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1.  Expression of CD31/PECAM-1 (Platelet Endothelial Cell Adhesion Molecule 1) by Blastic Plasmacytoid Dendritic Cell Neoplasms 
JAMA dermatology  2014;150(1):73-76.
IMPORTANCE
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant neoplasm with cutaneous manifestations and a rapidly progressive clinical course. The diagnosis relies on characteristic clinicopathologic and immunopathologic features. However, the overlap of immunophenotypic features with other cancers, as well as newly discovered interpersonal and intrapersonal phenotypic variations, renders the identification of BPDCN challenging. A greater understanding of the proteins expressed by BPDCN might facilitate its recognition and provide insights into its clinical behavior.
OBSERVATIONS
In 7 of 9 patients at 4 tertiary care institutions, immunohistochemical analysis demonstrated strong CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) expression by neoplastic cells. Combined with similar findings observed in 1 former patient, 8 of 10 cases of BPDCN were CD31/PECAM-1 positive.
CONCLUSIONS AND RELEVANCE
Expression of CD31/PECAM-1 by BPDCN adds new information about the antigenic profile of this unusual neoplasm. CD31/PECAM-1 influences multiple cell functions including adhesion, apoptosis, coagulation, host response, and protein synthesis that might affect clinical features of BPDCN such as hemorrhage, aggressive tumor growth, and resistance to therapy. Therefore, the potential role of this molecule in the tumor formation and progression of BPDCN warrants additional exploration.
doi:10.1001/jamadermatol.2013.7141
PMCID: PMC4058994  PMID: 24225899
2.  Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine 
Psychopharmacology  2009;207(4):535-545.
Rationale
Our previous studies in rats have shown that the adipocyte-derived hormone leptin induces antidepressant-like effects with a behavioral profile similar to selective serotonin reuptake inhibitor (SSRI) antidepressants. Acute SSRI treatment causes paradoxical anxiogenic responses, although chronic treatment has therapeutic effects on anxiety. However, the role of leptin in anxiety remains to be established.
Objectives
The scope of this study was to investigate the acute effects of leptin on anxiety-related behaviors in comparison with the SSRI antidepressant fluoxetine.
Materials and methods
Adult male C57BL/6J mice received intraperitoneal injection of leptin or fluoxetine. Thirty minutes after injection, mice were subjected to the tail suspension test (TST) and forced swim test (FST) for evaluating antidepressant activity. Anxiety-like behavior was assessed in the elevated plus maze (EPM), social interaction, and open field tests 30 min following drug treatment.
Results
While leptin and fluoxetine showed similar antidepressant-like behavioral effects in the TST and FST, they differed in the behavioral assays for anxiety. Open arm exploration in the EPM was increased by leptin but decreased by fluoxetine. Analysis of social interaction revealed that distinct social behavioral components were modulated by leptin and fluoxetine. The total time of active social behaviors was increased by leptin but reduced by fluoxetine. In addition, self-grooming, a non-social behavior, was suppressed by leptin treatment. Neither leptin nor fluoxetine produced significant effects in the open field test.
Conclusions
In contrast to anxiogenic-like effects induced by acute fluoxetine, leptin elicits anxiolytic-like effects after acute administration. These results suggest that leptin has both antidepressant-like and anxiolytic-like properties.
doi:10.1007/s00213-009-1684-3
PMCID: PMC4057895  PMID: 19823809
Leptin; Fluoxetine; Anxiety; Depression; Tail suspension; Forced swim; Elevated plus maze; Social interaction
3.  ROP18 Is a Key Factor Responsible for Virulence Difference between Toxoplasma gondii and Neospora caninum 
PLoS ONE  2014;9(6):e99744.
