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1.  Differential diagnosis of benign and malignant breast masses using diffusion-weighted magnetic resonance imaging 
Diffusion-weighted magnetic resonance imaging (DW-MRI) is different from conventional diagnostic methods and has the potential to delineate the microscopic anatomy of a target tissue or organ. The purpose of our study was to evaluate the value of DW-MRI in the diagnosis of benign and malignant breast masses, which would help the clinical surgeon to decide the scope and pattern of operation.
A total of 52 female patients with palpable solid breast masses received breast MRI scans using routine sequences, dynamic contrast-enhanced imaging, and diffusion-weighted echo-planar imaging at b values of 400, 600, and 800 s/mm2, respectively. Two regions of interest (ROIs) were plotted, with a smaller ROI for the highest signal and a larger ROI for the overall lesion. Apparent diffusion coefficient (ADC) values were calculated at three different b values for all detectable lesions and from two different ROIs. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of DW-MRI were determined for comparison with histological results.
A total of 49 (49/52, 94.2%) lesions were detected using DW-MRI, including 20 benign lesions (two lesions detected in the same patient) and 29 malignant lesions. Benign lesion had a higher mean ADC value than their malignant counterparts, regardless of b value. According to the receiver operating characteristic (ROC) curve, the smaller-range ROI was more effective in differentiation between benign and malignant lesions. The area under the ROC curve was the largest at a b value of 800 s/mm2. With a threshold ADC value at 1.23 × 10−3 mm2/s, DW-MRI achieved a sensitivity of 82.8%, specificity of 90.0%, positive predictive value of 92.3%, and positive likelihood ratio of 8.3 for differentiating benign and malignant lesions.
DW-MRI is an accurate diagnostic tool for differentiation between benign and malignant breast lesions, with an optimal b value of 800 s/mm2. A smaller-range ROI focusing on the highest signal has a better differential value.
PMCID: PMC4328303
breast lesions; b value; differential diagnosis; diffusion-weighted imaging; magnetic resonance imaging
2.  Arabidopsis HFR1 Is a Potential Nuclear Substrate Regulated by the Xanthomonas Type III Effector XopDXcc8004 
PLoS ONE  2015;10(2):e0117067.
XopDXcc8004, a type III effector of Xanthomonas campestris pv. campestris (Xcc) 8004, is considered a shorter version of the XopD, which lacks the N-terminal domain. To understand the functions of XopDXcc8004, in planta, a transgenic approach combined with inducible promoter to analyze the effects of XopDXcc8004 in Arabidopsis was done. Here, the expression of XopDXcc8004, in Arabidopsis elicited the accumulation of host defense-response genes. These molecular changes were dependent on salicylic acid and correlated with lesion-mimic phenotypes observed in XVE::XopDXcc8004 transgenic plants. Moreover, XopDXcc8004 was able to desumoylate HFR1, a basic helix-loop-helix transcription factor involved in photomorphogenesis, through SUMO protease activity. Interestingly, the hfr1-201 mutant increased the expression of host defense-response genes and displayed a resistance phenotype to Xcc8004. These data suggest that HFR1 is involved in plant innate immunity and is potentially regulated by XopDXcc8004.
PMCID: PMC4315394  PMID: 25647296
3.  14-3-3ζ Orchestrates Mammary Tumor Onset and Progression via miR221-Mediated Cell Proliferation 
Cancer research  2013;74(1):363-373.
14-3-3ζ is overexpressed in over 40% of breast cancers but its pathophysiological relevance to tumorigenesis has not been established. Here we show that 14-3-3ζ overexpression is sufficient to induce tumorigenesis in a transgenic mouse model of breast cancer. MMTV-LTR promoter driven HA-14-3-3ζ transgenic mice (MMTV-HA-14-3-3ζ) developed mammary tumors whereas control mice did not. Whey acidic protein promoter driven HA-14-3-3ζ transgenic mice (WAP-HA-14-3-3ζ) developed hyperplastic lesions and showed increased susceptibility to carcinogen-induced tumorigenesis. When crossed with MMTV-neu transgenic mice, 14-3-3ζ.neu transgenic mice exhibited accelerated mammary tumorigenesis and metastasis compared to MMTV-neu mice. Mechanistically, 14-3-3ζ overexpression enhanced MAPK/c-Jun signaling leading to increased miR-221 transcription, which inhibited p27 CDKI translation, and consequently, promoted cell proliferation. Importantly, this 14-3-3ζ/miR-221/p27/proliferation axis is also functioning in patients' breast tumors and associates with high grade cancers. Taken together, our findings show that 14-3-3ζ overexpression has a causal role in mammary tumorigenesis and progression, acting through miR-221 in cooperation with known oncogenic events to drive neoplastic cell proliferation.
