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1.  One-stage posterior-only approach in surgical treatment of single-segment thoracic spinal tuberculosis with neurological deficits in adults: a retrospective study of 34 cases 
There are quite a few controversies on the surgical management of single-segment thoracic spinal tuberculosis with neurological deficits (STSTND). In this study, the clinical efficacy and feasibility of one-stage posterior-only transpedicular debridement, interbody fusion, and posterior instrumentation for treating STSTND in adults were retrospectively evaluated.
Thirty-four cases with STSTND underwent one-stage posterior-only transpedicular debridement, interbody fusion and posterior instrumentation at the same institution from January 2003 to January 2013. Follow-up time was 34.4 ± 10.2 months (range, 18–48 months), and kyphosis angle was 34.1 ± 12.3°. The American Spinal Injury Association (ASIA) classification of spinal cord injury was employed to evaluate neurological deficits, while visual analogue scale (VAS) was employed to assess the degree of pain. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the activity of tuberculosis (TB).
All 34 patients with spinal tuberculosis (ST) were completely cured, and there was no recurrence of TB. Postoperative kyphosis angle was 8.2 ± 1.8°, and there was no significant loss of correction during the final follow-up. Solid fusion was achieved and pain was relieved in all cases. Neurological condition in all patients improved after surgery.
One-stage posterior-only transpedicular debridement, interbody fusion, and posterior fixation followed by chemotherapy seems to be adequate for obtaining satisfactory healing of single-segment thoracic spinal tuberculosis with neurological deficits. Careful patient selection is critical to the successful outcome with this technique.
PMCID: PMC4526180  PMID: 26242404
Spinal tuberculosis; Single-segment; Neurological deficits; Posterior-only approach; Thoracic
2.  Activation of GTP hydrolysis in mRNA-tRNA translocation by elongation factor G 
Science advances  2015;1(4):e1500169.
During protein synthesis, elongation of the polypeptide chain by each amino acid is followed by a translocation step in which mRNA and transfer RNA (tRNA) are advanced by one codon. This crucial step is catalyzed by elongation factor G (EF-G), a guanosine triphosphatase (GTPase), and accompanied by a rotation between the two ribosomal subunits. A mutant of EF-G, H91A, renders the factor impaired in guanosine triphosphate (GTP) hydrolysis and thereby stabilizes it on the ribosome. We use cryogenic electron microscopy (cryo-EM) at near-atomic resolution to investigate two complexes formed by EF-G H91A in its GTP state with the ribosome, distinguished by the presence or absence of the intersubunit rotation. Comparison of these two structures argues in favor of a direct role of the conserved histidine in the switch II loop of EF-G in GTPase activation, and explains why GTP hydrolysis cannot proceed with EF-G bound to the unrotated form of the ribosome.
PMCID: PMC4517844
3.  Comparison of three surgical approaches for cervicothoracic spinal tuberculosis: a retrospective case–control study 
Study design
This is a retrospective case–control study.
The surgical approaches to cervicothoracic spinal tuberculosis (CTSTB) were controversial. The aim of this research is to retrospectively compare the efficacy and feasibility of anterior-only (AO) approach, combined anterior and posterior (AP) surgeries, and posterior-only (PO) approach for the treatment of CTSTB.
AO approach was undertaken in 20 patients (group A), AP fusion was carried out in 18 patients (group B), and PO surgery was performed in 21 patients (group C). Surgery duration, intraoperative blood loss, length of hospitalization, neurological status, kyphosis angle correction, loss of correction, and complications of the three groups were compared.
Three surgical approaches all improved the kyphosis deformity and neurological function significantly (P < 0.05). The mean loss of correction in group A in the final follow-up was higher than in groups B and C (P < 0.05), and the difference between groups B and C was not significant (P > 0.05). The mean operation time, blood loss, and hospitalization days in group B were greater than in groups A and C. Complications were most prevalent in group A, more in group B, and the least in group C.
The AO approach surgery should be limitedly used for severe CTSTB. The AP approach had got satisfactory clinical and radiographic outcomes, but with larger trauma and more complications, which should be reservedly performed for mild CTSTB. Compared to traditional surgery, PO surgery can significantly improve clinical results and obviously relieve postoperative complications.
