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1.  Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits 
This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was significantly reduced by naringin at certain doses compared with those in the rabbits of the model group (P<0.01). The levels of P-selectin and platelet factor 4 (PF4) also decreased following treatment with naringin compared with those of the model group. Certain doses of naringin significantly reduced the total cholesterol (TC) levels and elevated the ratio of high-density lipoprotein cholesterol to TC compared with those in the model group, and significantly decreased the cytosolic free calcium concentration ([Ca2+]i). No significant difference in the coagulation function was observed between the control and drug-treatment groups. These results indicate that naringin improved platelet aggregation and inhibited the excessive release of P-selectin and PF4 in hyperlipidemic rabbits. This study suggests that the antiplatelet effect of naringin may be due to its ability to regulate the levels of blood cholesterol and [Ca2+]i in platelets. Naringin also did not cause bleeding in the hyperlipidemic rabbits.
PMCID: PMC4113534  PMID: 25120631
naringin; hyperlipidemic; aggregation; cytosolic free calcium concentration; P-selectin; platelet factor 4
2.  Suppression (but Not Reappraisal) Impairs Subsequent Error Detection: An ERP Study of Emotion Regulation's Resource-Depleting Effect 
PLoS ONE  2014;9(4):e96339.
Past event-related potentials (ERPs) research shows that, after exerting effortful emotion inhibition, the neural correlates of performance monitoring (e.g. error-related negativity) were weakened. An undetermined issue is whether all forms of emotion regulation uniformly impair later performance monitoring. The present study compared the cognitive consequences of two emotion regulation strategies, namely suppression and reappraisal. Participants were instructed to suppress their emotions while watching a sad movie, or to adopt a neutral and objective attitude toward the movie, or to just watch the movie carefully. Then after a mood scale, all participants completed an ostensibly unrelated Stroop task, during which ERPs (i.e. error-related negativity (ERN), post-error positivity (Pe) and N450) were obtained. Reappraisal group successfully decreased their sad emotion, relative to the other two groups. Compared with participants in the control group and the reappraisal group, those who suppressed their emotions during the sad movie showed reduced ERN after error commission. Participants in the suppression group also made more errors in incongruent Stroop trials than the other two groups. There were no significant main effects or interactions of group for reaction time, Pe and N450. Results suggest that reappraisal is both more effective and less resource-depleting than suppression.
PMCID: PMC4002454  PMID: 24777113
3.  Cathepsin L Plays a Role in Quinolinic Acid-Induced NF-Κb Activation and Excitotoxicity in Rat Striatal Neurons 
PLoS ONE  2013;8(9):e75702.
The present study seeks to investigate the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-κB) activation and excitotoxicity in rats striatal neurons. Stereotaxic administration of the N-methyl-d-aspartate (NMDA) receptor agonist Quinolinic acid (QA) into the unilateral striatum was used to produce the in vivo excitotoxic model. Co-administration of QA and the cathepsin L inhibitor Z-FF-FMK or 1-Naphthalenesulfonyl-IW-CHO (NaphthaCHO) was used to assess the contribution of cathepsin L to QA-induced striatal neuron death. Western blot analysis and cathepsin L activity assay were used to assess the changes in the levels of cathepsin L after QA treatment. Western blot analysis was used to assess the changes in the protein levels of inhibitor of NF-κB alpha isoform (IκB-α) and phospho-IκB alpha (p-IκBα) after QA treatment. Immunohistochemical analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced NF-κB. Western blot analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced IκB-α phosphorylation and degradation, changes in the levels of IKKα, p-IKKα, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced loss of striatal neurons were strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced degradation of IκB-α, NF-κB nuclear translocation, up-regulation of NF-κB responsive gene TP53, and activation of caspase-3 was strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced increases in beclin 1, LC3II/LC3I, and down-regulation of p62 were reduced by Z-FF-FMK or NaphthaCHO. These results suggest that cathepsin L is involved in glutamate receptor-induced NF-κB activation. Cathepsin L inhibitors have neuroprotective effects by inhibiting glutamate receptor-induced IκB-α degradation and NF-κB activation.
