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1.  Pretreatment Diffusion-Weighted MRI Can Predict the Response to Neoadjuvant Chemotherapy in Patients with Nasopharyngeal Carcinoma 
BioMed Research International  2015;2015:307943.
Purpose. To explore the potential of diffusion-weighted (DW) magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) for predicting the response to neoadjuvant chemotherapy in nasopharyngeal carcinoma (NPC). Methods and Materials. Ninety-two consecutive patients with NPC who underwent three cycles of neoadjuvant chemotherapy were retrospectively analyzed. DW and anatomical MRI were performed before and after neoadjuvant chemotherapy prior to radiotherapy. Pretreatment ADCs and percentage increases in ADC after chemotherapy were calculated for the primary lesions and metastatic adenopathies. Receiver operating characteristic curve analysis was used to select optimal pretreatment ADCs. Results. Pretreatment mean ADCs were significantly lower for responders than for nonresponders (primary lesions, P = 0.012; metastatic adenopathies, P = 0.013). Mean percentage increases in ADC were higher for responders than for nonresponders (primary lesions, P = 0.008; metastatic adenopathies, P < 0.001). The optimal pretreatment primary lesion and metastatic adenopathy ADCs for differentiating responders from nonresponders were 0.897 × 10−3 mm2/sec and 1.031 × 10−3 mm2/sec, respectively. Conclusions. NPC patients with low pretreatment ADCs tend to respond better to neoadjuvant chemotherapy. Pretreatment ADCs could be used as a new pretreatment imaging biomarker of response to neoadjuvant chemotherapy.
PMCID: PMC4564581  PMID: 26413513
2.  Nonlinear optical properties of near-infrared region Ag2S quantum dots pumped by nanosecond laser pulses 
This study investigates near-infrared region Ag2S quantum dots (QDs) and their nonlinear optical response under 532 nm nanosecond laser pulses. Our experimental result shows that nonlinear transmission is reduced from 0.084 to 0.04. The observed narrowing behavior of the output pulse width shows superior optical limiting. We discuss the physical mechanisms responsible for the nonlinear optical response of the QDs. The average size of the nanocrystals was 5.5 nm. Our results suggest the possibility of using these Ag2S QDs for photoelectric, biosensor, optical ranging, and self-adaptive technologies.
PMCID: PMC4578410  PMID: 26425430
nonlinear optics; quantum dots; silver sulfide (Ag2S); strong absorption
3.  SIMAT: GC-SIM-MS data analysis tool 
BMC Bioinformatics  2015;16(1):259.
Gas chromatography coupled with mass spectrometry (GC-MS) is one of the technologies widely used for qualitative and quantitative analysis of small molecules. In particular, GC coupled to single quadrupole MS can be utilized for targeted analysis by selected ion monitoring (SIM). However, to our knowledge, there are no software tools specifically designed for analysis of GC-SIM-MS data. In this paper, we introduce a new R/Bioconductor package called SIMAT for quantitative analysis of the levels of targeted analytes. SIMAT provides guidance in choosing fragments for a list of targets. This is accomplished through an optimization algorithm that has the capability to select the most appropriate fragments from overlapping chromatographic peaks based on a pre-specified library of background analytes. The tool also allows visualization of the total ion chromatograms (TIC) of runs and extracted ion chromatograms (EIC) of analytes of interest. Moreover, retention index (RI) calibration can be performed and raw GC-SIM-MS data can be imported in netCDF or NIST mass spectral library (MSL) formats.
We evaluated the performance of SIMAT using two GC-SIM-MS datasets obtained by targeted analysis of: (1) plasma samples from 86 patients in a targeted metabolomic experiment; and (2) mixtures of internal standards spiked in plasma samples at varying concentrations in a method development study. Our results demonstrate that SIMAT offers alternative solutions to AMDIS and MetaboliteDetector to achieve accurate detection of targets and estimation of their relative intensities by analysis of GC-SIM-MS data.
We introduce a new R package called SIMAT that allows the selection of the optimal set of fragments and retention time windows for target analytes in GC-SIM-MS based analysis. Also, various functions and algorithms are implemented in the tool to: (1) read and import raw data and spectral libraries; (2) perform GC-SIM-MS data preprocessing; and (3) plot and visualize EICs and TICs.