PMCID: PMC4490609  PMID: 26135121
Tuberculosis; Cervicothoracic; Surgery; Three approaches; Complication; Outcome
4.  Acute Interstitial Nephritis Following Multiple Asian Giant Hornet Stings 
Patient: Male, 42
Final Diagnosis: Acute interstitial nephritis
Symptoms: Difficulty breathing • headache • numbness • oliguria
Medication: Methylprednisolone
Clinical Procedure: Plasma exchange
Specialty: Nephrology
Rare disease
The Asian giant hornet is the largest wasp species in the world. Its stings can cause acute interstitial nephritis and acute renal failure. From July to October, 2013, Asian giant hornet attacks have killed 42 people and injured 1675 people with their powerful venomous stings in Hanzhong, Ankang, and Shangluo, three cities in the southern part of Shaanxi Province, China.
Case Report:
We report here a case of a 42-year-old man with acute interstitial nephritis following multiple Asian giant hornet stings. On admission, the patient had difficulty breathing, headache, and numbness in both limbs (arm and leg). He was treated in the Emergency Department and Department of Nephrology with plasma exchange and dialysis within 24 hours after being stung. A kidney biopsy revealed acute interstitial nephritis with interstitial infiltrations of eosinophils and lymphocytes. After intensive treatment, his liver function recovered within 10 days. Along with oral methylprednisolone, his renal function recovered 1 month later.
This case shows that acute interstitial nephritis happens several days after being stung. Since the number of deaths in southern Shaanxi province is much higher than other places, our report draws the attention of fellow clinicians to the acute interstitial nephritis following multiple Asian giant hornet stings.
PMCID: PMC4479185  PMID: 26076055
Acute Kidney Injury; Methylprednisolone; Wasp Venoms
5.  The preparation of core/shell structured microsphere of multi first-line anti-tuberculosis drugs and evaluation of biological safety 
To introduce a modified method, namely coaxial electrohydrodynamic atomization for the fabrication of distinct core/shell structured microspheres of four first-line ant-tuberculosis drugs with different characteristics in hydrophilic properties in one single step. In group B, we prepared microspheres in which the core and the shell contain hydrophobic and hydrophilic drugs, respectively. In contrast, in group C, the opposite is prepared. The detection of encapsulation efficiency and in vitro release test were performed to confirm the feasibility of the drug-loaded core/shell structured microspheres. Moreover, cell culture experiments and animal experiments have been carried out to evaluate the biological safety of different microspheres in cell growth, cell viability, osteogenesis and migration of BMSCs in vitro and the bone fusion in a bone deficits model in SD rat. Meanwhile, the distribution of drugs and liver and kidney toxicity were monitored. The release patterns of the two groups are significantly different. The release of drugs from Group B microspheres is rather sequential, whereas group C microspheres release drugs in a parallel (co-release) manner. And various concentrations of carrier materials produces core/shell structured microspheres with different appearance. Moreover, the biological safety of core/shell structured microspheres was testified to be satisfactory. These findings present the advantages and possible application of this kind of multi-drug release system in treating skeletal tuberculosis. Moreover, the characteristic sequential release of multi-drugs can be controlled and adjusted based on treatment need and used in treating other disorders.
PMCID: PMC4538136  PMID: 26309493
Core/shell structure; microspheres; multi drugs; co-release; ant-tuberculosis drugs
6.  Clarithromycin and dexamethasone show similar anti-inflammatory effects on distinct phenotypic chronic rhinosinusitis: an explant model study 
BMC Immunology  2015;16:37.
Phenotype of chronic rhinosinusitis (CRS) may be an important determining factor of the efficacy of anti-inflammatory treatments. Although both glucocorticoids and macrolide antibiotics have been recommended for the treatment of CRS, whether they have different anti-inflammatory functions for distinct phenotypic CRS has not been completely understood. The aim of this study is to compare the anti-inflammatory effects of clarithromycin and dexamethasone on sinonasal mucosal explants from different phenotypic CRS ex vivo.
Ethmoid mucosal tissues from CRSsNP patients (n = 15), and polyp tissues from eosinophilic (n = 13) and non-eosinophilic (n = 12) CRSwNP patients were cultured in an ex vivo explant model with or without dexamethasone or clarithromycin treatment for 24 h. After culture, the production and/or expression of anti-inflammatory molecules, epithelial-derived cytokines, pro-inflammatory cytokines, T helper (Th)1, Th2 and Th17 cytokines, chemokines, dendritic cell relevant markers, pattern recognition receptors (PRRs), and tissue remodeling factors were detected in tissue explants or culture supernatants by RT-PCR or ELISA, respectively.
