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1.  Low Dose of Valproate Improves Motor Function after Traumatic Brain Injury 
BioMed Research International  2014;2014:980657.
Background. Traumatic brain injuries (TBIs) are a major health care problem worldwide. Approximately 1.5 million new TBI cases occur annually in the United States, with mortality rates ranging between 35% and 40% in severe patients. Despite the incidence of these injuries and their substantial socioeconomic implications, no specific pharmacological intervention is available for clinical use. Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate (VPA) exhibits neuroprotective effects in animal models. However, humans cannot tolerate high doses of VPA. This study aims to investigate whether 30 mg/kg of VPA administered to rats affects TBIs. Methods. We used a rat model to test the effects of 30 mg/kg of VPA on TBIs. Molecular identifications for histone acetylation and phosphorylation of cAMP response element-binding protein (CREB) and phosphorylated extracellular signal regulated kinase (ERK) were performed. Results. The results indicated that treating adult rats with VPA after TBIs significantly decreased the contusion volume and recovery of contusion-related skilled forelimb reaching deficits. Applying VPA also increased histone acetylation, p-ERK, and p-CREB expression in the brain. Furthermore, applying VPA reduced inflammation, glial fibrillary acidic protein activation, and apoptosis. Conclusion. This study found that 30 mg/kg of VPA assists in treating TBIs in rat models.
doi:10.1155/2014/980657
PMCID: PMC3933527
2.  Nur77 Decreases Atherosclerosis Progression in apoE−/− Mice Fed a High-Fat/High-Cholesterol Diet 
PLoS ONE  2014;9(1):e87313.
Rationale
It is clear that lipid disorder and inflammation are associated with cardiovascular diseases and underlying atherosclerosis. Nur77 has been shown to be involved in inflammatory response and lipid metabolism.
Objective
Here, we explored the role of Nur77 in atherosclerotic plaque progression in apoE−/− mice fed a high-fat/high cholesterol diet.
Methods and Results
The Nur77 gene, a nuclear hormone receptor, was highly induced by treatment with Cytosporone B (Csn-B, specific Nur77 agonist), recombinant plasmid over-expressing Nur77 (pcDNA-Nur77), while inhibited by treatment with siRNAs against Nur77 (si-Nur77) in THP-1 macrophage-derived foam cells, HepG2 cells and Caco-2 cells, respectively. In addition, the expression of Nur77 was highly induced by Nur77 agonist Csn-B, lentivirus encoding Nur77 (LV-Nur77), while silenced by lentivirus encoding siRNA against Nur77 (si-Nur77) in apoE−/− mice fed a high-fat/high cholesterol diet, respectively. We found that increased expression of Nur77 reduced macrophage-derived foam cells formation and hepatic lipid deposition, downregulated gene levels of inflammatory molecules, adhesion molecules and intestinal lipid absorption, and decreases atherosclerotic plaque formation.
Conclusion
These observations provide direct evidence that Nur77 is an important nuclear hormone receptor in regulation of atherosclerotic plaque formation and thus represents a promising target for the treatment of atherosclerosis.
doi:10.1371/journal.pone.0087313
PMCID: PMC3909091  PMID: 24498071
3.  Prognostic Role of MicroRNA-221 in Various Human Malignant Neoplasms: A Meta-Analysis of 20 Related Studies 
PLoS ONE  2014;9(1):e87606.
Background
MicroRNA-221 (miR-221) has been shown to play an important role in cancer prognosis. In order to evaluate the predictive value of miR-221, we compiled the evidence from 20 eligible studies to perform a meta-analysis.
Design
All of relevant studies were identified by searching PubMed, Embase, and Web of Science, and were assessed by further quality evaluation. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of total and stratified analyses, for overall survival (OS) and recurrence-free survival (RFS), were calculated to investigate the association between high miR-221 expression and cancer prognosis.
Results
We found that high miR-221 expression can predict a poor OS in malignant tumors (pooled HR = 1.55, P = 0.017) but has no significant association with RFS (pooled HR = 1.02, P = 0.942). Further in stratified analyses, high miR-221 expression was significantly associated with a poor OS in Asians (pooled HR = 2.04, P = 0.010) or serum/ plasma subgroup (pooled HR = 2.28, P<0.001), and even showed significantly poor OS (pooled HR = 1.80, P<0.001) and RFS (pooled HR = 2.43, P = 0.010) in hepatocellular carcinoma (HCC) subgroup, but was correlated to a favorable RFS in prostate cancer subgroup (pooled HR = 0.51, P = 0.004).