Electronic supplementary material
The online version of this article (doi:10.1186/s12859-015-0681-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4539696  PMID: 26283310
Selected ion monitoring; Gas chromatography-mass spectrometry; Data analysis
5.  Visual function and vision-related quality of life after vitrectomy for idiopathic macular hole: a 12mo follow-up study 
To investigate the visual function and the relationship with vision-related quality of life (VRQOL) after macular hole repair surgery.
Prospective case series. Thirty-six consecutive eyes in 36 patients who underwent pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling were included. The 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was answered by the participants before and 3 and 12mo after operation. Follow-up visits examinations included best-corrected visual acuity (BCVA), clinical examination, and central macular thickness (CMT) measured by optical coherence tomography (OCT).
Macular-hole closure was achieved in 35 of 36 eyes (97.2%). At baseline and months 3 and 12, the logMAR BCVAs (mean±SD) were 1.15±0.47, 0.68±0.53 (P<0.0001 versus baseline), and 0.55±0.49 (P<0.001 versus baseline, P =0.273 versus month 3), respectively; the CMTs (µm) were 330±81, 244±62 (P<0.001 versus baseline), and 225±58 (P<0.001 versus baseline, P=0.222 versus month 3), respectively; the median preoperative VFQ-25 composite score of 73.50 (63.92-81.13) increased postoperatively to 85.50 (80.04-89.63) at 3mo (P<0.001) and 86.73(82.50-89.63) at 12mo (P<0.001) respectively. The improved BCVA was correlated with improvements in five subscales (r=-0.605 to -0.336, P<0.001 to P=0.046) at 12mo.
PPV with ILM peeling improved anatomic outcome, visual function, and VRQOL. The improved BCVA was an important factor related to the improved VRQOL.
PMCID: PMC4539656  PMID: 26309877
idiopathic macular hole; vitrectomy; quality of life; National Eye Institute Visual Function Questionnaire
6.  Fluorescent Probes for Subcellular Localization during Osteclast Formation 
ACS Medicinal Chemistry Letters  2014;5(8):911-914.
Labeling of a small bioactive molecule with fluorescent probe has been becoming an essential tool in cell biology to reveal the subcellular distribution and the location of a molecular target. QOA-8a is a novel molecule with potent antiosteoporotic effect in vivo. To investigate the molecular mechanism of QOA-8a, novel fluorescence-tagged chemical probes as bioactive as their parent molecule were designed and synthesized. The fluorescent compound 12 showed a more potent inhibitory activity on RANKL-induced osteoclastogenesis at 2 μM compared with that of QOA-8a. Microscopy experiments revealed that almost all of probe 12 accumulated in the fusing region, with little in the osteoclast precursors or the mature osteoclasts during osteoclast formation. The result suggests the location of the binding target of QOA-8a, which might greatly narrow down the search field of the target protein(s).
PMCID: PMC4137367  PMID: 25147613
Fluorescent derivative probes; osteoclasts; subcellular localization
7.  Protective effect of Salvia miltiorrhiza and Carthamus tinctorius extract against lipopolysaccharide-induced liver injury 
AIM: To investigate the hepatoprotective effects and mechanisms of an extract of Salvia miltiorrhiza and Carthamus tinctorius in vivo.
METHODS: C57BL/6J mice were randomly assigned to five groups and intraperitoneally administered 0.9% saline, Salvia miltiorrhiza and Carthamus tinctorius extract [Danhong injection (DHI), 0.75 and 3 g/kg mixed extract] or reduced glutathione for injection (RGI, 300 mg/kg) for 30 min before exposure to lipopolysaccharide (LPS, 16 mg/kg). After intraperitoneal LPS stimulation for 90 min or 6 h, the mice were sacrificed by ether anaesthesia, and serum and liver samples were collected. Histological analysis (H&E) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining were performed. Alanine transferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), glutathione-S-transferase (GST), malondialdehyde (MDA), tumour necrosis factor (TNF)-α, interleukin (IL)-6, and caspase-3 levels were measured. Bax, Bcl-2, P-IκBα, IκBα, P-NF-κB p65, and NF-κB p65 protein levels were determined by Western blot. TNF-α, IL-6, caspase-3, Bax and Bcl-2 mRNA expression was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS: Hematoxylin-eosin staining and TUNEL results suggested that DHI (3 g/kg) treatment alleviated inflammatory and apoptotic (P < 0.01) injury in the liver of mice. DHI treatment dose-dependently blunted the abnormal changes in biochemical parameters such as ALT (72.53 ± 2.83 for 3 g/kg, P < 0.01), AST (76.97 ± 5.00 for 3 g/kg, P < 0.01), TBil (1.17 ± 0.10 for 3 g/kg, P < 0.01), MDA (0.81 ± 0.36 for 3 g/kg, P < 0.01), and GST (358.86 ± 12.09 for 3 g/kg, P < 0.01). Moreover, DHI (3 g/kg) remarkably decreased LPS-induced protein expression of TNF-α (340.55 ± 10.18 for 3 g/kg, P < 0.01), IL-6 (261.34 ± 10.18 for 3 g/kg, P < 0.01), and enzyme activity of caspase-3 (0.93 ± 0.029 for 3 g/kg, P < 0.01). The LPS-induced mRNA expression of TNF-α, IL-6 and caspase-3 was also decreased by DHI. Western blot analysis revealed that DHI antagonised LPS-stimulated decrease of Bcl-2 and increase of Bax protein expression. Furthermore, DHI inhibited LPS-induced IκBα and NF-κB p65 phosphorylation.
