Background/AimsEarly adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. MethodsOne hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. ResultsCompared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxietylike behaviors in adulthood. ConclusionsMS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.
Background Long‐term stress was suggested to cause visceral hypersensitivity and promote functional gastrointestinal disorders (FGIDs). Some brain regions such as the anterior cingulate cortex (ACC) may play an important role for generating visceral hypersensitivity; however, its molecular mechanisms are not clear. This study aimed to explore the role of 5‐HT1A receptors (HTR1As) in activating ACC and corresponding mechanism, in stress‐induced visceral hyperalgesia rats. Methods The VH rat model was established by chronic water avoidance stress (WAS), and the visceral sensitivity was measured by electromyogram. Rat's anxiety‐like behaviors were evaluated by the open field test (OFT) and elevated plus maze (EPM). To overexpress or down‐regulate HTR1A expression, HTR1A‐specific lentivirus expressing the green fluorescent protein was administered into the ACC. Protein expression levels were observed by Western blot. Results The protein expression of HTR1A in bilateral ACC in WAS group was significantly lower than that in normal control (NC) and Sham‐WAS groups, while the levels of c‐fos in the ACC of WAS rats were significantly higher. Down‐regulation of HTR1As could induce VH in control rats with the increased expression of c‐fos, p‐ERK, and p‐Akt in ACC, while up‐regulation of HTR1As in the ACC could partly inhibit ACC sensitization and stress‐induced visceral hyperalgesia. Conclusions & Inferences Down‐regulation of HTR1As modulates ACC activation probably through activating ERK and Akt pathways, thus contributes to the formation of stress‐induced visceral hyperalgesia.
Gallbladder carcinoma (GBC) is one of the most common carcinomas of the biliary tract and is associated with aggressive malignancy and poor prognosis. Current therapeutic strategies, including surgery, radiotherapy, and chemotherapy, are not sufficient for the treatment of GBC, and new therapeutic strategies are urgently needed. The antitumor effects of oroxylin A (OrA), a natural flavonoid extracted from the dried roots of medicinal plants such as Scutellariae species (Radix Scutellariae), have been widely reported in various cancers. In this study, we first evaluated the antitumor activity and the underlying mechanism of action of OrA on GBC cells in vitro. Our results revealed that OrA significantly attenuated the proliferation, migration, and invasion of GBC cells, simultaneously promoting their apoptosis. Suppression of the phosphate on and tension homology deleted chromosome ten (PTEN)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway was found to be the underlying mechanism involved in the antitumor activity of OrA. In addition, experiments using a tumor xenograft mouse model confirmed the antitumor effects of OrA in vivo. Taken together, our findings indicate that OrA could be a potential antitumor agent for the prospective treatment of GBC. Key words oroxylin A; phosphatidylinositol-3 kinase (PI3K); protein kinase B (AKT); gallbladder carcinoma; phosphate and tension homology deleted on chromosome ten (PTEN)
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