Conclusions
Our findings demonstrate that miR-221 is more suitable to predict cancer prognosis in Asians, and it is a promising prognostic biomarker for HCC. The detection of miR-221 in serum or plasma samples may make it become an effective method for monitoring patients' prognosis and assessing therapeutic efficacy in the future.
doi:10.1371/journal.pone.0087606
PMCID: PMC3903772  PMID: 24475314
4.  Sequential Engagement of FcεRI on Mast Cells and Basophil Histamine H4 Receptor and FcεRI in Allergic Rhinitis 
Histamine H4 receptor (H4R)-deficient mice (H4R−/−), H4R antagonist-treated WT mice, and WT mice depleted of basophils failed to develop early (EPR) or late phase (LPR) nasal responses following allergen sensitization and challenge. Basophil transfer from WT but not H4R−/− mice restored the EPR and LPR in H4R−/− mice. Following passive sensitization with OVA-specific IgE, FcεRI−/− recipients of WT basophils plus OVA and histamine developed an EPR and LPR. OVA-IgE passively sensitized FcεRI−/− recipients of H4R−/− basophils and OVA and histamine challenge failed to develop an EPR or LPR, and basophils were not detected in nasal tissue. In contrast, recipients of basophils from IL-13−/− and IL-4−/−/IL-13−/− mice developed an EPR but not LPR. These results demonstrate the development of allergic rhinitis proceeded in two distinct stages: histamine release from FcεRI-activated mast cells, followed by histamine-mediated recruitment of H4R-expressing basophils to the nasal cavity and activation through FcεRI.
doi:10.4049/jimmunol.1202049
PMCID: PMC3538893  PMID: 23241885
Basophils; mast cells; histamine H4 receptor; FcεRI; rhinitis
5.  Cognitive Impairments Accompanying Rodent Mild Traumatic Brain Injury Involve p53-Dependent Neuronal Cell Death and Are Ameliorated by the Tetrahydrobenzothiazole PFT-α 
PLoS ONE  2013;8(11):e79837.
With parallels to concussive mild traumatic brain injury (mTBI) occurring in humans, anesthetized mice subjected to a single 30 g weight drop mTBI event to the right parietal cortex exhibited significant diffuse neuronal degeneration that was accompanied by delayed impairments in recognition and spatial memory. To elucidate the involvement of reversible p53-dependent apoptosis in this neuronal loss and associated cognitive deficits, mice were subjected to experimental mTBI followed by the systemic administration of the tetrahydrobenzothiazole p53 inactivator, PFT-α, or vehicle. Neuronal loss was quantified immunohistochemically at 72 hr. post-injury by the use of fluoro-Jade B and NeuN within the dentate gyrus on both sides of the brain, and recognition and spatial memory were assessed by novel object recognition and Y-maze paradigms at 7 and 30 days post injury. Systemic administration of a single dose of PFT-α 1 hr. post-injury significantly ameliorated both neuronal cell death and cognitive impairments, which were no different from sham control animals. Cellular studies on human SH-SY5Y cells and rat primary neurons challenged with glutamate excitotoxicity and H2O2 induced oxidative stress, confirmed the ability of PFT-α and a close analog to protect against these TBI associated mechanisms mediating neuronal loss. These studies suggest that p53-dependent apoptotic mechanisms underpin the neuronal and cognitive losses accompanying mTBI, and that these are potentially reversible by p53 inactivation.
doi:10.1371/journal.pone.0079837
PMCID: PMC3842915  PMID: 24312187
6.  The Effect of Bedding System Selected by Manual Muscle Testing on Sleep-Related Cardiovascular Functions 
BioMed Research International  2013;2013:937986.
Background. Different types of mattresses affect sleep quality and waking muscle power. Whether manual muscle testing (MMT) predicts the cardiovascular effects of the bedding system was explored using ten healthy young men. Methods. For each participant, two bedding systems, one inducing the strongest limb muscle force (strong bedding system) and the other inducing the weakest limb force (weak bedding system), were identified using MMT. Each bedding system, in total five mattresses and eight pillows of different firmness, was used for two continuous weeks at the participant's home in a random and double-blind sequence. A sleep log, a questionnaire, and a polysomnography were used to differentiate the two bedding systems. Results and Conclusion. Heart rate variability and arterial pressure variability analyses showed that the strong bedding system resulted in decreased cardiovascular sympathetic modulation, increased cardiac vagal activity, and increased baroreceptor reflex sensitivity during sleep as compared to the weak bedding system. Different bedding systems have distinct cardiovascular effects during sleep that can be predicted by MMT.
doi:10.1155/2013/937986
PMCID: PMC3859264  PMID: 24371836
7.  Responsiveness to respiratory syncytial virus in neonates is mediated through thymic stromal lymphopoietin and OX40 ligand 
Background
Recent studies revealed a critical role for thymic stromal lymphopoietin (TSLP) released from epithelial cells and OX40 ligand (OX40L) expressed on dendritic cells (DCs) in TH2 priming and polarization.