PMCID: PMC3779166  PMID: 24073275
4.  Differential expression and subcellular localization of Prohibitin 1 are related to tumorigenesis and progression of non-small cell lung cancer 
Lung cancer remains the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer. With a variety of biological functions, Prohibitin1 (PHB1) has been proved tumor-associated. But there are conflicting data regarding the involvement of PHB1 in tumorigenesis and few studies regarding the role of PHB1 in lung cancer. The studies reported herein used a combination of clinical observations and molecular methods to investigate the possible role of PHB1 in NSCLC tissues and cell lines. PHB1 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and immunohistochemistry analysis. Flow cytometric analysis was used to determine the surface expression profiles of PHB1 in lung cell lines. The results showed that PHB1 expression were generally increased in lung cancer tissues when compared with matched noncancerous tissues and closely related with tumor differentiation and lymph node invasion. PHB1 expression levels was also increased in three lung cancer cell lines (SK-MES-1, NCI-H157 and NCI-H292) as compared with BEAS-2B cells. Moreover, there were various subcellular localization of PHB1 in different lung cancer cells and the presence of PHB1 on the surface of lung cancer cells was significantly reduced. In conclusion, PHB1 expression is increased in NSCLC and the up-regulation of PHB1 is associated with clinically aggressive phenotype. The different subcellular localization of PHB1 in NSCLC cells and the loss of the membrane-associated PHB1 probably related to the tumorigenesis and progression of NSCLC and suggests that PHB1 may play different roles in various types of NSCLC.
PMCID: PMC3796231  PMID: 24133587
Prohibitin 1; up-regulation; subcellular localization; non-small cell lung cancer
5.  Treatment of radiation-induced hemorrhagic gastritis with prednisolone: A case report 
Radiation-induced gastritis is an infrequent cause of gastrointestinal bleeding. It is a serious complication arising from radiation therapy, and the standard treatment method has not been established. The initial injury is characteristically acute inflammation of gastric mucosa. We presented a 46-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for metastatic retroperitoneal lymph node of hepatocellular carcinoma. The endoscopic examination showed diffuse edematous hyperemicmucosa with telangiectasias in the whole muscosa of the stomach and duodenal bulb. Multiple hemorrhagic patches with active oozing were found over the antrum. Anti-secretary therapy was initiated for hemostasis, but melena still occurred off and on. Finally, he was successfully treated by prednisolone therapy. We therefore strongly argue in favor of perdnisolone therapy to effectively treat patients with radiation-induced hemorrhagic gastritis.
PMCID: PMC3544049  PMID: 23326152
Hemorrhagic gastritis; Radiation; Prednisolone; Hepatocellular carcinoma; Gastrointestinal bleeding
6.  In-depth Proteomic mapping of mouse (Mus musculus) epididymal constructive basis for sperm maturation 
Proteome Science  2015;13:20.
The mouse epididymis performs an essential role in sperm maturation, but global protein expression data in mouse epididymis are still lacking. Here, we reported the first in-depth gel-based profiling of mouse epididymis proteome and established a 2-DE map.
A total of 832 protein spots were detected in the reproducible gels, and 625 spots corresponding to 355 unique protein entries have been successfully identified by MALDI-TOF-MS. The confidence of proteome data was validated by Western blot. Functional annotations showed that these proteins were mainly related to general metabolism, antioxidant and structural molecule activity. Immunohistochemistry disclosed two structural proteins (myosin regulatory light polypeptide 9 and alpha-2 type I collagen) continuously expressed in the myoid cell since postpartum.
This study provides a first-draft reference map of the mouse epididymis proteome, which will greatly expand the knowledge of the epididymal structural basis and contribute to the better understanding of those proteins in the process of mouse epididymal sperm maturation.
Electronic supplementary material
The online version of this article (doi:10.1186/s12953-015-0076-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4518611
Sperm maturation; Structural proteins; Mouse epididymis; Bioinformatics; Proteomics
7.  Effects of Ankle Arthrodesis on Biomechanical Performance of the Entire Foot 
PLoS ONE  2015;10(7):e0134340.
Ankle arthrodesis is one popular surgical treatment for ankle arthritis, chronic instability, and degenerative deformity. However, complications such as foot pain, joint arthritis, and bone fracture may cause patients to suffer other problems. Understanding the internal biomechanics of the foot is critical for assessing the effectiveness of ankle arthrodesis and provides a baseline for the surgical plan. This study aimed to understand the biomechanical effects of ankle arthrodesis on the entire foot and ankle using finite element analyses. A three-dimensional finite element model of the foot and ankle, involving 28 bones, 103 ligaments, the plantar fascia, major muscle groups, and encapsulated soft tissue, was developed and validated. The biomechanical performances of a normal foot and a foot with ankle arthrodesis were compared at three gait instants, first-peak, mid-stance, and second-peak.