PMCID: PMC3947305  PMID: 24197133
Breast cancer; 14-3-3ζ; microRNA; transgenic mice
4.  Gender Differences in Cerebral Regional Homogeneity of Adult Healthy Volunteers: A Resting-State fMRI Study 
BioMed Research International  2015;2015:183074.
Objective. We sought to use the regional homogeneity (ReHo) approach as an index in the resting-state functional MRI to investigate the gender differences of spontaneous brain activity within cerebral cortex and resting-state networks (RSNs) in young adult healthy volunteers. Methods. One hundred and twelve healthy volunteers (56 males, 56 females) participated in the resting-state fMRI scan. The ReHo mappings in the cerebral cortex and twelve RSNs of the male and female groups were compared. Results. We found statistically significant gender differences in the primary visual network (PVN) (P < 0.004, with Bonferroni correction) and left attention network (LAtN), default mode network (DMN), sensorimotor network (SMN), executive network (EN), and dorsal medial prefrontal network (DMPFC) as well (P < 0.05, uncorrected). The male group showed higher ReHo in the left precuneus, while the female group showed higher ReHo in the right middle cingulate gyrus, fusiform gyrus, left inferior parietal lobule, precentral gyrus, supramarginal gyrus, and postcentral gyrus. Conclusions. Our results suggested that men and women had regional specific differences during the resting-state. The findings may improve our understanding of the gender differences in behavior and cognition from the perspective of resting-state brain function.
PMCID: PMC4299532  PMID: 25629038
5.  Cardioprotective effect of epigallocatechin-3-gallate against myocardial infarction in hypercholesterolemic rats 
Cardiovascular diseases are closely associated with a high-cholesterol or high-fat diet. The aim of the present study was to investigate the cadioprotective effect of epigallocatechin-3-gallate (EGCG) in high-fat diet-fed rats, with special emphasis on myocardial infarction. A high-fat diet was administered to male Wistar rats for 45 days and the rats of the treatment group were administered EGCG via intraperitoneal injection for the last 15 days. The serum lipid profile, antioxidant enzyme activity, lipid peroxidation, lipid metabolic proteins and cardiac tissue markers were assessed. The myocardium and aorta were also histopathologically examined. The high-fat diet-fed rats were found to be hypercholesterolemic or exhibited abnormal values in the selected parameters. However, these abnormalities were reversed to near-normal values in the rats administered EGCG. Similarly, the enzymatic antioxidant activity and non-enzymatic antioxidant levels were improved with EGCG treatment in high-fat diet-fed rats. In addition, EGCG activated sirtuin 1, endothelial nitric oxide synthase and AMP-activated protein kinase α, which suggests that its protective effect is mediated through the stimulation of lipid metabolism. The histopathological examination further revealed that EGCG significantly prevented the development of tissue abnormalities and improved the morphology of myocardial tissue. Taken together, our results suggested that EGCG plays a significant role in the protection of the cardiovascular system against the high-fat diet. This is a preliminary study, emphasizing on the cardioprotective properties of EGCG. We are currently analyzing the molecular mechanism underlying the protective effects of EGCG.