Objectives
We sought to determine the importance of the TSLP-OX40L axis in neonatal respiratory syncytial virus (RSV) infection.
Methods
Mice were initially infected with RSV as neonates or adults and reinfected 5 weeks later. Anti-OX40L or anti-TSLP were administered during primary or secondary infection. Outcomes included assessment of airway function and inflammation and expression of OX40L, TSLP, and IL-12.
Results
OX40L was expressed mainly on CD11c+MHC class II (MHCII)+CD11b+ DCs but not CD103+ DCs. Treatment of neonates with OX40L antibody during primary RSV infection prevented the subsequent enhancement of airway hyperresponsiveness and the development of airway eosinophilia and mucus hyperproduction on reinfection. Administration of anti-TSLP before neonatal RSV infection reduced the accumulation of lung DCs, decreased OX40L expression on lung DCs, and attenuated the enhancement of airway responses after reinfection.
Conclusions
In mice initially infected as neonates, TSLP expression induced by RSV infection is an important upstream event that controls OX40L expression, lung DC migration, and TH2 polarization, accounting for the enhanced response on reinfection.
doi:10.1016/j.jaci.2012.08.033
PMCID: PMC3593657  PMID: 23036746
Respiratory syncytial virus; OX40 ligand; thymic stromal lymphopoietin
8.  Stable superhydrophobic surface of hierarchical carbon nanotubes on Si micropillar arrays 
Nanoscale Research Letters  2013;8(1):412.
It is of great importance to construct a stable superhydrophobic surface with low sliding angle (SA) for various applications. We used hydrophobic carbon nanotubes (CNTs) to construct the superhydrophobic hierarchical architecture of CNTs on silicon micropillar array (CNTs/Si-μp), which have a large contact angle of 153° to 155° and an ultralow SA of 3° to 5°. Small water droplets with a volume larger than 0.3 μL can slide on the CNTs/Si-μp with a tilted angle of approximately 5°. The CNTs growing on planar Si wafer lose their superhydrophobic properties after exposing to tiny water droplets. However, the CNTs/Si-μp still show superhydrophobic properties even after wetting using tiny water droplets. The CNTs/Si-μp still have a hierarchical structure after wetting, resulting in a stable superhydrophobic surface.
doi:10.1186/1556-276X-8-412
PMCID: PMC3874759  PMID: 24098965
Carbon nanotube; Hierarchical architecture; Superhydrophobic surface
9.  Microbial Heat Shock Protein 65 Attenuates Airway Hyperresponsiveness and Inflammation by Modulating the Function of Dendritic Cells 
Heat shock proteins (HSPs), produced in response to stress are suppressive in disease models. We previously showed that Mycobacterium leprae HSP65 prevented development of airway hyperresponsiveness and inflammation in mice. Our goal here was to define the mechanism responsible for the suppressive effects of HSP. In one in vivo approach, BALB/c mice were sensitized to ovalbumin (OVA) followed by primary OVA challenges. Several weeks later, HSP65 was administered prior to a single, provocative secondary challenge. In a second in vivo approach, the secondary challenge was replaced by intratracheal instillation of allergen-pulsed bone marrow-derived dendritic cells (BMDCs). The in vitro effects of HSP65 on BMDCs were examined in co-culture experiments with CD4+ T cells. In vivo, HSP65 prevented development of airway hyperresponsiveness and inflammation. As well, Th1 cytokine levels in bronchoalveolar lavage (BAL) fluid were increased. In vitro, HSP65 induced notch receptor ligand Delta1 expression on BMDCs and HSP65-treated BMDCs skewed CD4+ T cells to Th1 cytokine production. Thus, HSP65-induced effects on allergen-induced airway hyperresponsiveness and inflammation were associated with increased Delta 1 expression on DCs, modulation of DC function, and CD4+ Th1 cytokine production.
doi:10.4049/jimmunol.1201138
PMCID: PMC3448847  PMID: 22933632
HSP65; asthma; dendritic cells; T cells
10.  Vitamin D Intake and Risk of Type 1 Diabetes: A Meta-Analysis of Observational Studies 
Nutrients  2013;5(9):3551-3562.