Principal Findings/Conclusions
Changes in plantar pressure distribution, joint contact pressure and forces, von Mises stress on bone and foot deformation were predicted. Compared with those in the normal foot, the peak plantar pressure was increased and the center of pressure moved anteriorly in the foot with ankle arthrodesis. The talonavicular joint and joints of the first to third rays in the hind- and mid-foot bore the majority of the loading and sustained substantially increased loading after ankle arthrodesis. An average contact pressure of 2.14 MPa was predicted at the talonavicular joint after surgery and the maximum variation was shown to be 80% in joints of the first ray. The contact force and pressure of the subtalar joint decreased after surgery, indicating that arthritis at this joint was not necessarily a consequence of ankle arthrodesis but rather a progression of pre-existing degenerative changes. Von Mises stress in the second and third metatarsal bones at the second-peak instant increased to 52 MPa and 34 MPa, respectively, after surgery. These variations can provide indications for outcome assessment of ankle arthrodesis surgery.
PMCID: PMC4519327  PMID: 26222188
8.  Radiological Findings of Prostatic Arterial Anatomy for Prostatic Arterial Embolization: Preliminary Study in 55 Chinese Patients with Benign Prostatic Hyperplasia 
PLoS ONE  2015;10(7):e0132678.
To describe the prostatic arterial supply using Cone-beam computed tomography (CT) and digital subtraction angiography (DSA) before prostatic arterial embolization (PAE) for benign prostatic hyperplasia (BPH).
In a retrospective study from January 2012 to January 2014, 55 male patients (110 hemipelves) with BPH who underwent PAE were evaluated by Cone-beam CT in addition to pelvic DSA during embolization planning. Each hemipelvis was evaluated regarding the number of prostatic arteries (PA) and their origins, diameters, territorial perfusion, and anastomoses with adjacent arteries.
A total of 114 PAs were identified in 110 hemipelves. There was one PA in 96.4% of the hemipelves (n=106), and two independent PAs in the other 3.6% (n=4). The PA was found to originate from the anterior trunk of the internal iliac artery in 39.5% of cases (n=45) , from the superior vesical artery in 32.6% (n=37), and from the internal pudendal artery in 27.9% of cases (n=32). Extra-prostatic anastomoses between PA and adjacent arteries were found in 39.1% of hemipelves (n=43). Intra-prostatic anastomoses between PAs and contra-lateral prostatic branches were found in 61.8% of hemipelves (n=68). In 67.3% of our study population (n=37), the prostate was dominantly supplied via a unilateral PA.
The prostatic vascularization is complex with frequent anatomic variations. Knowledge of the vascular anatomy of the prostate may provide indications for planning PAE and avoiding nontarget embolization.
PMCID: PMC4508051  PMID: 26191796
9.  MiR-135b-5p and MiR-499a-3p Promote Cell Proliferation and Migration in Atherosclerosis by Directly Targeting MEF2C 
Scientific Reports  2015;5:12276.
Proliferation and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are critical processes involved in atherosclerosis. Recent studies have revealed that microRNAs (miRNAs) can be detected in circulating blood with a stable form and the expression profiles differ in many cellular processes associated with coronary artery disease (CAD). However, little is known about their role, especially serum-derived miRNAs, in ECs and VSMCs phenotype modulation during atherosclerosis. We compared the miRNA expressions in serum samples from 13 atherosclerotic CAD patients and 5 healthy control subjects and identified 36 differentially expressed miRNAs. The expression of selected miRNAs (miR-135b-5p and miR-499a-3p) was further validated in 137 serum samples. Interestingly, miR-135b-5p and miR-499a-3p directly regulated a common target gene: myocyte enhancer factor 2C (MEF2C) which plays an important role in modulating cell phenotype of cardiovascular systems. Furthermore, our results indicated that the 2 elevated miRNAs could jointly promote ECs and VSMCs proliferation and migration by repressing MEF2C expression. Together, our findings demonstrated a serum-based miRNA expression profile for atherosclerotic CAD patients, potentially revealing a previously undocumented mechanism for cell proliferation and migration mediated by miR-135b-5p and miR-499a-3p, and might provide novel insights into the role of circulating miRNAs in atherosclerosis pathogenesis.
PMCID: PMC4505325  PMID: 26184978
10.  Screening Allelochemical-Resistant Species of the Alien Invasive Mikania micrantha for Restoration in South China 
PLoS ONE  2015;10(7):e0132967.
To screen allelochemical-resistant species of the alien invasive weed Mikania micrantha, we studied the allelopathic inhibition effects of the leaf aqueous extract (LAE) of Mikania on seed germination and seedling growth of the 26 species native or naturalized in the invaded region in South China. Seed germination was more strongly negatively affected by LAE than seedling growth. Responses of seed germination and seed growth to LAE differed differently among the target species. LAE more strongly negatively affected seed germination, but less strongly negatively affected seedling growth, in non-legume species than in legume species. LAE more strongly negatively affected seed germination and seedling growth in native species than naturalized exotic species. Therefore, naturalized exotic non-legume seedlings are more suitable than seeds of native legume species for restoration of Mikania-invaded habitats.
