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1.  Emergence of Genotype I of Japanese Encephalitis Virus as the Dominant Genotype in Asia ▿  
Journal of Virology  2011;85(19):9847-9853.
Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis worldwide. Previous phylogenetic studies based on the envelope protein indicated that there are four genotypes, and surveillance data suggest that genotype I is gradually replacing genotype III as the dominant strain. Here we report an evolutionary analysis based on 98 full-length genome sequences of JEV, including 67 new samples isolated from humans, pigs, mosquitoes, midges. and bats in affected areas. To investigate the relationships between the genotypes and the significance of genotype I in recent epidemics, we estimated evolutionary rates, ages of common ancestors, and population demographics. Our results indicate that the genotypes diverged in the order IV, III, II, and I and that the genetic diversity of genotype III has decreased rapidly while that of genotype I has increased gradually, consistent with its emergence as the dominant genotype.
PMCID: PMC3196406  PMID: 21697481
2.  Electroacupuncture activates enteric glial cells and protects the gut barrier in hemorrhaged rats 
AIM: To investigate whether electroacupuncture ST36 activates enteric glial cells, and alleviates gut inflammation and barrier dysfunction following hemorrhagic shock.
METHODS: Sprague-Dawley rats were subjected to approximately 45% total blood loss and randomly divided into seven groups: (1) sham: cannulation, but no hemorrhage; (2) subjected to hemorrhagic shock (HS); (3) electroacupuncture (EA) ST36 after hemorrhage; (4) vagotomy (VGX)/EA: VGX before hemorrhage, then EA ST36; (5) VGX: VGX before hemorrhage; (6) α-bungarotoxin (BGT)/EA: intraperitoneal injection of α-BGT before hemorrhage, then EA ST36; and (7) α-BGT group: α-BGT injection before hemorrhage. Morphological changes in enteric glial cells (EGCs) were observed by immunofluorescence, and glial fibrillary acidic protein (GFAP; a protein marker of enteric glial activation) was evaluated using reverse transcriptase polymerase chain reaction and western blot analysis. Intestinal cytokine levels, gut permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran, and the expression and distribution of tight junction protein zona occludens (ZO)-1 were also determined.
RESULTS: EGCs were distorted following hemorrhage and showed morphological abnormalities. EA ST36 attenuated the morphological changes in EGCs at 6 h, as compared with the VGX, α-BGT and HS groups. EA ST36 increased GFAP expression to a greater degree than in the other groups. EA ST36 decreased intestinal permeability to FITC-dextran (760.5 ± 96.43 ng/mL vs 2466.7 ± 131.60 ng/mL, P < 0.05) and preserved ZO-1 protein expression and localization at 6 h after hemorrhage compared with the HS group. However, abdominal VGX and α-BGT treatment weakened or eliminated the effects of EA ST36. EA ST36 reduced tumor necrosis factor-α levels in intestinal homogenates after blood loss, while vagotomy or intraperitoneal injection of α-BGT before EA ST36 abolished its anti-inflammatory effects.
CONCLUSION: EA ST36 attenuates hemorrhage-induced intestinal inflammatory insult, and protects the intestinal barrier integrity, partly via activation of EGCs.
PMCID: PMC4316089  PMID: 25663766
Hemorrhagic shock; Electroacupuncture; ST36; Cytokines; Intestinal barrier; Enteric glial cells
3.  The multifaceted role of CD146/MCAM in the promotion of melanoma progression 
Human malignant melanoma is a common primary malignant cutaneous tumour derived from transformed epidermal melanocytes. Patients with melanoma have a high rate of mortality due to resistance to chemotherapeutic drugs, a major obstacle to a successful treatment. Several reports have suggested that CD146 plays an important role as a signalling molecule in human melanoma. This role includes CD146 as a participant in inflammation, differentiation, adhesion, tumourigenicity, metastasis, invasion and angiogenesis among other processes, which suggests that this molecule promotes the progression of human melanoma as a multifaceted regulator. In this article, we explore the effects and corresponding mechanisms with respect to the role of CD146/MUC18 in the promotion of human melanoma progression. Collectively, the studies indicated that targeting CD146, because it is a suitable marker of poor patient outcome, might be useful in the design of future strategies for the prevention and treatment of human melanoma.