Vitamin D is suggested to have protective effects against type 1 diabetes. However, the results from observational studies have been inconsistent. We aimed to examine their association by conducting a meta-analysis of observational studies. Multiple databases were searched in June 2013 to identify relevant studies including both case-control and cohort studies. Either a fixed- or random-effects model was used to calculate the pooled risk estimate. We identified eight studies (two cohort studies and six case-control studies) on vitamin D intake during early life and three studies (two cohort studies and one case-control study) on maternal vitamin D intake during pregnancy. The pooled odds ratio for type 1 diabetes comparing vitamin D supplementation with non-supplementation during early life was 0.71 (95% confidence interval [CI], 0.51–0.98). Similar results were observed in the case-control subgroup analysis but not in the cohort subgroup analysis. The pooled odds ratio with maternal intake of vitamin D during pregnancy was 0.95 (95% CI, 0.66–1.36). In conclusion, vitamin D intake during early life may be associated with a reduced risk of type 1 diabetes. However, there was not enough evidence for an association between maternal intake of vitamin D and risk of type 1 diabetes in the offspring.
doi:10.3390/nu5093551
PMCID: PMC3798920  PMID: 24036529
vitamin D; type 1 diabetes; early life; pregnancy; meta-analysis
11.  Dihydrocapsaicin Attenuates Plaque Formation through a PPARγ/LXRα Pathway in apoE−/− Mice Fed a High-Fat/High-Cholesterol Diet 
PLoS ONE  2013;8(6):e66876.
Aims
Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. There is evidence that dihydrocapsaicin (DHC) can exert multiple pharmacological and physiological effects. Here, we explored the effect of DHC in atherosclerotic plaque progression in apoE−/− mice fed a high-fat/high-cholesterol diet.
Methods and Results
apoE−/− mice were randomly divided into two groups and fed a high-fat/high-cholesterol diet with or without DHC for 12 weeks. We demonstrated that cellular cholesterol content was significantly decreased while apoA1-mediated cholesterol efflux was significantly increased following treatment with DHC in THP-1 macrophage-derived foam cells. We also observed that plasma levels of TG, LDL-C, VLDL-C, IL-1β, IL-6, TNF-α and CRP were markedly decreased while plasma levels of apoA1 and HDL-C were significantly increased, and consistent with this, atherosclerotic lesion development was significantly inhibited by DHC treatment of apoE−/− mice fed a high-fat/high-cholesterol diet. Moreover, treatment with both LXRα siRNA and PPARγ siRNA made the up-regulation of DHC on ABCA1, ABCG1, ABCG5, SR-B1, NPC1, CD36, LDLR, HMGCR, apoA1 and apoE expression notably abolished while made the down-regulation of DHC on SRA1 expression markedly compensated. And treatment with PPARγ siRNA made the DHC-induced up-regulation of LXRα expression notably abolished while treatment with LXRα siRNA had no effect on DHC-induced PPARγ expression.
Conclusion
These observations provide direct evidence that DHC can significantly decrease atherosclerotic plaque formation involving in a PPARγ/LXRα pathway and thus DHC may represent a promising candidate for a therapeutic agent for the treatment or prevention of atherosclerosis.
doi:10.1371/journal.pone.0066876
PMCID: PMC3694162  PMID: 23840542
12.  Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in esophageal squamous cell carcinoma and its clinicopathologic significance 
Cancer Biology & Medicine  2013;10(2):81-85.
Objective
This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma (ESCC).
Methods
Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed.
Results
The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis (P<0.001). The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Although univariate regression analysis showed significant difference between the two groups (P=0.014), multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and residual tumor (P=0.026) were the independent prognostic factors.
Conclusion
LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.
doi:10.7497/j.issn.2095-3941.2013.02.003
PMCID: PMC3719196  PMID: 23882422
Esophageal squamous cell carcinoma; lymphatic vessel invasion; D2-40; lymph node metastasis; prognosis
13.  Outcome of Veno-Arterial Extracorporeal Membrane Oxygenation for Patients Undergoing Valvular Surgery 
PLoS ONE  2013;8(5):e63924.
Background
We evaluated retrospectively the early and midterm results of using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support in patients undergoing valvular surgery.
Methods
A total of 87 patients undergoing valvular surgery received VA-ECMO due to refractory postcardiotomy cardiogenic shock (PCS), who were eligible for inclusion were enrolled in this study. Preoperative, perioperative, and postoperative variables were assessed and analyzed for possible associations with mortality in hospital and after discharge.