PMCID: PMC4503634  PMID: 26177031
11.  Transforming berberine into its intestine-absorbable form by the gut microbiota 
Scientific Reports  2015;5:12155.
The gut microbiota is important in the pathogenesis of energy-metabolism related diseases. We focused on the interaction between intestinal bacteria and orally administered chemical drugs. Oral administration of berberine (BBR) effectively treats patients with metabolic disorders. However, because BBR exhibits poor solubility, its absorption mechanism remains unknown. Here, we show that the gut microbiota converts BBR into its absorbable form of dihydroberberine (dhBBR), which has an intestinal absorption rate 5-fold that of BBR in animals. The reduction of BBR to dhBBR was performed by nitroreductases of the gut microbiota. DhBBR was unstable in solution and reverted to BBR in intestine tissues via oxidization. Heat inactivation of intestinal homogenate did not inhibit dhBBR oxidization, suggesting the process a non-enzymatic reaction. The diminution of intestinal bacteria via orally treating KK-Ay mice with antibiotics decreased the BBR-to-dhBBR conversion and blood BBR; accordingly, the lipid- and glucose-lowering efficacy of BBR was reduced. Conclusively, the gut microbiota reduces BBR into its absorbable form of dhBBR, which then oxidizes back to BBR after absorption in intestine tissues and enters the blood. Thus, interaction(s) between the gut microbiota and orally administrated drugs may modify the structure and function of chemicals and be important in drug investigation.
PMCID: PMC4502414  PMID: 26174047
12.  Phylogenetic Lineage and Pilus Protein Spb1/SAN1518 Affect Opsonin-Independent Phagocytosis and Intracellular Survival of Group B Streptococcus 
Opsonin-independent phagocytosis of Group B Streptococcus (GBS) is important in defense against neonatal GBS infections. A recent study indicated a role for GBS pilus in macrophage phagocytosis. We studied 163 isolates from different phylogenetic backgrounds and those possessing or lacking the gene encoding the pilus backbone protein, Spb1 (SAN1518, PI-2b) and spb1-deficient mutants of wild-type (WT) serotype III-3 GBS 874391 in non-opsonic phagocytosis assays using J774A.1 macrophages. Numbers of GBS phagocytosed differed up to 23-fold depending on phylogenetic background; isolates possessing spb1 were phagocytosed more than isolates lacking spb1. Comparing WT GBS and isogenic spb1-deficient mutants showed WT was phagocytosed better compared to mutants; Spb1 also enhanced intracellular survival as mutants were killed more efficiently. Complementation of mutants restored phagocytosis and resistance to killing in J774A.1 macrophages. Spb1 antiserum revealed surface expression in WT GBS and spatial distribution relative to capsular polysaccharide. spb1 did not affect macrophage nitric oxide and TNF-alpha responses; differences in phagocytosis did not correlate with N-acetyl D-glucosamine (from GBS cell wall) according to enzyme-linked lectin-sorbent assay. Together, these findings support a role for phylogenetic lineage and Spb1 in opsonin-independent phagocytosis and intracellular survival of GBS in J774A.1 macrophages.
PMCID: PMC4500112  PMID: 21238599
13.  Synthesis and Evaluation of Chromogenic and Fluorogenic Substrates for High-Throughput Detection of Enzymes That Hydrolyze Inorganic Polyphosphate 
Biomacromolecules  2014;15(8):3190-3196.
Inorganic polyphosphates, linear polymers of orthophosphate, occur naturally throughout biology and have many industrial applications. Their biodegradable nature makes them attractive for a multitude of uses, and it would be important to understand how polyphosphates are turned over enzymatically. Studies of inorganic polyphosphatases are, however, hampered by the lack of high-throughput methods for detecting and quantifying rates of polyphosphate degradation. We now report chromogenic and fluorogenic polyphosphate substrates that permit spectrophotometric monitoring of polyphosphate hydrolysis and allow for high-throughput analyses of both endopolyphosphatase and exopolyphosphatase activities, depending on assay configuration. These substrates contain 4-nitrophenol or 4-methylumbelliferone moieties that are covalently attached to the terminal phosphates of polyphosphate via phosphoester linkages formed during reactions mediated by EDAC (1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide). This report identifies Nudt2 as an inorganic polyphosphatase and also adds to the known coupling chemistry for polyphosphates, permitting facile covalent linkage of alcohols with the terminal phosphates of inorganic polyphosphate.