We found that both clarithromycin and dexamethasone up-regulated the production of anti-inflammatory mediators (Clara cell 10-kDa protein and interleukin (IL)-10), whereas down-regulated the production of Th2 response and eosinophilia promoting molecules (thymic stromal lymphopoietin, IL-25, IL-33, CD80, CD86, OX40 ligand, programmed cell death ligand 1, CCL17, CCL22, CCL11, CCL5, IL-5, IL-13, and eosinophilic cationic protein) and Th1 response and neutrophilia promoting molecules (CXCL8, CXCL5, CXCL10, CXCL9, interferon-γ, and IL-12), from sinonasal mucosa from distinct phenotypic CRS. In contrast, they had no effect on IL-17A production. The expression of PRRs (Toll-like receptors and melanoma differentiation-associated gene 5) was induced, and the production of tissue remodeling factors (transforming growth factor-β1, epidermal growth factor, basic fibroblast growth factor, platelet derived growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9) was suppressed, in different phenotypic CRS by dexamethasone and clarithromycin in comparable extent.
Out of our expectation, our explant model study discovered herein that glucocorticoids and macrolides likely exerted similar regulatory actions on CRS and most of their effects did not vary by the phenotypes of CRS.
PMCID: PMC4456709  PMID: 26047816
Chronic rhinosinusitis; Nasal polyps; Clarithromycin; Dexamethasone; Eosinophil; Inflammation; Tissue remodeling; Innate immunity
7.  Ultrasound-Targeted Microbubble Destruction Improves the Migration and Homing of Mesenchymal Stem Cells after Myocardial Infarction by Upregulating SDF-1/CXCR4: A Pilot Study 
Stem Cells International  2015;2015:691310.
Mesenchymal stem cell (MSC) therapy shows considerable promise for the treatment of myocardial infarction (MI). However, the inefficient migration and homing of MSCs after systemic infusion have limited their therapeutic applications. Ultrasound-targeted microbubble destruction (UTMD) has proven to be promising to improve the homing of MSCs to the ischemic myocardium, but the concrete mechanism remains unclear. We hypothesize that UTMD promotes MSC homing by upregulating SDF-1/CXCR4, and this study was aimed at exploring this potential mechanism. We analyzed SDF-1/CXCR4 expression after UTMD treatment in vitro and in vivo and counted the number of homing MSCs in MI areas. The in vitro results demonstrated that UTMD not only led to elevated secretion of SDF-1 but also resulted in an increased proportion of MSCs that expressed surface CXCR4. The in vivo findings show an increase in the number of homing MSCs and higher expression of SDF-1/CXCR4 in the UTMD combined with MSCs infusion group compared to other groups. In conclusion, UTMD can increase SDF-1 expression in the ischemic myocardium and upregulate the expression of surface CXCR4 on MSCs, which provides a molecular mechanism for the homing of MSCs assisted by UTMD via SDF-1/CXCR4 axis.
PMCID: PMC4436519  PMID: 26074977
8.  Increased local IgE production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps 
Eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) display distinct patterns of inflammation. However, the pathogenic mechanisms underlying the heterogeneity of CRSwNP need further investigation.
To investigate local immunoglobulin E (IgE) production and phenotype of mast cells in eosinophilic and non-eosinophilic CRSwNP in Chinese.
Total and specific IgE levels were analyzed by means of the ImmunoCAP system. The molecular steps involved in class switch recombination to IgE were investigated using RT-PCR assays. Mast cell phenotypes, IgE- and high affinity IgE receptor (FcεRI)-positive cells, and allergen binding to specific IgE in sinonasal mucosa were determined by means of immunohistochemistry.
Compared with controls and non-eosinophilic CRSwNP, local total IgE levels were increased, and local specific IgE to common aeroallergens was more frequently found, in Chinese eosinophilic CRSwNP independent of atopy and without significant association with Staphylococcus aureus enterotoxins. The ε germline gene transcript was also more frequently detected in eosinophilic CRSwNP. The number of IgE- and FcεRI-positive cells was increased in eosinophilic CRSwNP. Most IgE- and FcεRI-positive cells were mast cells. Dust mite antigens could bind to IgE on mast cells in situ. The number of mast cells positive for both tryptase and chymase and activated mast cells was increased in eosinophilic CRSwNP and the number of activated mast cells positively correlated with local IgE level, eotaxin-1 level, and eosinophil count in CRSwNP.
