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1.  Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells 
Cancer Cell International  2015;15(1):12.
Background
Malignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest.
Methods
The anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student’s t-test was used to compare differences between treated groups and their controls.
Results
We found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice.
Coclusions
In summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.
doi:10.1186/s12935-015-0160-x
PMCID: PMC4326453
Glioma cells; Schisandrin B; Proliferation; Cell cycle; Apoptosis
2.  Sagittal spinopelvic alignment in adolescent thoracic scoliosis secondary to Chiari I malformation: a comparison between the left and the right curves 
European Spine Journal  2013;23(1):226-233.
Purpose
To investigate whether the sagittal morphology differs between the left and right thoracic curves in patients with Chiari malformation-associated scoliosis (CMS).
Methods
Thirty-four patients with a left thoracic curve constituted the CM-L group, whereas 44 patients with a right thoracic curve were assigned into the CM-R group. Another cohort of 90 age- and gender-matched asymptomatic adolescents was enrolled to serve as the control group. Seven sagittal parameters were evaluated on standing lateral radiographs, including thoracic kyphosis (TK), lumbar lordosis (LL), thoracolumbar junctional kyphosis (TJK), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS).
Results
Compared to the normal controls, the TK, LL and SS were significantly greater in the CM-L group, along with a significantly decreased PT. Similar changes in SS and PT were also demonstrated in the CM-R group, while the TK and LL were found to be relatively normal compared with the control group. Concerning CMS patients with different curve directions, significantly increased TK and LL were observed in the CM-L group, whereas all three pelvic parameters were similar for the two groups. In addition, no significant differences were noted between the three groups in PI, TJK or SVA. Moreover, the LL was strongly related to the TK and SS in all three groups, but to the PI only in the control and CM-R groups. A significant correlation was also noted between TK and SS in the CM-L group.
Conclusions
Significant differences in sagittal profiles indeed exist between CMS patients and healthy adolescents, as well as between CMS patients with different curve directions. In CMI patients with a left thoracic curve, compensatory alterations appear to occur in LL in response to the increased TK to maintain a balanced posture.
doi:10.1007/s00586-013-2980-5
PMCID: PMC3897820  PMID: 24026168
Chiari I malformation; Scoliosis; Curve direction; Sagittal spinopelvic alignment; Sagittal balance
3.  Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells 
Molecular Medicine Reports  2014;11(3):1647-1654.
Breast cancer is the most common type of malignancy among females. Previous studies examining breast cancer tissue have demonstrated the presence of stem cells, and have detected octamer-binding protein 4 (Oct4) and Nanog transcription factor expression. In the present study, breast cancer stem cells (CSCs) were isolated and enriched from MDA-MB-231 breast cancer cell lines, and were defined as MDA-MB-231 stem cells using flow cytometry. The expression of Oct4 and Nanog in breast CSCs were detected by quantitative polymerase chain reaction and western blotting. RNA interference (RNAi) was used in order to downregulate the expression of Oct4 and Nanog. Drug resistance and tumor-initiating capability following in vivo injection of MDA-MB-231 stem cells transduced with negative RNAi, Oct4 RNAi and Nanog RNAi were compared with that of MDA-MB-231 stem cells without siRNA transfection as a control group. In addition the capability of MDA-MB-231 breast cancer cells to initiate tumor formation in mice was compared with that of MDA-MB-231 stem cells. A paclitaxel inhibition test was also conducted in order to detect resistance of MDA-MB-231 breast cancer stem cells to this treatment. The MDA-MB-231 stem cells were revealed to exhibit elevated percentages of the cluster of differentiation (CD)44+CD24−/low subset, high tumorigenicity and resistance to chemotherapy, all of which are characteristic stem cell properties. In addition, the MDA-MB-231 stem cells were more tumorigenic in vivo. Furthermore, the breast CSCs also expressed high levels of the Oct4 and Nanog transcription factors. Therefore, downregulation of Oct4 or Nanog expression may reduce chemotherapeutic drug resistance and tumorigenicity in breast CSCs. In conclusion, Oct4 and Nanog expression may be a key factor in the development of resistance to chemotherapy and tumor growth of breast CSCs. This finding indicates that Oct4 or Nanog-targeted therapy may be a promising means of overcoming resistance to chemotherapy and inhibiting tumor growth in breast cancer treatment.
