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2.  Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery 
Scientific Reports  2016;6:22731.
Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-β, which was able to form inter-molecular β-sheet structures. Results showed that K-β peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.
doi:10.1038/srep22731
PMCID: PMC4783658  PMID: 26955887
3.  Cys34 Adducts of Reactive Oxygen Species in Human Serum Albumin 
Chemical research in toxicology  2012;25(8):1633-1642.
Long-term exposures to reactive oxygen species (ROS) have been linked to scores of chronic diseases. This has motivated interest in oxidation products of the only free cysteine residue (Cys34) of human serum albumin (HSA) as possible biomarkers of ROS exposure. However, Cys34 oxidation products have not been detected in human serum or plasma. Using liquid chromatography-high resolution tandem mass spectrometry, we report accurate masses and molecular compositions of Cys34 oxidation products in the 2432 Da peptide resulting from tryptic digestion of HSA. Peptides containing the expected sulfinic (Cys-SO2H) and sulfonic (Cys-SO3H) acids, as well as an adduct representing addition of one oxygen atom and loss of two hydrogen atoms, were detected in four archived samples of human plasma and one fresh sample of human serum. We speculate that this latter adduct is a sulfinamide formed by intramolecular reaction between either the Cys34 sulfenic acid (Cys-SOH) or sulfinic acid (Cys-SO2H) and the adjacent glutamine residue (Gln33). All three Cys34 adducts were measured in the five human samples with levels decreasing in the order sulfinic acid > (proposed) sulfinamide > sulfonic acid. Parallel measurements of a negative control detected only small amounts of the Cys34 sulfonic acid and the (proposed) sulfinamide and did not detect the sulfinic acid.
Graphical Abstract
Grigoryan et al. used high-resolution mass spectrometry to detect oxidation products of HSA-Cys34 in human plasma samples. In addition to the sulfinic acid (Cys-SO2H) and the sulfonic acid (Cys-SO3H), the authors detected an added mass of (+O,-H2), which they suspect to be a sulfinamide resulting from intramolecular reaction between the Cys34 sulfenic acid (Cys-SOH) or sulfinic acid (Cys-SO2H) and the amide group of Gln33.
doi:10.1021/tx300096a
PMCID: PMC4763613  PMID: 22591159
reactive oxygen species; HSA; Cys34; high resolution mass spectrometry; sulfinic acid; sulfonic acid; sulfinamide
4.  Adductomics: Characterizing exposures to reactive electrophiles 
Toxicology letters  2011;213(1):83-90.
To understand environmental causes of disease, unbiased methods are needed to characterize the human exposome, which represents all toxicants to which people are exposed from both exogenous and endogenous sources. Because they directly modify DNA and important proteins, reactive electrophiles are probably the most important constituents of the exposome. Exposures to reactive electrophiles can be characterized by measuring adducts from reactions between circulating electrophiles and blood nucleophiles. We define an ‘adductome’ as the totality of such adducts with a given nucleophilic target. Because of their greater abundance and residence times in human blood, adducts of hemoglobin (Hb) and human serum albumin (HSA) are preferable to those of DNA and glutathione for characterizing adductomes. In fact, the nucleophilic hotspot represented by the only free sulfhydryl group in HSA (HSA-Cys34) offers particular advantages for adductomic experiments. Although targeted adducts of HSA-Cys34 have been monitored for decades, an unbiased method has only recently been reported for visualizing the HSA-Cys34 ‘subadductome’. The method relies upon a novel mass spectrometry application, termed fixed-step selected reaction monitoring (FS-SRM), to profile Cys34 adducts in tryptic digests of HSA. Here, we selectively review the literature regarding the potential of adductomics to partially elucidate the human exposome, with particular attention to the HSA-Cys34 subadductome.
doi:10.1016/j.toxlet.2011.04.002
PMCID: PMC4758449  PMID: 21501670
Adductome; Exposome; Reactive electrophiles; HSA; Cys34; Selected reaction monitoring
5.  Morphometric traits capture the climatically driven species turnover of 10 spruce taxa across China 
Ecology and Evolution  2016;6(4):1203-1213.