PMCID: PMC4280953  PMID: 25574206
lipid profile; antioxidants; atherosclerosis; sirtuin 1
6.  Atorvastatin ameliorates myocardial ischemia/reperfusion injury through attenuation of endoplasmic reticulum stress-induced apoptosis 
Endoplasmic reticulum stress (ERS) is known to play an important role in mediating myocardial ischemic/reperfusion (I/R) injury. Some previous studies have shown that atorvastatin alleviates myocardial I/R injury in animal models, but whether attenuation of ERS-induced apoptosis contributes to this effect remains to be elucidated. Therefore, in this study, we sought to investigate the modulatory effect of atorvastatin on myocardial I/R-induced ERS in rats. Myocardial I/R injury was induced in rats by occlusion of the left anterior descending coronary artery (LAD) for 0.5 h followed by 2 h of reperfusion. Atorvastatin was administered at different dosages (10 mg/kg, 20 mg/kg, and 40 mg/kg) at the onset of reperfusion. The levels of the CK-MB and LDH were detected by ELISA. Myocardial ischemia and infarct size were evaluated by Evans blue and tetrazolium chloride (TTC) staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to investigate myocardial cell apoptosis. The expression levels of the genes encoding glucose-regulated protein-78 (GRP78, widely used as a marker of ERS), C/EBP homologous protein (CHOP) and caspase-12 (widely used as markers of ERS-induced apoptosis) were assessed using RT-PCR. The expression levels of the ERS proteins GRP78, CHOP, caspase-12, c-Jun NH2 terminal kinase (JNK) and phosphorylated JNK (p-JNK) were detected by western blot. Our results showed that atorvastatin treatment (20 mg/kg and 40 mg/kg) significantly reduced myocardial infarct size and myocardial cell apoptosis, and decreased the plasma levels of CK-MB and LDH in I/R rats. This treatment also significantly modulated mRNA and protein levels, specifically down-regulating GRP78, CHOP and caspase-12 expression along with JNK activation. These results suggest that the attenuation of ERS-induced apoptosis may be involved in the cardioprotective mechanisms of atorvastatin in myocardial I/R injury.
PMCID: PMC4307435  PMID: 25663988
Atorvastatin; ischemia reperfusion injury; endoplasmic reticulum stress; apoptosis
7.  The effect of dye-sensitized solar cell based on the composite layer by anodic TiO2 nanotubes 
Nanoscale Research Letters  2014;9(1):671.
TiO2 nanotube arrays are very attractive for dye-sensitized solar cells (DSSCs) owing to their superior charge percolation and slower charge recombination. Highly ordered, vertically aligned TiO2 nanotube arrays have been fabricated by a three-step anodization process. Although the use of a one-dimensional structure provides an enhanced photoelectrical performance, the smaller surface area reduces the adsorption of dye on the TiO2 surface. To overcome this problem, we investigated the effect of DSSCs constructed with a multilayer photoelectrode made of TiO2 nanoparticles and TiO2 nanotube arrays. We fabricated the novel multilayer photoelectrode via a layer-by-layer assembly process and thoroughly investigated the effect of various structures on the sample efficiency. The DSSC with a four-layer photoelectrode exhibited a maximum conversion efficiency of 7.22% because of effective electron transport and enhanced adsorption of dye on the TiO2 surface.
PMCID: PMC4273724  PMID: 25593557
DSSCs; Anodic oxidation; Photoelectrode; TiO2 nanotube array; Composite layer
8.  The histone demethylase JMJD2B is regulated by estrogen receptor alpha and hypoxia and is a key mediator of estrogen induced growth 
Cancer research  2010;70(16):6456-6466.
ERα plays an important role in breast cancer. Up-regulation of HIF-1α in ERα-positive cancers suggests that HIF-1α may cooperate with ERα to promote breast cancer progression and consequently affect breast cancer treatment. Here we show the histone demethylase JMJD2B is regulated by both ERα and HIF-1α, and drives breast cancer cell proliferation in normoxia and hypoxia, and epigenetically regulates the expression of cell cycle genes such as CCND1, CCNA1 and WEE1. We also demonstrate that JMJD2B and the hypoxia marker CA9 together stratify a subclass of breast cancer patients and predicts a worse outcome of these breast cancers. Our findings provide a biological rationale to support the therapeutic targeting of histone demethylases in breast cancer patients.
PMCID: PMC4261152  PMID: 20682797
Hypoxia; ERα; HIF-1α; Histone demethylase; JMJD2B; breast cancer
9.  Primary pulmonary amyloidosis misdiagnosed as malignancy on dual-time-point fluoro-deoxyglucose positron emission tomography/computed tomography: A case report and review of the literature 
Oncology Letters  2014;9(2):591-594.
