Saikosaponin a Ameliorates LPS-Induced Acute Lung Injury in Mice.

The purpose of this study was to investigate the protective effects of Saikosaponin a (SSa), a triterpene saponin derived from Radix bupleuri, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) using a murine model. The mice were given SSa 1 h after intranasal instillation of LPS. Then, lung histopathological examination, the wet/dry (W/D) ratio, myeloperoxidase (MPO), and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were detected in this study. The results showed that SSa reduced lung pathological injury induced by LPS. Furthermore, LPS-induced lung W/D ratio, MPO activity, and inflammatory cytokines TNF-α and IL-1ß in BALF were significantly inhibited by SSa. In addition, SSa suppressed LPS-induced NF-κB activation and NLRP3 inflammasome expression. In conclusion, we found that SSa played a critical anti-inflammatory effect through inhibition of NF-κB and NLRP3 signaling pathways and protected against LPS-induced ALI.

Dishevelled-1 (Dvl-1) protein: a potential participant of oxidative stress induced by selenium deficiency.

Oxidative stress induced by selenium deficiency has been shown to be associated with cardiovascular diseases. Nevertheless, the mechanism associated with oxidative stress induced by selenium deficiency is poorly understood. In the present study, 36 weaning C57BL/6 mice were randomly divided into 4 groups as follows: control (n =9), 4-week selenium deficiency (n =9), 8-week selenium deficiency (n = 9), and 12-week selenium deficiency (n =9). The levels of myocardial glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by Western blotting or commercial kits. Real-time PCR was performed to detect the mRNA expression of dishevelled-1 (Dvl-1) protein. Western blotting was conducted to evaluate the protein expression levels of Dvl-1 and ß-catenin. Our results demonstrated that the levels of GPx and SOD were significantly reduced, along with an increase in MDA in selenium-deficient mice. Importantly, Dvl-1 and ß-catenin were clearly upregulated under oxidative stress. Collectively, our findings indicate that Dvl-1 may be an underlying participant of oxidative stress induced by selenium deficiency.

[Relationship between antacid therapy and hospital acquired pneumonia in critically ill patients: a meta-analysis].

OBJECTIVE: To systematically review the effect of antacid medication on stress-related mucosal disease (SRMD) bleeding, hospital acquired pneumonia (HAP), and hospital mortality in critically ill patients admitted to intensive care unit (ICU). METHODS: Related articles were retrieved from Medline Database (from January 1980 to December 2012). Randomized control trials (RCTs) focused on comparison between antacid and sucralfate were collected, and then a meta-analysis was performed. RESULTS: Twelve studies including a total of 2537 patients admitted to ICU were qualified for analysis. Antacid medication significantly increased the incidence of HAP when compared with sucralfate in 11 trials [19.36% (249/1286) vs. 15.23% (184/1208), odds ratio (OR)=1.27, 95% confidence interval (95%CI): 1.03-1.57, P=0.02]. Subgroup analyses showed that antacid therapy significantly reduce the incidence of clinically significant bleeding compared with sucralfate [1.80% (12/667) vs. 3.86% (26/673), OR=0.46, 95%CI: 0.23-0.91, P=0.03], however, it did not lower the incidence of overt bleeding [7.09% (40/564) vs. 7.35% (36/490), OR=1.00, 95%CI: 0.62-1.62, P=0.99]. There was no significant difference between antacid group and sucralfate group on neither ICU mortality nor hospitalization mortality in 11 studies [25.58% (288/1126) vs. 23.65% (268/1133), OR=1.11, 95%CI: 0.92-1.35, P=0.28]. CONCLUSIONS: Antacid therapy used in critically ill patients may increase the incidence of HAP while reduce the rate of upper gastrointestinal bleeding, while it exerts no influence on mortality rate when compared with sucralfate treatment in this meta-analysis. It is imperative to restrict the overuse of such medication, and further RCTs focused on indication and withdrawal should be encouraged.

Recombinant Escherichia coli Trx-JZTX-III represses the proliferation of mouse hepatocellular carcinoma cells through induction of cell cycle arrest.