Abstract
This study explored the relative roles of climate and phylogenetic background in driving morphometric trait variation in 10 spruce taxa in China. The study further addressed the hypothesis that these variations are consistent with species turnover on climatic gradients. Nine morphometric traits of leaves, seed cones, and seeds for the 10 studied spruce taxa were measured at 504 sites. These data were analyzed in combination with species DNA sequences from NCBI GenBank. We detected the effects of phylogeny and climate through trait‐variation‐based K statistics and phylogenetic eigenvector regression (PVR) analyses. Multivariate analyses were performed to detect trait variation along climatic gradients with species replacement. The estimated K‐values for the nine studied morphometric traits ranged from 0.19 to 0.68, and the studied environmental variables explained 39–83% of the total trait variation. Trait variation tended to be determined largely by a temperature gradient varying from wet‐cool climates to dry‐warm summers and, additionally, by a moisture gradient. As the climate became wetter and cooler, spruce species tended to be replaced by other spruces with smaller needle leaves and seeds but larger cones and seed scales. A regression analysis showed that spruce species tended to be successively replaced by other species, along the gradient, although the trends observed within species were not necessarily consistent with the overall trend. The climatically driven replacement of the spruces in question could be well indicated by the between‐species variation in morphometric traits that carry lower phylogenetic signal. Between‐species variation in these traits is driven primarily by climatic factors. These species demonstrate a narrower ecological amplitude in temperature but wider ranges on the moisture gradient.
doi:10.1002/ece3.1971
PMCID: PMC4725448  PMID: 26839688
Ecological amplitude; geographical distribution; interspecific and intraspecific variation; phylogeny; Picea
6.  Morphometric traits capture the climatically driven species turnover of 10 spruce taxa across China 
Ecology and Evolution  2016;10.1002/ece3.1971.
Abstract
This study explored the relative roles of climate and phylogenetic background in driving morphometric trait variation in 10 spruce taxa in China. The study further addressed the hypothesis that these variations are consistent with species turnover on climatic gradients. Nine morphometric traits of leaves, seed cones, and seeds for the 10 studied spruce taxa were measured at 504 sites. These data were analyzed in combination with species DNA sequences from NCBI GenBank. We detected the effects of phylogeny and climate through trait‐variation‐based K statistics and phylogenetic eigenvector regression (PVR) analyses. Multivariate analyses were performed to detect trait variation along climatic gradients with species replacement. The estimated K‐values for the nine studied morphometric traits ranged from 0.19 to 0.68, and the studied environmental variables explained 39–83% of the total trait variation. Trait variation tended to be determined largely by a temperature gradient varying from wet‐cool climates to dry‐warm summers and, additionally, by a moisture gradient. As the climate became wetter and cooler, spruce species tended to be replaced by other spruces with smaller needle leaves and seeds but larger cones and seed scales. A regression analysis showed that spruce species tended to be successively replaced by other species, along the gradient, although the trends observed within species were not necessarily consistent with the overall trend. The climatically driven replacement of the spruces in question could be well indicated by the between‐species variation in morphometric traits that carry lower phylogenetic signal. Between‐species variation in these traits is driven primarily by climatic factors. These species demonstrate a narrower ecological amplitude in temperature but wider ranges on the moisture gradient.
