MiR-338-3p Is a Biomarker in Neonatal Acute Respiratory Distress Syndrome (ARDS) and Has Roles in the Inflammatory Response of ARDS Cell Models

To investigate the association between serum miR-338-3p levels and neonatal acute respiratory distress syndrome (ARDS) and its mechanism. The relative miR-338-3p expression in serum was detected by quantitative real-time RT-PCR. Interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) levels were detected by ELISAs. A receiver operating characteristic (ROC) curve analysis of serum miR-338-3p evaluated the diagnosis of miR-338-3p in neonatal ARDS. Pearson’s correlation analysis evaluated the correlation between serum miR-338-3p and neonatal ARDS clinical factors. Flow cytometry evaluated apoptosis, and a CCK-8 assay assessed cell viability. A luciferase assay evaluated the miR-338-3p/AKT3 relationship. The miR- 338-3p expression was decreased in neonatal ARDS patients and in lipopolysaccharide (LPS)-treated cells. The ROC curve showed the accuracy of miR-338-3p for evaluating neonatal ARDS patients. The correlation analysis demonstrated that miR-338-3p was related to PRISM-III, PaO2/FiO2, oxygenation index, IL-1β, IL-6, and TNF-α in neonatal ARDS patients. MiR-338-3p overexpression inhibited the secretion of inflammatory components, stifled cell apoptosis, and LPS-induced advanced cell viability. The double-luciferase reporter gene experiment confirmed that miR-338-3p negatively regulates AKT3 mRNA expression. Serum miR-338-3p levels were related to the diagnosis and severity of neonatal ARDS, which may be attributed to its regulatory effect on inflammatory response in ARDS

Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice

SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6-knockout mice generated by the Fabp4-Cre line (Sirt6f/f:Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line (Sirt6f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis

COULD LONG-TERM EXERCISE IMPROVE THE OBSTACLE-CROSSING ABILITY OF ELDERLY WOMEN? EFFECTS OF TAI CHI AND AEROBIC DANCE EXERCISES

The purpose of this study was to evaluate the effects of long-term exercises (TaiChi (TC), aerobic dance) on the obstacle-crossing ability of elderly women, as well as to identify whether the exercise could considerably improve stability. Forty-five elderly women include TC, aerobic dance and no exercising groups participated in our study. They walked a short distance to cross the obstacle (30% of leg length). Results showed that long-term exercise had a positive effect on muscle strength and the practitioners used an obstacle-crossing strategy that increasing the force in medial–lateral and anterior-posterior directions of the trailing foot to cross obstacle. The TC strategy was better than aerobic dance in improving balance and increasing the height of the leg during obstacle-crossing

EFFECT OF ILLUMINATION ON THE OBSTACLE-CROSSING BEHAVIORS OF ELDERLY WOMEN

The purpose of this study was to determine how illumination affect elderly women when stepping over obstacles. A motion capture system was used to collect the kinematics data of 15 elderly women. The results revealed that the obstacle-crossing behavior of elderly women were affected by the illumination. Compare to the high illumination condition, the elderly women decreased their toe distance and heel distance (

MicroRNA-33b inhibits liver cancer cell proliferation, migration and invasion via down-regulation of Fli-1 and MMP-2 protein expressions

Purpose: To study the influence of microRNA-33b (miR-33b) on liver cancer cell proliferation, migration and invasiveness, and the mechanism involved. Methods: MicroRNA-33b or Fli-1 overexpression plasmid was transfected into liver cancer (SMMC7721) cells. Cell proliferation, migration, and invasiveness were determined using cell counting kit 8 (CCK-8), scratch test, and Transwell invasion assay, respectively. The amounts of miR-33b and Fli-1 in liver cancer tissues,  paracancerous normal tissues, and miR-33b overexpression and control groups were measured using qRT-PCR, while protein concentration of matrix metalloproteinase 2 (MMP-2) was assayed using Western blotting. Results: Fli-1 protein was markedly upregulated in liver cancerous cells, relative to paracancerous normal tissues (p < 0.05). MicroRNA-33b protein expression was also significantly upregulated in miR33b overexpression group, but the corresponding Fli-1 expression was downregulated in miR-33b overexpression group, relative to control (p < 0.05). MicroRNA-33b overexpression significantly and time-dependently inhibited SMMC7721 cell proliferation and migration, but it reduced the degree of apoptosis (p < 0.05). Liver cancer (SMMC7721) cells in miR-33b overexpression group were less invasive than the control group (p < 0.05). Similarly, miR-33b overexpression significantly downregulated MMP-2 protein expression in SMMC7721cells (p < 0.05). Conclusion: Overexpression of miR-33b suppresses the proliferation, migratory and invasive potential of hepatic cancer cells via down-regulation of Fli-1 and MMP-2 protein expression. This finding may be useful in the identification of new liver cancer drugs

