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1.  Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma 
Molecular Cancer  2015;14(1):10.
Background
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.
Methods and results
We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis.
Conclusion
This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation.
doi:10.1186/s12943-014-0274-0
PMCID: PMC4320626  PMID: 25622857
Alcohol; Angiogenesis; Human hepatocellular cancer; Metastasis; Reactive oxygen species
2.  Dietary and inhalation exposure to polycyclic aromatic hydrocarbons and urinary excretion of monohydroxy metabolites – a controlled case study in Beijing, China 
Daily dietary and inhalation exposures to 16 parent polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 13 monohydroxy metabolites (OHPAHs) were monitored for 12 non-smoking university students in Beijing, China, during a controlled feeding experiment. The relationship between the urinary excretion of OHPAHs and the uptake of PAHs was investigated. The results suggest severe exposure of the subjects to PAHs via both dietary and inhalation pathways. Large increase of most urinary OHPAHs occurred after the ingestion of lamb kabob. Higher concentrations of OHPAHs were observed for female subjects, with the intakes of parent PAHs lower than those by males, likely due to the gender differences in metabolism. It appears that besides 1-PYR, metabolites of PHE could also be used as biomarkers to indicate the short-term dietary exposure to PAHs and urinary 3-BaA may serve as the biomarker for inhalation intake of high molecular weight PAHs.
doi:10.1016/j.envpol.2013.10.005
PMCID: PMC4299857  PMID: 24177434
Polycyclic aromatic hydrocarbons; dietary exposure; urinary excretion; biomarkers
3.  Silicon Improves Maize Photosynthesis in Saline-Alkaline Soils 
The Scientific World Journal  2015;2015:245072.
The research aimed to determine the effects of Si application on photosynthetic characteristics of maize on saline-alkaline soil, including photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (E), and intercellular CO2 concentration (Ci) of maize in the field with five levels (0, 45, 90, 150, and 225 kg·ha−1) of Si supplying. Experimental results showed that the values of Pn, gs, and Ci of maize were significantly enhanced while the values of E of maize were dramatically decreased by certain doses of silicon fertilizers, which meant that Si application with proper doses significantly increased photosynthetic efficiency of maize in different growth stages under stressing environment of saline-alkaline soil. The optimal dose of Si application in this experiment was 150 kg·ha−1 Si. It indicated that increase in maize photosynthesis under saline-alkaline stress took place by Si application with proper doses, which is helpful to improve growth and yield of maize.
doi:10.1155/2015/245072
PMCID: PMC4300146  PMID: 25629083
4.  Stevens–Johnson Syndrome and toxic epidermal necrolysis: a multi-aspect comparative 7-year study from the People’s Republic of China 
Background
Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous drug reactions. They are differentiated based on the fraction of the body surface area affected. Optimal therapy for SJS and TEN is a controversial issue.
Objective
We compared the treatments given to and the clinical outcomes of 39 cases of SJS and 48 cases of TEN seen at a single institution between January 2007 and December 2013 for better understanding of the clinical characteristics and development of the two conditions.
Methods
Demographic data, clinical characteristics, treatments given, and therapeutic responses observed were retrospectively collected.
Results
The incidence rates of hypoproteinemia and secondary infections are significantly higher in TEN than in SJS (P=0.001 and P=0.002, respectively). The corticosteroid dose did not influence the time from the initiation of therapy to control of the lesions in SJS, but increasing the dosage of corticosteroids progressively decreased the time from the initiation of therapy to control of the lesions in TEN. With increases in the utilization ratio of intravenous immunoglobulin (IVIG), the length of the hospital stay became shorter, whereas the time from the initiation of therapy to control of the lesions remained the same in SJS. However, for TEN, both the length of the hospital stay and the time from the initiation of therapy to control of the lesions became shorter with increases in the utilization ratio of IVIG.
Conclusion
SJS and TEN are two variants of the same spectrum, and they differ from each other not only in the severity of epidermal detachment but also in other clinical parameters and their distinct clinical courses. Thus, differential treatment of both conditions may have benefits for their prognosis.
doi:10.2147/DDDT.S71736
PMCID: PMC4271784  PMID: 25548516
corticosteroids; intravenous immunoglobulin; Stevens–Johnson Syndrome; toxic epidermal necrolysis; cutaneous drug reaction
5.  Influence of Hydroxyapatite-Coated and Growth Factor–Releasing Interference Screws on Tendon-Bone Healing in an Ovine Model 
Purpose
Our purpose was to determine whether a bioresorbable interference screw coated with a hydroxyapatite-based mineral layer designed to release an engineered peptide growth factor (linkBMP-2 [where “BMP-2” indicates bone morphogenetic protein 2]) improved tendon-bone healing compared with a screw without coating.