doi:10.1002/ece3.1971
PMCID: PMC4725448  PMID: 26839688
Ecological amplitude; geographical distribution; interspecific and intraspecific variation; phylogeny; Picea
7.  The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share 
Kottyan, Leah C. | Zoller, Erin E. | Bene, Jessica | Lu, Xiaoming | Kelly, Jennifer A. | Rupert, Andrew M. | Lessard, Christopher J. | Vaughn, Samuel E. | Marion, Miranda | Weirauch, Matthew T. | Namjou, Bahram | Adler, Adam | Rasmussen, Astrid | Glenn, Stuart | Montgomery, Courtney G. | Hirschfield, Gideon M. | Xie, Gang | Coltescu, Catalina | Amos, Chris | Li, He | Ice, John A. | Nath, Swapan K. | Mariette, Xavier | Bowman, Simon | Rischmueller, Maureen | Lester, Sue | Brun, Johan G. | Gøransson, Lasse G. | Harboe, Erna | Omdal, Roald | Cunninghame-Graham, Deborah S. | Vyse, Tim | Miceli-Richard, Corinne | Brennan, Michael T. | Lessard, James A. | Wahren-Herlenius, Marie | Kvarnström, Marika | Illei, Gabor G. | Witte, Torsten | Jonsson, Roland | Eriksson, Per | Nordmark, Gunnel | Ng, Wan-Fai | Anaya, Juan-Manuel | Rhodus, Nelson L. | Segal, Barbara M. | Merrill, Joan T. | James, Judith A. | Guthridge, Joel M. | Hal Scofield, R. | Alarcon-Riquelme, Marta | Bae, Sang-Cheol | Boackle, Susan A. | Criswell, Lindsey A. | Gilkeson, Gary | Kamen, Diane L. | Jacob, Chaim O. | Kimberly, Robert | Brown, Elizabeth | Edberg, Jeffrey | Alarcón, Graciela S. | Reveille, John D. | Vilá, Luis M. | Petri, Michelle | Ramsey-Goldman, Rosalind | Freedman, Barry I. | Niewold, Timothy | Stevens, Anne M. | Tsao, Betty P. | Ying, Jun | Mayes, Maureen D. | Gorlova, Olga Y. | Wakeland, Ward | Radstake, Timothy | Martin, Ezequiel | Martin, Javier | Siminovitch, Katherine | Moser Sivils, Kathy L. | Gaffney, Patrick M. | Langefeld, Carl D. | Harley, John B. | Kaufman, Kenneth M.
Human Molecular Genetics  2014;24(2):582-596.
Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5–TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5–TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10−49; OR = 1.38–1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10−27–10−32, OR = 1.7–1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5–TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5–TNPO3.
doi:10.1093/hmg/ddu455
PMCID: PMC4275071  PMID: 25205108
8.  Structural mechanism of DNA recognition by the p202 HINa domain: insights into the inhibition of Aim2-mediated inflammatory signalling 
Structural and biochemical data demonstrate that p202 recognizes foreign DNA in a distinct manner compared with AIM2/Aim2, leading to a new model for the negative regulation of Aim2-mediated inflammasome activation by p202.
The HIN-200 family of proteins play significant roles in inflammation-related processes. Among them, AIM2 (absent in melanoma 2) and IFI16 (γ-interferon-inducible protein 16) recognize double-stranded DNA to initiate inflammatory responses. In contrast, p202, a mouse interferon-inducible protein containing two HIN domains (HINa and HINb), has been reported to inhibit Aim2-mediated inflammatory signalling in mouse. To understand the inhibitory mechanism, the crystal structure of the p202 HINa domain in complex with a 20 bp DNA was determined, in which p202 HINa nonspecifically recognizes both strands of DNA through electrostatic attraction. The p202 HINa domain binds DNA more tightly than does AIM2 HIN, and the DNA-binding mode of p202 HINa is different from that of the AIM2 HIN and IFI16 HINb domains. These results, together with the reported data on p202 HINb, lead to an interaction model for full-­length p202 and dsDNA which provides a conceivable mechanism for the negative regulation of Aim2 inflammasome activation by p202.
doi:10.1107/S2053230X1303135X
PMCID: PMC3943098  PMID: 24419611
inflammatory response; p202; HIN domains; protein–DNA complexes
9.  Do tumor volume, percent tumor volume predict biochemical recurrence after radical prostatectomy? A meta-analysis 
The aim of this meta-analysis was to explore the effects of tumor volume (TV) and percent tumor volume (PTV) on biochemical recurrence (BCR) after radical prostatectomy (RP). An electronic search of Medline, Embase and CENTRAL was performed for relevant studies. Studies evaluated the effects of TV and/or PTV on BCR after RP and provided detailed results of multivariate analyses were included. Combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models. A total of 15 studies with 16 datasets were included in the meta-analysis. Our study showed that both TV (HR 1.04, 95% CI: 1.00-1.07; P=0.03) and PTV (HR 1.01, 95% CI: 1.00-1.02; P=0.02) were predictors of BCR after RP. The subgroup analyses revealed that TV predicted BCR in studies from Asia, PTV was significantly correlative with BCR in studies in which PTV was measured by computer planimetry, and both TV and PTV predicted BCR in studies with small sample sizes (<1000). In conclusion, our meta-analysis demonstrated that both TV and PTV were significantly associated with BCR after RP. Therefore, TV and PTV should be considered when assessing the risk of BCR in RP specimens.
