Search

Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species. In order to study the toxic effects, zebrafish embryos were exposed to metalaxyl at nominal concentrations of 5, 50 and 500 ng/L for 72 hr, and the cardiac development and functioning of larvae were observed. The results showed that metalaxyl exposure resulted in increased rates of pericardial edema, heart hemorrhage and cardiac malformation. The distance between the sinus venosus and bulbus arteriosus, stroke volume, cardiac output and heart rate were significantly increased in larvae exposed to 50 and 500 ng/L metalaxyl compared to solvent control larvae. Significant upregulation in the transcription of tbx5 , gata4 and myh6 was observed in the 50 and 500 ng/L treatments, and that of nkx2.5 and myl7 was observed in the 5, 50 and 500 ng/L groups. These disturbances may be related to cardiac developmental and functional defects in the larvae. The activity of Na+/K+-ATPase and Ca2+-ATPase was significantly increased in zebrafish embryos exposed to 500 ng/L metalaxyl, and the mRNA levels of genes related to ATPase (atp2a11, atp1b2b, and atp1a3b) (in the 50 and 500 ng/L groups) and calcium channels (cacna1ab) (in the 500 ng/L group) were significantly downregulated; these changes might be associated with heart arrhythmia and functional failure. Unlabelled Image [ABSTRACT FROM AUTHOR]

Procymidone (PCM), a dicarboximide fungicide, is widely used in agriculture to control plant diseases. In the present study, zebrafish embryos were exposed to PCM at 0, 10, 100 and 1000 ng/L for 72 h, the development and cardiac functioning of larvae were observed and determined. The results showed that hatching rate was significantly decreased in the 1000 ng/L treatment, and pericardial edema rate and spine curvature rate were significantly increased in the 100 and 1000 ng/L groups. The PCM-treated larvae exhibited an increased heart rate as well as arrhythmia, and shortened low jaw. The transcription levels of cardiac development-related genes tbx5, nkx2.5, tnnt2, gata4, myh6, myl7, cdh2, ryr2 were altered, which might be responsible for the cardiac developmental and functioning defects in the larvae. The deformation in bone development might be related with the impaired transcription levels of ihh, shh, bmp2b, bmp4, gh, igf1, sox9, gli2 . The activities of Na + /K + -ATPase and Ca 2+ -ATPase were significantly inhibited by 100 ng/L and 1000 ng/L PCM exposure, which might be a cause for the occurrence of pericardial edema and skeletal deformation. The results of this study will be helpful in evaluating the potential threat of PCM to fish population in the aquatic environment. [ABSTRACT FROM AUTHOR]

Schematic representation of constructing CS-Fc@SPCE electrochemical immunosensor for the detection of cTnI. [Display omitted] • A label-free electrochemical immunosensor based on ferrocene derivatives amplified signal for cTnI detection was created. • A novel redox-active hybrid material, CS-Fc, which significantly increases the electron transfer rate. • The immunosensor showed excellent analytical performances in the assay of AMI warning biomarker – cTnI. As a biomarker of acute myocardial infarction (AMI), screening for cardiac troponin I (cTnI) has extremely high clinical sensitivity and specificity, and is extremely important for early intervention and risk assessment of AMI. Therefore, a novel redox-active hybrid material, CS-Fc, was synthesized by the Schiff base reaction of chitosan (CS) and ferrocene-carboxylic acid (Fc(COOH)) to form an amide group bonded together, which was used as a substrate-modified material for screen-printed carbon electrode (SPCE), and then assembled with an antibody (Ab), which was constructed into a label-free electrochemical immunosensor for the highly sensitive and rapid detection of cTnI in this study. The redox activity and biocompatibility of the highly stable and conductive composite CS-Fc significantly increased the effective specific surface area, electron transfer rate, and achieved effective amplification and specific analysis of the response signal. Under the optimized experimental conditions, the immunosensor showed a good linear relationship between its response signal and cTnI concentration in the range of 2.44 × 10−2 ∼ 2.50 × 101 ng mL−1, with a limit of detection (LOD) as low as 3.70 × 10−3 ng mL−1 (3σ, n = 11). Meanwhile, when used for the detection of cTnI in actual serum samples, it showed better reproducibility and stability, and the analytical results were better than those of the ELISA method, which indicated that it has a great potential for the accurate and rapid detection of cTnI in serum samples. In addition, it also provides a reliable means and scientific basis for process screening, early warning and prognostic risk assessment of AMI. [ABSTRACT FROM AUTHOR]

• Circadian rhythm disruption promoted the development of periodontitis by promoting the proinflammatory response. • Kdm6a deficiency in macrophages alleviated periodontitis. • The aggravation of periodontitis by CRD can be attenuated by Kdm6a deletion in macrophages. Macrophages are highly implicated in the progression of periodontitis, while circadian rhythm disruption (CRD) promotes the inflammatory response of macrophages in many diseases. However, the effects of CRD on periodontitis and the role of macrophages in this process remain unclear. Histone lysine demethylase 6a (Kdm6a), a histone demethylase, has recently been identified as a key regulator of macrophage-induced inflammation. Here, we established an experimental periodontitis model by injecting lipopolysaccharide (LPS) derived from Porphyromonas gingivalis with or without periodontal ligation in mice exposed to an 8-h time shift jet-lag schedule every 3 days. By histomorphometry, tartrate acid phosphatase (TRAP) staining, RT-qPCR, ELISA, immunohistochemistry and immunofluorescence analysis, we found that CRD promoted the inflammatory response, alveolar bone resorption, macrophage infiltration and Kdm6a expression in macrophages. Macrophage-specific Kdm6a knockout mice were further used to elucidate the effects of Kdm6a deficiency on periodontitis. Kdm6a deletion in macrophages rescued periodontal tissue inflammation, osteoclastogenesis, and alveolar bone loss in a mouse model of periodontitis. These findings suggest that CRD may intensify periodontitis by increasing the infiltration and activation of macrophages. Kdm6a promotes the inflammatory response in macrophages, which may participate in aggravated periodontitis via CRD. [ABSTRACT FROM AUTHOR]