants, such as pesticides, often leach into aquatic environments and impact non-target organisms. Marine invertebrates have complex life cycles with multiple life-history stages. Exposure to pesticides during one life-history stage potentially influences subsequent stages; a process known as a carry-over effect. Here, we investigated carry-over effects on the jellyfish Aurelia coerulea. We exposed polyps to individual and combined concentrations of atrazine (2.5 μg/L) and chlorpyrifos (0.04 μg/L) for four weeks, after which they were induced to strobilate. The resultant ephyrae were then redistributed and exposed to either the same conditions as their parent-polyps or to filtered seawater to track potential carry-over effects. The percentage of deformities, ephyrae size, pulsation and respiration rates, as well as the metabolic profile of the ephyrae, were measured. We detected a subtle carry-over effect in two metabolites, acetoacetate and glycerophosphocholine, which are precursors of the neurotransmitter acetylcholine, important for energy metabolism and osmoregulation of the ephyrae. Although these carry-over effects were not reflected in the other response variables in the short-term, a persistent reduction of these two metabolites could have negative physiological consequences on A. coerulea jellyfish in the long-term. Our results highlight the importance of considering more than one life-history stage in ecotoxicology, and measuring a range of variables with different sensitivities to detect sub-lethal effects caused by anthropogenic stressors. Furthermore, since we identified few effects when using pesticides concentrations corresponding to Australian water quality guidelines, we suggest that future studies consider concentrations detected in the environment, which are higher than the water quality guidelines, to obtain a more realistic scenario by possible risk from pesticide exposure.
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