No abstract

This study investigated the effects of the exopolysaccharide from Lactiplantibacillus plantarum JLAU103 (EPS103) on the intestinal immune response, oxidative stress, intestinal mucosal barrier, and microbial community in cyclophosphamide-induced immune-suppressed mice. The results showed that EPS103 promoted the secretion of cytokines and the generation of secretory immunoglobulin A and mucin-2 in the small intestine of mice, which might be related to the activation of the MAPK pathway. Additionally, EPS103 protected against oxidative stress by activating antioxidation enzymes and Nrf2/Keap1 pathways. It also improved the intestinal physical barrier functions via regulating the ratio of villous height to crypt depth and upregulating the expression of tight-junction proteins. Meanwhile, EPS103 promoted the generation of short-chain fatty acids (SCFAs) and modulated the constituents of gut microbiota. These results suggested that EPS103 may modulate the intestinal immunoresponse relying on the regulation of SCFA production and gut microbiota in immunosuppressed mice, resulting in the activation of systemic immunity.

Oxidative stress is an important factor in the pathogenesis of insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Bioactive peptides from nuts have been shown to alleviate oxidative stress...

One of the hallmarks of placental dysfunction is the increase of oxidative stress. This process, along with the overexpression of the inflammasome, creates a downward spiral that can lead to a series of severe pregnancy complications. Ferroptosis is a form of iron-mediated cell death involving the accumulation of reactive oxygen species, lipid peroxides. In this study, the rats’ model of oxidative stress abortion was established, and hydrogen peroxide (H2O2) was used to establish a cellular model of placental oxidative stress. RNAi, western blot, and immunofluorescence were used to evaluate the expression of specific markers of ferroptosis and the expression of the inflammasome in placental trophoblast cells. We observed excessive levels of ferroptosis and inflammasome activation in both rats’ model and placental trophoblast cell model of oxidative stress. When the NLRP1 inflammasome was silenced, the expression levels of GSH and Glutathione peroxidase 4 (GPX4) were increased, while the expression levels of transferrin receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), Superoxide dismutase (SOD), and Malondialdehyde (MDA) were decreased. However, when an NLRP1 activator was applied, we observed the opposite phenomenon. We further explored the mechanisms underlying the actions of ferroptosis to inflammasomes. The expression levels of NLRP1, NLRP3, IL-1β, and caspase-1 were positively correlated with the ferroptosis following the application of ferroptosis inhibitor (ferrostatin-1) and ferroptosis activator (erastin). The existence of ferroptosis was demonstrated in the oxidative stress model of placental trophoblast cells; the results also indicate ferroptosis is linked with the expression of NLRP1 inflammasome. These findings may provide a valuable therapeutic target for the pathogenesis of pregnancy-related diseases.

No abstract

Y-box binding protein 1 (YB-1) is manifested as its involvement in cell proliferation and differentiation and malignant cell transformation. Overexpression of YB-1 is associated with glioma progression and patient survival. The aim of this study is to investigate the influence of YB-1 knockdown on glioma cell progression and reveal the mechanisms of YB-1 knockdown on glioma cell growth, migration, and apoptosis. It was found that the knockdown of YB-1 decreased the mRNA and protein levels of YB-1 in U251 glioma cells. The knockdown of YB-1 significantly inhibited cell proliferation, colony formation, and migration in vitro and tumor growth in vivo. Proteome and phosphoproteome data revealed that YB-1 is involved in glioma progression through regulating the expression and phosphorylation of major proteins involved in cell cycle, adhesion, and apoptosis. The main regulated proteins included CCNB1, CCNDBP1, CDK2, CDK3, ADGRG1, CDH-2, MMP14, AIFM1, HO-1, and BAX. Furthermore, it was also found that YB-1 knockdown is associated with the hypo-phosphorylation of ErbB, mTOR, HIF-1, cGMP-PKG, and insulin signaling pathways, and proteoglycans in cancer. Our findings indicated that YB-1 plays a key role in glioma progression in multiple ways, including regulating the expression and phosphorylation of major proteins associated with cell cycle, adhesion, and apoptosis.

No abstract

Recurrent spontaneous abortion (RSA) remains a critical and challenging problem in reproduction. To discover novel biomarkers for RSA, ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) metabolomics approach was applied to detect RSA serum metabolic profiles and explore its possible pathogenesis and mechanism. The abortion rat model was established, and a metabolomics analysis was performed to evaluate the differentially expressed metabolites between the control and model groups. Immunohistochemistry (IHC), qRT-PCR, and Western blot further examined the expression of Arachidonic acid metabolism-related genes in uterus tissues. To identify arachidonic acid metabolism-related changes in RSA, ELISA’s potential mechanisms were further confirmed in serum. Ninety-one metabolites were significantly different between the two groups, as indicated by a VIP ≥1, fold change ≥1. The metabolic pathways involving arachidonic acid metabolism pathway (P = 0.00044) are related to RSA. Verification by experimental showed that compared with the control rats, the expression of the COX-1, COX-2, PTGFR, and TBXA2R genes associated with the arachidonic acid metabolism pathway has significantly increased the uterus and serum of RSA rats (P < 0.05). Regulation of the arachidonic acid metabolism pathway might serve as a promising therapeutic strategy for relieving RSA women’s symptoms.