Additionally, we confirmed that cannabinoid receptor 1 (Cnr1) was the target gene of miR-338-5p by dual-luciferase reporter assays and that Rap1 was the downstream gene by the KEGG pathway analysis. We found that miR-338-5p increased cAMP accumulation as a consequence of downregulated expression of the target gene Cnr1, and then, Rap1 was activated by cAMP. Eventually, the activation of the PI3K/Akt pathway attenuated cell apoptosis and promoted neuronal survival by cAMP-mediated Rap1 activation. In brief, these findings showed that exosomes overexpressing miR-338-5p were a promising treatment strategy for SCI.Neuropathic pain is still one of the unsolved public health problems worldwide. Although the current reagents can attenuate neuropathic pain to a certain extent, their clinical application is very limited owing to larger toxicity and serious side effects. Trifluoro-icaritin (ICTF) has been documented to possess profound anti-inflammatory and neuroprotective activities, but whether ICTF exerts an anti-nociceptive effect on neuropathic pain remains unknown. Here, a rat model of spared nerve injury (SNI)-induced neuropathic pain was used. SNI rats were administrated with ICTF (i.p.) once daily lasting for 21 days, and subsequently the pain-related behaviors were evaluated by applying mechanical or thermal pain threshold, CatWalk gait parameter, and rotarod test on day 1 before and day 1, 3, 7, 10, 14, and 21 after SNI surgery, respectively. The results showed that ICTF (0.5 mg/kg, 1.5 mg/kg, and 5.0 mg/kg, i.p.) treatment alleviated SNI-induced mechanical allodynia but not thermal hyperalgesia in a dose-dependent manner. After administration of ICTF at the most effective dose of 5.0 mg/kg to SNI rats, CatWalk gait analysis revealed that ICTF not only significantly enhanced gait parameters including max contact max intensity, max intensity, print area, and stand time but also decreased the swing time; Rotarod test further exhibited that ICTF could effectively prolong the time on rod and increase the rotating speed in SNI rats. Additionally, following ICTF (5.0 mg/kg) treatment of SNI rats for 21 consecutive days, the max contact max intensity was found to be positively correlated with the rotating speed. Taken together, ICTF successfully ameliorates mechanical hypersensitivity and improves the motor coordination and balance in SNI rats, suggesting that ICTF may be exploited as a potential candidate in the management of neuropathic pain.Research has demonstrated the spreading of fear from threat-related stimuli to perceptually similar, but innocuous, stimuli. Less is known, however, about the generalization of avoidance behavior. Given that stress is known to affect learning and memory, we were interested in the effect of acute stress on (over)generalization of fear and avoidance responses. On the first day, one geometrical shape was paired with a mild electrical stimulus (CS+), whereas another shape was not (CS-). One day later, after participants had been exposed to the Maastricht Acute Stress Test or a control task, generalization of avoidance responses and fear (shock expectancy and skin conductance responses) was tested to a range of perceptual generalization stimuli. Generalization gradients were observed across different outcome measures. Stress enhanced generalization of shock expectancy to the stimulus most similar to the CS+. Our findings confirm that stress can affect the generalization of fear, but further studies are warranted.The genome of living organisms frequently undergoes various types of modifications which are recognized and repaired by the relevant repair mechanisms. These repair pathways are increasingly being deciphered to understand the mechanisms. Base excision repair (BER) is indispensable to maintain genome stability. One of the enigmatic repair proteins of BER, Apurinic/Apyrimidinic Endonuclease 2 (APE2), like APE1, is truly multifunctional and demonstrates the independent and non-redundant function in maintaining the genome integrity. APE2 is involved in ATR-Chk1 mediated DNA damage response. It also resolves topoisomerase1 mediated cleavage complex intermediate which is formed while repairing misincorporated ribonucleotides in the absence of functional RNase H2 mediated excision repair pathway. BER participates in the demethylation pathway and the role of Arabidopsis thaliana APE2 is demonstrated in this process. https://www.selleckchem.com/products/umi-77.html Moreover, APE2 is synthetically lethal to BRCA1, BRCA2, and RNase H2, and its homolog, APE1 fails to complement the function. Hence, the role of APE2 is not just an alternate to the repair mechanisms but has implications in diverse functional pathways related to the maintenance of genome integrity. This review analyses genomic features of APE2 and delineates its enzyme function as error-prone as well as efficient and accurate repair protein based on the studies on mammalian or its homolog proteins from model systems such as Arabidopsis thaliana, Schizosaccharomyces pombe, Trypanosoma curzi, Xenopus laevis, Danio rerio, Mus musculus, and Homo sapiens.Human exposure to bisphenol-A (BPA) is largely unavoidable because BPA is an environmental contaminant found in soil, water, food and indoor dust. The safety of authorized BPA amounts in consumer products is under question because new studies have reported adverse effects of BPA at doses far below that previously established by the NOAEL (50 μg/kg per day). To protect public health, the consequences of low-dose BPA exposure in different organs and organismal functions must be further studied to generate relevant data. This study attempted to investigate the effects and potential molecular mechanisms of short-term exposure to 1 μg/L BPA on zebrafish ovarian follicular development. We observed only minor changes at the histopathological level with a small (3 %) increase in follicular atresia. However, a shotgun proteomics approach indicated deep alterations in BPA-exposed ovarian cells, including induction of the oxidative stress response, metabolic shifts and degradome perturbations, which could drive oocytes towards premature maturation. Based on these results, it could be suggested that inadvertent exposure to small concentrations of BPA on a continuous basis causes alteration in biological processes that are essential for healthy reproduction.