Protein homeostasis is tightly regulated by protein quality control systems such as chaperones and proteases. In cyanobacteria, the ClpXP proteolytic complex is regarded as a representative proteolytic system and consists of a hexameric ATPase ClpX and a tetradecameric peptidase ClpP. However, the functions and molecular mechanisms of ClpX in cyanobacteria remain unclear. This study aimed to decipher the unique contributions and regulatory networks of ClpX in the model cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis). We showed that the interruption of clpX led to slower growth, decreased high light tolerance, and impaired photosynthetic cyclic electron transfer. A quantitative proteomic strategy was employed to globally identify ClpX-regulated proteins in Synechocystis cells. In total, we identified 172 differentially expressed proteins (DEPs) upon the interruption of clpX. Functional analysis revealed that these DEPs are involved in diverse biological processes, including glycolysis, nitrogen assimilation, photosynthetic electron transport, ATP-binding cassette (ABC) transporters, and two-component signal transduction. The expression of 24 DEPs was confirmed by parallel reaction monitoring (PRM) analysis. In particular, many hypothetical or unknown proteins were found to be regulated by ClpX, providing new candidates for future functional studies on ClpX. Together, our study provides a comprehensive ClpX-regulated protein network, and the results serve as an important resource for understanding protein quality control systems in cyanobacteria.
The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a widespread environmental pollutant. However, the target tissue and toxicity of DBDPE are still not clear. In the current study, female zebrafish were exposed to 1 and 100 nM DBDPE for 28 days. Chemical analysis revealed that DBDPE tended to accumulate in the brain other than the liver and gonad. Subsequently, tandem mass tag-based quantitative proteomics and parallel reaction monitoring verification were performed to screen the differentially expressed proteins in the brain. Bioinformatics analysis revealed that DBDPE mainly affected the biological process related to muscle contraction and estrogenic response. Therefore, the neurotoxicity and reproductive disruptions were validated via multilevel toxicological endpoints. Specifically, locomotor behavioral changes proved the potency of neurotoxicity, which may be caused by disturbance of muscular proteins and calcium homeostasis; decreases of sex hormone levels and transcriptional changes of genes related to the hypothalamic-pituitary-gonad-liver axis confirmed reproductive disruptions upon DBDPE exposure. In summary, our results suggested that DBDPE primarily accumulated in the brain and evoked neurotoxicity and reproductive disruptions in female zebrafish. These findings can provide important clues for a further mechanism study and risk assessment of DBDPE.
Context: Jinlong capsule (JLC) is an animal-derived traditional Chinese medical preparation for advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is still not well investigated. Objective: This study summarizes the efficacy and safety of JLC combined with trans-arterial chemoembolization (TACE) for patients with HCC. Methods: The databases PubMed, Cochrane Library, Web of Science, EMBASE, Medline, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database and Chinese Biological Medicine Database were systematically searched from the date of their inception until February 2020. Jinlong capsule, trans-arterial chemoembolization, and hepatocellular carcinoma were the key terms searched. Randomized controlled trials and high-quality prospective cohort trials comparing the combined use of JLC and TACE versus TACE for HCC were included. Data were pooled using random or fixed effect models depending on heterogeneity. Results: Data from 19 articles with 1,725 HCC patients were analysed. Compared with TACE treatment alone, the combination of TACE and JLC significantly prolonged patients' 6-36 month overall survival (p < 0.05), and markedly improved the overall response rate (RR ¼ 1.37, 95% CI ¼ 1.24-1.52, p < 0.00001) and disease control rate (RR ¼ 1.11, 95% CI ¼ 1.06-1.17, p < 0.0001) of patients. The liver function, quality of life, and immune function of patients were significantly improved; the partial adverse events related to TACE were also effectively relieved after the combination treatment. Conclusion: This meta-analysis suggests that the combination of TACE and JLC is more effective in the treatment of HCC than treatment with TACE alone.
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