Toxoplasma gondii (T. gondii) and Neospora caninum (N. caninum) are both obligate intracellular protozoan parasites and share many common morphological and biological features. Despite these similarities the two parasites differ dramatically in virulence in mice, but the factors involved in virulence differences between the two parasites remain unknown. A secreted serine-threonine kinase called rhoptry protein 18 (ROP18) was identified to play a crucial role on virulence differences among different T. gondii clonal lineages. Intriguingly, we found that ROP18 in Nc1 strain of N. caninum (NcROP18) is a pseudogene due to several interrupting stop codons in the sequence in our previous studies. We assume that the difference of ROP18 leads to virulence difference between T. gondii and N. caninum. We constructed a transgenic N. caninum Nc1 stain by transfecting the TgROP18 from the T. gondii RH strain. Phenotype and virulence assays showed that the expression of TgROP18 in N. caninum did not affect the motility and cell invasion, but resulted in a significant increase in intracellular parasite proliferation and virulence in mice. Immunity-Related GTPase (IRG) phosphorylation assay showed that the transgenic parasite Nc1-TgROP18 was able to phosphorylate IRGs as T. gondii did. The present study indicated that the ROP18 plays a crucial role in virulence of the closely related parasites T. gondii and N. caninum and it is indeed a key factor responsible for the virulence difference between T. gondii and N. caninum.
doi:10.1371/journal.pone.0099744
PMCID: PMC4057265  PMID: 24927100
4.  Learning Curve and Interobserver Agreement of Confocal Laser Endomicroscopy for Detecting Precancerous or Early-Stage Esophageal Squamous Cancer 
PLoS ONE  2014;9(6):e99089.
Background
Confocal laser endomicroscopy (CLE) can provide in vivo subcellular resolution images of esophageal lesions. However, the learning curve in interpreting CLE images of precancerous or early-stage esophageal squamous cancer is unknown. The goal of this study is to evaluate the diagnostic accuracy and inter-observer agreement for differentiating esophageal lesions in CLE images among experienced and inexperienced observers and to assess the learning curve.
Method
After a short training, 8 experienced and 14 inexperienced endoscopists evaluated in sequence 4 sets of high-quality CLE images. Their diagnoses were corrected and discussed after each set. For each image, the diagnostic results, confidence in diagnosis, quality and time to evaluate were recorded.
Results
Overall, diagnostic accuracy was greater for the second, third, fourth set of images as compared with the initial set (odds ratio [OR] 2.01, 95% CI 1.22–3.31; 7.95, 3.74–16.87; and 6.45, 3.14–13.27), respectively, with no difference between the third and fourth sets in accuracy (p = 0.67). Previous experience affected the diagnostic accuracy only in the first set of images (OR 3.70, 1.87–7.29, p<0.001). Inter-observer agreement was higher for experienced than inexperienced endoscopists (0.732 vs. 0.666, p<0.01)
Conclusion
CLE is a promising technology that can be quickly learned after a short training period; previous experience is associated with diagnostic accuracy only at the initial stage of learning.
doi:10.1371/journal.pone.0099089
PMCID: PMC4045985  PMID: 24897112
5.  Prevalence, Incidence, and Residual Risks for Transfusion Transmitted HIV-1/2 Infection among Chinese Blood Donors 
Transfusion  2012;53(6):1240-1249.
Background
There is little data on HIV prevalence, incidence or residual risks for transfusion transmitted HIV infection among Chinese blood donors.
Methods
Donations from five Chinese blood centers in 2008–2010 were screened using two rounds of ELISA testing for anti-HIV-1/2. A reactive result in either or both rounds led to Western Blot confirmatory testing. HIV prevalence and demographic correlates among first time donors, incidence rate and demographic correlates among repeat donors were examined. Weighted multivariable logistic regression analysis examined correlates of HIV confirmatory status among first time donors. Residual risks for transfusion transmitted HIV infection were evaluated based on incidence among repeat donors.