Primary pulmonary amyloidosis is an uncommon manifestation, characterized by amyloid deposition in the lungs and other associated tissue. The clinical presentation of amyloidosis is variable, with non-specific symptoms. The current study reports the case of a 59-year-old female presenting with primary pulmonary amyloidosis, indistinguishable from lung malignancy based on 18F-fluoro-deoxyglucose (18F-FDG) accumulation on dual-time-point (DTP) FDG-positron emission tomography/computed tomography (PET/CT) imaging and the similarities in morphological changes. A percutaneous CT-guided thoracoscopic biopsy was subsequently performed. Histological examination revealed that the specimens contained amorphous, homogeneous material with a number of polyclonal plasma cells, lymphocytes and giant cells. A diagnosis of primary nodular parenchymal pulmonary amyloidosis was determined, and the patient was discharged without chemotherapy. The patient remained in good clinical condition during follow-up. The present case indicated that localized nodular amyloidosis with increased FDG uptake on DTP FDG PET must be considered in the differential diagnosis of growing lung nodules, and that a histological examination must be conducted to distinguish this condition from malignancies of the lung.
PMCID: PMC4301551  PMID: 25624887
18F-fluoro-deoxyglucose positron emission tomography/computed tomography; pulmonary amyloidosis; lung malignancies
10.  Developing an in vitro model of T cell type of large granular lymphocyte leukemia 
Leukemia research  2013;37(12):10.1016/j.leukres.2013.10.002.
We developed a strategy that can prolong in vitro growth of T cell type of large granular lymphocyte (T-LGL) leukemia cells. Primary CD8+ lymphocytes from T-LGL leukemia patients were stably transduced with the retroviral tax gene derived from human T cell leukemia virus type 2. Expression of Tax overrode replicative senescence and promoted clonal expansion of the leukemic CD8+ T cells. These cells exhibit features characteristic of leukemic LGL, including resistance to FasL-mediated apoptosis, sensitivity to the inhibitors of sphingosine-1-phosphate receptor and IκB kinases as well as expression of cytotoxic gene products such as granzyme B, perforin and IFNγ. Collectively, these results indicate that this leukemia cell model can duplicate the main phenotype and pathophysiological characteristics of the clinical isolates of T-LGL leukemia. This model should be useful for investigating molecular pathogenesis of the disease and for developing new therapeutics targeting T-LGL leukemia.
PMCID: PMC3865428  PMID: 24183305
T-LGLL; Stat3; NF-κB; retroviral Tax oncoprotein
11.  The Value of Postoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Levels for the Early Detection of Gastric Cancer Recurrence after Curative Resection 
Journal of Gastric Cancer  2014;14(4):221-228.
This study aimed to evaluate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer recurrence.
Materials and Methods
We retrospectively reviewed 154 patients who developed recurrence within 2 years after curative gastric cancer surgery and analyzed the relationship between postoperative CEA and CA19-9 levels and recurrence. We readjusted the cut-off values to improve the detection of recurrence. Subgroup analysis according to clinicopathologic variables was performed to further investigate the relationship between recurrence and CEA and CA19-9 levels.
The sensitivity and specificity for elevated CEA levels to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9 were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of CEA was higher in patients with elevated preoperative CEA levels than in patients with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore, the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19-9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus 26.83%; P<0.001).
CEA and/or CA19-9 measurement with the readjusted cut-off values allows for more effective detection of gastric cancer recurrence.
PMCID: PMC4286900  PMID: 25580353
Stomach neoplasms; Tumor marker; Carcinoembryonic antigen; Carbohydrate antigen 19-9; Recurrence
12.  Unusual synchronous skeletal muscle and lung metastasis in papillary thyroid cancer: A case report and review of the literature 
Oncology Letters  2014;9(2):727-730.
Papillary thyroid cancer (PTC) frequently metastasizes to the cervical lymph region and less often to the lung and bone. Metastasis to the skeletal muscles from PTC is extremely rare, especially concurrent lung and skeletal muscle metastases. The present study reports the case of a 31-year-old man with synchronous metastasis to the skeletal muscle and lung from PTC, six years following total thyroidectomy and consecutive 131Iodine treatments. Magnetic resonance imaging (MRI) revealed a 1.7×1.2×1.5 cm mass in the left gastrocnemius muscle, indicating a neurogenic tumor. The mass was subsequently resected and confirmed via histopathology to be metastatic PTC. We propose that, in the follow-up of patients with PTC, the measurable serum thyroglobulin level, whole body scan and other imaging modalities including MRI or positron emission tomography/computed tomography, must be closely monitored for potential distant metastases, particularly in cases of PTC with aggressive pathological behavior.