PMCID: PMC4729995  PMID: 26885209
Tumor volume; percent tumor volume; prostate cancer; biochemical recurrence
10.  Transcript Quantification by RNA-Seq Reveals Differentially Expressed Genes in the Red and Yellow Fruits of Fragaria vesca 
PLoS ONE  2015;10(12):e0144356.
Fragaria vesca (2n = 2x = 14), the woodland strawberry, is a perennial herbaceous plant with a small sequenced genome (240 Mb). It is commonly used as a genetic model plant for the Fragaria genus and the Rosaceae family. Fruit skin color is one of the most important traits for both the commercial and esthetic value of strawberry. Anthocyanins are the most prominent pigments in strawberry that bring red, pink, white, and yellow hues to the fruits in which they accumulate. In this study, we conducted a de novo assembly of the fruit transcriptome of woodland strawberry and compared the gene expression profiles with yellow (Yellow Wonder, YW) and red (Ruegen, RG) fruits. De novo assembly yielded 75,426 unigenes, 21.3% of which were longer than 1,000 bp. Among the high-quality unique sequences, 45,387 (60.2%) had at least one significant match to an existing gene model. A total of 595 genes, representing 0.79% of total unigenes, were differentially expressed in YW and RG. Among them, 224 genes were up-regulated and 371 genes were down-regulated in the fruit of YW. Particularly, some flavonoid biosynthetic pathway genes, including C4H, CHS, CHI, F3H, DFR and ANS, as well as some transcription factors (TFs), including MYB (putative MYB86 and MYB39), WDR and MADS, were down-regulated in YW fruit, concurrent with a reduction in anthocyanin accumulation in the yellow pigment phenotype, whereas a putative transcription repressor MYB1R was up-regulated in YW fruit. The altered expression levels of the genes encoding flavonoid biosynthetic enzymes and TFs were confirmed by quantitative RT-PCR. Our study provides important insights into the molecular mechanisms underlying the yellow pigment phenotype in F. vesca.
doi:10.1371/journal.pone.0144356
PMCID: PMC4670188  PMID: 26636322
12.  A giant pelvic malignant schwannoma: a case report and literature review 
Schwannomas are usually benign tumors that arise from well-differentiated Schwann cells. They rarely occur in the retroperitoneum. Here, we present a case of a 60-year-old man with a giant retroperitoneal pelvic mass. Imageological diagnosis suggested a large heterogeneous mass of 16 cm in diameter located in the abdominopelvic retroperitoneum. Complete intralesional enucleation was achieved without any adjacent organs injury except a severe bleeding which was ceased as we applied the bilateral inferior vesical artery embolization. Final histopathological result showed the tumor was a low malignant Schwannoma. The patient’s symptoms were greatly improved after operation. Unfortunately, a local recurrence was detected at the six-month follow-up appointment with consequent losing to follow up.
PMCID: PMC4713681  PMID: 26823895
Giant malignant schwannoma; pelvic; diagnosis; complete resection
13.  Associations between occupation exposure to Formaldehyde and semen quality, a primary study 
Scientific Reports  2015;5:15874.