Results
Among 821,320 donations, 40% came from repeat donors.1,837 (0.34%) first time and 577 (0.17%) repeat donations screened reactive for anti-HIV-1/2, among which 1,310 and 419 were tested by Western Blot. 233 (17.7%) first time and 44 (10.5%) repeat donations were confirmed positive. Estimated prevalence was 66 infections per 100,000 (95% CI: 59–74) first time donors. Estimated incidence was 9/100,000 (95% CI: 7–12) person-years among repeat donors. Weighted multivariable logistic regression analysis indicate that first time donors 26–45 years old were 1.6–1.8 times likely to be HIV positive than those 25 years and younger. Donors with some college or above education were less likely to be HIV positive than those with middle school education, ORs ranging from 0.35 to 0.60. Minority were 1.6 times likely to be HIV positive than Han majority donors (OR: 1.6; CI: 1.2–2.1). No difference in prevalence was found between gender. Current HIV TTI residual risk was 5.4 (1.2–12.5) infections per million whole blood donations.
Conclusion
Despite the declining HIV epidemic China, estimated residual risks for transfusion transmitted HIV infection are still high, highlighting the potential blood safety yield of NAT implementation in donation screening.
doi:10.1111/j.1537-2995.2012.03940.x
PMCID: PMC3586939  PMID: 23113801
HIV infection; blood donors; China; Prevalence; Incidence; Residual Risks
6.  Regulation of VH Replacement by B Cell Receptor (BCR)-mediated Signaling in Human Immature B Cells 
VH replacement provides a unique RAG-mediated recombination mechanism to edit non-functional IgH genes or IgH genes encoding self reactive B cell receptors (BCRs) and contributes to the diversification of antibody repertoire in mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. Here we show that crosslinking BCRs induces VH replacement in human EU12 μHC+ cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases; but is inhibited by CD19 co-stimulation, presumably through activation of the PI3 kinase pathway. These results show for the first time that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.
doi:10.4049/jimmunol.1102503
PMCID: PMC3660396  PMID: 23630348
7.  Molecular phenotype predicts sensitivity of squamous cell carcinoma of the head and neck to epidermal growth factor receptor inhibition 
Molecular oncology  2012;7(3):359-368.
Despite nearly universal expression of the wild-type epidermal growth factor receptor (EGFR) and reproducible activity of EGFR inhibitors in patients with squamous cell carcinoma of the head and neck (SCCHN), the majority of patients will not have objective responses. The mechanisms of this intrinsic resistance are not well established. We hypothesized that sensitivity to EGFR inhibitors can be predicted based on the inhibitors’ effects on downstream signaling. Cell viability assays were used to assess sensitivity to the EGFR inhibitor gefitinib (ZD1839) in 8 SCCHN cell lines. Fluorescence in-situ hybridization showed the two most sensitive lines to be highly gene-amplified for EGFR. Western blotting confirmed that phosphoEGFR was inhibited at low concentrations of gefitinib in all lines tested. Phosphorylation of downstream signaling protein AKT was inhibited in sensitive lines while inhibition of phosphoERK displayed no relationship to gefitinib efficacy. Phosphatase and tensin homolog (PTEN) expression was evident in all cell lines. Activating PIK3CA mutations were found in two resistant cell lines where pAKT was not inhibited by gefitinib. In resistant cell lines harboring PIK3CA mutations, a PI3K inhibitor, LY294002, or AKT siRNA reduced cell viability with an additive effect demonstrated in combination with gefitinib. Additionally, LY294002 alone and in combination with gefitinib, was effective at treating PIK3CA mutated tumors xenografted into nude mice. Taken together this suggests that constitutively active AKT is a mechanism of intrinsic gefitinib resistance in SCCHN. This resistance can be overcome through targeting of the PI3K/AKT pathway in combination with EGFR inhibition.
