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Objective: The G‐allele of the ‐1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model (SEM) to examine whether the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous activity. Method: A sample of 1141 drug‐free healthy Han Chinese was recruited for HTR1A genotyping. Autonomic nervous function was assessed by short‐term spectral analysis of heart rate variability (HRV). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale (PSS) respectively. Results: The number of the HTR1A G allele was inversely correlated with high‐frequency power (HF), a parasympathetic index of HRV. The HF index was negatively associated with BAI scores. Furthermore, the good‐fitting SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs6295 variant to BAI scores via HF index modulation. Conclusion: These results are the first to show that HTR1A ‐1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of HTR1A in human anxiety. [ABSTRACT FROM AUTHOR]

Objectives: SL4, a chalcone-based compound, exhibits clearly inhibitory effects on HIF-1 and has been shown to effectively suppress tumour invasion and angiogenesis in vitro and in vivo. Here, studies were conducted to determine SL4's anti-apoptotic effects and its underlying mechanisms, in human cancer cells. Materials and methods: Cytotoxicity, apoptotic induction and its involved mechanisms of SL4 were investigated using normal cells, cancer cells and mouse xenograft models. The role of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signalling in SL4-induced apoptosis was explored by manipulating specific scavenger or signalling inhibitors, in cultured cells. Results: SL4 significantly inhibited cell population growth of human cancer cell lines but exhibited lower cytotoxicity against normal cells. In addition, SL4 effectively induced apoptosis of Hep3B and MDA-MB-435 cells by activating procaspase-8, -9 and -3, and down-regulating expression levels of XIAP, but did not affect HIF-1 apoptosis-related targets, Survivin and Bcl-XL. Further study showed that SL4 also reduced mitochondrial membrane potential and promoted generation of ROS. ROS generation and apoptotic induction by SL4 were blocked by NAC, a scavenger of ROS, suggesting SL4-induced apoptosis via ROS accumulation. We also found that MAPKs, JNK and p38, but not ERK1/2, to be critical mediators in SL4-induced apoptosis. SP600125 and SB203580, specific inhibitors of JNK kinase and p38 kinase, significantly retarded apoptosis induced by SL4. Moreover, anti-oxidant NAC blocked activation of JNK and p38 induced by SL4, indicating that ROS may act as upstream signalling of JNK and p38 activation. It is noteworthy that animal studies revealed dramatic reduction (49%) in tumour volume after 11 days SL4 treatment. Conclusions: These data demonstrate that SL4 induced apoptosis in human cancer cells through activation of the ROS/MAPK signalling pathway, suggesting that it may be a novel lead compound, as a cancer drug candidate, with polypharmacological characteristics. [ABSTRACT FROM AUTHOR]

Hu, X., Li, X.-C., Sun, B.-B., Fang, W.-H., Zhou, S., Hu, L.-L., Zhou, J.-F. Effects of enrofloxacin on cytochromes P4501A and P4503A in Carassius auratus gibelio (crucian carp). J. vet. Pharmacol. Therap. 35, 216-223. Currently, although enrofloxacin (EF) as a widely used veterinary medicine has begun to apply to treating fish bacterial infections, the researches on the effects of EF on their main drug metabolic enzymes are limited. To investigate the effects of EF on fish cytochromes P450 (CYPs) 1A and 3A, the enzymatic activities and expressions (mRNA and protein) of crucian carp CYP1A and CYP3A after EF administration were examined. For CYP1A, in the in vivo experiments, EF exhibited potent inhibition on the CYP1A-related ethoxyresorufin- O-deethylase (EROD) activity, as well as CYP1A expressions at both protein and mRNA levels, at 24 h after administration with different EF dosages (3, 10, 30, and 60 mg/kg); Furthermore, CYP1A enzymatic activity and expressions at both protein and mRNA levels decreased more with increasing EF dosages. Additionally, the in vitro experimental results showed that, after incubated with microsomes, EF did not change the EROD activity through interacting directly with CYP1A. For CYP3A, the in vitro and in vivo experimental results demonstrated that EF could inhibit the CYP3A-related erythromycin N-demethylase activity in a time- and dose-dependent manner, while it did not suppress CYP3A expressions at both protein and mRNA levels after administration with EF for a short period (no more than 24 h); however, after injection with EF at a high dose (10 mg/kg) for a long period, the CYP3A protein and mRNA reached their lowest levels at 96 and 48 h, respectively. These results indicate that EF can suppress CYP1A expressions in a dose-dependent manner, thereby inhibiting further its catalytic activity; meanwhile, both the interactions of EF with CYP3A and the expressions decrease (protein and mRNA) caused by EF contribute to the CYP3A inhibition. [ABSTRACT FROM AUTHOR]