PMCID: PMC4301470  PMID: 25621043
papillary thyroid cancer; skeletal muscle metastasis; lung metastasis
13.  Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy 
This study used a streptozotocin (STZ)-induced rat model of diabetes to investigate whether Ras-related C3 botulinum toxin substrate 1 (Rac1) was involved in the pathogenesis of diabetic retinopathy. The effects of Rac1 inhibition on vascular endothelial (VE)-cadherin and β-catenin expression in high glucose-induced rat retinal endothelial cells (RRECs) were additionally examined. Rac1 activation in the retinas from STZ-induced diabetic rats and in high glucose-induced RRECs was measured by reverse transcription-quantitative polymerase chain reaction analysis, immunohistochemistry and western blot analysis. The expression levels of VE-cadherin and β-catenin were also examined with or without Rac1 inhibition through small interfering (si)RNA transfection. STZ-induced diabetes was associated with an increase in the vascular permeability of the retina. Furthermore, Rac1 activation was increased in the retina of STZ-induced diabetic rats and in high glucose-induced RRECs compared with that in the controls. Immunohistochemistry showed that immunostaining of Rac1 was localized in the outer plexiform, inner nuclear, inner plexiform and ganglion cell layers and in the retinal microvasculature of rats. The expression of β-catenin was increased in the retinas of the diabetic rats at four, eight and 12 weeks after the induction of diabetes compared with that in the controls. Additionally, Rac1 activation was required for the high glucose-induced VE-cadherin expression decrease and for β-catenin expression in high glucose-induced RRECs. Rac1 inhibition by Rac1-siRNA transfection effectively prevented hyperpermeability, β-catenin expression and the VE-cadherin expression decrease in high glucose-induced RRECs. In conclusion, diabetes affects the expression of Rac1 in the retina. Rac1 may be involved in the diabetes-induced damage and/or alterations to the blood-retinal barrier through changes in VE-cadherin and β-catenin expression.
PMCID: PMC4247314  PMID: 25452781
Rac1; β-catenin; VE-cadherin; diabetes; retinopathy; rat; rat retinal endothelial cell
14.  Effects of Soluble Epoxide Hydrolase Deficiency on Acute Pancreatitis in Mice 
PLoS ONE  2014;9(11):e113019.
Acute pancreatitis (AP) is a frequent gastrointestinal disorder that causes significant morbidity, and its incidence has been progressively increasing. AP starts as a local inflammation in the pancreas that often leads to systemic inflammatory response and complications. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition in murine models has beneficial effects in inflammatory diseases, but its significance in AP remains unexplored.
Methodology/Principal Findings
To investigate whether sEH may have a causal role in AP we utilized Ephx2 knockout (KO) mice to determine the effects of sEH deficiency on cerulein- and arginine-induced AP. sEH expression increased at the protein and messenger RNA levels, as well as enzymatic activity in the early phase of cerulein- and arginine-induced AP in mice. In addition, amylase and lipase levels were lower in cerulein-treated Ephx2 KO mice compared with controls. Moreover, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B and IL-6 were lower in cerulein-treated Ephx2 KO mice compared with controls. Further, Ephx2 KO mice exhibited decreased cerulein- and arginine-induced NF-κB inflammatory response, MAPKs activation and decreased cell death. Conclusions -These findings demonstrate a novel role for sEH in the progression of cerulein- and arginine-induced AP.
PMCID: PMC4234494  PMID: 25402489
15.  Effect of cold adaptation on activities of relevant enzymes and antioxidant system in rats 
Exercise in cold environments can cause significant metabolic regulation and antioxidant behavior. For discussing enzymatic responses towards cold adaptation, we investigated enzyme activities of adenylate cyclase (AC) and phosphodiesterase (PDE) in liver, skeletal muscle, and brown adipose tissue (BAT), as well as Na+·K+ ATPase and Na+/K+ ratio in blood. Malondialdehyde (MDA) and superoxide dismutase (SOD) activity in blood were also studied to address the effect of cold adaptation on oxidative damage and antioxidant system. Experimental results indicated that enzyme activities in liver, skeletal muscle and BAT maintained relatively constant for the control group. For the cold adaptation group, enzyme activities in liver and skeletal muscle were in high levels at the beginning, and then gradually decreased to similar values with the control group. However, enzyme activities in BAT performed an increasing trend and significantly higher than the control at the end. In addition, decreased oxidative damage and activated antioxidant system was observed along with the cold adaptation process.