CONCLUSION: DHI may be a multi-function protectant against acute hepatic injury in mice through its anti-inflammatory, anti-oxidative and anti-apoptotic activities.
PMCID: PMC4533039  PMID: 26290634
Salvia miltiorrhiza; Carthamus tinctorius; Apoptosis; Anti-inflammatory; Antioxidant; Acute liver injury
8.  N-3 Polyunsaturated Fatty Acids and Inflammation in Obesity: Local Effect and Systemic Benefit 
BioMed Research International  2015;2015:581469.
Overwhelming consensus emerges among countless evidences that obesity is characterized by a chronic low-grade inflammation in the adipose tissue (AT), which subsequently develops into a systemic inflammatory state contributing to obesity-associated diseases. N-3 Polyunsaturated fatty acids (n-3 PUFA), known as important modulators participating in inflammatory process, turn out to be an effective mitigating strategy dealing with local and systemic inflammation observed in obesity. Some of the effects of n-3 PUFA are brought about by regulation of gene expression through interacting with nuclear receptors and transcription factors; other effects are elicited by modulation of the amount and type of mediator derived from PUFAs. The metabolic effects of n-3 PUFA mainly result from their interactions with several organ systems, not limited to AT. Notably, the attenuation of inflammation in hard-hit AT, in turn, contributes to reducing circulating concentrations of proinflammatory cytokines and detrimental metabolic derivatives, which is beneficial for the function of other involved organs. The present review highlights a bridging mechanism between n-3 PUFA-mediated inflammation relief in AT and systemic benefits.
PMCID: PMC4538411  PMID: 26339623
10.  Salvage Chemotherapy for Patients With Recurrent or Persistent Ovarian Clear Cell Carcinoma 
Medicine  2015;94(27):e1121.
The purpose of this study was to evaluate the effects of salvage chemotherapy on recurrent or persistent ovarian clear cell carcinoma (CCC) with the goal of identifying a more rational treatment regimen for this lethal disease.
The medical records of patients with CCC were retrospectively reviewed to select patients that were subsequently treated for recurrent or persistent disease.
Of the 164 women with recurrent or persistent CCC, 485 chemotherapy courses with 1766 cycles were administered. Overall, the clinical benefit rate (CBR) was 39.4%, and the mean progression-free survival (PFS) was 4.5 months. Grade 3/4 toxicities occurred in 94 courses (19.4%). The CBR for TC was 45.1%, with a PFS of 3.7 months. Compared to that of TC, the CBRs for PC and CC were significantly lower (P = 0.020 and 0.021, respectively). The CBRs and PFS for PAF-C were slightly higher (P = 0.518 and 0.077, respectively), but showed a significantly higher adverse event rate (AER, P = 0.039). The CBR for bevacizumab was 50% with an extraordinarily long PFS (49.8 months). Gemcitabine and oxaliplatin had similar values for CBRs (44.4% and 44.1%) and PFS (2.5 and 3.4 months), respectively. Docetaxel (weekly) exhibited a notably low AER of 2.7%, and topotecan was associated with a relatively long PFS (7.7 months).
For cis/carboplatin-pretreated patients, the existing active agents, such as oxaliplatin, gemcitabine, topotecan, and especially bevacizumab, are promising. Docetaxel (weekly) is well tolerated and might offer a particularly viable option for heavily pretreated patients. However, additional research to identify for a continued search for the optimal combination of chemotherapeutics or novel agents is still warranted.