doi:10.3892/mmr.2014.2972
PMCID: PMC4270319  PMID: 25405855
breast cancer stem cells; isolation and identification; octamer-binding protein 4; Nanog; tumorigenicity; drug resistance
4.  The clinical effects of dendritic cell vaccines combined with cytokine-induced killer cells intraperitoneal injected on patients with malignant ascites 
Malignant ascites (MA) is a pathological condition due to a variety of primary abdominal and extra-abdominal neoplasms. It is a primary cause of morbidity and presents many difficulties in evaluation and treatment. In this study we used dendritic cell vaccines combined with cytokine-induced killer (CIK) cells intraperitoneal injected in patients with MA, and evaluated the safety and efficacy of this treatment. The results showed that the percentage of CD3+ CD56+ CIK cells after treatment increased significantly while the percentage of CD4+ CD25+ Treg cells decreased (P < 0.05). The clinical response rate (RR) was 40.9% and disease control rate (DCR) was 77.3%. We then studied and identified the mechanisms of the anti-tumor effects of the vaccines by analyzing a series of cytokines that are commonly involved in tumor progression and ascitic development including granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-10 (IL-10), interferon-γ (IFN-γ), tumor necrosis factor-α (TGF-α), tumor necrosis factor-β (TGF-β), Vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1). These data demonstrated that intraperitoneal injection with DC vaccines combined with CIK cells in patients with malignant peritoneal effusion is safe and feasible. This therapy modality can achieve a certain clinical benefit even in patients resistant to conventional treatments.
PMCID: PMC4276200  PMID: 25550942
Dendritic cell; cytokine-induced killer cell; immunotherapy; cytokines; malignant ascites
5.  High-mobility group box 2 is associated with prognosis of glioblastoma by promoting cell viability, invasion, and chemotherapeutic resistance 
Neuro-Oncology  2013;15(9):1264-1275.
Background
The expression profile of high-mobility group box 2 (HMGB2) in patients with glioblastoma multiforme (GBM) and its clinical signature with underlying mechanisms were not fully explored.
Methods
HMGB2 protein levels were measured in 51 GBM patients by immunohistochemical studies. To clarify the precise role of HMGB2 on cell invasion and viability of 3 GBM cell lines, we did in vitro and in vivo analyses with lentivirus vectors and small interfering RNA. Transwell invasion assays and wound-healing assays were used to analyze the invasion of GBM cells. Expression of p53 and matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot.
Results
HMGB2 protein expression was significantly higher in GBM than in controlled brain tissues (P < .0001). HMGB2 overexpression was significantly correlated with shorter overall survival time, which was the only independent prognostic factor for overall survival in a multivariate analysis (P = .017). HMGB2 knockdown by small interfering RNA decreased cell viability and invasion in vitro and significantly decreased tumor volume in vivo, which might be involved in the change of p53 expression and the balance of MMP2/TIMP2. Moreover, silencing of HMGB2 could significantly increase the sensitivity of GBM cells to temozolomide chemotherapy.
Conclusions
Our present data suggest that HMGB2 expression is a significant prognostic factor and might play an important role in cell invasion and temozolomide-induced chemotherapeutic sensitivity of GBM. This study highlights the importance of HMGB2 as a novel prognostic marker and an attractive therapeutic target of GBM.
doi:10.1093/neuonc/not078
PMCID: PMC3748920  PMID: 23828241
glioblastoma; high-mobility group box 2; prognosis; invasion; temozolomide
6.  Adult congenital intestinal malrotation accompanied by midgut volvulus: report of eight cases 
Congenital midgut malrotation is a complex gastrointestinal anomaly, which could easily lead to midgut volvulus and gastrointestinal obstruction. Large studies on congenital midgut malrotation in adults are rarely investigated. The current study aimed to explore the clinical profile and diagnostic modalities of congenital midgut malrotation in Chinese adult patients. Clinical and radiological data of eight adult patients with intestinal malrotation were retrospectively analyzed and related literatures were simultaneously reviewed. Mean age of patients was 41.25 years range, 14 to 63 years. Abdominal radiography and computerized tomography (CT) were conducted for all studied patients prior to surgery, and the diagnosis of congenital midgut malrotation was confirmed during surgery. All patients underwent volvulus reduction, Ladd’s band loosening, and stage I appendectomy. In addition, three patients received additional extensive intestinal adhesion loosening, and one patient received resection of bowel up to 50 cm. All patients recovered well after surgery, and no recurrence and adhesive intestinal obstruction were reported. All three patients with malnutrition prior to surgery had gained significant weight. Thus, we consider that adult congenital intestinal malrotation accompanied with midgut volvulus should be treated with surgery as soon as possible. Preoperative colour ultrasonography and CT are helpful for definitive diagnosis.
