Mechanistic Investigation on the Regulation of FABP1 by the IL-6/miR-603 Signaling in the Pathogenesis of Hepatocellular Carcinoma.

BACKGROUND: Abnormal lipid metabolism is closely associated with the invasiveness and metastasis of cancer. Fatty acid-binding proteins (FABPs) play essential roles in lipid metabolism, and miRNAs can affect lipid metabolism by targeting FABPs. However, the exact mechanism is unknown. METHODS: FABP1 expression in HCC tissues was analyzed by immunochemistry with tissue microarrays. The lipid content was detected by Oil Red O staining, and the interaction between FABP1 and free fatty acid (FFA) was studied by a labeling and tracking method. miRNA arrays were used to detect the expression of miRNAs in IL-6-stimulated HCC cells. miR-603 expression was verified by qPCR. The proteins were checked by Western blot analysis. Gain and loss function evaluation was assessed by lentivirus and miRNA mimic transfection in Huh-7 cells, while reactive oxygen species (ROS) were detected by fluorescence. RESULTS: FABP1 expression was significantly decreased in approximately 90% (81/90) of HCC patients. FABP1 expression in adjacent tissues was closely associated with overall survival. Meanwhile, lipid was abundant in the adjacent tissues, yet significantly reduced in HCC tissues. FABP1 and FFA can promote each other for being uptaken by Huh-7 cells. FABP1 overexpression induced apoptosis and inhibited the proliferation, migration, invasion, and metastasis of Huh-7 cells. IL-6 treatment affected the expression of miRNAs, and miR-603 was overexpressed in HCC tissues. Also, miR-603 overexpression promoted the proliferation, migration, invasion, and metastasis of Huh-7 cells. Bioinformatic analysis predicted that miR-603 targets the 3'-UTR region of FABP1. However, miR-603 overexpression inhibited the expression of the FABP1 but increased the CPT1A, PPAR-α, and SREBP1 expressions. FABP1 overexpression reduced ROS in HCC cells, while miR-603 can reverse these effects. CONCLUSION: Our results indicate that in the pathogenesis of HCC, IL-6 induces miR-603 expression, which subsequently inhibits FABP1 expression, promotes the lipid metabolism- and synthesis-related proteins, and finally increases the cellular oxidative stress level and leads to the metastasis of HCC.

Clinical characteristics and electroencephalogram analysis of levetiracetam in the treatment of children with febrile seizure recurrence.

Febrile seizure is the most common neurologic disorder in infants and children. This study aimed to elaborate safe and effective therapy for preventing FS recurrence by levetiracetam (LEV). A prospective study was performed in two groups of children, the no treatment group (n=51, 24.1±9.0 months) and the LEV treatment group (n=45, 23.3±8.9 months). The findings demonstrated that a significant difference (P<0.01) was observed between the no treatment group 51.0% (26/51) and LEV treatment group 15.5% (7/45) in terms of FS recurrence after 50 weeks. FS recurrence/fever episode was 12.4% (12/97) in the LEV treatment group and 51.8% (57/110) in the no treatment group. Furthermore, LEV administration significantly improved (P<0.001) epileptiform + nonspecific EEG abnormalities (17.8%; 8/45), as compared with the no treatment group (68.6%; 35/51). In conclusion, LEV could function as an effective therapeutic agent for the prevention of FS recurrence and reducing the frequency of fever episodes. Furthermore, LEV administration significantly improved nonspecific EEG abnormalities, which may be used as a clinical monitoring index for LEV treatment in patients with FS.

[Research progress of TRPV4 and cerebral ischemic reperfusion injury].

Transient receptor potential vanilloid 4 (TRPV4) channel is a member of transient receptor potential superfamily. TRPV4 is selectively permeable to calcium. Activation of the TRPV4 channel induces an increase in intracellular calcium concentration and plays an important role under physiological and pathological conditions. Especially, there is evidence showing that TRPV4 is involved in cerebral ischemic reperfusion injury. The present paper reviewed some research progress about the role of TRPV4 in cerebral ischemic reperfusion injury.

[Risk factors for multidrug-resistant Klebsiella pneumoniae sepsis in children].

OBJECTIVE: To explore the risk factors for sepsis caused by multidrug-resistant Klebsiella pneumonia (MDR-KP) and to provide a reference for the prevention of MDR-KP sepsis and rational use of antibiotics. METHODS: A retrospective case-control study of 41 children with MDR-KP sepsis (case group) and 53 pediatric patients without MDR-KP sepsis (control group) between March 2010 and Febrary 2014 was conducted. Multiple logistic regression analysis was performed to estimate the independent risk factors for MDR-KP sepsis. RESULTS: Compared with the control group, the case group had a longer length of stay in the PICU before infection (P<0.05), more prolonged duration of mechanical ventilation before infection (P<0.05), a larger total number of days of mechanical ventilation (P<0.05), more days of antibiotic use before infection (P<0.05), more types of antibiotics used before infection (P<0.05), and a higher mortality (P<0.05). The logistic regression analysis showed that more types of antibiotics used before infection and use of third-generation cephalosporin and carbapenems were independent risk factors for MDR-KP sepsis (P<0.05). CONCLUSIONS: Rational use of antibiotics is an effective measure to prevent MDR-KP sepsis.