PMCID: PMC4504555  PMID: 26166110
11.  Application of chrysophanol in zebrafish to reduce dietary introduced lipid and its possible mechanism 
Purpose: To explore the therapeutic potential and mechanism of chrysophanol on lipid-lowering function. Methods: Zebrafish or larvae were employed to evaluate the effect of chrysophanol on lipid-lowering. Zebrafish of 5 day post fertilization (dpf, larva) and 13-week old were fed with high-cholesterol diet or high-fat to investigate the influence of chrysophanol comparing with atorvastain and co-administration of chrysophanol and atorvastain on subsistent blood lipid using the fluorescence microscope and lipid panel screen. Thereafter, we enrolled zebrafish of 7 dpf fed with high-fat diet to explore the lipid-lowering mechanism of chrysophanol basing on the frequency of peristalsis and the residual on the digestive wall. Results: Chrysophanol could significantly lower cholesterol both in zebrafish and larvae (P < 0.05), and the co-administration of chrysophanol and atorvastatin had the best performance in reducing cholesterol (P < 0.05). Chrysophanol and atorvastain could also significantly lower triglyceride. Moreover, we found that chrysophanol attached on the digestive wall for a long time and enhanced the frequency of peristalsis. Conclusions: Chrysophanol has lipid-lowering effect both in zebrafish and larvae which may be attributed to the effect on the frequency of peristalsis and fat absorption, and co-administration with atorvastain performs better lipid-lowering effect in zebrafish.
PMCID: PMC4565228  PMID: 26379845
Chrysophanol; atorvastain; zebrafish; lipid-lowering effect
12.  miR-137 regulates the constitutive androstane receptor and modulates doxorubicin sensitivity in parental and doxorubicin-resistant neuroblastoma cells 
Oncogene  2013;33(28):3717-3729.
Chemotherapy is the most common treatment for cancer. However, multidrug resistance (MDR) remains a major obstacle to effective chemotherapy, limiting the efficacy of both conventional chemotherapeutic and novel biologic agents. The constitutive androstane receptor (CAR), a xenosensor, is a key regulator of MDR. It functions in xenobiotic detoxification by regulating the expression of phase I drug metabolizing enzymes and ATP-binding cassette (ABC) transporters, whose overexpression in cancers and whose role in drug resistance make them potential therapeutic targets for reducing MDR. MicroRNAs (miRNAs) are endogenous negative regulators of gene expression and have been implicated in most cellular processes, including drug resistance. Here we report the inversely related expression of miR-137 and CAR in parental and doxorubicin-resistant neuroblastoma cells, wherein miR-137 is down-regulated in resistant cells. miR-137 over-expression resulted in down-regulation of CAR protein and mRNA (via mRNA degradation); it sensitized doxorubicin-resistant cells to doxorubicin (as shown by reduced proliferation, increased apoptosis, and increased G2-phase cell cycle arrest) and reduced the in vivo growth rate of neuroblastoma xenografts. We observed similar results in cellular models of hepatocellular and colon cancers, indicating that the doxorubicin-sensitizing effect of miR-137 is not tumor type-specific. Finally, we show for the first time a negative feedback loop whereby miR-137 down-regulates CAR expression and CAR down-regulates miR-137 expression. Hypermethylation of the miR-137 promoter and negative regulation of miR-137 by CAR contribute in part to reduced miR-137 expression and increased CAR and MDR1 expression in doxorubicin-resistant neuroblastoma cells. These findings demonstrate that miR-137 is a crucial regulator of cancer response to doxorubicin treatment, and they identify miR-137 as a highly promising target to reduce CAR-driven doxorubicin resistance.
PMCID: PMC3922897  PMID: 23934188
microRNA; constitutive androstane receptor; miR-137; MDR1; doxorubicin
13.  Genome-wide Identification and Expression Analysis of the CDPK Gene Family in Grape, Vitis spp 
BMC Plant Biology  2015;15:164.
Calcium-dependent protein kinases (CDPKs) play vital roles in plant growth and development, biotic and abiotic stress responses, and hormone signaling. Little is known about the CDPK gene family in grapevine.