Methods
Tagged linkBMP-2 peptides were used to quantify binding efficiency and release kinetics on 9 mineral-coated BIORCI screws (Smith & Nephew, Andover, MA). Fourteen mature female sheep were used in this study. In each of the 14 sheep, each stifle was randomized to either receive a linkBMP-2–coated or uncoated interference screw (n ± 14 per treatment). The sheep were euthanized at 6 weeks after surgery. Eight sheep were subjected to biomechanical testing for peak load at failure and stiffness, and six sheep were used for histologic analysis according to a semiquantitative scoring scale.
Results
The linkBMP-2 molecule bound efficiently to the surface of mineral-coated interference screws. Over 80% of the initially bound linkBMP-2 was released during a 6-week time frame in vitro. Peak load at failure in the linkBMP-2–coated interference screw group (mean ± SD, 449.3 ± 84.7 N) was not significantly different from that in the uncoated group (421.0 ± 61.8 N) (P = .22). Stiffness in the linkBMP-2–coated interference screw group (157.3 ± 39.6 N/mm) was not significantly different from that in the uncoated group (140.6 ± 20.3 N/mm) (P = .12). Histologic analysis showed that the tendons in the linkBMP-2–coated interference screw group had higher scores (better) than the uncoated group. In the linkBMP-2–coated interference screw group, mesenchymal cells were present at the interface between screw and tendon, whereas these cells were not present in the uncoated group.
Conclusions
We found that linkBMP-2 can be bound onto a mineral-coated BIORCI interference screw surface and subsequently released from the screw surface in a sustained manner. The histologic result of this study showed that the linkBMP-2–coated interference screw significantly improved the histologic scores of early tendon-bone healing in this sheep model.
Clinical Relevance
This linkBMP-2 coating material may improve early tendon/ligament fixation.
doi:10.1016/j.arthro.2009.06.008
PMCID: PMC4243967  PMID: 19962070
rhBMP-2; ACL; Tendon-bone healing; Growth factors; Interference screw; Sheep
6.  The association of asthma education centre characteristics on hospitalizations and emergency department visits in Ontario: a population-based study 
Background
International guidelines recommend patient education as an essential component of optimal asthma management. Since 1990 hospital-based asthma education centres (AECs) have been established in Ontario, Canada. It is unknown whether patient outcomes are related to the level of services provided.
Methods
Using linked, population-based health administrative and hospital survey data we analyzed a population of patients aged 2 to 55 years with a hospitalization for asthma (N = 12 029) or a high acuity asthma emergency department (ED) visit (N = 63 025) between April 2004 and March 2007 and followed for three years. Administrative data documenting individuals’ attendance at AECs were not available. Poisson models were used to test the association of potential access to various AEC service models (outpatient service availability and in-hospital services) with asthma readmissions, ED visits or death within 6 to 36 months following the index admission or ED visit.
Results
Fifty three of 163 acute care hospitals had an AEC (N = 36) or had access by referral (N = 17). All AECs documented use with guideline-based recommendations for AE programs. ED patients having access to an AEC that offered full-time, extended hours had reduced rates of adverse outcomes (adjusted relative rate [aRR] 0.78, 95% confidence interval [CI] 0.69, 0.90) compared to those with no AEC access. Hospitalized patients with access to asthma education during hospitalization had reduced rates of adverse events (aRR 0.87, 95% CI 0.75, 1.00) compared to those with no inhospital AEC access.
Conclusion
Although compliant with asthma guideline-based program elements, on a population basis access to asthma education centres is associated only with a modest benefit for some admitted and ED patients and depends on the level of access to services provided. Review of both services provided and strategies to address potential barriers to care are necessary.
doi:10.1186/s12913-014-0561-x
PMCID: PMC4233233  PMID: 25391295
Asthma; Asthma education; Hospitalizations; Emergency department visits; Outcomes
7.  Cyclic Nucleotide Phosphodiesterase 3A1 Protects the Heart Against Ischemia-Reperfusion Injury 
Journal of molecular and cellular cardiology  2013;64:10.1016/j.yjmcc.2013.08.003.