Conclusions and Clinical Relevance
The local IgE induced by common aeroallergens may mediate mast cell activation and contribute to subsequent eosinophilic inflammation in Chinese CRSwNP. This study offers a rationale for considering intervention strategies designed to target “local allergy” in eosinophilic CRSwNP.
PMCID: PMC4013492  PMID: 24597471
Chronic rhinosinusitis; nasal polyps; mast cell; eosinophil; immunoglobulin E
9.  Length Quantization of DNA Partially Expelled from Heads of a Bacteriophage T3 Mutant 
Virology  2014;0:157-170.
DNA packaging of phages phi29, T3 and T7 sometimes produces incompletely packaged DNA with quantized lengths, based on gel electrophoretic band formation. We discover here a packaging ATPase-free, in vitro model for packaged DNA length quantization. We use directed evolution to isolate a five-site T3 point mutant that hyper-produces tail-free capsids with mature DNA (heads). Three tail gene mutations, but no head gene mutations, are present. A variable-length DNA segment leaks from some mutant heads, based on DNase I-protection assay and electron microscopy. The protected DNA segment has quantized lengths, based on restriction endonuclease analysis: six sharp bands of DNA missing 3.7–12.3% of the last end packaged. Native gel electrophoresis confirms quantized DNA expulsion and, after removal of external DNA, provides evidence that capsid radius is the quantization-ruler. Capsid-based DNA length quantization possibly evolved via selection for stalling that provides time for feedback control during DNA packaging and injection.
PMCID: PMC4044629  PMID: 24889235
Agarose gel electrophoresis; native; Bacteriophage assembly; Capsid structure; DNA packaging; Mutant phenotype; Ultracentrifugation
10.  Colorectal cancer stem cell and chemoresistant colorectal cancer cell phenotypes and increased sensitivity to Notch pathway inhibitor 
Molecular Medicine Reports  2015;12(2):2417-2424.
Colorectal cancer stem cells (Co-CSCs) are a small subpopulation of tumor cells which have been proposed to be tumor-initiating cells in colorectal cancer (CRC) and to be implicated in resistance to standard chemotherapy. Chemoresistance is a common problem in the clinic. However, the interrelation between Co-CSCs and chemoresistant cells has yet to be elucidated. The present study investigated the Co-CSC phenotype in colonospheres and chemoresistant CRC cell lines and aimed to identify targets for therapy. Colonospheres and chemoresistant CRC cells were found to be enriched with the CSC markers CD133 and CD44, and exhibited similar phenotypes. Furthermore, it was found that Notch signaling may simultaneously regulate Co-CSCs and chemoresistant cells and may represent a novel strategy for targeting this pathway in CRC.
PMCID: PMC4464415  PMID: 25936357
colorectal cancer; cancer stem cells; chemoresistant cells; Notch pathway; CD133/CD44
11.  Long-term trends and seasonality of omphalocele during 1996–2010 in China: a retrospective analysis based on the hospital-based birth defects surveillance system 
Little is known about secular trends and seasonal variation in the birth prevalence of omphalocele in China. This study aimed to explore the long-term trends and seasonality of this birth defect, to provide insight into the etiology and prevention of omphalocele.
A retrospective analysis of all births with omphalocele (1322 cases in 8.8 million births) registered in the hospital-based Chinese Birth Defects Monitoring Network between January 1996 and September 2010. Negative binomial cyclical regression models were used to analyze the long-term trends and seasonal fluctuations of omphalocele occurrence in the southern and northern regions and urban and rural areas of China.
The total prevalence of omphalocele was 1.50 cases (95% confidence interval (CI): 1.42–1.58) per 10,000 births. There was no significant secular trend of omphalocele occurrence in China between 1996 and 2010. The observed prevalence of omphalocele in rural areas was 2.03–2.54 cases per 10,000 births between May and August, which was higher than that observed in other months. The highest prevalence of births with omphalocele in rural areas occurred at the end of June; on average, the prevalence of omphalocele at that time point increased by 20% (95% CI: 6–35%) compared with other months.
There were no long-term trends found for occurrence of omphalocele in China between 1996 and 2010; however, seasonality was observed for omphalocele in women living in rural areas. These results may help generate hypotheses for further study of environmental factors that vary by season.