In this study, we performed a genome-wide analysis of the 12X grape genome (Vitis vinifera) and identified nineteen CDPK genes. Comparison of the structures of grape CDPK genes allowed us to examine their functional conservation and differentiation. Segmentally duplicated grape CDPK genes showed high structural conservation and contributed to gene family expansion. Additional comparisons between grape and Arabidopsis thaliana demonstrated that several grape CDPK genes occured in the corresponding syntenic blocks of Arabidopsis, suggesting that these genes arose before the divergence of grapevine and Arabidopsis. Phylogenetic analysis divided the grape CDPK genes into four groups. Furthermore, we examined the expression of the corresponding nineteen homologous CDPK genes in the Chinese wild grape (Vitis pseudoreticulata) under various conditions, including biotic stress, abiotic stress, and hormone treatments. The expression profiles derived from reverse transcription and quantitative PCR suggested that a large number of VpCDPKs responded to various stimuli on the transcriptional level, indicating their versatile roles in the responses to biotic and abiotic stresses. Moreover, we examined the subcellular localization of VpCDPKs by transiently expressing six VpCDPK-GFP fusion proteins in Arabidopsis mesophyll protoplasts; this revealed high variability consistent with potential functional differences.
Taken as a whole, our data provide significant insights into the evolution and function of grape CDPKs and a framework for future investigation of grape CDPK genes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-015-0552-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4485369  PMID: 26122404
Grapevine (Vitis vinifera L.) (Vitis pseudoreticulata); CDPK; Synteny analysis; Phylogenetic tree; Subcellular localization; expression profiles
14.  Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory 
Scientific Reports  2015;5:11456.
Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understood. Here we show that integrin-linked kinase (ILK) levels are elevated upon EE stimuli in a BDNF-dependent manner. Using ILK-shRNA (siILK) lentivirus, we demonstrate that knockdown of ILK impairs EE-promoted hippocampal neurogenesis and memory by increasing glycogen synthase kinase-3β (GSK3β) activity. Finally, overexpressing ILK in the hippocampus could rescue the neurogenesis and memory deficits in BDNF+/− mice. These results indicate that ILK is indispensable for BDNF-mediated hippocampal neurogenesis and memory enhancement upon EE stimuli via regulating GSK3β activity. This is a new insight of the precise mechanism in EE-enhanced memory processes and ILK is a potentially important therapeutic target that merits further study.
PMCID: PMC4476098  PMID: 26095336
15.  A patient tumor-derived orthotopic xenograft mouse model replicating the group 3 supratentorial primitive neuroectodermal tumor in children 
Neuro-Oncology  2014;16(6):787-799.
Supratentorial primitive neuroectodermal tumor (sPNET) is a malignant brain tumor with poor prognosis. New model systems that replicate sPNET's molecular subtype(s) and maintain cancer stem cell (CSC) pool are needed.
A fresh surgical specimen of a pediatric sPNET was directly injected into the right cerebrum of Rag2/SCID mice. The xenograft tumors were serially sub-transplanted in mouse brains, characterized histopathologically, and subclassified into molecular subtype through qRT-PCR and immunohistochemical analysis. CSCs were identified through flow cytometric profiling of putative CSC markers (CD133, CD15, CD24, CD44, and CD117), functional examination of neurosphere forming efficiency in vitro, and tumor formation capacity in vivo. To establish a neurosphere line, neurospheres were propagated in serum-free medium.
Formation of intracerebral xenograft tumors was confirmed in 4 of the 5 mice injected with the patient tumor. These xenograft tumors were sub-transplanted in vivo 5 times. They replicated the histopathological features of the original patient tumor and expressed the molecular markers (TWIST1 and FOXJ1) of group 3 sPNET. CD133+ and CD15+ cells were found to have strong neurosphere-forming efficiency in vitro and potent tumor-forming capacity (with as few as 100 cells) in vivo. A neurosphere line BXD-2664PNET-NS was established that preserved stem cell features and expressed group 3 markers.
We have established a group 3 sPNET xenograft mouse model (IC-2664PNET) with matching neurosphere line (BXD-2664PNET-NS) and identified CD133+ and CD15+ cells as the major CSC subpopulations. This novel model system should facilitate biological studies and preclinical drug screenings for childhood sPNET.
PMCID: PMC4022216  PMID: 24470556
cancer stem cell; orthotopic xenograft model; supratentorial primitive neuroectodermal tumor
16.  Novel Mechanism Coupling Cyclic AMP-Protein Kinase A Signaling and Golgi Trafficking via Gyp1 Phosphorylation in Polarized Growth 
Eukaryotic Cell  2014;13(12):1548-1556.