The study was conducted to evaluate the pharmacokinetics of enrofloxacin following a single oral gavage (10 mg kg−1) in mud crab, Scylla serrata, at water temperatures of 19 and 26 °C. Enrofloxacin concentration in haemolymph was determined using high-performance liquid chromatography (HPLC). A multiple and repeated haemolymph sampling from the articular cavity of crab periopods was developed. The haemolymph of an individual crab was successfully sampled up to 11 times from the articular cavity. The profile of haemolymph enrofloxacin concentration of an individual crab versus time was thus achieved. The mean haemolymph enrofloxacin concentration versus time was described by a two-compartment model with first-order absorption at two water temperatures. The peak concentrations of haemolymph enrofloxacin at 19 and 26 °C were 7.26 and 11.03 μg mL−1, at 6 and 2 h, respectively. The absorption and distribution half-life time ( and t1/2 α) at 19 °C were 3.7 and 4.5 h, respectively, which were markedly larger than the corresponding values (1.1 and 1.5 h) at 26 °C; the elimination half-life time ( t1/2 β) was 79.1 and 56.5 h at 19 and 26 °C, respectively. The area under curve (AUC), total body clearance ( Cl) and mean residence time (MRT0–∞) at 19 °C were 636.0 mg L−1 h, 0.016 L h−1 kg−1 and 102.5 h, respectively; the corresponding values at 26 °C were 583.4 mg L−1 h, 0.018 L h−1 kg−1and 63.7 h. These results indicate that enrofloxacin is absorbed and eliminated more rapidly in mud crab at 26 °C than at 19 °C. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS) and classical swine fever (CSF) cause significant economic losses to the swine industry worldwide. As both diseases cause similar symptoms, rapid and reliable detection of these diseases is essential for disease surveillance. A quantitative SYBR Green I-based reverse transcription-polymerase chain reaction (RT-PCR) is described for simultaneous and differential diagnosis. The established RT-PCR for the quantitation of PRRSV and CSFV cDNA was found to provide a broad dynamic range, detecting from 103 to 1011 and 102 to 1011 copies of cDNA per reaction, respectively. Sensitivity and specificity of this method were compared with those of conventional RT-PCR and both were equal or superior to the reference method. Reproducibility was tested and the assay was proved very reliable. The assay is timesaving, easy to handle, and highly sensitive and specific. Therefore, it is a powerful tool for detecting PRRSV and CSFV simultaneously for routine outbreak investigation. [ABSTRACT FROM AUTHOR]

Objective: The G-allele of the -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model (SEM) to examine whether the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous activity., Method: A sample of 1141 drug-free healthy Han Chinese was recruited for HTR1A genotyping. Autonomic nervous function was assessed by short-term spectral analysis of heart rate variability (HRV). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale (PSS) respectively., Results: The number of the HTR1A G allele was inversely correlated with high-frequency power (HF), a parasympathetic index of HRV. The HF index was negatively associated with BAI scores. Furthermore, the good-fitting SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs6295 variant to BAI scores via HF index modulation., Conclusion: These results are the first to show that HTR1A -1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of HTR1A in human anxiety., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)