PMCID: PMC4326486
CD146/MCAM; Melanoma; Structure; Mechanism; Metastasis; Angiogenesis
5.  The glycosyltransferase involved in thurandacin biosynthesis catalyzes both O- and S-glycosylation 
The S-glycosyltransferase SunS is a recently discovered enzyme that selectively catalyzes the conjugation of carbohydrates to the cysteine thiol of proteins. This study reports the discovery of a second S-glycosyltransferase, ThuS, and shows that ThuS catalyzes both S-glycosylation of the thiol of cysteine and O-glycosylation of the hydroxyl group of serine in peptide substrates. ThuS-catalyzed S-glycosylation is more efficient than O-glycosylation and the enzyme demonstrates high tolerance with respect to both nucleotide sugars and peptide substrates. The biosynthesis of the putative products of the thuS gene cluster were reconstituted in vitro and the resulting S-glycosylated peptides thurandacin A and thurandacin B exhibit highly selective antimicrobial activity towards Bacillus thuringiensis.
PMCID: PMC3913795  PMID: 24325644
6.  The simulated microgravity enhances multipotential differentiation capacity of bone marrow mesenchymal stem cells 
Cytotechnology  2013;66(1):119-131.
Multi-differentiation capability is an essential characteristic of bone marrow mesenchymal stem cells (BMSCs). Method on obtaining higher-quality stem cells with an improved differentiation potential has gained significant attention for the treatment of clinical diseases and developmental biology. In our study, we investigated the multipotential differentiation capacity of BMSCs under simulated microgravity (SMG) condition. F-actin staining found that cytoskeleton took on a time-dependent change under SMG condition, which caused spindle to round morphological change of the cultured cells. Quantitative PCR and Western Blotting showed the pluripotency marker OCT4 was up-regulated in the SMG condition especially after SMG of 72 h, which we observed would be the most appropriate SMG duration for enhancing pluripotency of BMSCs. After dividing BMSCs into normal gravity (NG) group and SMG group, we induced them respectively in endothelium oriented, adipogenic and neuronal induction media. Immunostaining and Western Blotting found that endothelium oriented differentiated BMSCs expressed higher VWF and CD31 in the SMG group than in the NG group. The neuron-like cells derived from BMSCs in the SMG group also expressed higher level of MAP2 and NF-H. Furthermore, the quantity of induced adipocytes increased in the SMG group compared to the NG group shown by Oil Red O staining, The expression of PPARγ2 increased significantly under SMG condition. Therefore, we demonstrated that SMG could promote BMSCs to differentiate into many kinds of cells and predicted that enhanced multi-potential differentiation capacity response in BMSCs following SMG might be relevant to the changes of cytoskeleton and the stem cell marker OCT4.
Electronic supplementary material
The online version of this article (doi:10.1007/s10616-013-9544-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3886541  PMID: 23579245
Simulated microgravity; Bone marrow mesenchymal stem cells; Pluripotency; Differentiation; OCT4
7.  Fitting magnetic field gradient with Heisenberg-scaling accuracy 
Scientific Reports  2014;4:7390.
The linear function is possibly the simplest and the most used relation appearing in various areas of our world. A linear relation can be generally determined by the least square linear fitting (LSLF) method using several measured quantities depending on variables. This happens for such as detecting the gradient of a magnetic field. Here, we propose a quantum fitting scheme to estimate the magnetic field gradient with N-atom spins preparing in W state. Our scheme combines the quantum multi-parameter estimation and the least square linear fitting method to achieve the quantum Cramér-Rao bound (QCRB). We show that the estimated quantity achieves the Heisenberg-scaling accuracy. Our scheme of quantum metrology combined with data fitting provides a new method in fast high precision measurements.
PMCID: PMC4260217  PMID: 25487218
8.  Adult hepatic cavernous hemangioma with highly elevated α-fetoprotein: A case report and review of the literature 
Oncology Letters  2014;9(2):637-640.
A 47-year-old male presented with a six-month history of fatigue and a four-month history of alanine and aspartate aminopherase elevation. Laboratory examination revealed that the serum α-fetoprotein (AFP) level was 371.51 μg/l (normal range, 0–20 μg/l), and a computed tomography scan revealed a hypodense lesion in the left hepatic lobe. During laparotomy, a dark red-colored soft tumor (1.5×1.7 cm in diameter) was found in segment eight of the liver. Intra-operative pathology and post-operative histopathology examinations revealed that the tumor was a hepatic cavernous hemangioma. The serum AFP level was decreased to 24.45 μg/l by the second post-operative week. The literature was searched and only three similar cases were found. A brief review of this rare disease entity was produced, which attempted to explain this appearance reasonably.