Phosphodiesterase 3A (PDE3A) is a major regulator of cAMP in cardiomyocytes. PDE3 inhibitors are used for acute treatment of congestive heart failure, but are associated with increased incidence of arrhythmias and sudden death with long-term use. We previously reported that chronic PDE3A downregulation or inhibition induced myocyte apoptosis in vitro. However, the cardiac protective effect of PDE3A has not been demonstrated in vivo in disease models. In this study, we examined the role of PDE3A in regulating myocardial function and survival in vivo using genetically engineered transgenic mice with myocardial overexpression of the PDE3A1 isozyme (TG). TG mice have reduced cardiac function characterized by reduced heart rate and ejection fraction (52.5 ± 7.8% vs. 83.9 ± 4.7%) as well as compensatory expansion of left ventricular diameter (4.19 ± 0.19 mm vs. 3.10 ± 0.18 mm). However, there was no maladaptive increase of fibrosis and apoptosis in TG hearts compared to wild type (WT) hearts, and the survival rates also remained the same. The diminution of cardiac contractile function is very likely attributed to a decrease in beta-adrenergic receptor (β-AR) response in TG mice. Importantly, the myocardial infarct size (4.0 ± 1.8% vs. 24.6 ± 3.8%) and apoptotic cell number (1.3 ± 1.0% vs. 5.6 ± 1.5%) induced by ischemia/reperfusion (I/R) injury were significantly attenuated in TG mice. This was associated with decreased expression of inducible cAMP early repressor (ICER) and increased expression of anti-apoptotic protein BCL-2. To further verify the anti-apoptotic effects of PDE3A1, we performed in vitro apoptosis study in isolated adult TG and WT cardiomyocytes. We found that the apoptotic rates stimulated by hypoxia/reoxygenation or H2O2 were indeed significantly reduced in TG myocytes, and the differences between TG and WT myocytes were completely reversed in the presence of the PDE3 inhibitor milrinone. These together indicate that PDE3A1 negatively regulates β-AR signaling and protects against I/R injury by inhibiting cardiomyocyte apoptosis.
doi:10.1016/j.yjmcc.2013.08.003
PMCID: PMC3869570  PMID: 23988739
PDE3A; transgenic mice; myocardial injury; myocyte apoptosis; myocyte contractility
8.  Concordant Effects of Aromatase Inhibitors on Gene Expression in ER+ Rat and Human Mammary Cancers and Modulation of the Proteins Coded by these Genes An uninvited scientific article 
Cancer prevention research (Philadelphia, Pa.)  2013;6(11):10.1158/1940-6207.CAPR-13-0126.
Aromatase inhibitors (AIs) are effective in therapy/prevention of ER+ breast cancers. Rats bearing methylnitrosourea (MNU)-induced ER+ mammary cancers were treated with the AI vorozole (1.25 mg/kg BW/day) for 5 days. RNA expression showed 162 down-regulated and 180 up-regulated (p < 0.05 and fold change >1.5) genes. Genes modulated by vorozole were compared with published data from four clinical neoadjuvant trials employing AIs (anastrozole or letrozole). More than thirty genes and multiple pathways exhibited synchronous changes in animal and human data sets. Cell cycle genes related to chromosome condensation in prometaphase (APC pathway, including Aurora-A kinase, BUBR1B, TOP2, Cyclin A, Cyclin B CDC2 and TPX-2) were down-regulated in animal and human studies reflecting the strong anti-proliferative effects of AIs. Comparisons of rat arrays with a cell culture study where estrogen was removed from MCF-7 cells showed decreased expression of E2F1-modulated genes as a major altered pathway. Alterations of the cell cycle and E2F related genes were confirmed in a large independent set of human samples (81 pairs baseline and 2 weeks anastrozole treatment). Decreases in proliferation related genes were confirmed at the protein level for Cyclin A2, BuRB1, cdc2, Pttg and TPX-2. Interestingly, the proteins down-regulated in tumors were similarly down-regulated in vorozole treated normal rat mammary epithelium. Finally, decreased expression of known estrogen responsive genes (including TFF 1,3, progesterone receptor, etc.) were decreased in the animal model. These studies demonstrate that gene expression changes (pathways and individual genes) are similar in humans and the rat model.
doi:10.1158/1940-6207.CAPR-13-0126
PMCID: PMC3874590  PMID: 24067424
Microarray; vorozole; mammary cancer
9.  Endothelin-1, oxidative stress and endogenous ANGII: mechanisms of AT1-AA-enhanced Renal and Blood Pressure Response during pregnancy 
Hypertension  2013;62(5):10.1161/HYPERTENSIONAHA.113.01648.
Hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (MAP) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index (RARI) in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared to control pregnant rats. In order to examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy we examined the role of endogenous ANGII in AT1-AA infused pregnant rats, Endothelin-1 and oxidative stress in AT1-AA+ANGII treated rats. Chronic ANGII increased MAP from 95 +/−2 in NP rats to 115 +/−2 mmHg. Chronic AT1-AA increased MAP to 118+/−1 mmHg in NP rats which further increased to 123+/−2 with AT1-AA+ANGII. Increasing ANGII from (10−11-10−8) decreased Af-Art diameter 15-20% but sharply decreased Af-Art diameter 60% in AT1-AA pretreated vessels. RARI increased from 0.67 in NP rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA + ANGII infused rats. AT1-AA-induced hypertension decreased with Enalapril but was not attenuated. Both tissue ET-1 and ROS increased with AT1-AA+ANGII compared to AT1-AA alone and blockade of either of these pathways had significant effects on MAP or RARI. These data support the hypothesis that AT1-AA, via activation of ET-1 and oxidative stress and interaction with endogenous ANGII, are important mechanisms whereby MAP and renal vascular responses are enhanced during preeclampsia.
doi:10.1161/HYPERTENSIONAHA.113.01648
PMCID: PMC3845356  PMID: 24041954
Angiotensin II; AT1-AA; Preeclampsia
10.  Efficacy of four different irrigation techniques combined with 60°C 3% sodium hypochlorite and 17% EDTA in smear layer removal 
BMC Oral Health  2014;14(1):114.
Background
Efforts to improve the efficacy of smear layer removal by applying irrigant activation at the final irrigation or by elevating the temperature of the irrigant have been reported. However, the combination of such activation protocols with 60°C 3% sodium hypochlorite (NaOCl) has seldom been mentioned. The aim of this study was to compare the efficacy in smear layer removal of four different irrigation techniques combined with 60°C 3% NaOCl and 17% EDTA.
Methods
Fifty single-rooted teeth were randomly divided into five groups (n = 10) according to the irrigant agitation protocols used during chemomechanical preparation(Dentsply Maillefer, Ballaigues, Switzerland): a side-vented needle group, a ultrasonic irrigation (UI) group, a NaviTip FX group, an EndoActivator group, and a control group (no agitation). After each instrumentation, the root canals were irrigated with 1 mL of 3% NaOCl at 60°C for 1 minute, and after the whole instrumentation, the root canals were rinsed with 1 mL of 17% EDTA for 1 minute. Both NaOCl and EDTA were activated with one of the five irrigation protocols. The efficacy of smear layer removal was scored at the apical, middle and coronal thirds. The Data were statistically analyzed using SAS version 9.2 for Windows (rank sum test for a randomised block design and ANOVA).
Results
No significant differences among the NaviTip FX group, EndoActivator group and control groups, and each of these groups showed a lower score than that of UI group (P < 0.05). Within each group, all three thirds were ranked in the following order: coronal > middle > apical (P < 0.05). In the coronal third, the NaviTip FX group was better than UI group. In the middle and apical third, the differences were not significant among any of the groups.
Conclusions
Even without any activation, the combination of 60°C 3% NaOCl and 17% EDTA could remove the smear layer effectively, similar to NaviTip FX or EndoActivator, and these three protocols were more effective than UI. However, regardless of different types of irrigation technique applied, complete removal of the smear layer was not achieved, particularly in the apical third.
doi:10.1186/1472-6831-14-114
PMCID: PMC4168203  PMID: 25201549
EDTA; EndoActivator; Irrigant activation; Ultrasonic irrigation; Smear layer; Sodium hypochlorite
11.  Circulating tumor cell count during zoledronic acid treatment in men with metastatic prostate cancer: a pilot study 
Prostate International  2014;2(3):147-151.
Purpose
Recent clinical trials have demonstrated that zoledronic acid (ZOL) significantly prolongs survival in prostate cancer patients undergoing androgen deprivation therapy. This pilot study investigated the influence of ZOL on circulating tumor cell (CTC) counts in prostate cancer patients in association with prostate-specific antigen (PSA) used as a serum biomarker.
Methods
Patients with metastatic castration-resistant prostate cancer (CRPC) who were CTC-positive (n=4) were enrolled in treatment with ZOL between April 2012 and December 2013. CTCs were detected using the Cell Search System. The study evaluated CTC fluctuations at 1, 2, and 3 months versus baseline, as well as patient outcomes and adverse events.
Results
Two patients showed evidence of temporally decreased CTCs after ZOL treatment. Instead of decreasing the number of CTCs, the PSA level did not go down during the ZOL treatment. One patient could not undergo ZOL treatment due to rapid disease progression.