PMCID: PMC4130250  PMID: 25000340
14.  PPI versus Histamine H2 Receptor Antagonists for Prevention of Upper Gastrointestinal Injury Associated with Low-Dose Aspirin: Systematic Review and Meta-analysis 
PLoS ONE  2015;10(7):e0131558.
This study compared proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs) for prevention of low-dose aspirin (LDA)-related gastrointestinal (GI) erosion, ulcer and bleeding. Electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Data were searched from the date of their establishment to December 31, 2013. Randomized controlled trials comparing PPIs and H2RAs for prevention of GI injury associated with low-dose aspirin (LDA) were collected. Two reviewers independently abstracted studies and patient characteristics and appraised study quality using the Cochrane risk-of-bias tool. Meta-analysis was performed using RevMan 5.1 software. We included nine RCTs involving 1047 patients. The meta-analysis showed that PPIs were superior to H2RAs for prevention of LDA-associated GI erosion/ulcer [odds ratio (OR=0.28, 95% confidence interval (CI): 0.16–0.50] and bleeding (OR=0.28, 95% CI: 0.14–0.59). In conclusion, PPIs were superior to H2RAs for prevention of LDA-related GI erosion/ulcer and bleeding. Higher quality, large, multicenter RCTs are needed to demonstrate the preventive effect of the two acid-suppressive drugs.
PMCID: PMC4493004  PMID: 26147767
15.  Combined Approach for Government E-Tendering Using GA and TOPSIS with Intuitionistic Fuzzy Information 
PLoS ONE  2015;10(7):e0130767.
As E-government continues to develop with ever-increasing speed, the requirement to enhance traditional government systems and affairs with electronic methods that are more effective and efficient is becoming critical. As a new product of information technology, E-tendering is becoming an inevitable reality owing to its efficiency, fairness, transparency, and accountability. Thus, developing and promoting government E-tendering (GeT) is imperative. This paper presents a hybrid approach combining genetic algorithm (GA) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) to enable GeT to search for the optimal tenderer efficiently and fairly under circumstances where the attributes of the tenderers are expressed as fuzzy number intuitionistic fuzzy sets (FNIFSs). GA is applied to obtain the optimal weights of evaluation criteria of tenderers automatically. TOPSIS is employed to search for the optimal tenderer. A prototype system is built and validated with an illustrative example from GeT to verify the feasibility and availability of the proposed approach.
PMCID: PMC4493125  PMID: 26147468
16.  De novo Transcriptome Assembly of Common Wild Rice (Oryza rufipogon Griff.) and Discovery of Drought-Response Genes in Root Tissue Based on Transcriptomic Data 
PLoS ONE  2015;10(7):e0131455.
The perennial O. rufipogon (common wild rice), which is considered to be the ancestor of Asian cultivated rice species, contains many useful genetic resources, including drought resistance genes. However, few studies have identified the drought resistance and tissue-specific genes in common wild rice.
In this study, transcriptome sequencing libraries were constructed, including drought-treated roots (DR) and control leaves (CL) and roots (CR). Using Illumina sequencing technology, we generated 16.75 million bases of high-quality sequence data for common wild rice and conducted de novo assembly and annotation of genes without prior genome information. These reads were assembled into 119,332 unigenes with an average length of 715 bp. A total of 88,813 distinct sequences (74.42% of unigenes) significantly matched known genes in the NCBI NT database. Differentially expressed gene (DEG) analysis showed that 3617 genes were up-regulated and 4171 genes were down-regulated in the CR library compared with the CL library. Among the DEGs, 535 genes were expressed in roots but not in shoots. A similar comparison between the DR and CR libraries showed that 1393 genes were up-regulated and 315 genes were down-regulated in the DR library compared with the CR library. Finally, 37 genes that were specifically expressed in roots were screened after comparing the DEGs identified in the above-described analyses.
This study provides a transcriptome sequence resource for common wild rice plants and establishes a digital gene expression profile of wild rice plants under drought conditions using the assembled transcriptome data as a reference. Several tissue-specific and drought-stress-related candidate genes were identified, representing a fully characterized transcriptome and providing a valuable resource for genetic and genomic studies in plants.
PMCID: PMC4489613  PMID: 26134138
17.  Identification of miRNAs that specifically target tumor suppressive KLF6-FL rather than oncogenic KLF6-SV1 isoform 
RNA Biology  2014;11(7):845-854.