PMCID: PMC4301549  PMID: 25624892
hepatic cavernous hemangioma; α-fetoprotein; cancer stem cell
9.  Myeloid Sarcoma: A Rare Case of an Orbital Mass Mimicking Orbital Pseudotumor Requiring Neurosurgical Intervention 
Objective. A rare case of myeloid sarcoma (MS), previously referred to as granulocytic sarcoma or chloroma, is presented. Representing a unique form of acute myeloid leukemia (AML), MS may rarely occur in adults. Even rarer, MS may occur as the initial presentation of AML. Methods. We report a singular and illustrative case of an orbital pseudotumor mimicking mass in a 65-year-old male as the initial presentation of AML. Results. Neurosurgical intervention was required to establish the definitive diagnosis via right modified orbitofrontozygomatic craniotomy as well as to decompress the optic canal, superior orbital fissure, and orbit. Conclusion. Postoperatively, he reported decreased pain and improvement of his vision. Further examination revealed decreased proptosis and improved extraocular mobility. Pathological findings demonstrated MS. We review the literature and discuss the neurosurgical relevance of MS as the initial presentation of AML.
PMCID: PMC4247931  PMID: 25478260
10.  Regional Principal Color Based Saliency Detection 
PLoS ONE  2014;9(11):e112475.
Saliency detection is widely used in many visual applications like image segmentation, object recognition and classification. In this paper, we will introduce a new method to detect salient objects in natural images. The approach is based on a regional principal color contrast modal, which incorporates low-level and medium-level visual cues. The method allows a simple computation of color features and two categories of spatial relationships to a saliency map, achieving higher F-measure rates. At the same time, we present an interpolation approach to evaluate resulting curves, and analyze parameters selection. Our method enables the effective computation of arbitrary resolution images. Experimental results on a saliency database show that our approach produces high quality saliency maps and performs favorably against ten saliency detection algorithms.
PMCID: PMC4224509  PMID: 25379960
11.  Regulation of NADPH-dependent Nitric Oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive NADPH analogue 
Oncotarget  2014;5(21):10650-10664.
Nitric Oxide (NO) and Reactive oxygen species (ROS) are endogenous regulators of angiogenesis-related events as endothelial cell proliferation and survival, but NO/ROS defect or unbalance contribute to cancers. We recently designed a novel photoactive inhibitor of NO-Synthases (NOS) called NS1, which binds their NADPH site in vitro. Here, we show that NS1 inhibited NO formed in aortic rings. NS1-induced NO decrease led to an inhibition of angiogenesis in a model of VEGF-induced endothelial tubes formation. Beside this effect, NS1 reduced ROS levels in endothelial and melanoma A375 cells and in aorta. In metastatic melanoma cells, NS1 first induced a strong decrease of VEGF and blocked melanoma cell cycle at G2/M. NS1 decreased NOX4 and ROS levels that could lead to a specific proliferation arrest and cell death. In contrast, NS1 did not perturb melanocytes growth.
Altogether, NS1 revealed a possible cross-talk between eNOS- and NOX4 –associated pathways in melanoma cells via VEGF, Erk and Akt modulation by NS1 that could be targeted to stop proliferation. NS1 thus constitutes a promising tool that modulates NO and redox stresses by targeting and directly inhibiting eNOS and, at least indirectly, NADPH oxidase(s), with great potential to control angiogenesis.