PMCID: PMC4100975  PMID: 25035789
Congenital intestinal malrotation; midgut volvulus; computed tomography
7.  A Meta-Analysis of Red Yeast Rice: An Effective and Relatively Safe Alternative Approach for Dyslipidemia 
PLoS ONE  2014;9(6):e98611.
Objective
To explore whether red yeast rice is a safe and effective alternative approach for dyslipidemia.
Methods
Pubmed, the Cochrane Library, EBSCO host, Chinese VIP Information (VIP), China National Knowledge Infrastructure (CNKI), Wanfang Databases were searched for appropriate articles. Randomized trials of RYR (not including Xuezhikang and Zhibituo) and placebo as control in patients with dyslipidemia were considered. Two authors read all papers and independently extracted all relevant information. The primary outcomes were serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The secondary outcomes were increased levels of alanine transaminase, aspartate aminotransferase, creatine kinase, creatinine and fasting blood glucose.
Results
A total of 13 randomized, placebo-controlled trials containing 804 participants were analyzed. Red yeast rice exhibited significant lowering effects on serum TC [WMD = −0.97 (95% CI: −1.13, −0.80) mmol/L, P<0.001], TG [WMD = −0.23 (95% CI: −0.31, −0.14) mmol/L, P<0.001], and LDL-C [WMD = −0.87 (95% CI: −1.03, −0.71) mmol/L, P<0.001] but no significant increasing effect on HDL-C [WMD = 0.08 (95% CI: −0.02, 0.19) mmol/L, P = 0.11] compared with placebo. No serious side effects were reported in all trials.
Conclusions
The meta-analysis suggests that red yeast rice is an effective and relatively safe approach for dyslipidemia. However, further long-term, rigorously designed randomized controlled trials are still warranted before red yeast rice could be recommended to patients with dyslipidemia, especially as an alternative to statins.
doi:10.1371/journal.pone.0098611
PMCID: PMC4045580  PMID: 24897342
8.  Evaluating team-based, lecture-based, and hybrid learning methods for neurology clerkship in China: a method-comparison study 
BMC Medical Education  2014;14:98.
Background
Neurology is complex, abstract, and difficult for students to learn. However, a good learning method for neurology clerkship training is required to help students quickly develop strong clinical thinking as well as problem-solving skills. Both the traditional lecture-based learning (LBL) and the relatively new team-based learning (TBL) methods have inherent strengths and weaknesses when applied to neurology clerkship education. However, the strengths of each method may complement the weaknesses of the other. Combining TBL with LBL may produce better learning outcomes than TBL or LBL alone. We propose a hybrid method (TBL + LBL) and designed an experiment to compare the learning outcomes with those of pure LBL and pure TBL.
Methods
One hundred twenty-seven fourth-year medical students attended a two-week neurology clerkship program organized by the Department of Neurology, Sun Yat-Sen Memorial Hospital. All of the students were from Grade 2007, Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University. These students were assigned to one of three groups randomly: Group A (TBL + LBL, with 41 students), Group B (LBL, with 43 students), and Group C (TBL, with 43 students). The learning outcomes were evaluated by a questionnaire and two tests covering basic knowledge of neurology and clinical practice.
Results
The practice test scores of Group A were similar to those of Group B, but significantly higher than those of Group C. The theoretical test scores and the total scores of Group A were significantly higher than those of Groups B and C. In addition, 100% of the students in Group A were satisfied with the combination of TBL + LBL.
Conclusions
Our results support our proposal that the combination of TBL + LBL is acceptable to students and produces better learning outcomes than either method alone in neurology clerkships. In addition, the proposed hybrid method may also be suited for other medical clerkships that require students to absorb a large amount of abstract and complex course materials in a short period, such as pediatrics and internal medicine clerkships.
doi:10.1186/1472-6920-14-98
PMCID: PMC4037118  PMID: 24884854
Lecture-based learning; Team-based learning; Neurology; Clerkship; Hybrid learning method
9.  Effects of antioxidants on the microleakage of composite resin restorations after external tooth bleaching 
European Journal of Dentistry  2014;8(2):147-153.