Formaldehyde (FA), a ubiquitous environmental pollutant, has long been suspected of having male reproductive toxicity. However, FA male reproductive toxicity was inconclusive due to dearth of human studies. Therefore, we sought to investigate whether occupational exposure to FA affects semen quality. Semen quality including five conventional parameters and seven kinematics parameters were compared between 114 male workers occupationally exposed to FA and 76 referents. FA exposure index (FEI) was measured and calculated. Our results showed that sperm progressive motility, total sperm motility, VCL, VSL and VAP were statistically significant decreased in FA exposure workers compared with the referents. Moreover, FEI was significantly negative associated with sperm progressive motility (β = −0.19, P = 0.01) and total sperm motility (β = −0.23, P = 0.004). In addition, a significant elevated risk of abnormal sperm progressive motility were observed in both low- (OR = 2.58; 95% CI: 1.11–5.97) and high-FA-exposed group (OR = 3.41; 95% CI: 1.45–7.92) respectively. Furthermore, a significant increased risk was also estimated for abnormal total sperm motility in both low- (OR = 3.21; 95% CI: 1.24–8.28) and high-FA-exposed group (OR = 4.84; 95% CI: 1.83–12.81) respectively. In conclusion, our study revealed the adverse effects of FA occupation exposure on semen quality, especially on sperm motion parameters.
doi:10.1038/srep15874
PMCID: PMC4626826  PMID: 26515386
14.  Electrochemical Sensors and Biosensors Based on Nanomaterials and Nanostructures 
Analytical Chemistry  2014;87(1):230-249.
doi:10.1021/ac5039863
PMCID: PMC4287168  PMID: 25354297
15.  Meat, dairy and plant proteins alter bacterial composition of rat gut bacteria 
Scientific Reports  2015;5:15220.
Long-term consumption of red meat has been considered a potential risk to gut health, but this is based on clinic investigations, excessive intake of fat, heme and some injurious compounds formed during cooking or additions to processed meat products. Whether intake of red meat protein affects gut bacteria and the health of the host remains unclear. In this work, we compared the composition of gut bacteria in the caecum, by sequencing the V4-V5 region of 16S ribosomal RNA gene, obtained from rats fed with proteins from red meat (beef and pork), white meat (chicken and fish) and other sources (casein and soy). The results showed significant differences in profiles of gut bacteria between the six diet groups. Rats fed with meat proteins had a similar overall structure of caecal bacterial communities separated from those fed non-meat proteins. The beneficial genus Lactobacillus was higher in the white meat than in the red meat or non-meat protein groups. Also, rats fed with meat proteins and casein had significantly lower levels of lipopolysaccharide-binding proteins, suggesting that the intake of meat proteins may maintain a more balanced composition of gut bacteria, thereby reducing the antigen load and inflammatory response in the host.
doi:10.1038/srep15220
PMCID: PMC4604471  PMID: 26463271
16.  Enhanced Biological Behavior of In Vitro Human Gingival Fibroblasts on Cold Plasma-Treated Zirconia 
PLoS ONE  2015;10(10):e0140278.
Objective
To evaluate whether atmospheric-pressure dielectric-barrier-discharge plasma treatment of zirconia enhances its biocompatibility with human gingival fibroblasts.
Materials and Methods
The zirconia disks were divided into four groups and treated using helium atmospheric-pressure dielectric-barrier-discharge plasmas for 30, 60 or 90 s or left untreated. The surface morphology, wettability and chemical elements were analyzed. Fibroblasts density, morphology, morphometry and attachment-related genes expression were measured at different time points from 3 to 72 h.
Results
After plasma treatment, the surface morphology and roughness remained the same, while the contact angle decreased from 78.31° to 43.71°, and the surface C/O ratio decreased from 3.17 to 0.89. The surficial areas and perimeters of HGFs were increased two-fold in the treated groups at 3 h. Fibroblasts density increased on treated disks at all time points, especially the ones treated for 60 s. Attachment-related genes in the groups treated for 30 and 60 s were significantly higher at 3 and 24 h.
Conclusion
The helium atmospheric-pressure dielectric-barrier-discharge plasma treatment enhances the biological behavior of fibroblasts on zirconia by increasing the expression of attachment-related genes within 24 h and promoting the cell density during longer culture times. Wettability of zirconia, an important physicochemical property, has a vital influence on the cell behaviors.
doi:10.1371/journal.pone.0140278
PMCID: PMC4603669  PMID: 26461253
17.  Relationships between the resting-state network and the P3: Evidence from a scalp EEG study 
Scientific Reports  2015;5:15129.