doi:10.1016/j.molonc.2012.11.001
PMCID: PMC3661759  PMID: 23200321
EGFR; Gefitinib; Head and neck squamous; cell carcinoma; AKT; PIK3CA mutations
8.  Associations Between Single-Nucleotide Polymorphisms and Epidural Ropivacaine Consumption in Patients Undergoing Breast Cancer Surgery 
Up to date, few published studies indicated the associations between genetic polymorphisms and epidural local anesthetics consumption. In this study, we investigated the associations between seven single-nucleotide polymorphisms (SNPs) and epidural ropivacaine consumption during breast cancer surgery in women from northeastern China. These seven SNPs (rs3803662 and rs12443621 in TNCR9, rs889312 in MAP3K1, rs3817198 in LSP1, rs13387042 at 2q35, rs13281615 at 8q24, and rs2046210 at 6q25.1) were identified by recent genome-wide association studies associated with tumor susceptibility. A total of 418 breast cancer women received thoracic epidural anesthesia with ropivacaine for elective mastectomy with axillary clearance. Their blood samples were genotyped for the seven SNPs using the SNaPshot method. For SNP rs13281615, the subjects with genotype AG and GG consumed a greater amount of the total epidural ropivacaine and the mean ropivacaine dose than the subjects with genotype AA (p=0.047 and p=0.003, respectively). Furthermore, no statistical differences were found in the total dose of ropivacaine, the mean consumption of ropivacaine, the onset of ropivacaine, or the initial dose of lidocaine among the three genotypic groups for the other six SNPs studied. Our study indicated that SNP rs13281615 at 8q24 was associated with the consumption of epidural ropivacaine during breast cancer surgery in northeastern Chinese women. It might provide new insights into the mechanisms of ropivacaine action and metabolism and facilitate the development of personalized medicine.
doi:10.1089/gtmb.2012.0388
PMCID: PMC3668497  PMID: 23577780
9.  Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation 
Genesis (New York, N.Y. : 2000)  2013;51(6):436-442.
Cre/LoxP-mediated recombination allows for conditional gene activation or inactivation. When combined with an independent lineage-tracing reporter allele, this technique traces the lineage of presumptive genetically modified Cre-expressing cells. Several studies have suggested that floxed alleles have differential sensitivities to Cre-mediated recombination, which raises concerns regarding utilization of common Cre-reporters to monitor recombination of other floxed loci of interest. Here, we directly investigate the recombination correlation, at cellular resolution, between several floxed alleles induced by Cre-expressing mouse lines. The recombination correlation between different reporter alleles varied greatly in otherwise genetically identical cell types. The chromosomal location of floxed alleles, distance between LoxP sites, sequences flanking the LoxP sites, and the level of Cre activity per cell all likely contribute to observed variations in recombination correlation. These findings directly demonstrate that, due to non-parallel recombination events, commonly available Cre reporter mice cannot be reliably utilized, in all cases, to trace cells that have DNA recombination in independent-target floxed alleles, and that careful validation of recombination correlations are required for proper interpretation of studies designed to trace the lineage of genetically modified populations, especially in mosaic situations.
doi:10.1002/dvg.22384
PMCID: PMC3696028  PMID: 23441020
Mosaic analysis; lineage tracing; cell autonomous; Cre detection; non-parallel recombination
10.  The Association between Within-Visit Blood Pressure Variability and Carotid Artery Atherosclerosis in General Population 
PLoS ONE  2014;9(5):e97760.
Objectives
To determine whether within-visit blood pressure (BP) variability based on three measurements over minutes is associated with increased carotid intima-media thickness (IMT) and plaque in a general population.
Methods
A cross-sectional survey was performed in 2007, and a total of 1222 Beijing community residents aged 50–79 years belonging to part of the Chinese Multi-Provincial Cohort Study (CMCS) were recruited in this study. BP was measured three times at 5-minute intervals during a single visit, and the maximum absolute difference (MAD) between any two readings of three measurements was used to indicate within-visit BP variability. Carotid IMT and plaque scanned by B-mode ultrasound were identified as the surrogate end points in the intermediate stage of atherosclerosis.
Results
After adjustment for established cardiovascular risk factors, the odds ratio (OR) (95% confidence interval (CI)) for increased carotid IMT and internal carotid plaque associated with the highest within-visit diastolic BP (DBP) variability (MAD > mean + standard deviation (SD)) compared with participants in the lowest within-visit DBP variability (MAD ≤ mean −SD) was 4.92 (1.48–16.42) and 6.07 (1.31–28.10), respectively, in the normotensives (P = 0.01; P = 0.02). The OR (95% CI) for internal carotid plaque associated with the highest within-visit systolic BP (SBP) variability (MAD >mean +SD) compared with participants in the lowest within-visit SBP variability (MAD ≤ mean −SD) was 3.54 (1.26–10.00) in the hypertensives on antihypertensive therapy (P = 0.02).