PMCID: PMC4276194  PMID: 25550936
Cold adaptation; adenylate cyclase; phosphodiesterase; Na+·K+ ATPase; malondialdehyde; superoxide dismutase
16.  Phase-controlled synthesis of α-NiS nanoparticles confined in carbon nanorods for High Performance Supercapacitors 
Scientific Reports  2014;4:7054.
A facile and phase-controlled synthesis of α-NiS nanoparticles (NPs) embedded in carbon nanorods (CRs) is reported by in-situ sulfurating the preformed Ni/CRs. The nanopore confinement by the carbon matrix is essential for the formation of α-NiS and preventing its transition to β-phase, which is in strong contrast to large aggregated β-NiS particles grown freely without the confinement of CRs. When used as electrochemical electrode, the hybrid electrochemical charge storage of the ultrasmall α-NiS nanoparticels dispersed in CRs is benefit for the high capacitor (1092, 946, 835, 740 F g−1 at current densities of 1, 2, 5, 10 A g−1, respectively.). While the high electrochemical stability (approximately 100% retention of specific capacitance after 2000 charge/discharge cycles) is attributed to the supercapacitor-battery electrode, which makes synergistic effect of capacitor (CRs) and battery (NiS NPs) components rather than a merely additive composite. This work not only suggests a general approach for phase-controlled synthesis of nickel sulfide but also opens the door to the rational design and fabrication of novel nickel-based/carbon hybrid supercapacitor-battery electrode materials.
PMCID: PMC4231331  PMID: 25394517
17.  Impact of losartan and angiotensin II on the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat vascular smooth muscle cells 
Molecular Medicine Reports  2014;11(3):1587-1594.
The present study aimed to investigate the impact of losartan and angiotensin II (AngII) on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), secreted by rat vascular smooth muscle cells (VSMCs). Rat VSMCs were isolated and cultured in different concentrations of AngII and losartan for 24 h and western blot analysis and quantitative polymerase chain reaction were performed to observe the subsequent impact on the gene and protein expression of MMP-9 and TIMP-1. AngII was shown to promote the protein and gene expression of MMP-9 in VSMCs in a concentration-dependent manner. No effect was observed on the expression of TIMP-1, therefore, an increase in the MMP-9/TIMP-1 ratio was observed. Losartan was shown to be able to inhibit MMP-9 protein and gene expression in a concentration-dependent manner, whilst promoting an increase in TIMP-1 expression, thus decreasing the ratio of MMP-9/TIMP-1. The combined action of losartan and AngII resulted in the same directional changes in MMP-9 and TIMP-1 expression as observed for losartan alone. The comparison of AngII, losartan and the combinatory effect on the expression of MMP-9 and TIMP-1 in VSMCs indicated that losartan inhibited the effects of AngII, therefore reducing the MMP-9/TIMP-1 ratio, which may contribute to the molecular mechanism of losartan in preventing atherosclerosis. In atherosclerosis, the development of the extracellular matrix of plaque is closely correlated with the evolution of AS. The balance between MMPs and TIMPs is important in maintaining the dynamic equilibrium between the ECM, and the renin-angiotensin-aldosterone system, which is involved in the pathologenesis of AS, and in which AngII has a central role.
PMCID: PMC4270314  PMID: 25405958
losartan; angiotensin II; vascular smooth muscle cells; matrix metalloproteinase-9; tissue inhibitor of metalloproteinase-1
18.  Evaluation of Reported Prostate Cancer Risk-Associated SNPs From Genome-Wide Association Studies of Various Racial Populations in Chinese Men 
The Prostate  2013;73(15):1623-1635.
Several genome-wide association studies (GWAS) of prostate cancer (PCa) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with PCa risk in various racial groups. The objective of this study is to evaluate which of these SNPs are associated with PCa risk in Chinese men and estimate their strength of association.