The cyclic AMP (cAMP)-protein kinase A (PKA) signaling activates virulence expression during hyphal development in the fungal human pathogen Candida albicans. The hyphal growth is characterized by Golgi polarization toward the hyphal tips, which is thought to enhance directional vesicle transport. However, how the hypha-induction signal regulates Golgi polarization is unknown. Gyp1, a Golgi-associated protein and the first GTPase-activating protein (GAP) in the Rab GAP cascade, critically regulates membrane trafficking from the endoplasmic reticulum to the plasma membrane. Here, we report a novel pathway by which the cAMP-PKA signaling triggers Golgi polarization during hyphal growth. We demonstrate that Gyp1 plays a crucial role in actin-dependent Golgi polarization. Hyphal induction activates PKA, which in turn phosphorylates Gyp1. Phosphomimetic mutation of four PKA sites identified by mass spectrometry (Gyp14E) caused strong Gyp1 polarization to hyphal tips, whereas nonphosphorylatable mutations (Gyp14A) abolished it. Gyp14E exhibited enhanced association with the actin motor Myo2, while Gyp14A showed the opposite effect, providing a possible mechanism for Golgi polarization. A GAP-dead Gyp1 (Gyp1R292K) showed strong polarization similar to that seen with Gyp14E, indicating a role for the GAP activity. Mutating the PKA sites on Gyp1 also impaired the recruitment of a late Golgi marker, Sec7. Furthermore, proper PKA phosphorylation and GAP activity of Gyp1 are required for virulence in mice. We propose that the cAMP-PKA signaling directly targets Gyp1 to promote Golgi polarization in the yeast-to-hypha transition, an event crucial for C. albicans infection.
PMCID: PMC4248690  PMID: 25326521
17.  Clinical and Pathological Characteristics of Hard Nodules Resistant to Morcellation During Holmium Laser Enucleation of the Prostate 
To identify the clinical and pathological characteristics of hard nodules resistant to morcellation (HNRM) during holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH).
Between July 2008 and October 2011, 246 patients underwent HoLEP for symptomatic BPH. The first 30 patients were excluded from the analysis due to the learning curve of the procedure. The remaining patients were divided into HNRM (n=29) and non-HNRM groups (n=187), and comparative analysis of the clinical parameters of the two groups was performed. International prostate symptom score analysis and urodynamic studies were performed preoperatively. Histological analysis was performed after hematoxylin and eosin staining and Masson trichrome staining of the HNRM specimens.
Twenty-nine patients (13.4%) had HNRM. The patients in the HNRM group had significantly higher proportions of advanced age (≥65 years, P=0.029), total prostate volume ≥65 mL (P<0.001), transition zone volume ≥35 mL (P<0.001), serum prostate-specific antigen levels ≥10 ng/mL (P=0.007), and functional urethral length ≥70 mm (P=0.009); larger enucleation weight (P<0.001); longer operation (P=0.001), enucleation (P=0.042), and morcellation times (P<0.001); and higher enucleation ratio (P=0.028) and enucleation efficacy (P=0.001). After adjusting for confounding factors, multivariate logistic regression analysis revealed that age ≥65 years and total prostate volume ≥65 mL were independent risk factors for HNRM. Pathological examination did not reveal any malignant cells, with mainly dense fibrous tissue found in the HNRM.
HNRM can make morcellation cumbersome and time-consuming, and older patients with larger prostates have a higher incidence of HNRM. However, the histopathology of HNRM revealed mainly fibrotic tissue.
PMCID: PMC4490320  PMID: 26126438
Laser Therapy; Prostate; Prostatic Hyperplasia; Transurethral Resection of Prostate
18.  Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice 
Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ), is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD). However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO) C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day) for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.
PMCID: PMC4490440  PMID: 26035752
pioglitazone; non-alcoholic fatty liver disease; Affymetrix Mouse GeneChip; inflammation response; lipid metabolism
19.  De Novo Characterization of Flower Bud Transcriptomes and the Development of EST-SSR Markers for the Endangered Tree Tapiscia sinensis 
Tapiscia sinensis Oliv (Tapisciaceae) is an endangered species native to China famous for its androdioecious breeding system. However, there is a lack of genomic and transcriptome data on this species. In this study, the Tapiscia sinensis transcriptomes from two types of sex flower buds were sequenced. A total of 97,431,176 clean reads were assembled into 52,169 unigenes with an average length of 1116 bp. Through similarity comparison with known protein databases, 36,662 unigenes (70.27%) were annotated. A total of 10,002 (19.17%) unigenes were assigned to 124 pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Additionally, 10,371 simple sequence repeats (SSRs) were identified in 8608 unigenes, with 16,317 pairs of primers designed for applications. 150 pairs of primers were chosen for further validation, and the 68 pairs (45.5%) were able to produce clear polymorphic bands. Six polymorphic SSR markers were used to Bayesian clustering analysis of 51 T. sinensis individuals. This is the first report to provide transcriptome information and to develop large-scale SSR molecular markers for T. sinensis. This study provides a valuable resource for conservation genetics and functional genomics research on T. sinensis for future work.