Conclusions
Although CTC count arguably provides useful information about patients undergoing ZOL treatment, the positive influence of ZOL may be limited to temporary effects for CRPC.
doi:10.12954/PI.14056
PMCID: PMC4186959  PMID: 25325027
Zoledronic acid; Circulating neoplatic cells; Prostate neoplasms
12.  Femtosecond laser-assisted deep anterior lamellar keratoplasty for keratoconus and keratectasia 
AIM
To describe the initial outcomes and safety of femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) for keratoconus and post-LASIK keratectasia.
METHODS
In this non-comparative case series, 10 eyes of 9 patients underwent DALK procedures with a femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany). Of the 9 patients, 7 had keratoconus and 2 had post-LASIK keratectasia. A 500 kHz VisuMax femtosecond laser was used to perform corneal cuts on both donor and recipient corneas. The outcome measures were the uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), corneal thickness, astigmatism, endothelial density count (EDC), and corneal power.
RESULTS
All eyes were successfully treated. Early postoperative evaluation showed a clear graft in all cases. Intraoperative complications included one case of a small Descemet's membrane perforation. Postoperatively, there was one case of stromal rejection, one of loosened sutures, and one of wound dehiscence. A normal corneal pattern topography and transparency were restored, UCVA and BCVA improved significantly, and astigmatism improved slightly. There was no statistically significant decrease in EDC.
CONCLUSION
Our early results indicate that femtosecond laser-assisted deep anterior lamellar keratoplasty could improve UCVA and BCVA in patients with anterior corneal pathology. This approach shows promise as a safe and effective surgical choice in the treatment of keratoconus and post-LASIK keratectasia.
doi:10.3980/j.issn.2222-3959.2014.04.09
PMCID: PMC4137198  PMID: 25161934
femtosecond laser; deep anterior lamellar keratoplasty; keratoconus; post-LASIK keratectasia
13.  Allogeneic corneoscleral limbus tissue transplantation for treatment of the necrosis in porphyria eye disease 
Porphyria cutanea tarda (PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these. Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.
doi:10.3980/j.issn.2222-3959.2014.04.27
PMCID: PMC4137216  PMID: 25161952
porphyria; scleral necrosis; allogeneic; transplantation
14.  Effects of Soil Temperature, Flooding, and Organic Matter Addition on N2O Emissions from a Soil of Hongze Lake Wetland, China 
The Scientific World Journal  2014;2014:272684.
The objectives of this study were to test the effects of soil temperature, flooding, and raw organic matter input on N2O emissions in a soil sampled at Hongze Lake wetland, Jiangsu Province, China. The treatments studied were—peat soil (I), peat soil under flooding (II), peat soil plus raw organic matter (III), and peat soil under flooding plus organic matter. These four treatments were incubated at 20°C and 35°C. The result showed that temperature increase could enhance N2O emissions rate and cumulative emissions significantly; moreover, the flooded soil with external organic matter inputs showed the lowest cumulative rise in N2O emissions due to temperature increment. Flooding might inhibit soil N2O emissions, and the inhibition was more pronounced after organic matter addition to the original soil. Conversely, organic matter input explained lower cumulative N2O emissions under flooding. Our results suggest that complex interactions between flooding and other environmental factors might appear in soil N2O emissions. Further studies are needed to understand potential synergies or antagonisms between environmental factors that control N2O emissions in wetland soils.
doi:10.1155/2014/272684
PMCID: PMC4123519  PMID: 25133216
15.  Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα 
The Journal of Clinical Investigation  2014;124(8):3501-3513.
Hepatosteatosis is characterized by an aberrant accumulation of triglycerides in the liver; however, the factors that drive obesity-induced fatty liver remain largely unknown. Here, we demonstrated that the secreted cell adhesion protein periostin is markedly upregulated in livers of obese rodents and humans. Notably, overexpression of periostin in the livers of WT mice promoted hepatic steatosis and hypertriglyceridemia. Conversely, both genetic ablation of periostin and administration of a periostin-neutralizing antibody dramatically improved hepatosteatosis and hypertriglyceridemia in obese mice. Overexpression of periostin resulted in reduced expression of peroxisome proliferator–activated receptor α (PPARα), a master regulator of fatty acid oxidation, and activation of the JNK signaling pathway. In mouse primary hepatocytes, inhibition of α6β4 integrin prevented activation of JNK and suppression of PPARα in response to periostin. Periostin-dependent activation of JNK resulted in activation of c-Jun, which prevented RORα binding and transactional activation at the Ppara promoter. Together, these results identify a periostin-dependent pathway that mediates obesity-induced hepatosteatosis.
doi:10.1172/JCI74438
PMCID: PMC4109546  PMID: 25003192
16.  Arabidopsis pentatricopeptide repeat protein SOAR1 plays a critical role in abscisic acid signalling 
Journal of Experimental Botany  2014;65(18):5317-5330.
