Neonates acquire from their mothers maternal antibody (MatAb) which results in poor immune response to vaccination. We previously demonstrated that ginseng stem-leaf saponins in combination with selenium (GSe) had adjuvant effect on the immune response to an attenuated pseudorabies virus (aPrV) vaccine. The present study was to evaluate GSe for its effect on the immune response to aPrV vaccine in neonatal mice with MatAb. Results showed that GSe had adjuvant effect on the immune response to aPrV vaccine in neonates. When GSe was co-administered with aPrV vaccine (aP-GSe), specific gB antibody, Th1 cytokines (IL-2, IL-12 and IFN-γ) and Th2 cytokines (IL-4, IL-6 and IL-10) responses were significantly increased in association with enhanced protection of vaccinated neonates against the lethal PrV challenge even though MatAb existed when compared to the neonates immunized with aPrV vaccine alone. GSe-enhanced immune response depended on its use in the primary immunization. The mechanisms underlying the adjuvant effect of GSe may be due to more innate immune related pathways activated by GSe. Transcriptome analysis of splenocytes from neonates immunized with aP-GSe, aPrV or saline solution showed that there were 3976 differentially expressed genes (DEGs) in aP-GSe group while 5959 DEGs in aPrV group when compared to the control. Gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that innate immune responses and cytokine productions related terms or pathways were predominantly enriched in aP-GSe group, such as “NOD-like receptor signaling pathway”, “Natural killer cell mediated cytotoxicity”, “NF-κB signaling pathway”, “cytokine-cytokine receptor interaction”, and “Th1 and Th2 cell differentiation”. Considering the potent adjuvant effect of GSe on aPrV vaccine in neonatal mice with MatAb, it deserves further investigation in piglets.
Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated-dose toxicity of Hu7691 in male and female Sprague Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg/day, while female rats received doses of 12.5, 25, 50, and 75 mg/kg/day for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg/day. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg/day, while for female animals, it should be less than 50 mg/kg/day.
Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated dose toxicity of Hu7691 in male and female Sprague-Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg, while female rats received doses of 12.5, 25, 50, and 75 mg/kg for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg, while for female animals, it should be less than 50 mg/kg.
Objective: To explore the effect and mechanism of Polysaccharide extracted from raw Atractylodes Macrocephala on Loperamide-induced constipation in rats.