The P3 is an important event-related potential that can be used to identify neural activity related to the cognitive processes of the human brain. However, the relationships, especially the functional correlations, between resting-state brain activity and the P3 have not been well established. In this study, we investigated the relationships between P3 properties (i.e., amplitude and latency) and resting-state brain networks. The results indicated that P3 amplitude was significantly correlated with resting-state network topology, and in general, larger P3 amplitudes could be evoked when the resting-state brain network was more efficient. However, no significant relationships were found for the corresponding P3 latency. Additionally, the long-range connections between the prefrontal/frontal and parietal/occipital brain regions, which represent the synchronous activity of these areas, were functionally related to the P3 parameters, especially P3 amplitude. The findings of the current study may help us better understand inter-subject variation in the P3, which may be instructive for clinical diagnosis, cognitive neuroscience studies, and potential subject selection for brain-computer interface applications.
doi:10.1038/srep15129
PMCID: PMC4601035  PMID: 26456594
18.  The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins 
Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field.
doi:10.3389/fmicb.2015.01091
PMCID: PMC4594021  PMID: 26500631
aflatoxins; antifungal; Aspergillus species; marine bacterium; Shewanella algae; VOCs; volatiles
19.  Expression and functional perspectives of miR-184 in pancreatic ductal adenocarcinoma 
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors, with its 5-year survival rate lower than 5%. MicroRNAs (miR) have been known as important regulators for the tumorigenesis, progression, invasion and metastasis of various cancers. MiR-184 was found to be abnormally expressed in various cancers including glioma and oral carcinoma. The expression and functional role of miR-184 in PDAC, however, remains unclear. PDAC cell line PANC-1 was transfected with miR-184 inhibitor. Real-time PCR was used to detect the expression of miR-184 in untreated PANC-1, miR-184 inhibitor transfected PANC-1 and controlled normal pancreatic ductal epithelial cell line HPDE6c7. MTT assay was used to detect the effect of miR-184 on the proliferation of PANC-1 cells, while invasion assay and Western blotting were employed to describe the effect on cell invasion ability and expression of caspase-3, respectively. In PANC-1 cells, miR-184 was abundantly expressed. The transfection of inhibitor effectively suppressed the expression of miR-184, and further inhibited both cell proliferation and invasion abilities, in addition to the up-regulation of pro-apoptotic protein caspase 3 expression. The up-regulation of miR-184 in PDAC may facilitate the proliferation and invasion ability, and inhibit apoptosis of tumor cells, thus potentiating the occurrence and development of PDAC. MiR-184, therefore, is a potential molecular target for therapy.
PMCID: PMC4680363  PMID: 26722418
Pancreatic ductal adenocarcinoma; micro RNA inhibitor; tumor proliferation and metastasis
20.  Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice 
World Journal of Gastroenterology : WJG  2015;21(36):10375-10384.
AIM: To investigate the effects of Recql5 deficiency on liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal).
METHODS: Liver injury was induced in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by histological, serum transaminases, and mortality analyses. Hepatocellular apoptosis was quantified by transferase dUTP nick end labeling assay and Western blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome P450 expression was analyzed by quantitative reverse transcription-PCR. Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot. Oxidative stress was evaluated by measuring malondialdehyde production and nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity.
RESULTS: Following LPS/D-Gal exposure, Recql5-deficient mice exhibited enhanced liver injury, as evidenced by more severe hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3 levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by increased γ-H2A.X levels. Inflammatory cytokine levels, neutrophil infiltration, and ERK phosphorylation were also significantly increased in the knockout mice. Additionally, Recql5-deficicent mice exhibited increased malondialdehyde production and elevated inducible nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression was significantly downregulated in Recql5-deficient mice after LPS/D-Gal treatment.
CONCLUSION: Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.
doi:10.3748/wjg.v21.i36.10375
PMCID: PMC4579884  PMID: 26420964
Recql5; Liver injury; Apoptosis; Oxidative stress; CYP450
21.  Telocytes in the Spleen 
PLoS ONE  2015;10(9):e0138851.