All SNPs that were reported to be associated with PCa risk in GWAS from populations of European, African American, Japanese, and Chinese descent were evaluated in 1,922 PCa cases and 2,175 controls selected from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). A logistic regression analysis was used to estimate allelic odds ratios (ORs) of these SNPs for PCa.
Among the 53 SNPs, 50 were polymorphic in the Chinese population. Of which, 10 and 24 SNPs were significantly associated with PCa risk in Chinese men at P < 0.001 and <0.05, respectively. These 24 significant SNPs included 17, 5, and 2 SNPs that were originally discovered in European, Japanese, and Chinese descent, respectively. The estimated ORs ranged from 1.10 to 1.49 and the direction of association was consistent with previous studies. When ORs were estimated separately for PCa with Gleason score ≤7 and ≥8, a marginally significant difference in ORs was found only for two of the 24 SNPs (P = 0.02 and 0.04).
About half of PCa risk-associated SNPs identified in GWAS of various populations are associated with PCa risk in Chinese men. Information on PCa risk-associated SNPs and their ORs may facilitate risk assessment of PCa risk in Chinese men.
PMCID: PMC3928594  PMID: 24038036
prostate cancer; SNPs; genome-wide association; Chinese
19.  Long Non-Coding RNAs: Critical Players in Hepatocellular Carcinoma 
Hepatocellular carcinoma (HCC) is a complex disease with multiple underlying pathogenic mechanisms caused by a variety of etiologic factors. Emerging evidence showed that long non-coding RNAs (lncRNAs), with size larger than 200 nucleotides (nt), play important roles in various types of cancer development and progression. In recent years, some dysregulated lncRNAs in HCC have been revealed and roles for several of them in HCC have been characterized. All these findings point to the potential of lncRNAs as prospective novel therapeutic targets in HCC. In this review, we summarize known dysregulated lncRNAs in HCC, and review potential biological roles and underlying molecular mechanisms of lncRNAs in HCC. Additionally, we discussed prospects of lncRNAs as potential biomarker and therapeutic target for HCC. In conclusion, this paper will help us gain better understanding of molecular mechanisms by which lncRNAs perform their function in HCC and also provide general strategies and directions for future research.
PMCID: PMC4264176  PMID: 25387074
long noncoding RNA; hepatocellular carcinoma; dysregulation; biological roles; molecular mechanism
20.  Cobalt Alleviates GA-Induced Programmed Cell Death in Wheat Aleurone Layers via the Regulation of H2O2 Production and Heme Oxygenase-1 Expression 
Heme oxygenase-1 (HO-1) and hydrogen peroxide (H2O2) are key signaling molecules that are produced in response to various environmental stimuli. Here, we demonstrate that cobalt is able to delay gibberellic acid (GA)-induced programmed cell death (PCD) in wheat aleurone layers. A similar response was observed when samples were pretreated with carbon monoxide (CO) or bilirubin (BR), two end-products of HO catalysis. We further observed that increased HO-1 expression played a role in the cobalt-induced alleviation of PCD. The application of HO-1-specific inhibitor, zinc protoporphyrin-IX (ZnPPIX), substantially prevented the increases of HO-1 activity and the alleviation of PCD triggered by cobalt. The stimulation of HO-1 expression, and alleviation of PCD might be caused by the initial H2O2 production induced by cobalt. qRT-PCR and enzymatic assays revealed that cobalt-induced gene expression and the corresponding activities of superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX), three enzymes that metabolize reactive oxygen species, were consistent with the H2O2 accumulation during GA treatment. These cobalt responses were differentially blocked by co-treatment with ZnPPIX. We therefore suggest that HO-1 functions in the cobalt-triggered alleviation of PCD in wheat aleurone layers, which is also dependent on the enhancement of the activities of antioxidant enzymes.
PMCID: PMC4264218  PMID: 25405743
aleurone layers; cobalt; heme oxygenase-1; H2O2; programmed cell death; Triticum aestivum
21.  CAMK2N1 inhibits prostate cancer progression through androgen receptor-dependent signaling 
Oncotarget  2014;5(21):10293-10306.