PMCID: PMC4279400  PMID: 25296975
Cellular signaling; Angiogenesis; NADPH analogue; cell proliferation; ROS; melanoma; endothelium
12.  Intraoperative systemic lidocaine inhibits the expression of HMGB1 in patients undergoing radical hysterectomy 
Surgery stressors trigger inflammatory response and excessive inflammatory response leads to organ failure or even septic shock. HMGB1 as a later inflammatory cytokines and a critical mediator of severe sepsis is always associated with the aggravation of organ failure. Previous study shows that lidocaine can inhibit the expression of HMGB1 in macrophage of septic rats and protect animals from organ failure. The present study sought to determine whether intraoperative systemic lidocaine could attenuate the level of HMGB1 by inhibiting it expression in PBMC from patients underwent radical hysterectomy. Thirty patients were recruited and divided randomly into two groups according to the difference of study medicine. Patients in lidocaine group received an intravenous bolus infusion of 1.5 mg/kg of lidocaine followed by a continuous infusion of 1.5 mg/kg/h till discharged from operating room, and those in the control group received normal saline. Peripheral blood sample was drawn at pre-surgery, discharge from operating room and 48 h post-surgery. Monocytes were isolated and cultured with medium alone or with LPS. HMGB1 protein in serum or in supernatant of PBMC was detected with ELISA, while the HMGB1 mRNA in PBMC was determined by real-time quantitative PCR. The result showed that lidocaine not only attenuated the level of HMGB1 protein in serum and supernatant, but inhibited the transcription of HMGB1 mRAN in PBMC. The present study of us demonstrated that intraoperative systemic lidocaine can attenuate the level of HMGB1 and inhibit its expression in PBMC from patients underwent radical hysterectomy. Therefore, lidocaine may play an important role in many other clinical diseases by inhibiting HMGB1.
PMCID: PMC4238473  PMID: 25419374
High mobility group box1; lidocaine; monocytes; gynecologic oncology
13.  Key changes in denervated muscles and their impact on regeneration and reinnervation 
Neural Regeneration Research  2014;9(20):1796-1809.
The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle's residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.
PMCID: PMC4239769  PMID: 25422641
nerve regeneration; denervation; reinnervation; fibrillation potential; muscle fiber conduction velocity; muscle fiber diameter; maximal isometric force; neuromuscular junction; gene expression; neural regeneration
14.  Local mechanical properties of white matter structures in the human brain 
NeuroImage  2013;79:145-152.
The noninvasive measurement of the mechanical properties of brain tissue using magnetic resonance elastography (MRE) has emerged as a promising method for investigating neurological disorders. To date, brain MRE investigations have been limited to reporting global mechanical properties, though quantification of the stiffness of specific structures in the white matter architecture may be valuable in assessing the localized effects of disease. This paper reports the mechanical properties of the corpus callosum and corona radiata measured in healthy volunteers using MRE and atlas-based segmentation. Both structures were found to be significantly stiffer than overall white matter, with the corpus callosum exhibiting greater stiffness and less viscous damping than the corona radiata. Reliability of both local and global measures was assessed through repeated experiments, and the coefficient of variation for each measure was less than 10%. Mechanical properties within the corpus callosum and corona radiata demonstrated correlations with measures from diffusion tensor imaging pertaining to axonal microstructure.
PMCID: PMC3676712  PMID: 23644001
elastography; brain; white matter; corpus callosum; microstructure
15.  Big effects of small RNAs on legume root biotic interactions 
Genome Biology  2014;15(9):475.
Comprehensive profiling of microRNAs (miRNAs) from the legume Medicago truncatula reveals the organization of miRNA-based regulatory modules in root biotic interactions.
PMCID: PMC4318186  PMID: 25315222
16.  HIF-1α Signaling Activation by Post-Ischemia Treatment with Astragaloside IV Attenuates Myocardial Ischemia-Reperfusion Injury 
PLoS ONE  2014;9(9):e107832.
In this study, we evaluated the effect of astragaloside IV (Ast IV) post-ischemia treatment on myocardial ischemia-reperfusion (IR) injury (IRI). We also examined whether hypoxia inducible factor-1α (HIF-1α) and its downstream gene-inducible nitric oxide (NO) synthase (iNOS) play roles in the cardioprotective effect of Ast IV. Cultured cardiomyocytes and perfused isolated rat hearts were exposed to Ast IV during reperfusion in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2). The post-ischemia treatment with Ast IV protected cardiomyocytes from the apoptosis and death induced by simulated IRI (SIRI). Additionally, in cardiomyocytes, 2-MeOE2 and HIF-1α siRNA treatment each not only abolished the anti-apoptotic effect of post-ischemia treatment with Ast IV but also reversed the upregulation of HIF-1α and iNOS expression. Furthermore, after treatment with Ast IV, post-ischemic cardiac functional recovery and lactate dehydrogenase (LDH) release in the coronary flow (CF) were improved, and the myocardial infarct size was decreased. Moreover, the number of apoptotic cells was reduced, and the upregulation of the anti-apoptotic protein Bcl2 and downregulation of the pro-apoptotic protein Caspase3 were reversed. 2-MeOE2 reversed these effects of Ast IV on IR-injured hearts. These results suggest that post-ischemia treatment with Ast IV can attenuate IRI by upregulating HIF-1α expression, which transmits a survival signal to the myocardium.