Summary
The authors identify a pentatricopeptide repeat (PPR) protein SOAR1 as a crucial player of ABA signalling, which localizes to both the cytosol and nucleus probably to regulate nuclear gene expression.
A dominant suppressor of the ABAR overexpressor, soar1-1D, from CHLH/ABAR [coding for Mg-chelatase H subunit/putative abscisic acid (ABA) receptor (ABAR)] overexpression lines was screened to explore the mechanism of the ABAR-mediated ABA signalling. The SOAR1 gene encodes a pentatricopeptide repeat (PPR) protein which localizes to both the cytosol and nucleus. Down-regulation of SOAR1 strongly enhances, but up-regulation of SOAR1 almost completely impairs, ABA responses, revealing that SOAR1 is a critical, negative, regulator of ABA signalling. Further genetic evidence supports that SOAR1 functions downstream of ABAR and probably upstream of an ABA-responsive transcription factor ABI5. Changes in the SOAR1 expression alter expression of a subset of ABA-responsive genes including ABI5. These findings provide important information to elucidate further the functional mechanism of PPR proteins and the complicated ABA signalling network.
doi:10.1093/jxb/eru293
PMCID: PMC4157714  PMID: 25005137
Abscisic acid signalling; Arabidopsis thaliana; Mg-chelatase H subunit; pentatricopeptide repeat (PPR) protein; post-germination growth; seed germination.
17.  Enhanced dissolution and stability of Tanshinone IIA base by solid dispersion system with nano-hydroxyapatite 
Pharmacognosy Magazine  2014;10(39):332-337.
Background:
Tanshinone IIA (TSIIA) exhibits a variety of cardiovascular effects; however, it has low solubility in water. The preparation of poorly soluble drugs for oral delivery is one of the greatest challenges in the field of formulation research. Among the approaches available, solid dispersion (SD) technique has proven to be one of the most commonly used these methods for improving dissolution and bioavailability of drugs, because of its relative simplicity and economy in terms of both preparation and evaluation.
Objective:
This study was aimed at investigating the dissolution behavior and physical stability of SDs of TSIIA by employing nano-hydroxyapatite (n-HAp).
Materials and Methods:
The TSIIA SDs was prepared to use a spray-drying method. First, an in vitro dissolution test was performed to assess dissolution characteristics. Next, a set of complementary techniques (differential scanning calorimetry, scanning electron microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy) was used to monitor the physicochemical properties of the SDs. The SDs was stored at 40°C/75% relative humidity for 6 months, after which their stability was assessed.
Results:
TSIIA dissolution remarkably improved because of the formulation of the SDs with n-HAp particles. Comparisons with the corresponding physical mixtures revealed changes in the SDs and explained the formation of the amorphous phase. In the stability test, virtually no time-dependent decrease was observed in either in vitro drug dissolution or drug content.
Conclusion:
SD formulation with n-HAp may be a promising approach for enhancing the dissolution and stability of TSIIA.
doi:10.4103/0973-1296.137375
PMCID: PMC4159928  PMID: 25210322
Dissolution; nano-hydroxyapatite; solid dispersion; stability; Tanshinone IIA
18.  Full Genome Sequence of a Bovine Enterovirus Isolated in China 
Genome Announcements  2014;2(3):e00620-14.
We report the full genome sequence of an isolate of bovine enterovirus type B from China. The virus (BEV-BJ001) was isolated from Beijing, China, from fecal swabs of cattle suffering from severe diarrhea. This genome sequence will give useful insight for future molecular epidemiological studies in China.
doi:10.1128/genomeA.00620-14
PMCID: PMC4073116  PMID: 24970832
19.  Hydrogen-Saturated Saline Protects Intensive Narrow Band Noise-Induced Hearing Loss in Guinea Pigs through an Antioxidant Effect 
PLoS ONE  2014;9(6):e100774.
The purpose of the current study was to evaluate hydrogen-saturated saline protecting intensive narrow band noise-induced hearing loss. Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections (1 ml/100 g) 3 days before and 1 h before narrow band noise exposure (2.5–3.5 kHz 130 dB SPL, 1 h). The guinea pigs in the control group received no treatment. The hearing function was assessed by the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) recording. The changes of free radicals in the cochlea before noise exposure, and immediately and 7 days after noise exposure were also examined. By Scanning electron microscopy and succinate dehydrogenase staining, we found that pre-treatment with hydrogen-saturated saline significantly reduced noise-induced hair cell damage and hearing loss. We also found that the malondialdehyde, lipid peroxidation, and hydroxyl levels were significantly lower in the hydrogen-saturated saline group after noise trauma, indicating that hydrogen-saturated saline can decrease the amount of harmful free radicals caused by noise trauma. Our findings suggest that hydrogen-saturated saline is effective in preventing intensive narrow band noise-induced hearing loss through the antioxidant effect.
doi:10.1371/journal.pone.0100774
PMCID: PMC4063935  PMID: 24945316
20.  Global atmospheric emissions of polycyclic aromatic hydrocarbons from 1960 to 2008 and future predictions 
Environmental science & technology  2013;47(12):6415-6424.