PMCID: PMC4456719  PMID: 25909955
Omphalocele; Birth prevalence, Secular trend, Seasonality; Negative binomial cyclical regression model
12.  Integrative chemical biology approaches to examine ‘erasers’ for protein lysine fatty-acylation 
Protein fatty-acylation is important for the regulation of membrane association, trafficking, subcellular localization and activity of many cellular proteins. While significant progress has been made on our understanding of the two major forms of protein fatty-acylation, N-myristoylation and S-palmitoylation, studies of fatty-acylation of protein lysine residues have lagged behind. This is in large part due to a lack of knowledge about the enzymes that regulate the addition and removal of lysine fatty-acylation. To fill this knowledge gap, here we demonstrate the use of integrative chemical biology approaches to examine human sirtuins as a de-fatty-acylase in vitro and in cells. We used a photo-cross-linking-based chemical approach to investigate enzymes that recognize lysine fatty-acylation. This approach enables the identification of human Sirt2 as a robust lysine de-fatty-acylase in vitro. Using a bioorthogonal chemical reporter for protein fatty-acylation, we show that Sirt2 can regulate protein lysine fatty-acylation in cells. This finding not only opens a new avenue to investigate the biological significances of protein lysine fatty-acylation, but also may help to unravel unrecognized cellular functions of Sirt2 that has been considered solely as a deacetylase until now. Furthermore, the photo-cross-linking-based chemical approach used in this study should also be useful to examine the interactions between other protein posttranslational modifications and their ‘erasers’.
PMCID: PMC4382910  PMID: 25476551
posttranslational modifications; photo-cross-linking; bioorthogonal reaction; chemical reporter; fatty-acylation
13.  Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1 
Ovarian cancer is the fourth most ordinary cause of cancer-related deaths in women. In recent, combination chemotherapy with carboplatin and docetaxel was developed as first-line drug to treat ovarian carcinoma. However, the detailed molecular mechanism, which accounts for the cells to apoptosis induced by administration of carboplatin and docetaxel, was unrecognized. In present study, we provide the mechanistic link between mixture of carboplatin plus docetaxel and its anticancer activity. Primarily, a majority of 30 cancer-related long non-coding RNA (lncRNA) showed differential alteration in carboplatin-docetaxel-treated 3AO cells. Among six up-regulating lncRNAs, we screened out carboplatin-docetaxel-induced lncRNA PVT1 which may be a central downstream target of carboplatin plus docetaxel because expression of PVT1 positively correlates with anticancer action of carboplatin plus docetaxel. Besides, p53 and tissue inhibitor of matrix metalloproteinases-1 (TIMP1) were mediated by lncRNA PVT1, which may explain partially the anticancer activity of lncRNA PVT1. Collectively, we have identified a potential mechanism by which PVT1 regulated by carboplatin plus docetaxel contributes to the carboplatin-docetaxel-induced anticancer action in ovarian cancer. These discoveries also give proof of the potential of PVT1 as significant downstream targets for therapeutic intervention in ovarian cancer.
PMCID: PMC4466949  PMID: 26097562
Ovarian cancer; lncRNA PVT1; carboplatin; docetaxel; p53
14.  Crystal and EM Structures of Human Phosphoribosyl Pyrophosphate Synthase I (PRS1) Provide Novel Insights into the Disease-Associated Mutations 
PLoS ONE  2015;10(3):e0120304.
Human PRS1, which is indispensable for the biosynthesis of nucleotides, deoxynucleotides and their derivatives, is associated directly with multiple human diseases because of single base mutation. However, a molecular understanding of the effect of these mutations is hampered by the lack of understanding of its catalytic mechanism. Here, we reconstruct the 3D EM structure of the PRS1 apo state. Together with the native stain EM structures of AMPNPP, AMPNPP and R5P, ADP and the apo states with distinct conformations, we suggest the hexamer is the enzymatically active form. Based on crystal structures, sequence analysis, mutagenesis, enzyme kinetics assays, and MD simulations, we reveal the conserved substrates binding motifs and make further analysis of all pathogenic mutants.
PMCID: PMC4363470  PMID: 25781187
15.  An iron-based green approach to 1-h production of single-layer graphene oxide 
Nature Communications  2015;6:5716.
As a reliable and scalable precursor of graphene, graphene oxide (GO) is of great importance. However, the environmentally hazardous heavy metals and poisonous gases, explosion risk and long reaction times involved in the current synthesis methods of GO increase the production costs and hinder its real applications. Here we report an iron-based green strategy for the production of single-layer GO in 1 h. Using the strong oxidant K2FeO4, our approach not only avoids the introduction of polluting heavy metals and toxic gases in preparation and products but also enables the recycling of sulphuric acid, eliminating pollution. Our dried GO powder is highly soluble in water, in which it forms liquid crystals capable of being processed into macroscopic graphene fibres, films and aerogels. This green, safe, highly efficient and ultralow-cost approach paves the way to large-scale commercial applications of graphene.
