Scientific reports
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Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated during inflammation, and can subsequently modulate sensitivity to nociceptive stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within proteins whose expression was enriched in nociceptors and identified the chemo-responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be phosphorylated by Cdk5 and this interaction was blocked by TFP5, an inhibitor that prevents activation of Cdk5. ⋯ Calcium imaging of trigeminal ganglion neurons from genetically engineered mice overexpressing or lacking the Cdk5 activator p35 displayed increased or decreased responsiveness, respectively, to stimulation with the TRPA1 agonist allylisothiocyanate (AITC). AITC-induced chemo-nociceptive behavior was also heightened in vivo in mice overexpressing p35 while being reduced in p35 knockout mice. Our findings demonstrate that TRPA1 is a substrate of Cdk5 and that Cdk5 activity is also able to modulate TRPA1 agonist-induced calcium influx and chemo-nociceptive behavioral responses.
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Partial thrombosis of the false lumen in uncomplicated type B aortic dissection (uTBAD) is associated with an increased late mortality risk. Whether the serum cortisol level can affect false lumen thrombosis in patients with uTBAD has not been well characterized. This study was performed on 87 patients with uTBAD. ⋯ The results of univariate and multivariate logistic regression analyses suggested that when trisecting the serum cortisol level into three parts, the low and high levels of serum cortisol could significantly affect the occurrence of false lumen partial thrombosis compared with the middle level. The odds ratio value of the low and high levels of serum cortisol was 6.12 and 4.65, respectively, in the univariate analysis, and 24.32 and 3.93, respectively, in the multivariate analysis. Low or high levels of serum cortisol might influence the natural result of uTBAD through affecting the false lumen thrombosis.
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The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Many bacteria employ quorum sensing (QS) to govern the production of virulence factors and formation of drug-resistant biofilms. Targeting the mechanism of QS has proven to be a functional alternative to conventional antibiotic control of infections. ⋯ The effect was next validated by experiments using AiiA as QQE and G1 as QSI on Pseudomonas aeruginosa LasR/I and RhlR/I QS circuits. Combination of QQE and QSI almost completely blocked the P. aeruginosa las and rhl QS systems. Our findings provide a potential chemical biology application strategy for bacterial QS disruption.
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Osteosarcoma (OS) is the most common type of primary malignant bone tumor and mainly occurs in children and adolescent. Because of its early migration and invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs) play a crucial role in the occurrence and development of multiple tumors. ⋯ Finally, we found FOSL2 expression in OS cells was significantly higher compared with normal cells and negatively correlated with miR-143-3p. Thus, miR-143-3p directly and negatively targets FOSL2 to affect OS characteristics. This provides a new target for the treatment of OS and deserves further study.
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Meta Analysis
Chemotherapy plus Panitumumab Versus Chemotherapy plus Bevacizumab in Metastatic Colorectal Cancer: A Meta-analysis.
Panitumumab and bevacizumab have been widely used in combination with chemotherapy for patients with wild type RAS metastatic colorectal cancer (mCRC). Whether panitumumab or bevacizumab was the optimal option remained controversial. Thus, we conducted a meta-anaylsis to evaluate chemotherapy plus panitumumab (C + P) versus chemotherapy plus bevacizumab (C + B) in wild type RAS mCRC. ⋯ In wild type RAS population, PFS [hazard ratio (HR) = 0.96; 95% confidence interval (CI), 0.76 to 1.15] and OS (HR = 0.90; 95% CI, 0.54 to 1.27) and ORR [relative ratio (RR) = 2.06; 95% CI, 0.86 to 4.90] appeared similar between the two treatments, the incidence of AEs slightly increased (RR = 1.16; 95% CI 1.08 to 1.26). In conclusion, there was insufficient evidence to precisely conclude that combination treatment of C + P had an improved efficacy compared with C + B. Further large-scale and better-designed clinical trials are still needed to evaluate the combination treatment of C + P in patients with wild type RAS mCRC.