Conclusions
Within-visit DBP variability was associated with increased carotid IMT and internal carotid plaque in the normotensive population, and within-visit SBP variability was associated with internal carotid plaque in hypertensive patients undergoing antihypertensive therapy.
doi:10.1371/journal.pone.0097760
PMCID: PMC4024014  PMID: 24835667
11.  CistromeFinder for ChIP-seq and DNase-seq data reuse 
Bioinformatics  2013;29(10):1352-1354.
Summary: Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing have greatly accelerated the understanding of transcriptional and epigenetic regulation, although data reuse for the community of experimental biologists has been challenging. We created a data portal CistromeFinder that can help query, evaluate and visualize publicly available Chromatin immunoprecipitation and DNase I hypersensitivity assays with high-throughput sequencing data in human and mouse. The database currently contains 6378 samples over 4391 datasets, 313 factors and 102 cell lines or cell populations. Each dataset has gone through a consistent analysis and quality control pipeline; therefore, users could evaluate the overall quality of each dataset before examining binding sites near their genes of interest. CistromeFinder is integrated with UCSC genome browser for visualization, Primer3Plus for ChIP-qPCR primer design and CistromeMap for submitting newly available datasets. It also allows users to leave comments to facilitate data evaluation and update.
Availability: http://cistrome.org/finder.
Contact: xsliu@jimmy.harvard.edu or henry_long@dfci.harvard.edu
doi:10.1093/bioinformatics/btt135
PMCID: PMC3654708  PMID: 23508969
12.  The genus Omalus Panzer, 1801 (Hymenoptera, Chrysididae) from China, with descriptions of four new species 
ZooKeys  2014;29-54.
The Chinese species of the genus Omalus Panzer, 1801 are revised and keyed for the first time. Eight species are recorded, of which four are new to science and one is new to China: Omalus aeneus (Fabricius, 1787), Omalus berezovskii (Semenov-Tian-Shanskij, 1932), Omalus potanini (Semenov-Tian-Shanskij, 1932), Omalus imbecillus (Mocsáry, 1889) (new to China), Omalus helanshanus sp. n., Omalus probiaccinctus sp. n., Omalus pseudoimbecillus sp. n., and Omalus tibetanus sp. n.
doi:10.3897/zookeys.407.7531
PMCID: PMC4042702  PMID: 24899830
Chrysididae; Omalus; new species; Palaearctic; Oriental; China
13.  Efficacy of ultrasound-guided radial artery catheterization: a systematic review and meta-analysis of randomized controlled trials 
Critical Care  2014;18(3):R93.
Introduction
Ultrasound guidance has emerged as an adjunct for central vein catheterization in both adults and children. However, the use of ultrasound guidance for radial arterial catheterization has not been well established. We conducted a systematic review and meta-analysis to evaluate the efficacy of ultrasound guidance for radial artery catheterization.
Methods
PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) comparing ultrasound guidance with other techniques (palpation or Doppler) in adult or pediatric patients requiring radial artery catheterization were included. The primary outcome was first-attempt success.
Results
Seven RCTs enrolling 546 patients met the inclusion criteria, and all the selected trials were considered as at high risk of bias. Ultrasound-guided radial artery catheterization was associated with an increased first-attempt success (relative risk (RR) 1.55, 95% confidence interval (CI) 1.02 to 2.35). There was significant heterogeneity among the studies (I2 = 74%). Ultrasound-guided radial artery catheterization in small children and infants also provided an increased chance for first-attempt success (RR 1.94, 95% CI 1.31 to 2.88). Ultrasound guidance further significantly reduced mean attempts to success (weighted mean difference (WMD) −1.13, 95% CI −1.58 to −0.69), mean time to success (WMD −72.97 seconds, 95% CI −134.41 to −11.52), and incidence of the complication of hematoma (RR 0.17, 95% CI 0.07 to 0.41).