Objective:
To compare the effects of three antioxidants (sodium ascorbate, sodium ascorbate combined with a surfactant, and catalase) on the microleakage of composite resin restorations after external tooth bleaching with 10% carbamide peroxide.
Materials and Methods:
Buccal cavities were prepared on the surface of 60 intact premolars, which were randomly divided into six groups. All cavities were filled with composite resin. In group 1, teeth were not bleached; in group 2, cavities were filled immediately after bleaching; in group 3, cavities were delay-filled for 3 weeks; in group 4, cavities were treated with sodium ascorbate after bleaching and then filled; in group 5, cavities were treated with sodium ascorbate combined with surfactant after bleaching and then filled; and in group 6, cavities were treated with catalase after bleaching and then filled. Microleakage of the restorations was measured from sections using a stereomicroscope.
Results:
Group 1 displayed the least amount of microleakage, while group 2 showed the greatest amount of microleakage (P < 0.05). Groups 3 and 4 were similar to group 2 (P > 0.05). However, groups 5 and 6 showed a significantly lower amount of microleakage compared to group 2 (P < 0.05).
Conclusion:
Microleakage increased significantly after external bleaching with 10% carbamide peroxide, and decreased when the bleached teeth were treated with sodium ascorbate combined with Tween® 80, or with catalase. Catalase was more effective in decreasing microleakage, while delayed filling or treatment with sodium ascorbate alone did not effectively decrease the microleakage.
doi:10.4103/1305-7456.130581
PMCID: PMC4054042  PMID: 24966762
Antioxidant; composite resin; external tooth bleaching; microleakage
10.  Photothermal therapy of cancer cells using novel hollow gold nanoflowers 
This article presents a new strategy for fabricating large gold nanoflowers (AuNFs) that exhibit high biological safety under visible light and very strong photothermal cytotoxicity to HeLa cells under irradiation with near-infrared (NIR) light. This particular type of AuNF was constructed using vesicles produced from a multiamine head surfactant as a template followed by depositing gold nanoparticles (AuNPs) and growing their crystallites on the surface of vesicles. The localized surface plasmon-resonance spectrum of this type of AuNF can be easily modulated to the NIR region by controlling the size of the AuNFs. When the size of the AuNFs increased, biosafety under visible light improved and cytotoxicity increased under NIR irradiation. Experiments in vitro with HeLa cells and in vivo with small mice have been carried out, with promising results. The mechanism for this phenomenon is based on the hypothesis that it is difficult for larger AuNFs to enter the cell without NIR irradiation, but they enter the cell easily at the higher temperatures caused by NIR irradiation. We believe that these effects will exist in other types of noble metallic NPs and cancer cells. In addition, the affinity between AuNPs and functional biomolecules, such as aptamers and biomarkers, will make this type of AuNF a good recognition device in cancer diagnosis and therapy.
doi:10.2147/IJN.S55800
PMCID: PMC3897319  PMID: 24549034
HeLa cells; endocytosis; cytotoxicity; AuNFs; NIR; cancer therapy
12.  Progress risk assessment of oral premalignant lesions with saliva miRNA analysis 
BMC Cancer  2013;13:129.
Background
Oral cancer develops through multi-stages: from normal to mild (low grade) dysplasia (LGD), moderate dysplasia, and severe (high grade) dysplasia (HGD), to carcinoma in situ (CIS) and finally invasive oral squamous cell carcinomas (OSCC). Clinical and histological assessments are not reliable in predicting which precursor lesions will progress. The aim of this study was to assess the potential of a noninvasive approach to assess progress risk of oral precancerous lesions.
Methods
We first used microRNA microarray to profile progressing LGD oral premaligant lesions (OPLs) from non-progressing LGD OPLs in order to explore the possible microRNAs deregulated in low grade OPLs which later progressed to HGD or OSCC. We then used RT-qPCR to detect miRNA targets from the microarray results in saliva samples of these patients.
Results
We identified a specific miRNA signature that is aberrantly expressed in progressing oral LGD leukoplakias. Similar expression patterns were detected in saliva samples from these patients.
Conclusions
These results show promise for using saliva miRNA signature for monitoring of cancer precursor lesions and early detection of disease progression.
doi:10.1186/1471-2407-13-129
PMCID: PMC3637283  PMID: 23510112
Oral leukoplakia; Malignant transformation; Risk assessment; miRNAs; Salivary biomarker
13.  Evaluation of Ca3Co2O6 as cathode material for high-performance solid-oxide fuel cell 
Scientific Reports  2013;3:1125.