Telocytes, a novel type of interstitial cells with very long and thin prolongations, have been identified in many organs in mammals. At present, the ultrastructural, immunocytochemical and electrophysiological properties of telocytes in multiple organs have been understood. However, telocytes in spleen, especially their roles in spleen have not been reported. The aim of this study was to investigate the ultrastructure, distribution and immunophenotypes of splenic telocytes. Rat spleen was harvested for the ultrastructure analysis by transmission electron microscopy (TEM). The primary culture of telocytes was performed after combined enzymatic digestion. The characteristic morphology was analyzed by a scanning electron microscopy (SEM). It was shown that telocytes displayed a piriform/spindle/triangular shape with long and slender telopods and extremely long prolongation contracting with surrounding cells in the spleen. Their dynamic profiles of cytoplasmic separation were recorded by the Live Cell Imaging System. The length of telopods was mostly distributing in 20–30 μm, in accordance with normal distribution. Most telocytes had three or two telopods (28.71% and 22.58% respectively). Immunostaining indicated that these cells were positive for vimentin, CD34, nanog and sca-1, but negative for c-kit. These data prove the existence of telocytes in the spleen, which may serve as the experimental base for exploring their roles in the spleen.
doi:10.1371/journal.pone.0138851
PMCID: PMC4580423  PMID: 26397114
22.  Association of APE1 Gene Asp148Glu Variant with Digestive Cancer: A Meta-Analysis 
Background
Apurinic/apyrimidinic endonuclease-1 (APE1) is a rate-limiting enzyme in DNA base excision repair and has been implicated in carcinogenesis. In this study, we summarize available data to examine the susceptibility of APE1 gene Asp148Glu variant to digestive cancer via a meta-analysis.
Material/Methods
Study selection and data abstraction were conducted independently by 2 authors. Random-effects model was utilized to pool effect estimates. Heterogeneity and publication bias were addressed.
Results
Sixteen articles involving 4916 digestive cancer patients and 7748 controls were qualified for this meta-analysis. Overall association showed an indicative association between Asp148Glu variant and digestive cancer under allelic (odds ratio or OR=1.11; 95% confidence interval or CI: 0.99–1.25; P=0.074) and dominant (OR=1.18; 95% CI: 1.00–1.40; P=0.056) models, with strong evidence of heterogeneity. Deviation from Hardy-Weinberg equilibrium was an obvious source of heterogeneity. In subgroup analyses by cancer sites, this variant was significantly associated with the increased risk for hepatocellular cancer under allelic (OR=1.50; 95% CI: 1.25–1.80; P<0.001) and homozygous genotypic (OR=1.55; 95% CI: 1.02–2.29; P=0.028) models. There were low probabilities of publication bias for the above comparisons.
Conclusions
The results of this meta-analysis collectively suggest that APE1 gene Asp148Glu variant is not a risk-conferring factor for digestive cancer. Further large and well-designed studies are required.
doi:10.12659/MSM.893954
PMCID: PMC4548740  PMID: 26292623
Digestive System Neoplasms; Genetic Association Studies; Meta-Analysis
23.  A concordant expression pattern of fatty acid synthase and membranous human epidermal growth factor receptor 2 exists in gastric cancer and is associated with a poor prognosis in gastric adenocarcinoma patients 
Oncology Letters  2015;10(4):2107-2117.
Fatty acid synthase (FAS) and human epidermal growth factor receptor 2 (HER2) are overexpressed in gastric cancer (GC), and certain interactions have been found between FAS and HER2. A total of 94 patients were enrolled in the present study, each of whom underwent a D2 radical surgery in Zhongshan Hospital affiliated with Fudan University (Shanghai, China) between 2000 and 2005. The expression of FAS and HER2 was assessed by immunohistochemistry analysis of tissue microarrays generated from GC and non-tumor tissues. All data were analyzed by GraphPad Prism 5.0 to investigate the association between FAS and HER2 and to detect the potential association with prognosis. FAS (P<0.0001) and membranous HER2 (mHER2; P=0.0021) were overexpressed in the GC tissues, and a bidirectional and strong correlation was demonstrated between FAS and mHER2 in the tumor tissues. The expression of cytoplasmic HER2 (cHER2) was significantly lower in the GC tissues compared with the non-tumor tissues (P=0.0005), and cHER2 was expressed at a higher level in tumors that had better differentiation compared with poorly-differentiated tissues (P=0.0503). Patients with a concordant expression pattern of FAS and mHER2 showed a significantly poorer prognosis than the non-concordant group (P=0.0096; hazards ratio, 3.2801; 95% confidence interval, 1.5781–6.8176). GC tissues significantly overexpress FAS and mHER2 and the expression of these two markers is associated. Patients with a concordant expression of FAS and mHER2 are more likely to suffer a poor prognosis.