PMCID: PMC4169594  PMID: 25238237
17.  Determination of production regions for pollution-free Chinese medicinal materials by geographic information system: Achyranthes bidentata (Niu Qi) in Tianjin as an example  
Chinese Medicine  2014;9:25.
The land and ecology suitability for producing pollution-free Chinese medicinal materials should be evaluated based on Geographic Information System (GIS). This study aims to determine production regions for pollution-free Achyranthes bidentata in Tianjin as a case to illustrate the workflow based on GIS.
The slopes, land usage, residential areas and roads were selected to evaluate the land suitability, to avoid the potential pollution sources. The ecology suitability evaluation was performed based on the soil type and nine climate factors, such as active accumulated temperature, mean January temperature, mean July temperature, the lowest temperature in January, the highest temperature in July, mean annual temperature, sunshine duration, relative humidity, annual precipitation, affecting the natural growth of A. bidentata.
The best production regions for pollution-free A. bidentata in Tianjin, with a total area of approximately 575 km2, were found in Jinghai County, Ninghe County, Wuqing District, and Dagang District.
This study illustrated a workflow based on GIS for determining the production regions in Tianjin for pollution-free A. bidentata.
PMCID: PMC4177713  PMID: 25342961
18.  Neurenteric Cyst of the Area Postrema 
Neurenteric cysts are CNS lesions most frequently occurring in the spinal cord. Intracranial neurenteric cysts are rarer, typically presenting with headache, mass effect, or location-specific symptoms. The area postrema is known as the emetic center of the brain; lesions can cause nausea and vomiting. Our case, featuring a neurenteric cyst of the area postrema, illustrates the importance of considering a neurological etiology for nonspecific symptoms that otherwise elude explanation. Our patient presented with acute decompensated hydrocephalus upon exploratory abdominal laparoscopy for unresolving abdominal pain. The patient had an eight-month history of unexplained intermittent nausea, vomiting, and abdominal pain. These bouts increased in frequency during the weeks before acute presentation, prompting exploratory abdominal laparoscopy. The acute decompensation was managed by ventriculostomy, and cranial MRI revealed a cystic mass by the floor of the fourth ventricle. After the patient stabilized and returned to neurological baseline, suboccipital craniectomy and resection were performed. The mass was histologically identified as a neurenteric cyst. The patient was free from neurological complaints at one-year follow-up, indicating that the successful resection of the area postrema-associated neurenteric cyst resolved her previous symptoms. Thus, some intracranial lesions can masquerade as nonspecific symptoms, presenting a challenge to accurate diagnosis.
PMCID: PMC4181999  PMID: 25317345
19.  Suppression of inflammatory response by flurbiprofen following focal cerebral ischemia involves the NF-κB signaling pathway 
Some studies of animal models of middle cerebral artery occlusion indicate that inflammation plays a key role in the pathogenesis of cerebral ischemia and secondary damage. Flurbiprofen has been suggested to alleviate cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanisms underlying the protective action are still incompletely understood. In this study we want to investigate the protective effect of flurbiprofen after transient middle cerebral artery occlusion (MCAO) in rats and the role of the NF-κB signaling pathway on this neuroprotective effect. Male Wistar rats were subjected to transient middle cerebral artery occlusion for 2 h, followed by 24 h reperfusion. Flurbiprofen was administrated via tail-vein injection at the onset of reperfusion. HE staining and Immunohistochemistry were carried out to detect the morphological changes in ischemic penumbra cortex. The expression of inflammatory cytokines genes (IL-1β, IL-6 and TNF-α) and the levels of p-NF-κB (p65) in ischemic penumbra cortex were measured by RT-PCR and western blot. Administration of flurbiprofen at the doses of 5 mg/kg and 10 mg/kg significantly attenuated cerebral ischemia/reperfusion injury, as shown by a reduction in the morphological changes and inhibition of pro-inflammatory cytokine expression in ischemic penumbra cortex. Moreover, our findings further demonstrated that the inhibition of NF-κB activity was involved in the neuroprotective effect of flurbiprofen on inflammatory responses. Flurbiprofen protects against cerebral injury by reducing expression of inflammatory cytokines genes and this effect may be partly due to the inhibition of NF-κB signaling pathway.