The Krüppel like factor 6 (KLF6) gene encodes multiple protein isoforms derived from alternative mRNA splicing, most of which are intimately involved in hepatocarcinogenesis and tumor progression. Recent bioinformatics analysis shows that alternative mRNA splicing of the KLF6 gene produces around 16 alternatively spliced variants with divergent or even opposing functions. Intriguingly, the full-length KLF6 (KLF6-FL) is a tumor suppressor gene frequently inactivated in liver cancer, whereas KLF6 splice variant 1 (KLF6-SV1) is an oncogenic isoform with antagonistic function against KLF6-FL. Compelling evidence indicates that miRNA, the small endogenous non-coding RNA (ncRNA), acts as a vital player in modulating a variety of cellular biological processes through targeting different mRNA regions of protein-coding genes. To identify the potential miRNAs specifically targeting KLF6-FL, we utilized bioinformatics analysis in combination with the luciferase reporter assays and screened out two miRNAs, namely miR-210 and miR-1301, specifically targeted the tumor suppressive KLF6-FL rather than the oncogenic KLF6-SV1. Our in vitro experiments demonstrated that stable expression of KLF6-FL inhibited cell proliferation, migration and angiogenesis while overexpression of miR-1301 promoted cell migration and angiogenesis. Further experiments demonstrated that miR-1301 was highly expressed in liver cancer cell lines as well as clinical specimens and we also identified the potential methylation and histone acetylation for miR-1301 gene. To sum up, our findings unveiled a novel molecular mechanism that specific miRNAs promoted tumorigenesis by targeting the tumor suppressive isoform KLF6-FL rather than its oncogenic isoform KLF6-SV1.
PMCID: PMC4179959  PMID: 24921656
Alternative splicing; KLF6; miRNA
18.  PKA turnover by the REGγ-proteasome modulates FoxO1 cellular activity and VEGF-induced angiogenesis 
The REGγ-proteasome serves as a short-cut for the destruction of certain intact mammalian proteins in the absence of ubiquitin-and ATP. The biological roles of the proteasome activator REGγ are not completely understood. Here we demonstrate that REGγ controls degradation of protein kinase A catalytic subunit-α (PKAca) both in primary human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblast cells (MEFs). Accumulation of PKAca in REGγ-deficient HUVECs or MEFs results in phosphorylation and nuclear exclusion of the transcription factor FoxO1, indicating that REGγ is involved in preserving FoxO1 transcriptional activity. Consequently, VEGF-induced expression of the FoxO1 responsive genes, VCAM-1 and E-Selectin, was tightly controlled by REGγ in a PKA dependent manner. Functionally, REGγ is crucial for the migration of HUVECs. REGγ−/− mice display compromised VEGF-instigated neovascularization in cornea and aortic ring models. Implanted matrigel plugs containing VEGF in REGγ−/− mice induced fewer capillaries than in REGγ+/+ littermates. Taken together, our study identifies REGγ as a novel angiogenic factor that plays an important role in VEGF-induced expression of VCAM-1 and E-Selectin by antagonizing PKA signaling. Identification of the REGγ–PKA–FoxO1 pathway in endothelial cells (ECs) provides another potential target for therapeutic intervention in vascular diseases.
PMCID: PMC4237316  PMID: 24560667
Angiogenesis; E-Selectin; FoxO1; PKAca; REGγ; VCAM-1
19.  Early versus delayed laparoscopic common bile duct exploration for common bile duct stone-related nonsevere acute cholangitis 
Scientific Reports  2015;5:11748.
It is undetermined when and how laparoscopic common bile duct exploration (LCBDE) should be used in patients with common bile duct (CBD) stone-related nonsevere acute cholangitis. We aimed to evaluate the effect of LCBDE on the clinical outcome of those patients within (early) or beyond (delayed) 72 hours of emergent admission. Surgery-related complications, length of hospital stay (LOS), and total cost, as well as demographic and clinical parameters were compared between the two groups. Finally, 3 and 5 patients in early and delayed LCBDE group, respectively, had retained stones, which were removed by choledochoscopy before T-tube was removed. Each group had 3 patients who developed biliary leak, which was conservatively cured by the drainage. Shorter LOS and less total cost were observed in early group compared to the late one (13.34 ± 4.48 vs. 18.32 ± 9.13, p < 0.05; 17712 ± 5446.63 vs. 21776 ± 7230.41 ¥RMB, p < 0.05). Improvement of cholangitis was achieved in all patients with LCBDE. None of the patients developed stricture of the CBD after LCBDE. To conclude, both early and delayed LCBDE are safe and effective for the treatment of CBD stone-related nonsevere acute cholangitis during emergent admissions. Early LCBDE may be superior to delayed procedure due to the shorter LOS and less cost.