doi:10.3892/ol.2015.3609
PMCID: PMC4579914  PMID: 26622804
fatty acid synthase; human epidermal growth factor receptor 2; gastric cancer
24.  Eyelid and Sternum Fibroblasts Differ in Their Contraction Potential and Responses to Inflammatory Cytokines 
Background:
Adverse skin scarring varies by anatomical site with, for example, presternal skin showing a greater hypertrophic response when compared with eyelid; such differences have traditionally been attributed to regional variations in skin tension, thickness, and Langer’s lines. Fibroblasts are the main cell implicated in fibrosis, and they too are known to show anatomical variation in their expression, differentiation, and intercellular interactions. We, therefore, investigated whether intrinsic differences in skin fibroblasts derived from separate locations might contribute to the observed discrepancies in clinical scarring.
Methods:
Primary in vitro cultures were established using matched eyelid and presternal skin from 3 healthy donors undergoing blepharoplasty surgery. We used an in vitro collagen gel model of fibroblast-mediated tissue contraction to compare the properties of the dermal fibroblasts from each site. Cell contractile force and matrix stiffness were assessed in 3-dimensional tissue constructs using an automated high-throughput device.
Results:
Dermal fibroblasts isolated from eyelid and sternum differ both in their ability to contract a gel matrix and in their response to cytokine stimulation; despite having lower intrinsic contractile force (P < 0.01) and resting stiffness (P < 0.02), the presternal cells were more contractile (P < 0.001) following stimulation with serum, or inflammatory cytokines transforming growth factor-β (P < 0.01) and interleukin-1β (P < 0.05).
Conclusions:
The propensity to cutaneous scarring may, at least in part, result from intrinsic differences in the local fibroblasts’ ability to contract and their sensitivity to inflammatory cytokines. Improved understanding of the underlying molecular pathways should prove useful in identifying new therapeutic targets for altering surgical and other scarring.
doi:10.1097/GOX.0000000000000340
PMCID: PMC4527622  PMID: 26301137
25.  Near Work Related Parameters and Myopia in Chinese Children: the Anyang Childhood Eye Study 
PLoS ONE  2015;10(8):e0134514.
Purpose
To examine the associations of near work related parameters with spherical equivalent refraction and axial length in Chinese children.
Methods
A total of 1770 grade 7 students with mean age of 12.7 years were examined with cycloplegic autorefraction and axial length. Questions were asked regarding time spent in near work and outdoors per day, and near work related parameters.
Results
Multivariate models revealed the following associations with greater odds of myopia: continuous reading (> 45min), odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8; close television viewing distance (≤ 3m), OR, 1.7; 95% CI, 1.2-2.3; head tilt when writing, OR, 1.3; 95% CI, 1.1-1.7, and desk lighting using fluorescent vs. incandescent lamp, OR, 1.5; 95% CI, 1.2-2.0. These factors, together with close reading distance and close nib-to-fingertip distance were significantly associated with greater myopia (P<0.01). Among near work activities, only reading more books for pleasure was significantly associated with greater myopia (P=0.03). Television viewing distance (≤ 3 m), fluorescent desk light, close reading distance (≤20 cm) and close nib-to-fingertip distance (≤ 2 cm) were significantly associated with longer axial length (P<0.01). Reading distance, desk light, and reading books for pleasure had significant interaction effects with parental myopia.
Conclusions
Continuous reading, close distances of reading, television viewing and nib-to-fingertip, head tilt when writing, reading more books for pleasure and use of fluorescent desk light were significantly associated with myopia in 12-year-old Chinese children, which indicates that visual behaviors and environments may be important factors mediating the effects of near work on myopia.
doi:10.1371/journal.pone.0134514
PMCID: PMC4526691  PMID: 26244865

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