The aim of the present study was to investigate the effects of recombinant Escherichia coli (E. coli) Trx-jingzhaotoxin (JZTX)-III on cell growth in the mouse hepatocellular carcinoma (HCC) cell line Hepa1-6. The JZTX-III gene sequence was synthesized and cloned into the pET-32a(+) vector to construct the recombinant fusion protein Trx-JZTX-III, which was subsequently purified. Hepa1-6 cells were treated with 0 to 1,000-µg/ml concentrations of Trx-JZTX-III; this was demonstrated to affect cell viability, as determined by the 3-(4,5-dimethylthiazol­2-yl)-2,5-diphenyltetra-zolium bromide (MTT) assay. The expression of the proliferating cell nuclear antigen (PCNA) protein was investigated using western blot analysis. A colony formation assay was used to determine Hepa1-6 cell proliferation, and the migration ability of cells was determined using a wound­healing assay. Additionally, flow cytometry was employed to observe changes in the cell cycle. The MTT assay and quantification of PCNA expression indicated that recombinant E. coli Trx-JZTX-III significantly repressed the proliferation of Hepa1-6 cells. Colony formation and the migration of malignant cells was inhibited following treatment with recombinant E. coli Trx-JZTX-III. Flow cytometry showed that recombinant E. coli Trx-JZTX-III induced G0/G1 cell cycle arrest. In conclusion, recombinant E. coli Trx-JZTX-III functions as a tumor suppressor drug in mouse HCC and its underlying mechanism may involve the induction of G0/G1 cell cycle arrest.

MicroRNA-30b-5p is involved in the regulation of cardiac hypertrophy by targeting CaMKIIδ.

BACKGROUND: MicroRNAs (miRNAs) participate in the regulation of cardiac hypertrophy. However, it remains largely unknown as to how miRNAs are integrated into the hypertrophic program. Ca/calmodulin-dependent protein kinase II (CaMKII) is a hypertrophic signaling marker. It is not yet clear which miRNAs can regulate CaMKIIδ. PURPOSE: In this study, we identified which miRNAs could regulate CaMKIIδ and how to regulate CaMKIIδ. METHODS: Through computational and expression analyses, miR-30b-5p was identified as a candidate regulator of CaMKIIδ. Quantitative expression analysis of hypertrophic models demonstrated significant down-regulation of miR-30b-5p compared with control groups. Luciferase reporter assay showed that miR-30b-5p could significantly inhibit the expression of CaMKIIδ. Moreover, through gain-of-function and loss-of-function approaches, we found miR-30b-5p could negatively regulate the expression of CaMKIIδ and miR-30b-5p was a regulator of cardiac hypertrophy. CONCLUSION: Our study demonstrates that the expression of miR-30b-5p is down-regulated in cardiac hypertrophy, and restoration of its function inhibits the expression of CaMKIIδ, suggesting that miR-30b-5p may act as a hypertrophic suppressor.

Tetrodotoxin attenuates isoproterenol-induced hypertrophy in H9c2 rat cardiac myocytes.

Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either α- or ß- adrenergic stimulation. The present study was carried out to determine whether the reversible sodium channel blocker tetrodotoxin (TTX) exerts a direct anti-hypertrophic effect on isoproterenol (ISO)-induced cell hypertrophy and find the underlying mechanism that regulate [Na(+)]( i ). The experiments were performed on cultured H9c2 cells exposed to ISO (10 µM) alone or combined with TTX (1 µM) for 48 h. Our results showed that ISO significantly increased cell surface area by 30 % and atrial natriuretic peptide gene expression by nearly twofold (p < 0.05 for both). These effects were associated with a significant reduction in the gene expression of Na(+)/K(+)-ATPase isoforms α2 and α3, whereas the α1 isoform was unaffected. Conversely, ISO increased Na(+)-H(+) exchanger 1 (NHE-1) gene expression by approximately 40 % and significantly increased [Na(+)]( i ) level by 50 % (p < 0.05 for both). ISO was also found to significantly increase aquaporin 4 gene expression by nearly ninefold (p < 0.05). All these effects were prevented when identical experiments were carried out in the presence of TTX, but the expression of NHE-1. The expression of sodium channel protein type 5 subunit alpha was unaffected by either ISO or TTX. When taken together, these studies show that TTX attenuates the hypertrophic effect of ISO and suggest a possible approach to limiting ISO-induced hypertrophy in clinical treatment.