PMCID: PMC4490475  PMID: 26057749
Tapiscia sinensis; transcriptome; Illumina sequencing; EST-SSRs (Expressed sequence tag simple sequence repeats)
20.  Forward Looking Radar Imaging by Truncated Singular Value Decomposition and Its Application for Adverse Weather Aircraft Landing 
Sensors (Basel, Switzerland)  2015;15(6):14397-14414.
The forward looking radar imaging task is a practical and challenging problem for adverse weather aircraft landing industry. Deconvolution method can realize the forward looking imaging but it often leads to the noise amplification in the radar image. In this paper, a forward looking radar imaging based on deconvolution method is presented for adverse weather aircraft landing. We first present the theoretical background of forward looking radar imaging task and its application for aircraft landing. Then, we convert the forward looking radar imaging task into a corresponding deconvolution problem, which is solved in the framework of algebraic theory using truncated singular decomposition method. The key issue regarding the selecting of the truncated parameter is addressed using generalized cross validation approach. Simulation and experimental results demonstrate that the proposed method is effective in achieving angular resolution enhancement with suppressing the noise amplification in forward looking radar imaging.
PMCID: PMC4507589  PMID: 26094627
aircraft landing; radar imaging; truncated singular value decomposition; deconvolution
21.  Mannose prevents acute lung injury through mannose receptor pathway and contributes to regulate PPARγ and TGF-β1 level 
Mannose has been reported to prevent acute lung injury (ALI), and mannose receptor (MR) has been demonstrated to have a role. The rationale for this study is to characterize the mechanism by which mannose and MR prevent lipopolysaccharide (LPS)-induced ALI. Male ICR mice were pretreated mannose by intravenous injection 5 min before and 3 h after intratracheal instillation of LPS. Pathological changes, proinflammatory mediator, peroxisome proliferator activated receptor gamma (PPARγ), MR, and transforming growth factor β1 (TGF-β1) levels were determined. The RAW264.7 cells were pretreated with mannose and stimulated with LPS for 3 h. Proinflammatory mediator and TGF-β1 in the culture media, PPARγ, MR, and TGF-β1 expression in RAW 264.7 cells were measured. Mannose markedly attenuated the LPS-induced histological alterations and inhibited the production of proinflammatory mediator in mice and in RAW 264.7 cells. Mannose increased PPARγ and MR expression, and inhibited TGF-β1 stimulated by LPS. Interestingly, competitive inhibition of MR with mannan was associated with elimination of the anti-inflammatory effects of mannose, and reversed effects of mannose of regulation to PPARγ and TGF-β1. MR is important in increasing PPARγ and decreasing TGF-β1 expression and plays a critical role in mannose’s protection against ALI.
PMCID: PMC4525832  PMID: 26261498
Acute lung injury; anti-inflammation; mannose; mannose receptor; PPARγ; TGF-β1
22.  Adrenergic receptor β2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment 
BMB Reports  2015;48(5):295-300.
Stress and its related hormones epinephrine (E) and norepinephrine (NE) play a crucial role in tumor progression. Macrophages in the tumor microenvironment (TME) polarized to M2 is also a vital pathway for tumor deterioration. Here, we explore the underlying role of macrophages in the effect of stress and E promoting breast cancer growth. It was found that the weight and volume of tumor in tumor bearing mice were increased, and dramatically accompanied with the rising E level after chronic stress using social isolation. What is most noteworthy, the number of M2 macrophages inside tumor was up-regulated with it. The effects of E treatment appear to be directly related to the change of M2 phenotype is reproduced in vitro. Moreover, E receptor ADRβ2 involved in E promoting M2 polarization was comprehended simultaneously. Our results imply psychological stress is influential on specific immune system, more essential for the comprehensive treatment against tumors. [BMB Reports 2015; 48(5): 295-300]
PMCID: PMC4578570  PMID: 25748171
Adrenergic receptor; Breast cancer; Epinephrine; Macrophage polarization; Stress
23.  The Role of Cyclooxygenase-2, Interleukin-1β and Fibroblast Growth Factor-2 in the Activation of Matrix Metalloproteinase-1 in Sheared-Chondrocytes and Articular Cartilage 
Scientific Reports  2015;5:10412.