Results
The mean age, additive EuroSCORE, and left ventricular ejection fraction (LVEF) for all patients was 65±7 years, 6.1±1.9 points, and 46% ±12%, respectively. The mean duration of VA-ECMO support was 61±37 hours. Intra-aortic balloon pumps (IABP) were implanted in 47.1% of patients. Weaning from VA-ECMO was successful in 59% of patients, and 49% were discharged. Multivariate analysis revealed that being >65 years old (odds ratio [OR], 2.75), receiving postoperative renal replacement treatment (OR, 2.47), having a peak lactate level ≥12 mmol L–1 (OR, 2.18), and receiving VA-ECMO for >60 hours (OR, 3.2) were independent predictors of in-hospital mortality. IABP support (OR, 0.46) was protective. In addition, persistent heart failure with an LVEF <40% was an independent predictor of mortality after discharge.
Conclusions
VA-ECMO is an acceptable technique for the treatment of PCS in patients undergoing valvular surgery, who would otherwise die. It is justified by the good long-term outcomes of hospital survivors, but the use of VA-ECMO must be decided on an individual risk profile basis because of high morbidity and mortality rates.
doi:10.1371/journal.pone.0063924
PMCID: PMC3662767  PMID: 23717509
14.  Genome-wide identification and functional analyses of calmodulin genes in Solanaceous species 
BMC Plant Biology  2013;13:70.
Background
Calmodulin (CaM) is a major calcium sensor in all eukaryotes. It binds calcium and modulates the activity of a wide range of downstream proteins in response to calcium signals. However, little is known about the CaM gene family in Solanaceous species, including the economically important species, tomato (Solanum lycopersicum), and the gene silencing model plant, Nicotiana benthamiana. Moreover, the potential function of CaM in plant disease resistance remains largely unclear.
Results
We performed genome-wide identification of CaM gene families in Solanaceous species. Employing bioinformatics approaches, multiple full-length CaM genes were identified from tomato, N. benthamiana and potato (S. tuberosum) genomes, with tomato having 6 CaM genes, N. benthamiana having 7 CaM genes, and potato having 4 CaM genes. Sequence comparison analyses showed that three tomato genes, SlCaM3/4/5, two potato genes StCaM2/3, and two sets of N. benthamiana genes, NbCaM1/2/3/4 and NbCaM5/6, encode identical CaM proteins, yet the genes contain different intron/exon organization and are located on different chromosomes. Further sequence comparisons and gene structural and phylogenetic analyses reveal that Solanaceous species gained a new group of CaM genes during evolution. These new CaM genes are unusual in that they contain three introns in contrast to only a single intron typical of known CaM genes in plants. The tomato CaM (SlCaM) genes were found to be expressed in all organs. Prediction of cis-acting elements in 5' upstream sequences and expression analyses demonstrated that SlCaM genes have potential to be highly responsive to a variety of biotic and abiotic stimuli. Additionally, silencing of SlCaM2 and SlCaM6 altered expression of a set of signaling and defense-related genes and resulted in significantly lower resistance to Tobacco rattle virus and the oomycete pathogen, Pythium aphanidermatum.
Conclusions
The CaM gene families in the Solanaceous species tomato, N. benthamiana and potato were identified through a genome-wide analysis. All three plant species harbor a small set of genes that encode identical CaM proteins, which may manifest a strategy of plants to retain redundancy or enhanced quantitative gene function. In addition, Solanaceous species have evolved one new group of CaM genes during evolution. CaM genes play important roles in plant disease resistance to a variety of pathogens.
doi:10.1186/1471-2229-13-70
PMCID: PMC3751459  PMID: 23621884
Calcium; Calmodulin; Gene Structure; Phylogenetic Analysis; Defense; Resistance; Tomato; Nicotiana Benthamiana; Potato
15.  Modern Prospection for Hepatic Arterial Infusion Chemotherapy in Malignancies with Liver Metastases 
Malignancy with liver metastasis plays an important role in daily oncology practice, especially for primary cancers of the gastrointestinal tract and hepatopancreatobiliary system. On account of the dual vascular supply system and the fact that most metastatic liver tumors are supplied by the hepatic artery, hepatic artery infusion chemotherapy (HAIC) is an appealing method for the treatment of liver metastases. Herein, we summarize recent study results reported in the literature regarding the use of HAIC for metastatic liver tumors, with special focus on colorectal cancer.
doi:10.1155/2013/141590
PMCID: PMC3652147  PMID: 23691329
16.  “What is this?” Gesture as a potential cue to identify referents in discourse 
Applied psycholinguistics  2012;33(2):329-342.