Conclusions
Ultrasound guidance is an effective and safe technique for radial artery catheterization, even in small children and infants. However, the results should be interpreted cautiously due to the heterogeneity among the studies.
doi:10.1186/cc13862
PMCID: PMC4056628  PMID: 24887241
14.  A Novel Stent Coated with Antibodies to Endoglin Inhibits Neointimal Formation of Porcine Coronary Arteries 
BioMed Research International  2014;2014:428619.
Endoglin/CD105 is an accessory protein of the transforming growth factor-β receptor system that plays a critical role in proliferation of endothelial cells and neovasculature. Here, we aimed to assess the effect of novel stents coated with antibodies to endoglin (ENDs) on coronary neointima formation. Thirty ENDs, thirty sirolimus-eluting stents (SESs), and thirty bare metal stents (BMSs) were randomly assigned and placed in the coronary arteries in 30 juvenile pigs. Histomorphometric analysis and scanning electron microscopy were performed after stent implantation. Our results showed that after 7 days, there was no difference in the neointimal area and percent area stenosis in ENDs compared with SMSs or BMSs. After 14 days, the neointima area and percent area stenosis in ENDs were markedly decreased than those in BMSs or SESs (P < 0.05). Moreover, the percentage of reendothelialization was significantly higher in ENDs than that in SESs or BMSs (P < 0.01) at 7 and 14 days. The artery injury and the inflammation scores were similar in all groups at 7 and 14 days. In conclusion, our results demonstrated for the first time to our knowledge that endoglin antibody-coated stents can markedly reduce restenosis by enhancing reendothelialization in the porcine model and potentially offer a new approach to prevent restenosis.
doi:10.1155/2014/428619
PMCID: PMC4026940  PMID: 24883312
17.  The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients 
Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammation pathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthma with rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88 healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcal superantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameters were retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%, and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, and TSST-1 were also significantly higher in group I (0.300±1.533 kU/L, 0.663±2.933 kU/L, and 0.581±1.931 kU/L) and group II (0.502±2.011 kU/L, 0.695±3.337 kU/L, and 1.067±4.688 kU/L) compared to those in group III (0.03±0.133 kU/L, 0.03±0.14 kU/L, and 0.028±0.112 kU/L). The prevalence of serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higher in patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE to TSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR and AR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation.
doi:10.4168/aair.2014.6.3.263
PMCID: PMC4021246  PMID: 24843803
Superantigen; specific IgE; allergic rhinitis; bronchial asthma
18.  Combined probiotic bacteria promotes intestinal epithelial barrier function in interleukin-10-gene-deficient mice 
AIM: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
METHODS: IL-10 KO mice were used to assess the benefits of Bifico in vivo. IL-10 KO and control mice received approximately 1.5 × 108 cfu/d of Bifico for 4 wk. Colons were then removed and analyzed for epithelial barrier function by Ussing Chamber, while an ELISA was used to evaluate proinflammatory cytokines. The colon epithelial cell line, Caco-2, was used to test the benefit of Bifico in vitro. Enteroinvasive Escherichia coli (EIEC) and the probiotic mixture Bifico, or single probiotic strains, were applied to cultured Caco-2 monolayers. Barrier function was determined by measuring transepithelial electrical resistance and tight junction protein expression.
RESULTS: Treatment of IL-10 KO mice with Bifico partially restored body weight, colon length, and epithelial barrier integrity to wild-type levels. In addition, IL-10 KO mice receiving Bifico treatment had reduced mucosal secretion of tumor necrosis factor-α and interferon-γ, and attenuated colonic disease. Moreover, treatment of Caco-2 monolayers with Bifico or single-strain probiotics in vitro inhibited EIEC invasion and reduced the secretion of proinflammatory cytokines.