Castration resistance is a major obstacle to hormonal therapy for prostate cancer patients. Although androgen independence of prostate cancer growth is a known contributing factor to endocrine resistance, the mechanism of androgen receptor deregulation in endocrine resistance is still poorly understood. Herein, the CAMK2N1 was shown to contribute to the human prostate cancer cell growth and survival through AR-dependent signaling. Reduced expression of CAMK2N1 was correlated to recurrence-free survival of prostate cancer patients with high levels of AR expression in their tumor. CAMK2N1 and AR signaling form an auto-regulatory negative feedback loop: CAMK2N1 expression was down-regulated by AR activation; while CAMK2N1 inhibited AR expression and transactivation through CAMKII and AKT pathways. Knockdown of CAMK2N1 in prostate cancer cells alleviated Casodex inhibition of cell growth, while re-expression of CAMK2N1 in castration-resistant cells sensitized the cells to Casodex treatment. Taken together, our findings suggest that CAMK2N1 plays a tumor suppressive role and serves as a crucial determinant of the resistance of prostate cancer to endocrine therapies.
PMCID: PMC4279373  PMID: 25296973
CAMK2N1; Androgen receptor (AR); prostate cancer; tumor suppressor
22.  Cassava genome from a wild ancestor to cultivated varieties 
Nature Communications  2014;5:5110.
Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology.
Cassava is a major source of food in tropical and subtropical regions. Here the authors sequence the genomes of wild and domesticated cassava varieties and identify genes that have been selected for and against during the evolution and domestication of this economically important crop.
PMCID: PMC4214410  PMID: 25300236
23.  Biliary stenting with or without sphincterotomy for malignant biliary obstruction: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(38):14033-14039.
AIM: To investigate the benefits of endoscopic sphincterotomy (EST) before stent placement by meta-analysis of randomized controlled trials (RCTs).
METHODS: PubMed, EMBASE, Cochrane Library, and Science Citation Index databases up to March 2014 were searched. The primary outcome was incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and successful stent insertion rate. The secondary outcomes were the incidence of post-ERCP bleeding, stent migration and occlusion. The free software Review Manager was used to perform the meta-analysis.
RESULTS: Three studies (n = 338 patients, 170 in the EST group and 168 in the non-EST group) were included. All three studies described a comparison of baseline patient characteristics and showed that there were no statistically significant differences between the two groups. Three RCTs, including 338 patients, were included in this meta-analysis. Most of the analyzed outcomes were similar between the groups. Although EST reduced the incidence of PEP, it also led to a higher incidence of post-ERCP bleeding (OR = 0.34, 95%CI: 0.12-0.93, P = 0.04; OR = 9.70, 95%CI: 1.21-77.75, P = 0.03, respectively).
CONCLUSION: EST before stent placement may be useful in reducing the incidence of PEP. However, EST-related complications, such as bleeding and perforation, may offset this effect.
PMCID: PMC4194589  PMID: 25320543
Biliary stent; Endoscopic sphincterotomy; Endoscopic retrograde cholangiopancreatography; Malignant biliary obstruction
24.  Draft Genome Sequence of Antagonistic Agent Lysobacter antibioticus 13-6 
Genome Announcements  2014;2(5):e00566-14.
Lysobacter antibioticus 13-6, isolated from the roots of Chinese cabbage, effectively controls the pathogens Plasmodiophora brassicae, Xanthomonas oryzae pv. oryzicola, X. oryzae pv. oryzae, Xanthomonas axonopodis pv. dieffenbachiae, and Pseudomonas syringae pv. tabaci. We report the first draft genome sequence of the L. antibioticus species in China.
PMCID: PMC4192370  PMID: 25301638
25.  Single-Molecule Study of Proteins by Biological Nanopore Sensors 
Sensors (Basel, Switzerland)  2014;14(10):18211-18222.
Nanopore technology has been developed for detecting properties of proteins through monitoring of ionic current modulations as protein passes via a nanosize pore. As a real-time, sensitive, selective and stable technology, biological nanopores are of widespread concern. Here, we introduce the background of nanopore researches in the area of α-hemolysin (α-HL) nanopores in protein conformation detections and protein–ligand interactions. Moreover, several original biological nanopores are also introduced with various features and functions.
PMCID: PMC4239869  PMID: 25268917
α-hemolysin; protein conformation; protein-ligand interactions; new nanopores

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