This study explores whether caregivers follow the discourse-pragmatic principle of information status of referents (given vs. new) in their gestures and how children respond to their caregivers’ gestures. Chinese and American caregivers were videotaped while interacting spontaneously with their children. Their speech and gestures were coded for referential expressions. Even though Chinese caregivers gestured more often than American caregivers, we found that both groups produced more gestures when asking their children to identify new referents than when asking their children to identify given referents. In addition, both groups of children were sensitive to the gestures accompanying new referents and using these gestures to identify the referents. Thus, we conclude that gesture serves as a potential cue for both caregivers and children to identify referents according to the discourse-pragmatic principle of information status.
doi:10.1017/S0142716411000373
PMCID: PMC3322668  PMID: 22505785
17.  Inhibition of Pim1 Kinase Activation Attenuates Allergen-Induced Airway Hyperresponsiveness and Inflammation 
Pim kinases are a family of serine/threonine kinases whose activity can be induced by cytokines involved in allergy and asthma. These kinases play a role in cell survival and proliferation, but have not been examined, to the best of our knowledge, in the development of allergic disease. This study sought to determine the role of Pim1 kinase in the development of allergic airway responses. Mice were sensitized and challenged with antigen (primary challenge), or were sensitized, challenged, and rechallenged with allergen in a secondary model. To assess the role of Pim1 kinase, a small molecule inhibitor was administered orally after sensitization and during the challenge phase. Airway responsiveness to inhaled methacholine, airway and lung inflammation, cell composition, and cytokine concentrations were assessed. Lung Pim1 kinase concentrations were increased after ovalbumin sensitization and challenge. In the primary allergen challenge model, treatment with the Pim1 kinase inhibitor after sensitization and during airway challenges prevented the development of airway hyperresponsiveness, eosinophilic airway inflammation, and goblet cell metaplasia, and increased Th2 cytokine concentrations in bronchoalveolar fluid in a dose-dependent manner. These effects were also demonstrated after a secondary allergen challenge, where lung allergic disease was established before treatment. After treatment with the inhibitor, a significant reduction was evident in the number of CD4+ and CD8+ T cells and concentrations of cytokines in the airways. The inhibition of Pim1 kinase was effective in preventing the development of airway hyperresponsiveness, airway inflammation, and cytokine production in allergen-sensitized and allergen-challenged mice. These data identify the important role of Pim1 kinase in the full development of allergen-induced airway responses.
doi:10.1165/rcmb.2011-0190OC
PMCID: PMC3359953  PMID: 22074702
airway hyperresponsiveness; inflammation; Pim1 kinase; T cells
18.  Eco-friendly synthesis for MCM-41 nanoporous materials using the non-reacted reagents in mother liquor 
Nanoscale Research Letters  2013;8(1):120.
Nanoporous materials such as Mobil composite material number 41 (MCM-41) are attractive for applications such as catalysis, adsorption, supports, and carriers. Green synthesis of MCM-41 is particularly appealing because the chemical reagents are useful and valuable. We report on the eco-friendly synthesis of MCM-41 nanoporous materials via multi-cycle approach by re-using the non-reacted reagents in supernatant as mother liquor after separating the solid product. This approach was achieved via minimal requirement of chemical compensation where additional fresh reactants were added into the mother liquor followed by pH adjustment after each cycle of synthesis. The solid product of each successive batch was collected and characterized while the non-reacted reagents in supernatant can be recovered and re-used to produce subsequent cycle of MCM-41. The multi-cycle synthesis is demonstrated up to three times in this research. This approach suggests a low cost and eco-friendly synthesis of nanoporous material since less waste is discarded after the product has been collected, and in addition, product yield can be maintained at the high level.
doi:10.1186/1556-276X-8-120
PMCID: PMC3599658  PMID: 23497184
MCM-41; Green synthesis; Mother liquor; Chemical compensation; Chemical waste
19.  Lower circulating preptin levels in male patients with osteoporosis are correlated with bone mineral density and bone formation 
Background
Serum preptin levels among subjects with different bone mineral densities (BMD) were measured and investigated to determine the correlation between BMD and bone-metabolic markers.