A cobalt-based thermoelectric compound Ca3Co2O6 (CCO) has been developed as new cathode material with superior performance for intermediate-temperature (IT) solid-oxide fuel cell (SOFC). Systematic evaluation has been carried out. Measurement of thermal expansion coefficient (TEC), thermal-stress (σ) and interfacial shearing stress (τ) with the electrolyte show that CCO matches well with several commonly-used IT electrolytes. Maximum power density as high as 1.47 W cm−2 is attained at 800°C, and an additional thermoelectric voltage of 11.7 mV is detected. The superior electrochemical performance, thermoelectric effect, and comparable thermal and mechanical behaviors with the electrolytes make CCO to be a promising cathode material for SOFC.
doi:10.1038/srep01125
PMCID: PMC3553459  PMID: 23350032
14.  A reinforced composite structure composed of polydiacetylene assemblies deposited on polystyrene microspheres and its application to H5N1 virus detection 
In this study, we immobilized polydiacetylene vesicles (PDAVs) onto the surface of polystyrene (PS) microspheres (1 μm in diameter) by using both electrical charge and conjugated forces to form a reinforced composite structure. These reinforced complexes could be easily washed, separated by centrifugation, and resuspended by gentle agitation. After passing through a narrow 200 μm-diameter channel, the composite structures maintained their original shape, demonstrating their resilience and potential for use in microfluidic technologies. The number of PDAVs in the composite structure could be mediated by changing the extent of layer deposition, which affected the sensitivity of detection. It showed that PDAVs did not change their blue color after addition of detecting probes such as anti-H5N1, which was of great importance in the fabrication and modification of stable color-changeable biosensors based on PDAVs. By conjugating anti-H5N1 antibodies to the PS@PDAV via N -hydroxysuccinimide and 1-ethyl3-(3-dimethylaminopropyl) carbodiimide chemistry, a stable blue complex, anti-H5N1 microsphere (PS@PDAV-anti-H5N1) was formed. A target antigen of H5N1 (HAQ [H5N1 strain A/ environment/Qinghai/1/2008{H5N1} in clade 0]) was detected by PS@PDAV-anti-H5N1. At an optimal PDAV deposition level of three layers, the limit of detection was determined to be approximately 3 0 ng/mL of HAQ by using optical spectrum measurement and visual inspection, meeting the needs of fast and simple color-changeable detection. However, a much lower limitation of detection (1 ng/mL) was able to be obtained using laser-scanning confocal microscopy, which could be compared with the results obtained with other sophisticated equipment.
doi:10.2147/IJN.S39676
PMCID: PMC3565586  PMID: 23403826
reinforced composite structure; polystyrene; polydiacetylene; H5N1 virus detection
15.  Expression and role of SDF-1α-CXCR4 axis in Human Dental Pulp 
Journal of endodontics  2008;34(8):939-944.
Recent reports have suggested that SDF (Stromal cell-derived factor)-1α- CXCR4 axis has a direct effect on stem and progenitor cell recruitment in muscle and neural tissue repair after injury. No information is available about SDF-1α or CXCR4 in dental tissues. The aim of this study was to assess the expression of SDF-1α and its receptor, CXCR4, in healthy or inflamed human dental pulp and to evaluate the effects of SDF-1α on dental pulp cells (DPCs) in both proliferation and migration in vitro. Immunohistochemical staining and RT-PCR detected weak expression of SDF-1α and CXCR4 in healthy dental pulp and strong expression of SDF-1a and CXCR4 in inflamed dental pulp. An MTT assay demonstrated that SDF-1α could not promote DPCs proliferation. A transmigration assay, however, indicated that SDF-1α enhanced DPCs migration, and which could be abolished by anti-CXCR4 antibodies. Taken together, these results imply that the SDF-1α-CXCR4 axis may play a role in the recruitment of CXCR4-positive DPCs toward the damaged sites
doi:10.1016/j.joen.2008.05.015
PMCID: PMC3508770  PMID: 18634924
16.  HLA-A*0201-restricted CD8+ T-cell epitopes identified in dengue viruses 
Virology Journal  2012;9:259.