In vitro evaluation of dual agonists for PPARγ/ß from the flower of Edgeworthia gardneri (wall.) Meisn.

ETHNOPHARMACOLOGICAL RELEVANCE: In Tibet, the flower of Edgeworthia gardneri (Wall.) Meisn., locally named "Lvluohua, [symbols: see text]", has been traditionally used to treat diabetes mellitus for many years. AIM OF THIS STUDY: To evaluate the activity of dual agonists for PPARγ/ß from the flower of E.gardneri in vitro. MATERIALS AND METHODS: HeLa cells were transiently co-transfected with the re-constructed plasmids of pBIND-PPARγ-LBD or pBIND-PPARß-LBD and rL4.35. The activities of crude extracts, secondary fractions and compounds from the flower of E.gardneri were evaluated with the transfected cells. Rosiglitazone (at 0.5 µg/mL) and L-165041 (at 0.5 µg/mL) were used as the positive controls for PPARγ and PPARß respectively. RESULTS: The results demonstrated that n-hexane, ethyl acetate and n-butanol extracts from the flower of E.gardneri were able to significantly activate PPARγ and PPARß respectively, and the activity of ethyl acetate extract was much better. We further observed that, among the 11 secondary fractions of ethyl acetate extract, the fr. 9 could activate PPARγ and PPARß significantly. Moreover, umbelliferone (from fr.9) and pentadecanoic acid could activate PPARγ and PPARß at the same time. CONCLUSIONS: The extracts from the flower of E.gardneri could significantly activate PPARγ and PPARß. Besides, umbelliferone and pentadecanoic acid isolated from the flower of E.gardneri were the new agonists for PPARγ and PPARß.

[Investigation of disease spectrum in the PICU of Shengjing Hospital of China Medical University between 2005 and 2012].

OBJECTIVE: To summarize the spectrum of disease and common diseases that cause death in children admitted to the Pediatric Intensive Care Unit (PICU), Shengjing Hospital of China Medical University between 2005 and 2012. METHODS: A retrospective analysis was carried out on the clinical data of 4484 children admitted to the PICU of Shengjing Hospital between 2005 and 2012. RESULTS: Acute bronchopneumonia, which was found in 1099 (24.51%) of the 4484 cases, was the most common disease in the PICU between 2005 and 2012. The incidence of intracranial infection, sepsis, hand-foot-mouth disease and trauma showed an increasing trend from 2005 to 2012, but that of non-traumatic intracranial hemorrhage, epilepsy and congenital heart disease showed a decreasing trend. The mortality decreased from 11.5% in 2005 to 3.1% in 2012, and the overall mortality was significantly higher in 2005-2008 than in 2009-2012 (11.98% vs 4.41%; P<0.01). The main causes of death included severe acute bronchial pneumonia, severe sepsis, complex congenital heart disease, severe cerebral trauma, respiratory failure, severe hand-foot-mouth disease, acute poisoning and circulatory failure. CONCLUSIONS: Acute bronchopneumonia was the most common disease in the PICU of Shengjing Hospital between 2005 and 2012, but the spectrum of disease changed over time. The mortality showed a decreasing trend among the children in the PICU between 2005 and 2012, and the main causes of death included severe acute bronchial pneumonia and severe sepsis.

Development of a cell-based high-throughput peroxisome proliferator-activated receptors (PPARs) screening model and its application for evaluation of the extracts from Rhizoma Coptis.

To date, peroxisome proliferator-activated receptors (PPARs) are becoming the new therapeutic targets for the treatment of metabolic diseases, such as Type 2 diabetes, obesity, and cardiovascular disease. In this study, a cell-based high-throughput PPARs (PPARα/ß/γ) model was developed for the screening of PPARs agonists. The screening conditions were evaluated through analyzing the expression value of luciferase. Finally, 24 h of drug acting time, 5 times of the dilution factor of luciferase zymolyte, and about 2 × 10(4) cells/ well on HeLa cells in 96-well plates were used, respectively. Furthermore, the quality of high-throughput screening (HTS) in stability and reliability was evaluated by the Z'-factor. Additionally, different extracts of Rhizoma Coptis and berberine were tested by the developed method. The results suggested that both the EtOAc extract and berberine were able to activate PPARα/ß/γ, and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine. In conclusion, the developed HTS assay is a simple, rapid, stable, and specific method for the screening of PPARs natural agonists.