Methods
Approximately 52 elderly male patients with osteoporosis, 50 elderly men with osteopaenia, and 31 age-matched normal bone mass controls participated in the study. The serum preptin levels and bone metabolic markers were measured by enzyme-linked immunosorbent assay. The relationships between preptin levels, BMD, and metabolic parameters were also assessed.
Results
The serum preptin level was the lowest in the osteoporosis group and positively correlated with BMD. All the bone formation markers in the osteoporosis and osteopaenia groups were significantly reduced compared with those in the normal group. Serum preptin level was positively correlated with all the bone formation markers, whereas no correlation was observed with the bone resorption marker TRACP-5b.
Conclusions
Serum preptin levels are decreased in osteoporosis and osteopaenia patients and positively correlated with BMD. Therefore, preptin is involved in the pathogenesis of osteoporosis, probably through bone formation rather than bone resorption.
doi:10.1186/1471-2474-14-49
PMCID: PMC3570288  PMID: 23363476
Preptin; Osteoporosis; Bone density; Bone metabolic marker
20.  miR-1-Mediated Induction of Cardiogenesis in Mesenchymal Stem Cells via Downregulation of Hes-1 
BioMed Research International  2012;2013:216286.
MicroRNAs (miRNAs, miRs) have the potential to control stem cells fate decisions. The cardiac- and skeletal-muscle-specific miRNA, miR-1, can regulate embryonic stem cells differentiation to cardiac lineage by suppressing gene expression of alternative lineages. Accordingly, we hypothesized that overexpression of miR-1 may also promote cardiac gene expression in mesenchymal stem cells. Since Notch signaling could inhibit muscle differentiation, a process in contrast with the effect of miR-1, miR-1-mediated repression of Notch signaling may contribute to the observed effects of miR-1 in mesenchymal stem cells. Thus, mesenchymal stem cells were infected by lentiviral vectors carrying miR-1, and cells expressing miR-1 were selected. Alterations in Notch signaling and cardiomyocyte markers, Nkx2.5, GATA-4, cTnT, and CX43, were identified by Western blot in the infected cells on days 1, 7, and 14. Our study showed that the downstream target molecule of Notch pathway, Hes-1, was obviously decreased in mesenchymal stem cells modified with miR-1, and overexpression of miR-1 promotes the specific cardiac gene expression in the infected cells. Knockdown of Hes-1 leads to the same effects on cell lineage decisions. Our results indicated that miR-1 promotes the differentiation of MSCs into cardiac lineage in part due to negative regulation of Hes-1.
doi:10.1155/2013/216286
PMCID: PMC3591156  PMID: 23509692
21.  TiO2-Coated Carbon Nanotube-Silicon Solar Cells with Efficiency of 15% 
Scientific Reports  2012;2:884.
Combining carbon nanotubes (CNTs), graphene or conducting polymers with conventional silicon wafers leads to promising solar cell architectures with rapidly improved power conversion efficiency until recently. Here, we report CNT-Si junction solar cells with efficiencies reaching 15% by coating a TiO2 antireflection layer and doping CNTs with oxidative chemicals, under air mass (AM 1.5) illumination at a calibrated intensity of 100 mW/cm2 and an active device area of 15 mm2. The TiO2 layer significantly inhibits light reflectance from the Si surface, resulting in much enhanced short-circuit current (by 30%) and external quantum efficiency. Our method is simple, well-controlled, and very effective in boosting the performance of CNT-Si solar cells.
doi:10.1038/srep00884
PMCID: PMC3504926  PMID: 23181192
22.  Magnesium Intake and Risk of Type 2 Diabetes 
Diabetes Care  2011;34(9):2116-2122.
OBJECTIVE
Emerging epidemiological evidence suggests that higher magnesium intake may reduce diabetes incidence. We aimed to examine the association between magnesium intake and risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies.
RESEARCH DESIGN AND METHODS
We conducted a PubMed database search through January 2011 to identify prospective cohort studies of magnesium intake and risk of type 2 diabetes. Reference lists of retrieved articles were also reviewed. A random-effects model was used to compute the summary risk estimates.
RESULTS
Meta-analysis of 13 prospective cohort studies involving 536,318 participants and 24,516 cases detected a significant inverse association between magnesium intake and risk of type 2 diabetes (relative risk [RR] 0.78 [95% CI 0.73–0.84]). This association was not substantially modified by geographic region, follow-up length, sex, or family history of type 2 diabetes. A significant inverse association was observed in overweight (BMI ≥25 kg/m2) but not in normal-weight individuals (BMI <25 kg/m2), although test for interaction was not statistically significant (Pinteraction = 0.13). In the dose-response analysis, the summary RR of type 2 diabetes for every 100 mg/day increment in magnesium intake was 0.86 (95% CI 0.82–0.89). Sensitivity analyses restricted to studies with adjustment for cereal fiber intake yielded similar results. Little evidence of publication bias was observed.