Background
All four dengue virus (DV) serotypes (D1V, D2V, D3V and D4V) can cause a series of disorders, ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). Previous studies have revealed that DV serotype-specific CD8+ T cells are involved in controlling DV infection. Serotype cross-reactive CD8+ T-cells may contribute to the immunopathogenesis of DHF/DSS. The aim of the study was to identify HLA-A*0201-binding peptides from four DV serotypes. We then examined their immunogenicity in vivo and cross-reactivity within heterologous peptides.
Methods
D1V-derived candidate CD8+ T-cell epitopes were synthesized and evaluated for their affinity to the HLA-A*0201 molecule. Variant peptides representing heterologous D2V, D3V, D4V serotypes were synthesized. The immunogenicity of the high-affinity peptides were evaluated in HLA-A*0201 transgenic mice.
Results
Of the seven D1V-derived candidate epitopes [D1V-NS4a56–64(MLLALIAVL), D1V-C46–54(LVMAFMAFL), D1V-NS4b562–570(LLATSIFKL), D1V-NS2a169–177(AMVLSIVSL), D1V-NS4a140–148(GLLFMILTV), D1V-NS2a144–152(QLWAALLSL) and D1V-NS4b183–191(LLMRTTWAL)], three peptides [D1V-NS4a140–148, D1V-NS2a144–152 and D1V-NS4b183–191] had a high affinity for HLA-A*0201 molecules. Moreover, their variant peptides for D2V, D3V and D4V [D2V-NS4a140–148(AILTVVAAT), D3V-NS4a140-148(GILTLAAIV), D4V-NS4a140-148(TILTIIGLI), D2V-NS2a144–152(QLAVTIMAI), D3V-NS2a144–152(QLWTALVSL), D4V-NS2a143–151(QVGTLALSL), D2V-NS4b182–190(LMMRTTWAL), D3V-NS4b182–190 (LLMRTSWAL) and D4V-NS4b179–187(LLMRTTWAF)] also had a high affinity for HLA-A*0201 molecules. Furthermore, CD8+ T cells directed to these twelve peptides were induced in HLA-A*0201 transgenic mice following immunization with these peptides. Additionally, cross-reactivity within four peptides (D1V-NS4b183–191, D2V-NS4b182–190, D3V-NS4b182–190 and D4V-NS4b179–187) was observed.
Conclusions
Two novel serotype-specific HLA-A*0201-restricted CD8+ T-cell epitopes (NS4a140-148 and NS2a144–152) and one cross-reactive HLA-A*0201-restricted CD8+ T-cell epitopes which is similar to a previously identified epitope were identified in D1V-D4V. Combining prediction algorithms and HLA transgenic mice is an effective strategy to identify HLA-restricted epitopes. Serotype-specific epitopes would be used to determine the protective role of serotype-specific CD8+ T cells, while cross-reactive epitopes may provide assistance in exploring the role of serotype cross-reactive CD8+ T cells in the immunopathogenesis of DHF/DSS.
doi:10.1186/1743-422X-9-259
PMCID: PMC3546861  PMID: 23121866
Dengue virus; CD8+ T-cell epitope; Immunogenicity
17.  Constructions of two polycatenanes and one polypseudo-rotaxane by discrete tetrahedral cages and stool-like building units 
Scientific Reports  2012;2:668.
Mechanically Interlocked molecules, such as catenanes and rotaxanes, are of great interest due to their fascinating structures and potential applications, while such molecules have been mainly restricted to comprising components of interlocked rings or polygons. The constructions of infinite polycatenanes and polyrotaxanes by discrete cages remain great challenge, and only two infinite polycatenanes fabricated by discrete cages have been reported so far, while the structures of polyrotaxanes and polypseudo-rotaxanes fabricated by discrete build units have not been documented to date. Herein we report the first example of a two-dimensional (2D) polypseudo-rotaxane fabricated by stool-like build units, the second example of a one-dimensional (1D) polycatenane, and the second example of a three-dimensional (3D) polycatenane, which were assemblied by discrete tetrahedral cages. The pores of dehydrated 3D polycatenane are dynamic, and display size-dependent adsorption/desorption behaviors of alcohols.
doi:10.1038/srep00668
PMCID: PMC3444800  PMID: 22993693
18.  2-(4-Fluoro­phen­yl)quinoxaline 
In the title compound, C14H9FN2, the dihedral angle between the benzene ring and the quinoxaline ring system is 22.2 (3)°. Any aromatic π–π stacking in the crystal must be very weak, with a minimum centroid–centroid separation of 3.995 (2) Å.