Genetic changes in fetal cerebral cortex after maternal exposure to sevoflurane

Purpose: To investigate the acute changes in transcriptome of radial glial progenitor cells after maternal exposure to sevoflurane.Methods: Two groups of sample data were collected from the data set in the GEO database. Pregnant mice in sevoflurane group were exposed to 2.5 % sevoflurane for 6 h on day 14.5 of the pregnancy, while the mice in control group were exposed to 100 % oxygen for 6 h. At the end of the exposure period, the cerebral cortex of the two groups of fetuses was isolated and analyzed by RNA sequencing. Differentially expressed genes (DEG) were analyzed using limma package of R language. The Gene Ontology (GO) and KEGG pathway enrichment were based on DEG through a cluster profile package of R. Moreover, protein-protein interactions (PPI) network construction and central gene prediction were carried out using a string database and R package.Results: Bioinformatics analysis revealed 289 up-regulated genes and 311 down-regulated DEGs, respectively. Gene Ontology and KEGG enrichment analysis revealed terms related to neural development and transcriptional function. Based on the central genes of the PPI network, it was found that certain genes may play significant roles in the regulation of neural development. These genes are hnRNPM, AURKA, NCBP, SRSF6, ASF1B, HNRNPA2B1, DDX21, H3F3B, KPNA2 and ABCE1 (p < 0.05).Conclusion: The findings of this study suggest that hub genes and a variety of signal pathways may play key roles in the development of radial glial progenitor cells

CI431, an Aqueous Compound from Ciona intestinalis L., Induces Apoptosis through a Mitochondria-Mediated Pathway in Human Hepatocellular Carcinoma Cells

In the present studies, a novel compound with potent anti-tumor activity from Ciona intestinalis L. was purified by acetone fractionation, ultrafiltration, gel chromatography and High Performance Liquid Chromatography. The molecular weight of the highly purified compound, designated CI431, was 431Da as determined by HPLC-MS analysis. CI431 exhibited significant cytotoxicity to several cancer cell types. However, only a slight inhibitory effect was found when treating the benign human liver cell line BEL-7702 with the compound. To explore its mechanism against hepatocellular carcinoma, BEL-7402 cells were treated with CI431 in vitro. We found that CI431 induced apoptotic death in BEL-7402 cells in a dose- and time-dependent manner. Cell cycle analysis demonstrated that CI431 caused cell cycle arrest at the G2/M phase, and a sub-G1 peak appeared after 24 h. The mitochondrial-mediated pathway was implicated in this CI431-induced apoptosis as evidenced by the disruption of mitochondrial membrane potential. The results suggest that the CI431 induces apoptosis in BEL-7402 human hepatoma cells by intrinsic mitochondrial pathway

Cornel Iridoid Glycoside Inhibits Tau Hyperphosphorylation via Regulating Cross-Talk Between GSK-3β and PP2A Signaling

Neurofibrillary pathology contributes to neuronal dysfunction and correlates with the clinical progression of Alzheimer’s disease (AD). Tau phosphorylation is mainly regulated by a balance of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) activities. Cornel iridoid glycoside (CIG) is a main component extracted from Cornus officinalis. The purpose of this study was to investigate the effects of CIG on GSK-3β and PP2A, thus to explore the mechanisms of CIG to inhibit tau hyperphosphorylation. The rat model of tau hyperphosphorylation was established by intraventricular injection of wortmannin and GF-109203X (GFX) to activate GSK-3β. The results showed that intragastrical administration of CIG inhibited tau hyperphosphorylation in the brain of rats induced by wortmannin/GFX. The results in vivo and in vitro exhibited that CIG inhibited tau hyperphosphorylation and GSK-3β over-activation. In the mechanism of action, CIG’s attenuating GSK-3β activity was found to be dependent on PI3K/AKT signaling pathway. PP2A catalytic C subunit (PP2Ac) siRNA abrogated the effect of CIG on PI3K/AKT/GSK-3β. Additionally and crucially, we also found that CIG inhibited the demethylation of PP2Ac at Leu309 in vivo and in vitro. It enhanced PP2A activity, decreased tau hyperphosphorylation, and protected cell morphology in okadaic acid (OA)-induced cell model in vitro. PP2Ac siRNA abated the inhibitory effect of CIG on tau hyperphosphorylation. Moreover, CIG inhibited protein phosphatase methylesterase-1 (PME-1) and demethylation of PP2Ac, enhanced PP2A activity, and decreased tau hyperphosphorylation in PME-1-transfectd cells. Taken together, CIG inhibited GSK-3β activity via promoting P13K/AKT and PP2A signaling pathways. In addition, CIG also elevated PP2A activity via inhibiting PME-1-induced PP2Ac demethylation to inhibit GSK-3β activity, thus regulated the cross-talk between GSK-3β and PP2A signaling and consequently inhibited tau hyperphosphorylation. These results suggest that CIG may be a promising agent for AD therapy