Global atmospheric emissions of 16 polycyclic aromatic hydrocarbons (PAHs) from 69 major sources were estimated for a period from 1960 to 2030. Regression models and a technology split method were used to estimate country and time specific emission factors, resulting in a new estimate of PAH emission factor variation among different countries and over time. PAH emissions in 2007 were spatially resolved to 0.1°× 0.1° grids based on a newly developed global high-resolution fuel combustion inventory (PKU-FUEL-2007). The global total annual atmospheric emission of 16 PAHs in 2007 was 504 Gg (331-818 Gg, as interquartile range), with residential/commercial biomass burning (60.5%), open-field biomass burning (agricultural waste burning, deforestation, and wildfire, 13.6%), and petroleum consumption by on-road motor vehicles (12.8%) as the major sources. South (87 Gg), East (111 Gg), and Southeast Asia (52 Gg) were the regions with the highest PAH emission densities, contributing half of the global total PAH emissions. Among the global total PAH emissions, 6.19% of the emissions were in the form of high molecular weight carcinogenic compounds and the percentage of the carcinogenic PAHs was higher in developing countries (6.22%) than in developed countries (5.73%), due to the differences in energy structures and the disparities of technology. The potential health impact of the PAH emissions was greatest in the parts of the world with high anthropogenic PAH emissions, because of the overlap of the high emissions and high population densities. Global total PAH emissions peaked at 592 Gg in 1995 and declined gradually to 499 Gg in 2008. Total PAH emissions from developed countries peaked at 122 Gg in the early 1970s and decreased to 38 Gg in 2008. Simulation of PAH emissions from 2009 to 2030 revealed that PAH emissions in developed and developing countries would decrease by 46-71% and 48-64%, respectively, based on the six IPCC SRES scenarios.
doi:10.1021/es400857z
PMCID: PMC3753807  PMID: 23659377
Polycyclic aromatic hydrocarbons; global emission; source profile; time trend
21.  The Multicopper Ferroxidase Hephaestin Enhances Intestinal Iron Absorption in Mice 
PLoS ONE  2014;9(6):e98792.
Hephaestin is a vertebrate multicopper ferroxidase important for the transfer of dietary iron from intestinal cells to the blood. Hephaestin is mutated in the sex-linked anemia mouse, resulting in iron deficiency. However, sex-linked anemia mice still retain some hephaestin ferroxidase activity. They survive, breed, and their anemia improves with age. To gain a better understanding of the role of hephaestin in iron homeostasis, we used the Cre-lox system to generate knockout mouse models with whole body or intestine-specific (Villin promoter) ablation of hephaestin. Both types of mice were viable, indicating that hephaestin is not essential and that other mechanisms, multicopper ferroxidase-dependent or not, must compensate for hephaestin deficiency. The knockout strains, however, both developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and confirming that hephaestin plays an important role in body iron acquisition. Consistent with this, the knockout mice accumulated iron in duodenal enterocytes and had reduced intestinal iron absorption. In addition, the similarities of the phenotypes of the whole body and intestine-specific hephaestin knockout mice clarify the important role of hephaestin specifically in intestinal enterocytes in maintaining whole body iron homeostasis. These mouse models will serve as valuable tools to study the role of hephaestin and associated proteins in iron transport in the small intestine and other tissues.
doi:10.1371/journal.pone.0098792
PMCID: PMC4045767  PMID: 24896847
22.  Biosorption of Fe(II) and Mn(II) Ions from Aqueous Solution by Rice Husk Ash 
BioMed Research International  2014;2014:973095.