Oxidants currently used in the preparation of graphene oxide (GO) require long reaction times, relatively high temperatures and costly waste treatment. Here, the authors propose the use of a strong green oxidant, K2FeO4, establishing a fast, safe, toxicity-free route to GO production.
PMCID: PMC4354147  PMID: 25607686
16.  Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis 
BioMed Research International  2015;2015:903720.
Sepsis, the leading cause of mortality in intensive care unit, is characterized by hyperinflammatory response in the early stage and followed by a period of immunosuppression. This immune disorder is believed to be the potent factor that is tightly associated with high mortality in sepsis. Dendritic cells (DCs) serve as professional antigen-presenting cells that play a vital role in immune response by activating T lymphocytes. During the progression of sepsis, DCs have been reported to take part in the aberrant immune response and be necessary for survival. Therefore, a better understanding of the DCs pathology will be undoubtedly beneficial for resolving the problems occurring in sepsis. This review discusses effects of sepsis on DCs number and function, including surface molecules expression, cytokines secretion, and T cell activation, and the underlying mechanism as well as some potential therapeutic strategies.
PMCID: PMC4363672  PMID: 25821827
17.  YY1 suppresses FEN1 over-expression and drug resistance in breast cancer 
BMC Cancer  2015;15:50.
Drug resistance is a major challenge in cancer therapeutics. Abundant evidence indicates that DNA repair systems are enhanced after repetitive chemotherapeutic treatments, rendering cancers cells drug-resistant. Flap endonuclease 1 (FEN1) plays critical roles in DNA replication and repair and in counteracting replication stress, which is a key mechanism for many chemotherapeutic drugs to kill cancer cells. FEN1 was previously shown to be upregulated in response to DNA damaging agents. However, it is unclear about the transcription factors that regulate FEN1 expression in human cancer. More importantly, it is unknown whether up-regulation of FEN1 has an adverse impact on the prognosis of chemotherapeutic treatments of human cancers.
To reveal regulation mechanism of FEN1 expression, we search and identify FEN1 transcription factors or repressors and investigate their function on FEN1 expression by using a combination of biochemical, molecular, and cellular approaches. Furthermore, to gain insights into the impact of FEN1 levels on the response of human cancer to therapeutic treatments, we determine FEN1 levels in human breast cancer specimens and correlate them to the response to treatments and the survivorship of corresponding breast cancer patients.
We observe that FEN1 is significantly up-regulated upon treatment of chemotherapeutic drugs such as mitomycin C (MMC) and Taxol in breast cancer cells. We identify that the transcription factor/repressor YY1 binds to the FEN1 promoter and suppresses the expression of FEN1 gene. In response to the drug treatments, YY1 is dissociated from the FEN1 promoter region leading over-expression of FEN1. Overexpression of YY1 in the cells results in down-regulation of FEN1 and sensitization of the cancer cells to MMC or taxol. Furthermore, we observe that the level of FEN1 is inversely correlated with cancer drug and radiation resistance and with survivorship in breast cancer patients.
Altogether, our current data indicate that YY1 is a transcription repressor of FEN1 regulating FEN1 levels in response to DNA damaging agents. FEN1 is up-regulated in human breast cancer and its levels inversely correlated with cancer drug and radiation resistance and with survivorship in breast cancer patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12885-015-1043-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4348373  PMID: 25885449
Flap endonuclease 1 (FEN1); YY1; Over-expression; Promoter; Drug resistance
18.  Predictors of Percutaneous Catheter Drainage (PCD) after Abdominal Paracentesis Drainage (APD) in Patients with Moderately Severe or Severe Acute Pancreatitis along with Fluid Collections 
PLoS ONE  2015;10(2):e0115348.
Although we previously demonstrated abdominal paracentesis drainage (APD) preceding percutaneous catheter drainage (PCD) as the central step for treating patients with moderately severe (MSAP) or severe acute pancreatitis (SAP), the predictors leading to PCD after APD have not been studied.
Consecutive patients with MSAP or SAP were recruited between June 2011 and June 2013. As a step-up approach, all patients initially received medical management, later underwent ultrasound-guided APD before PCD, if necessary, followed by endoscopic necrosectomy through the path formed by PCD. APD primarily targeted fluid in the abdominal or pelvic cavities, whereas PCD aimed at (peri)pancreatic fluid.
