We conducted an extended time course study to compare markers of liver damage, inflammation and proliferation between male and female mice exposed postnatally to 600 nmol ABP or 10 mg/kg DEN, and also in HBV transgenic (HBVTg) mice, over the duration of time that mice are normally maintained for standard liver tumor development protocols. Postnatal exposure to either ABP or DEN produced no evidence of either acute or chronic hepatocyte damage, liver inflammation or proliferation in either male or female mice. In contrast, HBVTg mice showed increased liver damage, inflammation and proliferation with age, but with no observed sex difference. These findings suggest that although chronic liver damage, inflammation and proliferation may be drivers for liver cancer development, they are unlikely to contribute directly to observed sex differences in liver tumor risk.The specific mechanism of paraquat (PQ)-induced acute lung injury (ALI) is unclear, though inflammation is a likely contributor. Amlexanox, a TANK binding kinase 1 (TBK1) inhibitor, is a strong anti-inflammatory drug. We investigated the role of TBK1 and the potential therapeutic effect of amlexanox in the pathogenesis of PQ-induced ALI. After 30 mg/kg PQ treatment for 72 h, mouse lung pathological injury occurred, and the protein concentration in alveolar lavage fluid was increased. Next, RAW264.7 mouse macrophages were treated with 100 μM PQ for 24 h, which decreased cell viability. PQ induced oxidative damage and increased IL-1β, IFNβ, NF-κBp65, IRF3, and pTBK1/TBK1 levels in mouse lungs and RAW264.7 cells. Inhibiting the activation of TBK1 with amlexanox (100 mg/kg in mice and 50 μM in RAW264.7 cells) attenuated mouse lung injury and decreased the protein concentration in alveolar lavage fluid. Further, amlexanox relieved the oxidative damage in mouse lungs and RAW264.7 cells, reduced the levels of inflammatory factors such as IL-1β and IFNβ, and inhibited the activation of NF-κBp65 and IRF3. These results suggest that TBK1 plays a key role in the pathogenesis of PQ-induced ALI. Further, amlexanox treatment alleviates PQ-induced ALI by inhibiting the TBK1-NF-κB/IRF3 signalling pathway. Our study provides evidence that TBK1 inhibition by amlexanox alleviates PQ-induced ALI and may be a new therapeutic strategy.The kappa opioid receptor (KOP) system modulates social play responding, however a paucity of studies have examined effects on social motivation and cognition in the absence of play. Prenatal exposure to the anti-epileptic and mood stabiliser valproic acid (VPA) is associated with impaired social responding and altered gene expression of KOP (oprk1) and dynorphin (pdyn) in several brain regions. The present study examined if pharmacological modulation of KOP altered social motivation and cognition, immediate early gene (IEG) and oprk1-pdyn expression in adolescent male rats and rats prenatally exposed to VPA. In control rats, the KOP antagonist DIPPA enhanced sociability, while both DIPPA and the KOP agonist U50488 decreased social novelty preference. In rats exposed prenatally to VPA, neither U50488 nor DIPPA altered sociability or social novelty preference. Analysis of IEG expression revealed that DIPPA reduced expression of egr-1 expression in the prefrontal cortex of control rats and U50488 increased junb expression in the PFC of both control and VPA-exposed rats. VPA-exposed rats exhibited increased expression of oprk1 and pdyn in the prefrontal cortex and amygdala compared with control rats. DIPPA and U50488 increased oprk1 expression in the amygdala of control rats and decreased oprk1 expression in the prefrontal cortex of VPA-exposed rats. Taken together, these data demonstrate that pharmacological modulation of the KOP system alters social motivation and cognition in control rats, an effect not observed in rats prenatally exposed to VPA. These data provide support that prenatal exposure to VPA is associated with alterations in the expression and functionality of KOP system.Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below 4,4'-thiodiphenol (TDP) less then bisphenol S (BPS) less then 4,4'-dihydroxybenzophenone (DHBP) less then tetrabromobisphenol A (TBBPA) less then tetrachlorobisphenol A (TCBPA) less then bisphenol E (BPE) less then bisphenol F (BPF) less then bisphenol B (BPB) less then bisphenol AF (BPAF) less then bisphenol A (BPA) less then bisphenol C (BPC) less then tetramethylbisphenol A (TMBPA) less then bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid β-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs.Neurogenesis process in the chronic phase of ischemic stroke has become the focus of research on stroke treatment recently, mainly through the activation of related pathways to increase the differentiation of neural stem cells (NSCs) in the brain sub-ventricular zone (SVZ) and subgranular zone (SGZ) of hippocampal dentate gyrus (DG) areas into neurons, promoting neurogenesis. While there is still debate about the longevity of active adult neurogenesis in humans, the SVZ and SGZ have the capacity to upregulate neurogenesis in response to cerebral ischemia, which opens discussion about potential treatment strategies to harness this neuronal regenerative response. https://www.selleckchem.com/products/zx703.html Wnt signaling pathway is one of the most important approaches potentially targeting on neurogenesis after cerebral ischemia, appropriate activation of which in NSCs may help to improve the sequelae of cerebral ischemia. Various therapeutic approaches are explored on preclinical stage to target endogenous neurogenesis induced by Wnt signaling after stroke onset.