BackgroundSinomenine (SIN) is an extract of the Chinese medicinal herb Sinomenium acutum; it has various pharmacological properties, including immunosuppression and anti-inflammation. The present study aimed to investigate whether SIN has an anti-depressant-like effect in a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms.Material/MethodsA mouse model of depression was established and treated with different concentrations of SIN (30, 100, or 300 mg/kg). Then, behavioral tests, including sucrose preference test (SPT), forced swimming test (FST), and the tail suspension test (TST), were performed. The levels of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and proinflammatory cytokines (interleukin-1β [IL-1β] interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in the hippocampus of mice were detected by ELISA assay. The levels of p-p38, p-p65, NLRP3, ASC, and caspase-1 were measured by Western blot or/and qRT-PCR.ResultsThe results showed that SIN significantly relieved CUMSinduced depressive-like behaviors. Compared with the model mice, SIN treatment significantly increased the sucrose preference of the mice, and the immobility time in the forced swimming and the tail suspension test were shortened. In addition, SIN decreased CUMS-induced reduction in the concentrations of NE and 5-HT in the hippocampus of mice. SIN reduced CUMS-induced increases in the levels of IL-1β, IL-6, and TNF-α in the hippocampus of mice. Furthermore, activation of the p38MAPK-NF-κB pathway and the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome induced by CUMS were inhibited by SIN treatment.ConclusionsIn conclusion, our results indicate the antidepressantlike effects of SIN on chronic unpredictable mild stress-induced depression in a mouse model.
The regenerated Araneus ventricosus spider dragline silk protein fibrous scaffold with moderate strength and flexibility was fabricated by electrospinning and post treatment with 90 vol % acetone. The effect of collection method on the morphology of regenerated spider silk protein (RSSP) fibrous scaffold, the effects of the post treatment solvents and their concentrations on the molecular conformation, crystallinity and mechanical properties were studied. The results show that the morphology was affected by the solvent used in the coagulation bath. The molecular conformation, crystallinity and mechanical property of this scaffold were strongly affected by the kind of post treatment solvent and slightly influenced by its concentration when it was higher than 50 vol %. The degradation rate of this scaffold was very slow and resulting in little pH change of the degradation medium within 5 months. PC 12 cells were cultured on the electrospun RSSP fibrous scaffold and in its extraction fluid to examine the changes of PC 12 cells after different times of culture. The results show that the electrospun RSSP fibrous scaffold had good biocompatibility with PC 12 cells.
AIM:To explore whether antisense blocking of protein kinase C alpha (PKCα) would reverse multi-drug resistance (MDR) in the vincristine (VCR)-resistant human gastric cancer cell line SGC7901/VCR.
bVibrio vulnificus, which can lead to rapidly expanding cellulitis or septicemia, is present in the marine environment. Here, we present the draft genome sequence of strain B2, which was isolated from a septicemia patient in 2010.
BackgroundInduction of broad immune responses at mucosal site remains a primary goal for most vaccines against mucosal pathogens. Abundance of evidence indicates that the co-delivery of mucosal adjuvants, including cytokines, is necessary to induce effective mucosal immunity. In the present study, we set out to evaluate the role of a chemokine, CCL20, as an effective mucosal adjuvant for HIV vaccine.MethodsTo evaluate the role of CCL20 as a potent adjuvant for HIV vaccine, we examined its effects on antigen-specific antibody responses, level of antibody-secreting cells, cytokine production and intestinal homing of plasma cells in vaccine immunized mice.ResultsCCL20-incorporated VLP administered by mucosal route (intranasal (n = 10, p = 0.0085) or intravaginal (n = 10, p = 0.0091)) showed much higher potency in inducing Env-specific IgA antibody response than those administered by intramuscular route (n = 10). For intranasal administration, the HIV Env-specific IFN-γ(751 pg/ml), IL-4 (566 pg/ml), IL-5 (811 pg/ml) production and IgA-secreting plasma cells (62 IgA-secreting plasma cells/106 cells) in mucosal lamina propria were significantly augmented in CCL20-incorporated VLP immunized mice as compared to those immunized with Env only VLPs (p = 0.0332, 0.0398, 0.033, 0.0302 for IFN-γ, IL-4, IL-5, and IgA-secreting plasma cells, respectively).Further, anti-CCL20 mAb partially suppressed homing of Env-specific IgA ASCs into small intestine in mice immunized with CCL20-incorporated VLP by intranasal (62 decreased to 16 IgA- secreting plasma cells/106 cells, p = 0.0341) or intravaginal (52 decreased to 13 IgA- secreting plasma cells/106 cells, p = 0.0332) routes.ConclusionOur data indicated that the VLP-incorporated CCL20 can enhance HIV Env-specific immune responses in mice, especially those occurring in the mucosal sites. We also found that i.m. prime followed by mucosal boost is critical and required for CCL20 to exert its full function as an effective mucosal adjuvant. Therefore, co-incorporation of CCL20 into Env VLPs when combined with mucosal administration could represent a novel and promising HIV vaccine candidate.
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