Of the 92 enrolled patients, 40 were managed with APD alone and 52 received PCD after APD (14 required necrosectomy after initial PCD). The overall mortality was 6.5%. Univariate analysis showed that among the 20 selected parameters, 13 factors significantly affected PCD intervention after APD. Multivariate analysis revealed that infected (peri)pancreatic collections (P = -0.001), maximum extent of necrosis of more than 30% of the pancreas (P = -0.024), size of the largest necrotic peri(pancreatic) collection (P = -0.007), and reduction of (peri)pancreatic fluid collections by <50% after APD (P = -0.008) were all independent predictors of PCD.
Infected (peri)pancreatic collections, a largest necrotic peri(pancreatic) collection of more than 100 ml, and reduction of (peri)pancreatic fluid collections by <50% after APD could effectively predict the need for PCD in the early course of the disease.
PMCID: PMC4319763  PMID: 25659143
19.  Nephroblastoma overexpressed gene (NOV) enhances RCC cell motility through upregulation of ICAM-1 and COX-2 expression via Akt pathway 
Renal cell carcinoma (RCC) carries a high risk of malignancy and metastasis. The inducible isoform of prostaglandin synthase, cyclooxygenase (COX)-2, and ICAM-1 may be involved in tumor metastasis. CCN3, also called nephroblastoma overexpressed gene (NOV), has been found to regulate the proliferation and differentiation of cancer cells. The effects of NOV on RCC cell migration and expression of COX-2 and ICAM-1 have not described yet in detail. But here, NOV was found to promote the migration and expression of COX-2 and ICAM-1 in human RCC cells. Akt inhibitor was found to interfere with this NOV-induced migration and up-regulation of COX-2 and ICAM-1 in RCC cells. NOV stimulation was here found to promote the phosphorylation of Akt. RCC tissue chips were subjected to IHC staining, which showed COX-2 expression in RCC tissues to be a significantly closely correlated with NOV expression, with significance determined using Pearson correlation testing (P < 0.05). The results of the current work indicate that NOV activates COX-2 and ICAM-1 through Akt, promoting the migration of RCC cells.
PMCID: PMC4396272  PMID: 25973014
NOV; renal cell carcinoma; cell motility; COX-2; ICAM-1; akt pathway
20.  Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer 
Purpose: Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa. Methods: Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens. Results: Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020). Conclusions: Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.
PMCID: PMC4396295  PMID: 25973080
C-MYC; ERG; prostate cancer; TMPRSS2-ERG; immunohistochemistry
21.  Applied anatomical study of the vascularized ulnar nerve and its blood supply for cubital tunnel syndrome at the elbow region 
Neural Regeneration Research  2015;10(1):141-145.
Cubital tunnel syndrome is often accompanied by paresthesia in ulnar nerve sites and hand muscle atrophy. When muscle weakness occurs, or after failure of more conservative treatments, anterior transposition is used. In the present study, the ulnar nerve and its blood vessels were examined in the elbows of 18 adult cadavers, and the external diameter of the nutrient vessels of the ulnar nerve at the point of origin, the distances between the origin of the vessels and the medial epicondyle of the humerus, and the length of the vessels accompanying the ulnar nerve in the superior ulnar collateral artery, the inferior ulnar collateral artery, and the posterior ulnar recurrent artery were measured. Anterior transposition of the vascularized ulnar nerve was performed to treat cubital tunnel syndrome. The most appropriate distance that the vascularized ulnar nerve can be moved to the subcutaneous tissue under tension-free conditions was 1.8 ± 0.6 cm (1.1–2.5 cm), which can be used as a reference value during the treatment of cubital tunnel syndrome with anterior transposition of the vascularized ulnar nerve.
PMCID: PMC4357098  PMID: 25788935
nerve regeneration; ulnar nerve; blood supply; compressive neuropathy; cubital tunnel syndrome; superior ulnar collateral artery; inferior ulnar collateral artery; posterior ulnar recurrent artery; anterior transposition; neural regeneration
22.  Using the Plasmon Linewidth to Calculate the Time and Efficiency of Electron Transfer between Gold Nanorods and Graphene 
ACS nano  2013;7(12):11209-11217.