PMCID: PMC4211836  PMID: 25356186
Flurbiprofen; focal cerebral ischemia; inflammation; nuclear factor-κB
20.  Downregulation of leaf flavin content induces early flowering and photoperiod gene expression in Arabidopsis 
BMC Plant Biology  2014;14(1):237.
Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), essential cofactors for many metabolic enzymes that catalyze a variety of biochemical reactions. Previously we showed that free flavin (riboflavin, FMN, and FAD) concentrations were decreased in leaves of transgenic Arabidopsis plants expressing a turtle riboflavin-binding protein (RfBP). Here, we report that flavin downregulation by RfBP induces the early flowering phenotype and enhances expression of floral promoting photoperiod genes.
Early flowering was a serendipitous phenomenon and was prudently characterized as a constant phenotype of RfBP-expressing transgenic Arabidopsis plants in both long days and short days. The phenotype was eliminated when leaf free flavins were brought back to the steady-state levels either by the RfBP gene silencing and consequently nullified production of the RfBP protein, or by external riboflavin feeding treatment. RfBP-induced early flowering was correlated with enhanced expression of floral promoting photoperiod genes and the florigen gene FT in leaves but not related to genes assigned to vernalization, autonomous, and gibberellin pathways, which provide flowering regulation mechanisms alternative to the photoperiod. RfBP-induced early flowering was further correlated with increased expression of the FD gene encoding bZIP transcription factor FD essential for flowering time control and the floral meristem identity gene AP1 in the shoot apex. By contrast, the expression of FT and photoperiod genes in leaves and the expression of FD and AP1 in the shoot apex were no longer enhanced when the RfBP gene was silenced, RfBP protein production canceled, and flavin concentrations were elevated to the steady-state levels inside plant leaves.
Token together, our results provide circumstantial evidence that downregulation of leaf flavin content by RfBP induces early flowering and coincident enhancements of genes that promote flowering through the photoperiod pathway.
Electronic supplementary material
The online version of this article (doi:10.1186/s12870-014-0237-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4172855  PMID: 25201173
21.  A Novel Role of CDX1 in Embryonic Epicardial Development 
PLoS ONE  2014;9(7):e103271.
The molecular mechanism that regulates epicardial development has yet to be understood. In this study, we explored the function of CDX1, a Caudal-related family member, in epicardial epithelial-to-mesenchymal transition (EMT) and in the migration and the differentiation of epicardium-derived progenitors into vascular smooth muscle cells. We detected a transient expression of CDX1 in murine embryonic hearts at 11.5 days post coitum (dpc). Using a doxycycline-inducible CDX1 mouse model, primary epicardium, and ex vivo heart culture, we further demonstrated that ectopic expression of CDX1 promoted epicardial EMT. In addition, a low-dose CDX1 induction led to enhanced migration and differentiation of epicardium-derived cells into α-SMA+ vascular smooth muscles. In contrast, either continued high-level induction of CDX1 or CDX1 deficiency attenuated the ability of epicardium-derived cells to migrate and to mature into smooth muscles induced by TGF-β1. Further RNA-seq analyses showed that CDX1 induction altered the transcript levels of genes involved in neuronal development, angiogenesis, and cell adhesions required for EMT. Our data have revealed a previously undefined role of CDX1 during epicardial development, and suggest that transient expression of CDX1 promotes epicardial EMT, whereas subsequent down-regulation of CDX1 after 11.5 dpc in mice is necessary for further subepicardial invasion of EPDCs and contribution to coronary vascular endothelium or smooth muscle cells.
PMCID: PMC4113346  PMID: 25068460
22.  Malignant melanoma of the vagina: A case report and review of the literature 
Oncology Letters  2014;8(4):1585-1588.