Rice husk ash (RHA), an agricultural waste, was used as biosorbent for the removal of Iron(II) and Manganese(II) ions from aqueous solutions. The structural and morphological characteristics of RHA and its elemental compositions before and after adsorption of Fe(II) and Mn(II) were determined by scanning electron microscopic (SEM) and X-ray fluorescence (XRF) analyses. Batch experiments were carried out to determine the influence of initial pH, contact time, adsorbent dosage, and initial concentration on the removal of Fe(II) and Mn(II) ions. Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) models were applied to describe the biosorption isotherm of the metal ions by RHA. The correlation coefficient (R2) of Langmuir and Freundlich isotherm models equals 0.995 and 0.901 for Fe(II), 0.9862 and 0.8924 for Mn(II), respectively, so the Langmuir model fitted the equilibrium data better than the Freundlich isotherm model. The mean free energy values evaluated from the D-R model indicated that the biosorption of Fe(II) and Mn(II) onto RHA was physical in nature. Experimental data also showed that the biosorption processes of both metal ions complied with the pseudo-second-order kinetics.
doi:10.1155/2014/973095
PMCID: PMC4058686  PMID: 24982918
23.  Isolation, Structure Determination, and Anti-HIV Evaluation of Tigliane-type Diterpenes and Biflavonoid from Stellera chamaejasme 
Journal of natural products  2013;76(5):852-857.
Five novel tigliane-type diterpenes, stelleracins A–E (3–7), a novel flavanone dimer, chamaeflavone A (8), and six known compounds were isolated from roots of Stellera chamaejasme. Their structures were elucidated by extensive spectroscopic analyses. The isolated compounds were evaluated for anti-HIV activity in MT4 cells. New compounds 3–5 showed potent anti-HIV activity (EC90 0.00056–0.0068 μM) and relatively low or no cytotoxicity (IC50 4.4–17.2 μM). These new compounds represent promising new leads for development into anti-AIDS clinical trial candidates.
doi:10.1021/np300815t
PMCID: PMC3715147  PMID: 23611151
24.  Distribution Characteristic of Soil Organic Carbon Fraction in Different Types of Wetland in Hongze Lake of China 
The Scientific World Journal  2014;2014:487961.
Soil organic carbon fractions included microbial biomass carbon (MBC), dissolved organic carbon (DOC), and labile organic carbon (LOC), which was investigated over a 0–20 cm depth profile in three types of wetland in Hongze Lake of China. Their ecoenvironmental effect and the relationships with soil organic carbon (SOC) were analyzed in present experiment. The results showed that both active and SOC contents were in order reduced by estuarine wetland, flood plain, and out-of-lake wetland. Pearson correlative analysis indicated that MBC and DOC were positively related to SOC. The lowest ratios of MBC and DOC to SOC in the estuarine wetland suggested that the turnover rate of microbial active carbon pool was fairly low in this kind of wetland. Our results showed that estuarine wetland had a strong carbon sink function, which played important role in reducing greenhouse gas emissions; besides, changes of water condition might affect the accumulation and decomposition of organic carbon in the wetland soils.
doi:10.1155/2014/487961
PMCID: PMC4055677  PMID: 24971377
25.  Characterization of Multidrug-Resistant Salmonella enterica Serovars Indiana and Enteritidis from Chickens in Eastern China 
PLoS ONE  2014;9(5):e96050.
A total of 310 Salmonella isolates were isolated from 6 broiler farms in Eastern China, serotyped according to the Kauffmann-White classification. All isolates were examined for susceptibility to 17 commonly used antimicrobial agents, representative isolates were examined for resistance genes and class I integrons using PCR technology. Clonality was determined by pulsed-field gel electrophoresis (PFGE). There were two serotypes detected in the 310 Salmonella strains, which included 133 Salmonella enterica serovar Indiana isolates and 177 Salmonella enterica serovar Enteritidis isolates. Antimicrobial sensitivity results showed that the isolates were generally resistant to sulfamethoxazole, ampicillin, tetracycline, doxycycline and trimethoprim, and 95% of the isolates sensitive to amikacin and polymyxin. Among all Salmonella enterica serovar Indiana isolates, 108 (81.2%) possessed the blaTEM, floR, tetA, strA and aac (6')-Ib-cr resistance genes. The detected carriage rate of class 1 integrons was 66.5% (206/310), with 6 strains carrying gene integron cassette dfr17-aadA5. The increasing frequency of multidrug resistance rate in Salmonella was associated with increasing prevalence of int1 genes (rs = 0.938, P = 0.00039). The int1, blaTEM, floR, tetA, strA and aac (6')-Ib-cr positive Salmonella enterica serovar Indiana isolates showed five major patterns as determined by PFGE. Most isolates exhibited the common PFGE patterns found from the chicken farms, suggesting that many multidrug-resistant isolates of Salmonella enterica serovar Indiana prevailed in these sources. Some isolates with similar antimicrobial resistance patterns represented a variety of Salmonella enterica serovar Indiana genotypes, and were derived from a different clone.
doi:10.1371/journal.pone.0096050
PMCID: PMC4008530  PMID: 24788434

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