CONCLUSION: Bifico reduced colon inflammation in IL-10 KO mice, and promoted and improved epithelial-barrier function, enhanced resistance to EIEC invasion, and decreased proinflammatory cytokine secretion.
doi:10.3748/wjg.v20.i16.4636
PMCID: PMC4000500  PMID: 24782616
Probiotic bacteria; Intestinal barrier function; Tight junction proteins; Interleukin-10 gene-deficient mice; Caco-2 monolayers
19.  Strong anisotropic lifetime orientation distributions of a two-level quantum emitter around a plasmonic nanorod 
Nanoscale Research Letters  2014;9(1):194.
Spontaneous emission lifetime orientation distributions of a two-level quantum emitter in metallic nanorod structures are theoretically investigated by the rigorous electromagnetic Green function method. It was found that spontaneous emission lifetime strongly depended on the transition dipole orientation and the position of the emitter. The anisotropic factor defined as the ratio between the maximum and minimum values of the lifetimes along different dipole orientations can reach up to 103. It is much larger than those in dielectric structures which are only several times usually. Our results show that the localized plasmonic resonance effect provides a new degree of freedom to effectively control spontaneous emission by the dipole orientation of the quantum emitters.
doi:10.1186/1556-276X-9-194
PMCID: PMC4006315  PMID: 24808801
Surface plasmons; Spontaneous emission; Lifetime distribution; Nanorod; 78.67.Qa; 73.20.Mf; 42.50.-p
20.  NuMA promotes homologous recombination repair by regulating the accumulation of the ISWI ATPase SNF2h at DNA breaks 
Nucleic Acids Research  2014;42(10):6365-6379.
Chromatin remodeling factors play an active role in the DNA damage response by shaping chromatin to facilitate the repair process. The spatiotemporal regulation of these factors is key to their function, yet poorly understood. We report that the structural nuclear protein NuMA accumulates at sites of DNA damage in a poly[ADP-ribose]ylation-dependent manner and functionally interacts with the ISWI ATPase SNF2h/SMARCA5, a chromatin remodeler that facilitates DNA repair. NuMA coimmunoprecipitates with SNF2h, regulates its diffusion in the nucleoplasm and controls its accumulation at DNA breaks. Consistent with NuMA enabling SNF2h function, cells with silenced NuMA exhibit reduced chromatin decompaction after DNA cleavage, lesser focal recruitment of homologous recombination repair factors, impaired DNA double-strand break repair in chromosomal (but not in episomal) contexts and increased sensitivity to DNA cross-linking agents. These findings reveal a structural basis for the orchestration of chromatin remodeling whereby a scaffold protein promotes genome maintenance by directing a remodeler to DNA breaks.
doi:10.1093/nar/gku296
PMCID: PMC4041463  PMID: 24753406
21.  Wen-Dan Decoction Improves Negative Emotions in Sleep-Deprived Rats by Regulating Orexin-A and Leptin Expression 
Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression.
doi:10.1155/2014/872547
PMCID: PMC4016855  PMID: 24864160
22.  Study on In-Vivo Anti-Tumor Activity of Verbena Officinalis Extract 
We investigated the anti-tumor effects of Verbena officinalis extract on H22 tumor-bearing mice and its effect on immune function. Mice model of H22 solid tumor was established, the mice were divided into five groups and administered the extract, later, tumors were removed and inhibition rates were calculated; spleens were removed and spleen indices were calculated, and the sheep red blood cell-delayed-type hypersensitivity (SRBC-DTH) and the serum hemolysin level were determined. The Verbena officinalis extract had anti-tumor effect, with the inhibition rate reaching 38.78%, it also increased the spleen index to a certain extent, in addition, the changes in DTA and HA were not obvious compared with the model group. The Verbena officinalis extract had in vivo anti-tumor effect, while causing no damage on the immune function.
PMCID: PMC3777594  PMID: 24146482
Verbena officinalis extract; H22 mouse; tumor inhibition; immune function
23.  Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro 
Scientific Reports  2014;4:4619.
