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Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death （SCD） caused by hyperlipidemia combined with the restraint stress.

As a serious and elusive syndrome caused by infection, sepsis causes a high rate of mortality around the world. Our investigation aims at exploring the role and possible mechanism of specificity protein-1 (SP1) in the development of sepsis. A mouse model of sepsis was established by cecal ligation perforation, and a cellular model was stimulated by lipopolysaccharide (LPS), followed by determination of the SP1 expression. It was determined that SP1 was poorly expressed in the intestinal tissues of septic mice and LPS-treated cells. Next, we examined the interactions among SP1, histone deacetylase 4 (HDAC4), and high mobility group box 1 (HMGB1) and found that SP1 bound to the HDAC4 promoter to upregulate its expression, thereby promoting the deacetylation of HMGB1. Meanwhile, gain- or loss-of-function approaches were applied to evaluate the intestinal barrier dysfunction, oxidative stress, and inflammatory response. Overexpression of SP1 or underexpression of HMGB1 was observed to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory injury. Collectively, these experimental data provide evidence reporting that SP1 could promote the HDAC4-mediated HMGB1 deacetylation to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory response induced by sepsis, providing a novel therapeutic target for sepsis prevention and treatment.

Abstract Background Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. Methods First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. Results Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. Conclusion Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

The B7 family consists of activating and inhibitory molecules that regulate immune responses. Recent research demonstrated the roles of soluble B7-H3 (sB7-H3) and soluble B7-H1 (sB7-H1) in the blood serum of various tumors; however, none of these studies investigated the expression of these proteins in the cerebral spinal fluid (CSF) and blood serum of patients with glioma. The aim of the present study was to investigate the expression of B7-H3 and B7-H1 in the CSF, blood serum and tissues of patients with glioma and their correlation with clinicopathological data. Between January 2012 and November 2012, samples were obtained from 78 patients with glioma, four CSF samples were obtained from patients with a moderate traumatic brain injury, four brain tissue samples were obtained from patients with a traumatic brain injury and 40 blood serum samples were obtained from healthy individuals. The expression of B7-H3 and B7-H1 in the CSF, blood serum and tumor samples of the patients with high-grade glioma was found to be higher than that in the patients with low-grade glioma. However, no significant differences in sB7-H3 and sB7-H1 expression were observed in the blood serum of the patients with glioma compared with the healthy control subjects. In addition, the expression of sB7-H3 and sB7-H1 in the CSF of the patients with glioma was higher than that in the CSF of the patients with a moderate traumatic brain injury. Furthermore, in the patients with glioma, B7-H3 and B7-H1 expression in the CSF and tumor tissue, although not in the blood serum, correlated with the glioma grade. [ABSTRACT FROM AUTHOR]

summary. HDN attributed to the rare Rh variants has become more and more significant caused by anti-D, but the compatible blood is usually very difficult to obtain when exchange transfusion is required. We treated a 10-hour neonate of O, D + C + c − E − e + blood group with severe HDN due to anti-Rh17 with least incompatible blood typed O, D + C − c + E + e −. The neonatal hemolysis was relieved obviously and bilirubin was reduced gradually after exchange transfusion. The infant was discharged in good health 13 days after birth with 135.0 g/L, 28.0 μmol/L and 10.7 μmol/L of Hb, total bilirubin and direct bilirubin, respectively. No sequelae were observed in a three-year follow-up. The result suggesting that the least incompatible blood is an alternative choice for exchange transfusion in severe HDN due to anti-Rh17 in case that Rh17 antigen-negative blood is unavailable. [ABSTRACT FROM AUTHOR]