Primary malignant melanoma of the vagina is an extremely rare variant of melanoma that accounts for <3% of all vaginal malignancies. Primary malignant melanoma of the vagina has a worse prognosis as compared with non-genital melanomas or other vaginal malignant neoplasms. A-35-year-old female had a diagnosis of primary malignant melanoma of the vagina. A local excision of the tumor was first performed, followed by a radical excision as a further therapeutic measure. The patient returned after three weeks, presenting with a vesico-vaginal fistula. A conservative operation was subsequently performed in order to improve the quality of life of the patient. Pelvic metastases were identified 6 months after the completion of the last surgical therapy and subsequent follow-up examinations were performed in another hospital. The present case study describes the clinical features and surgical procedures of this patient with primary malignant melanoma of the vagina. In conclusion, melanoma of the vagina is an extremely aggressive cancer and the overall prognosis is poor despite the various treatment options.
PMCID: PMC4156219  PMID: 25202372
malignant melanoma; vagina
23.  Nodal involvement by marginal zone B-cell lymphoma harboring t(14;22)(q32;q11) involving immunoglobulin heavy chain and light chain lambda as the sole karyotypically recognizable abnormality in a patient with systemic lupus erythematosus 
Recurrent non-random balanced chromosomal translocation, usually involving the immunoglobulin heavy chain (IgH) gene or an immunoglobulin light chain gene and a proto-oncogene, which results in the overexpression of the latter under the control of an enhancer or promoter of the former, is a hallmark of many types of non-Hodgkin lymphoma (NHL) of B-cell origin. However, translocations between IgH and the immunoglobulin (Ig) light chain lambda gene (IgL), namely, a t(14;22)(q32;q11), have rarely been described in B-cell NHL. Herein we report the first case of marginal zone B-cell lymphoma harboring a t(14;22)(q32;q11) as its sole genetic abnormality in a patient with a 12-year history of systemic lupus erythematosus (SLE). Other interesting findings of this case include: 1) the neoplastic B-cells lack expression of both surface and cytoplasmic Ig light chain as revealed by flow cytometry and 2) monoclonal rearrangement of Ig light chain kappa (IgK) only due to k-deleting element (kde) recombination event. This case illustrates the necessity of utilizing a multi-modality approach in the diagnosis of B-cell NHL.
PMCID: PMC4152091  PMID: 25197401
t(14;22)(q32;q11); K-deleting element; marginal zone B-cell lymphoma; systemic lupus erythematosus
24.  Size evolution of ion beam synthesized Pb nanoparticles in Al 
Nanoscale Research Letters  2014;9(1):346.
The size evolution of Pb nanoparticles (NPs) synthesized by ion implantation in an epitaxial Al film has been experimentally investigated. The average radius R of Pb NPs was determined as a function of implantation fluence f. The R(f) data were analyzed using various growth models. Our observations suggest that the size evolution of Pb NPs is controlled by the diffusion-limited growth kinetics (R2∝f). With increasing implantation current density, the diffusion coefficient of Pb atoms in Al is evident to be enhanced. By a comparative analysis of the R(f) data, values of the diffusion coefficient of Pb in Al were obtained.
PMCID: PMC4112978  PMID: 25114640
Ion implantation; Pb nanoparticles; Size evolution
25.  Fat Accumulation in the Liver of Obese Rats is Alleviated by Soy Protein Isolate through β-catenin signaling 
Obesity (Silver Spring, Md.)  2013;22(1):151-158.
The current study aim to investigate the effects of SPI on Wnt/β-catenin signaling in the liver of obese rats, as well as the roles of this pathway in regulating the hepatic fat accumulation.
Design and Methods
Obese and lean Zucker rats were fed diets containing either casein or SPI as protein source for 17 weeks. Histology and biochemical analysis, real-time PCR, Western blot, immunostaining, short interfering RNA assay were performed for liver samples.
Our study showed that fat content was significantly lowered in the liver of SPI-fed obese rats, accompanied by a reduction in hepatocellular vacuolation, compared to the casein-fed control. β-catenin protein level in the liver of obese rats was down-regulated compared to the lean group, indicating that the obese genotype exhibits an overall reduction in Wnt signaling. Importantly the repression of β-catenin in the obese rats was alleviated by feeding the SPI diet. siRNA treatment in rat hepatoma cells confirmed that silencing of β-catenin exacerbated fatty acid-induced fat accumulation, which implicated an important function of Wnt/β-catenin signaling in hepaticfat metabolism.
SPI intake restored β-catenin signaling and alleviated hepatic fat accumulation and liver damage in the obese rats.
PMCID: PMC3690171  PMID: 23512909
diet; hepatic fat; β-catenin signaling; SPI; obese Zucker rat

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