CONCLUSIONS
This meta-analysis provides further evidence supporting that magnesium intake is significantly inversely associated with risk of type 2 diabetes in a dose-response manner.
doi:10.2337/dc11-0518
PMCID: PMC3161260  PMID: 21868780
23.  Role of Dietary Long-Chain Polyunsaturated Fatty Acids in Infant Allergies and Respiratory Diseases 
Maternal nutrition has critical effects on the developing structures and functions of the fetus. Malnutrition during pregnancy can result in low birth weight and small for gestational age babies, increase risk for infection, and impact the immune system. Long-chain polyunsaturated fatty acids (PUFAs) have been reported to have immunomodulatory effects. Decreased consumption of omega-6 PUFAs, in favor of more anti-inflammatory omega-3 PUFAs in modern diets, has demonstrated the potential protective role of omega-3 PUFAs in allergic and respiratory diseases. In this paper, we examine the role of PUFAs consumption during pregnancy and early childhood and its influence on allergy and respiratory diseases. PUFAs act via several mechanisms to modulate immune function. Omega-3 PUFAs may alter the T helper (Th) cell balance by inhibiting cytokine production which in turn inhibits immunoglobulin E synthesis and Th type 2 cell differentiation. PUFAs may further modify cellular membrane, induce eicosanoid metabolism, and alter gene expression. These studies indicate the benefits of omega-3 PUFAs supplementation. Nevertheless, further investigations are warranted to assess the long-term effects of omega-3 PUFAs in preventing other immune-mediated diseases, as well as its effects on the later immunodefense and health status during early growth and development.
doi:10.1155/2012/730568
PMCID: PMC3461300  PMID: 23049602
24.  Low-temperature synthesis of multilayer graphene/amorphous carbon hybrid films and their potential application in solar cells 
Nanoscale Research Letters  2012;7(1):453.
The effect of reaction temperature on the synthesis of graphitic thin film on nickel substrate was investigated in the range of 400°C to 1,000°C. Amorphous carbon (a-C) film was obtained at 400°C on nickel foils by chemical vapor deposition; hybrid films of multilayer graphene (MLG) and a-C were synthesized at a temperature of 600°C, while MLG was obtained at temperatures in excess of 800°C. Schottky-junction solar cell devices prepared using films produced at 400°C, 600°C, 800°C, and 1,000°C coupled with n-type Si demonstrate power conversion efficiencies of 0.003%, 0.256%, 0.391%, and 0.586%, respectively. A HNO3 treatment has further improved the efficiencies of the corresponding devices to 0.004%, 1.080%, 0.800%, and 0.820%, respectively. These films are promising materials for application in low-cost and simple carbon-based solar cells.
doi:10.1186/1556-276X-7-453
PMCID: PMC3479036  PMID: 22883426
Graphene; Amorphous carbon; Temperature effect; Nickel foil; Solar cell; HNO3 treatment
25.  Genetic polymorphisms of human platelet antigens-1 to -6, and -15 in the Malaysian population 
Blood Transfusion  2012;10(3):368-376.
Background.
Human platelet antigens (HPA) are determinant in several platelet-specific alloimmune disorders, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura and platelet transfusion refractoriness. The distribution of HPA systems in the Malaysian population is not known. Defining the patterns of HPA systems provides a basis for risk assessment and management of the above complications.
Materials and methods.
The aim of this study was to investigate the distribution of HPA -1 to -6 and -15 in the three major ethnic groups (Malay, Chinese and Indian) in the Malaysian population. A total of 600 random donor samples, 200 from each of the three ethnic groups, were genotyped by means of real time polymerase chain reaction (PCR) with hydrolysis probes and PCR-restriction fragment length polymorphism (PCR-RFLP).
Results.
The most common genotype observed in this study was HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b (17%) followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b (14.33%). The allele frequencies of HPA in Malays and Chinese were found to be similar those of other East and South-East Asian populations, while those of Indians were comparable to the frequencies found in Europeans.
Conclusion.
The results of this study have been useful for determining the distribution of HPA polymorphisms in this region and for potential clinical implications.
doi:10.2450/2012.0095-11
PMCID: PMC3417737  PMID: 22682339
HPA; genotyping; Malay; Southeast Asia

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