MMP-1 expression is detected in fluid shear stress (20 dyn/cm2)-activated and osteoarthritic human chondrocytes, however, the precise mechanisms underlying shear-induced MMP-1 synthesis remain unknown. Using primary chondrocytes and T/C-28a2 chondrocytic cells as model systems, we report that prolonged application of high fluid shear to human chondrocytes induced the synthesis of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and fibroblast growth factor-2 (FGF-2), which led to a marked increase in MMP-1 expression. IL-1β, COX-2-dependent PGE2 activated the PI3-K/AKT and p38 signaling pathways, which were in turn responsible for MMP-1 synthesis via NF-κB- and c-Jun-transactivating pathways. Prolonged shear stress exposure (>12 h) induced 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) synthesis. Although 15d-PGJ2 suppressed PI3-K/AKT and p38 signaling pathways, it stimulated MMP-1 expression via activating heme oxygenase 1 (HO-1). The critical role of COX-2 in regulating MMP-1 expression in articular cartilage in vivo was demonstrated using COX-2+/− transgenic mice in the absence or presence of rofecoxib oral administration. These findings provide novel insights for developing therapeutic strategies to combat OA.
PMCID: PMC4438667  PMID: 25992485
24.  A pooled analysis of alcohol intake and colorectal cancer 
Object: In order to provide an updated quantification of the association between alcohol intake and colorectal cancer, we conducted a meta-analysis of published observational studies. Method: Two cohort and 22 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before July 2014. Data were extracted independently by two reviewers. Random effects meta-analyses, subgroup analyses, and meta regression were performed for modeling the dose-response relation. Result: The pooled relative risk (RR) for any alcohol intake compared with non/occasional drinking was 1.13 [95% confidence interval (CI), 1.09-1.17]. The RRs were 1.07 (95% CI, 1.02-1.13), 1.23 (95% CI, 1.15-1.32) and 1.37 (95% CI, 1.26-1.49) for light (≤12.5 g/day), moderate (12.6 to 49.9 g/day) and heavy drinking (≥50 g/day), respectively. The risks were consistent in the subgroup analyses of sex and tumor site. Conclusion: This meta-analysis provides strong evidence for an association between alcohol intake and colorectal cancer risk.
PMCID: PMC4509170  PMID: 26221225
Alcohol intake; colorectal neoplasms; meta-analysis
25.  The association between NFKB1-94ins/del ATTG polymorphism and non-small cell lung cancer risk in a Chinese Han population 
This study aimed to clarify the influence of a common insertion/deletion polymorphism (-94ins/del ATTG, rs28362491) in the Nuclear factor-κB1 (NFKB1) promoter on non-small cell lung cancer (NSCLC) susceptibility. We genotyped the NFKB1 -94ins/del ATTG polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and assessed the association with NSCLC risk, clinicopathological parameters in a case-control study of 421 cases and 425 controls. Heterozygous (ID) genotype disclosed a statistically significantly increased risk of developing NSCLC (OR = 1.57, 95% CI 1.13-2.19, P = 0.007). Homozygous (II) genotype also showed an increased risk of NSCLC (OR = 1.87, 95% CI 1.27-2.75, P = 0.001). Statistically significant difference was observed when the patients and controls were compared according to ID + II versus DD (OR = 2.01, 95% CI 1.47-2.76, P<0.001). The I allele was significantly higher in the NSCLC cases compared to the controls (52.9% versus 45.1%). The I allele was significantly associated with NSCLC risk (OR = 1.37, 95% CI 1.12-1.65, P = 0.001). There was a significantly higher frequency of ID + II genotypes observed in smokers, compared to non-smokers (OR = 1.99, 95% CI 1.22-3.24, P = 0.005) and in patients with stage III + IV, compared to stage I + II (OR = 2.16, 95% CI 1.34-3.49, P = 0.002). This study suggested that NFKB1 -94ins/del ATTG polymorphism was significantly associated with NSCLC risk in Chinese Han population.
PMCID: PMC4509329  PMID: 26221384
Non-small cell lung cancer; nuclear factor-κB; polymorphism; genetics

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