PMCID: PMC4485235  PMID: 26123122
20.  Association of Lp-PLA2 Mass and Aysmptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients 
PLoS ONE  2015;10(6):e0130473.
Background and Purpose
Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA2 and asymptomatic ICAS or extracranial arterial stenosis (ECAS). Wehereby sought to explore the relationship of Lp-PLA2 and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population.
All the subjects were evaluated for the presence and severity of ICAS and ECAS through computerized tomographic angiography (CTA) covered the whole brain down to the level of aortic arch. Lp-PLA2 mass was measured by enzyme linked immunoassay. The association of Lp-PLA2 and vascular stenosis was analyzed through multivariate logistic regression.
Among 414 participants, 163 (39.4%) had no ICAS or ECAS, 63 (15.2%) had ECAS only, 111 (26.8%) had ICAS only and 77 (18.6%) had concurrent extraintracranial stenosis. Lp-PLA2 mass was significantly associated with isolated ICAS (OR: 2.3; 95% CI: 1.14-4.64), and concurrent stenosis (OR: 3.93; 95% CI: 1.62-9.51), but was not related to isolated ECAS (OR: 1.54; 95% CI: 0.68-3.48). Lp-PLA2 mass was also associated with moderate to severe ICAS no matter how was the ECAS. Moreover, patients with higher Lp-PLA2 mass showed more sever ICAS and had more intracranial arterial lesions.
This study revealed the association of Lp-PLA2 mass with ICAS in stroke-free hypertensive patients in Chinese population. The further long-term cohort study was warranted to elucidate the concrete effect of Lp-PLA2 on the asymptomatic ICAS.
PMCID: PMC4476589  PMID: 26098634
21.  Therapeutic effects of C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me; bardoxolone methyl) on radiation-induced lung inflammation and fibrosis in mice 
The C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO-Me), one of the synthetic triterpenoids, has been found to have potent anti-inflammatory and anticancer properties in vitro and in vivo. However, its usefulness in mitigating radiation-induced lung injury (RILI), including radiation-induced lung inflammation and fibrosis, has not been tested. The aim of this study was to explore the therapeutic effect of CDDO-Me on RILI in mice and the underlying mechanisms. Herein, we found that administration of CDDO-Me improved the histopathological score, reduced the number of inflammatory cells and concentrations of total protein in bronchoalveolar lavage fluid, suppressed secretion and expression of proinflammatory cytokines, including transforming growth factor-β and interleukin-6, elevated expression of the anti-inflammatory cytokine interleukin-10, and downregulated the mRNA level of profibrotic genes, including for fibronectin, α-smooth muscle actin, and collagen I. CDDO-Me attenuated radiation-induced lung inflammation. CDDO-Me also decreased the Masson’s trichrome stain score, hydroxyproline content, and mRNA level of profibrotic genes, and blocked radiation-induced collagen accumulation and fibrosis. Collectively, these findings suggest that CDDO-Me ameliorates radiation-induced lung inflammation and fibrosis, and this synthetic triterpenoid is a promising novel therapeutic agent for RILI. Further mechanistic, efficacy, and safety studies are warranted to elucidate the role of CDDO-Me in the management of RILI.
PMCID: PMC4482372  PMID: 26124639
CDDO-Me; radiotherapy; radiation-induced lung injury; cytokine; fibrosis; inflammation; transforming growth factor-β; mouse
22.  Context-Aware Reviewer Assignment for Trust Enhanced Peer Review 
PLoS ONE  2015;10(6):e0130493.
Reviewer assignment is critical to peer review systems, such as peer-reviewed research conferences or peer-reviewed funding applications, and its effectiveness is a deep concern of all academics. However, there are some problems in existing peer review systems during reviewer assignment. For example, some of the reviewers are much more stringent than others, leading to an unfair final decision, i.e., some submissions (i.e., papers or applications) with better quality are rejected. In this paper, we propose a context-aware reviewer assignment for trust enhanced peer review. More specifically, in our approach, we first consider the research area specific expertise of reviewers, and the institution relevance and co-authorship between reviewers and authors, so that reviewers with the right expertise are assigned to the corresponding submissions without potential conflict of interest. In addition, we propose a novel cross-assignment paradigm, and reviewers are cross-assigned in order to avoid assigning a group of stringent reviewers or a group of lenient reviewers to the same submission. More importantly, on top of them, we propose an academic CONtext-aware expertise relevanCe oriEnted Reviewer cross-assignmenT approach (CONCERT), which aims to effectively estimate the “true” ratings of submissions based on the ratings from all reviewers, even though no prior knowledge exists about the distribution of stringent reviewers and lenient reviewers. The experiments illustrate that compared with existing approaches, our proposed CONCERT approach can less likely assign more than one stringent reviewers or lenient reviewers to a submission simultaneously and significantly reduce the influence of ratings from stringent reviewers and lenient reviewers, leading to trust enhanced peer review and selection, no matter what kind of distributions of stringent reviewers and lenient reviewers are.