doi:10.1107/S1600536812017771
PMCID: PMC3379358  PMID: 22719556
19.  Methyl 4-(5-meth­oxy-1H-indol-3-yl)benzoate 
In the title compound, C17H15NO3, the dihedral angle between the benzene ring and the indole ring system is 22.5 (3)°. In the crystal, mol­ecules are linked by N—H⋯π and C—H⋯O inter­actions.
doi:10.1107/S1600536811052135
PMCID: PMC3254479  PMID: 22259421
20.  Ethyl 8-chloro-1-cyclo­propyl-6,7-difluoro-4-oxo-1,4-dihydro­quinoline-3-carboxyl­ate 
In the mol­ecule of the title compound, C15H12ClF2NO3, the quinoline ring system is not planar, the dihedral angle between the pyridine and benzene rings being 3.55 (8)°. In the crystal, inter­molecular C—H⋯O hydrogen bonds link the mol­ecules into layers parallel to (101).
doi:10.1107/S160053681104205X
PMCID: PMC3247378  PMID: 22219996
21.  6-Benzyl-6,7-dihydro-5H-pyrrolo­[3,4-b]pyridine-5,7-dione 
In the title compound, C14H10N2O2, the dihedral angle between the heterocyclic ring system and the phenyl ring is 45.8 (5)°. Weak inter­molecular C—H⋯N hydrogen bonding is present in the crystal structure.
doi:10.1107/S1600536811041006
PMCID: PMC3247312  PMID: 22219930
22.  Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B 
Background
Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition.
Methods
Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data.
Results
Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated.
Conclusions
Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma.
doi:10.1186/1472-6882-11-54
PMCID: PMC3158556  PMID: 21726465
23.  4-[4,5-Bis(pyridin-2-yl)-1H-imidazol-2-yl]phenol monohydrate 
In the title hydrate, C19H14N4O·H2O, the dihedral angle between the two pyridine rings is 38.0 (2)°. The dihedral angle between the imidazole and benzene rings is 25.3 (2)°. The crystal structure is stabilized by inter­molecular O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds.
doi:10.1107/S1600536810052062
PMCID: PMC3050325  PMID: 21522668
24.  Centrally Administered Pertussis Toxin Inhibits Microglia Migration to the Spinal Cord and Prevents Dissemination of Disease in an EAE Mouse Model 
PLoS ONE  2010;5(8):e12400.
Background
Experimental autoimmune encephalomyelitis (EAE) models are important vehicles for studying the effect of infectious elements such as Pertussis toxin (PTx) on disease processes related to acute demyelinating encephalomyelitis (ADEM) or multiple sclerosis (MS). PTx has pleotropic effects on the immune system. This study was designed to investigate the effects of PTx administered intracerebroventricularly (icv) in preventing downstream immune cell infiltration and demyelination of the spinal cord.
Methods and Findings
EAE was induced in C57BL/6 mice with MOG35–55. PTx icv at seven days post MOG immunization resulted in mitigation of clinical motor symptoms, minimal T cell infiltration, and the marked absence of axonal loss and demyelination of the spinal cord. Integrity of the blood brain barrier was compromised in the brain whereas spinal cord BBB integrity remained intact. PTx icv markedly increased microglia numbers in the brain preventing their migration to the spinal cord. An in vitro transwell study demonstrated that PTx inhibited migration of microglia.
Conclusion
Centrally administered PTx abrogated migration of microglia in EAE mice, limiting the inflammatory cytokine milieu to the brain and prevented dissemination of demyelination. The effects of PTx icv warrants further investigation and provides an attractive template for further study regarding the pleotropic effects of infectious elements such as PTx in the pathogenesis of autoimmune disorders.
doi:10.1371/journal.pone.0012400
PMCID: PMC2928301  PMID: 20811645
25.  Changes of the immunological barrier of intestinal mucosa in rats with sepsis 
BACKGROUND:
Sepsis has become the greatest threat to in-patients, with a mortality of over 25%. The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture.
METHODS:
Sixty Sprague-Dawley rats were randomly divided into a sepsis group (n=45) and a control group (n=15). The rats in the sepsis group were subjected to cecal ligation and puncture (CLP), whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3 (TFF3) mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected.
RESULTS:
The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased (P<0.05) in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group (P<0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52). In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group.
CONCLUSION:
The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.
PMCID: PMC4129746  PMID: 25214957
Sepsis; Mucosal immunology; Defensin-5; Trefoil factor family 3; Cecal ligation and puncture

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