Basal cells in nasal epithelium have stemness/progenitor characters and play essential roles in the epithelial remodeling in nasal polyps (NP). We investigate whether the human nasal epithelial stem/progenitor cells (hNESPCs) from patients with NP are inherently distinct from those obtained from healthy controls. Epithelial basal cells were isolated and cultured for four passages from NP tissues and control nasal mucosa. hNESPCs from controls were stained positively with stem cell marker p63 and KRT5 and presented a consistent high Ki67 expression level over four passages. In contrast, hNESPCs from NP patients showed: i). a reduced growth and proliferation rate at each passage by evaluating colony-forming efficiency and doubling time; ii). a lower percentage of Ki67+ cells among p63+ cells in the colonies in late passages, which was also confirmed by immunostaining in the NP tissues. Thus reduced growth/proliferation dynamics in hNESPCs from NP could be an important pathological phenomenon in NP development.
doi:10.1038/srep04619
PMCID: PMC3980221  PMID: 24714674
24.  Personal electronics printing via tapping mode composite liquid metal ink delivery and adhesion mechanism 
Scientific Reports  2014;4:4588.
Printed electronics is becoming increasingly important in a variety of newly emerging areas. However, restricted to the rather limited conductive inks and available printing strategies, the current electronics manufacture is usually confined to industry level. Here, we show a highly cost-effective and entirely automatic printing way towards personal electronics making, through introducing a tapping-mode composite fluid delivery system. Fundamental mechanisms regarding the reliable printing, transfer and adhesion of the liquid metal inks on the substrate were disclosed through systematic theoretical interpretation and experimental measurements. With this liquid metal printer, a series of representative electronic patterns spanning from single wires to desired complex configurations such as integrated circuit (IC), printed-circuits-on-board (PCB), electronic paintings, or more do-it-yourself (DIY) devices, were demonstrated to be printed out with high precision in a moment. And the total machine cost already reached personally affordable price. This is hard to achieve by a conventional PCB technology which generally takes long time and is material, water and energy consuming, while the existing printed electronics is still far away from the real direct printing goal. The present work opens the way for large scale personal electronics manufacture and is expected to generate important value for the coming society.
doi:10.1038/srep04588
PMCID: PMC3975221  PMID: 24699375
25.  Prevalence of Serological Markers for Hepatitis B and C Viruses in Brazilian Blood Donors, and Incidence and Residual Risk of Transfusion-Transmission of Hepatitis C Virus 
Transfusion  2012;53(4):827-834.
Background
We evaluate the current prevalence of serological markers for HBV and HCV in blood donors and estimated HCV incidence and residual transfusion-transmitted risk at three large Brazilian blood centers.
Material and Methods
Data on whole blood and platelet donations were collected from January through December 2007 and analyzed by center, donor type (replacement vs. community), age, sex, donation status (first-time vs. repeat), and serological results for HBsAg, anti-HBc and anti-HCV. HBV (HBsAg+/anti-HBc+) and HCV (anti-HCV) prevalence rates were calculated for all first time donations. HCV incidence was derived including inter-donation intervals that preceded first repeat donations given during the study and HCV residual risk was estimated for transfusions derived from repeat donors.
Results
There were 307,354 donations from January through December 2007. Overall prevalence of concordant HBsAg and anti-HBc reactivity was 289 per 100,000 donations and of anti-HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% CI 0.77-7.03) per 100,000 person-years, and residual risk of HCV window-phase infections was estimated at 5.0 per million units transfused.
Conclusion
Improvement in blood donor selection, socioeconomic conditions and preventive measures, implemented over time, may have helped to decrease prevalence of hepatitis B and C viruses, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of hepatitis B and C viral markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening methods and counseling strategies.
doi:10.1111/j.1537-2995.2012.03840.x
PMCID: PMC3499633  PMID: 22882510
Blood donors; Brazil; Residual Risk; Hepatitis B; Hepatitis C; Prevalence; Incidence

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