We present a quantitative analysis of the electron transfer between single gold nanorods and monolayer graphene under no electrical bias. Using single particle dark-field scattering and photoluminescence spectroscopy to access the homogenous linewidth, we observe broadening of the surface plasmon resonance for gold nanorods on graphene compared to nanorods on a quartz substrate. Because of the absence of spectral plasmon shifts, dielectric interactions between the gold nanorods and graphene are not important and we instead assign the plasmon damping to charge transfer between plasmon-generated hot electrons and the graphene that acts as an efficient acceptor. Analysis of the plasmon linewidth yields an average electron transfer time of 160 ± 30 fs, which is otherwise difficult to measure directly in the time domain with single particle sensitivity. In comparison to intrinsic hot electron decay and radiative relaxation, we furthermore calculate from the plasmon linewidth that charge transfer between the gold nanorods and the graphene support occurs with an efficiency of ~ 10%. Our results are important for future applications of light harvesting with metal nanoparticle plasmons and efficient hot electron acceptors as well as for understanding hot electron transfer in plasmon-assisted chemical reactions.
PMCID: PMC3932108  PMID: 24266755
Plasmon damping; hot electrons; one-photon photoluminescence; single particle spectroscopy; surface plasmon resonance; graphene; plasmon linewidth
23.  Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats 
Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1) via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MBSDF-1 destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.
PMCID: PMC4263441  PMID: 25516709
mesenchymal stem cell; ultrasound; microbubbles; homing; stromal cell-derived factor-1; diabetic nephropathy
24.  Formation of quantum spin Hall state on Si surface and energy gap scaling with strength of spin orbit coupling 
Scientific Reports  2014;4:7102.
For potential applications in spintronics and quantum computing, it is desirable to place a quantum spin Hall insulator [i.e., a 2D topological insulator (TI)] on a substrate while maintaining a large energy gap. Here, we demonstrate a unique approach to create the large-gap 2D TI state on a semiconductor surface, based on first-principles calculations and effective Hamiltonian analysis. We show that when heavy elements with strong spin orbit coupling (SOC) such as Bi and Pb atoms are deposited on a patterned H-Si(111) surface into a hexagonal lattice, they exhibit a 2D TI state with a large energy gap of ≥0.5 eV. The TI state arises from an intriguing substrate orbital filtering effect that selects a suitable orbital composition around the Fermi level, so that the system can be matched onto a four-band effective model Hamiltonian. Furthermore, it is found that within this model, the SOC gap does not increase monotonically with the increasing strength of SOC. These interesting results may shed new light in future design and fabrication of large-gap topological quantum states.
PMCID: PMC4236754  PMID: 25407432
25.  Peroxisome Proliferator-Activated Receptor γ Deficiency in T Cells Accelerates Chronic Rejection by Influencing the Differentiation of CD4+ T Cells and Alternatively Activated Macrophages 
PLoS ONE  2014;9(11):e112953.
In a previous study, activation of the peroxisome proliferator–activated receptor γ (PPARγ) inhibited chronic cardiac rejection. However, because of the complexity of chronic rejection and the fact that PPARγ is widely expressed in immune cells, the mechanism of the PPARγ - induced protective effect was unclear.
Materials and Methods
A chronic rejection model was established using B6.C-H-2bm12KhEg (H-2bm12) mice as donors, and MHC II-mismatched T-cell-specific PPARγ knockout mice or wild type (WT) littermates as recipients. The allograft lesion was assessed by histology and immunohistochemistry. T cells infiltrates in the allograft were isolated, and cytokines and subpopulations were detected using cytokine arrays and flow cytometry. Transcription levels in the allograft were measured by RT-PCR. In vitro, the T cell subset differentiation was investigated after culture in various polarizing conditions. PPARγ-deficient regularory T cells (Treg) were cocultured with monocytes to test their ability to induce alternatively activated macrophages (AAM).
T cell-specific PPARγ knockout recipients displayed reduced cardiac allograft survival and an increased degree of pathology compared with WT littermates. T cell-specific PPARγ knockout resulted in more CD4+ T cells infiltrating into the allograft and altered the Th1/Th2 and Th17/Treg ratios. The polarization of AAM was also reduced by PPARγ deficiency in T cells through the action of Th2 and Treg. PPARγ-deficient T cells eliminated the pioglitazone-induced polarization of AAM and reduced allograft survival.
PPARγ-deficient T cells influenced the T cell subset and AAM polarization in chronic allograft rejection. The mechanism of PPARγ activation in transplantation tolerance could yield a novel treatment without side effects.
PMCID: PMC4226585  PMID: 25383620

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