PMCID: PMC4474895  PMID: 26090849
23.  Clinical application of multimodality imaging in radiotherapy treatment planning for rectal cancer 
Cancer Imaging  2013;13(4):495-501.
Radiotherapy plays an important role in the treatment of rectal cancer. Three-dimensional conformal radiotherapy and intensity-modulated radiotherapy are mainstay techniques of radiotherapy for rectal cancer. However, the success of these techniques is heavily reliant on accurate target delineation and treatment planning. Computed tomography simulation is a cornerstone of rectal cancer radiotherapy, but there are limitations, such as poor soft-tissue contrast between pelvic structures and partial volume effects. Magnetic resonance imaging and positron emission tomography (PET) can overcome these limitations and provide additional information for rectal cancer treatment planning. PET can also reduce the interobserver variation in the definition of rectal tumor volume. However, there is a long way to go before these image modalities are routinely used in the clinical setting. This review summarizes the most promising studies on clinical applications of multimodality imaging in target delineation and treatment planning for rectal cancer radiotherapy.
PMCID: PMC3864219  PMID: 24334539
Rectal cancer; radiotherapy treatment planning; computed tomography; magnetic resonance imaging; positron emission tomography/computed tomography
24.  Y-junction carbon nanocoils: synthesis by chemical vapor deposition and formation mechanism 
Scientific Reports  2015;5:11281.
Y-junction carbon nanocoils (Y-CNCs) were synthesized by thermal chemical vapor deposition using Ni catalyst prepared by spray-coating method. According to the emerging morphologies of Y-CNCs, several growth models were advanced to elucidate their formation mechanisms. Regarding the Y-CNCs without metal catalyst in the Y-junctions, fusing of contiguous CNCs and a tip-growth mechanism are considered to be responsible for their formation. However, as for the Y-CNCs with catalyst presence in the Y-junctions, the formation can be ascribed to nanoscale soldering/welding and bottom-growth mechanism. It is found that increasing spray-coating time for catalyst preparation generates agglomerated larger nanoparticles strongly adhering to the substrate, resulting in bottom-growth of CNCs and appearance of the metal catalyst in the Y-junctions. In the contrary case, CNCs catalyzed by isolated smaller nanoparticles develop Y-junctions with an absence of metal catalyst by virtue of weaker adhesion of catalyst with the substrate and tip-growth of CNCs.
PMCID: PMC4462766  PMID: 26063127
25.  A Nematode Calreticulin, Rs-CRT, Is a Key Effector in Reproduction and Pathogenicity of Radopholus similis 
PLoS ONE  2015;10(6):e0129351.
Radopholus similis is a migratory plant-parasitic nematode that causes severe damage to many agricultural and horticultural crops. Calreticulin (CRT) is a Ca2+-binding multifunctional protein that plays key roles in the parasitism, immune evasion, reproduction and pathogenesis of many animal parasites and plant nematodes. Therefore, CRT is a promising target for controlling R. similis. In this study, we obtained the full-length sequence of the CRT gene from R. similis (Rs-crt), which is 1,527-bp long and includes a 1,206-bp ORF that encodes 401 amino acids. Rs-CRT and Mi-CRT from Meloidogyne incognita showed the highest similarity and were grouped on the same branch of the phylogenetic tree. Rs-crt is a multi-copy gene that is expressed in the oesophageal glands and gonads of females, the gonads of males, the intestines of juveniles and the eggs of R. similis. The highest Rs-crt expression was detected in females, followed by juveniles, eggs and males. The reproductive capability and pathogenicity of R. similis were significantly reduced after treatment with Rs-crt dsRNA for 36 h. Using plant-mediated RNAi, we confirmed that Rs-crt expression was significantly inhibited in the nematodes, and resistance to R. similis was significantly improved in transgenic tomato plants. Plant-mediated RNAi-induced silencing of Rs-crt could be effectively transmitted to the F2 generation of R. similis; however, the silencing effect of Rs-crt induced by in vitro RNAi was no longer detectable in F1 and F2 nematodes. Thus, Rs-crt is essential for the reproduction and pathogenicity of R. similis.
PMCID: PMC4465493  PMID: 26061142

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