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This paper discusses the influence mechanism and boundary factors of the origin image of regional brand on consumers' purchasing intention. Hierarchical linear regression analysis is a common method to verify the regulatory effect. Taking Fujian tea as an example, this paper uses hierarchical linear regression analysis and spss26.0 to analyze the collected data of 353 questionnaires, and draws the following conclusions: regional brand origin image has a certain impact on consumers' perceived value and purchase intention, and the industrial scale, natural resources and cultural environment have significant positive effects on different degrees. Consumer professionalism, product involvement and consumer group ownership play a moderating role between the origin image and consumer perceived value. The lower the consumers' professionalism, the lower the product involvement, and the consumers belong to the inner group, the more significant the impact of regional brand's origin image on consumer's perceived value.

Guided waves have been widely utilized in various structural health monitoring (SHM) techniques because of their long propagation distance and high sensitivity to small-scale defects in str...

Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Although cardiac cell death is a well-recognized pathological mechanism of MI, therapeutic blockade of cell death to treat MI is not straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis factor (TNF)–related apoptosis- inducing ligand] are up-regulated in MI, but their roles in pathological remodeling are unknown. Here, we report that blocking TRAIL with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, directly and indirectly causing cardiac injury. Transcriptome profiling revealed increased expression of inflammatory cytokines in infarcted heart tissue, which was markedly reduced by TRAIL blockade. Together, our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy for treating MI.

We previously demonstrated that intramuscular immunization with virus-like particles (VLPs) composed of the haemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of A/meerkat/Shanghai/SH-1/2012 (clade 2.3.2.1) protected mice from lethal challenge with viruses from other H5 HPAI clades. The inclusion of additional proteins that can serve as immunological adjuvants in VLPs may enhance adaptive immune responses following vaccination, and oral vaccines may represent the safest choice. Here, we report the generation of H5N1 VLPs composed of the viral HA, NA, and M1 proteins and membrane-anchored forms of the Escherichia coli heat-labile enterotoxin B subunit protein (LTB) or the Toll-like receptor 5 ligand flagellin (Flic). Mice intramuscularly or orally immunized with VLPs containing LTB or Flic generated greater humoural and cellular immune responses than those administered H5N1 VLPs without LTB or Flic. Intramuscular immunization with VLPs protected mice from lethal challenge with homologous or heterologous H5N1 viruses irrespective of whether the VLPs additionally included LTB or Flic. In contrast, oral immunization of mice with LTB- or Flic-VLPs conferred substantial protection against lethal challenge with both homologous and heterologous H5N1 influenza viruses, whereas mice immunized orally with VLPs lacking LTB and Flic universally succumbed to infection. Mice immunized orally with LTB- or Flic-VLPs showed 10-fold higher virus-specific IgG titres than mice immunized with H5N1-VLPs lacking LTB or Flic. Collectively, these results indicate that the inclusion of immunostimulatory proteins, such as LTB and Flic, in VLP-based vaccines may represent a promising new approach for the control of current H5N1 HPAI outbreaks by eliciting higher humoural and cellular immune responses and conferring improved cross-clade protection.

The H7N9 influenza virus epidemic has been associated with a high mortality rate in China. Therefore, to prevent the H7N9 virus from causing further damage, developing a safe and effective vaccine is necessary. In this study, a vaccine candidate consisting of virus-like particles (VLPs) based on H7N9 A/Shanghai/2/2013 and containing hemagglutinin (HA), neuraminidase (NA), and matrix protein (M1) was successfully produced using a baculovirus (BV) expression system. Immunization experiments showed that strong humoral and cellular immune responses could be induced by the developed VLPs when administered via either the intramuscular (IM) or intranasal (IN) immunization routes. Notably, VLPs administered via both immunization routes provided 100% protection against lethal infection caused by the H7N9 virus. The IN immunization with 40μg of H7N9 VLPs induced strong lung IgA and lung tissue resident memory (TRM) cell-mediated local immune responses. These results provide evidence for the development of an effective preventive vaccine against the H7N9 virus based on VLPs administered through both the IM and IN immunization routes.

Genetic mutations in heat shock factor 4 (Hsf4) is associated with both congenital and age-related cataracts. Hsf4 regulates lens development through its ability to both activate and inhibit transcription. Previous studies suggested Hsf4 is involved in modulating cellular senescence depending on p21cip1 and p27 kip1 expression in MEF cells. Here, we found that Hsf4 acts as a suppressor of p21cip1 expression and plays an anti-senescence role during lens development. Knocking out Hsf4 facilitated UVB-induced cellular senescence in mouse lens epithelial cells (mLECs). p21cip1 was upregulated at both the mRNA and protein levels in HSF4−/− mLECs under control and UVB-treated conditions, and knockdown of p21cip1 by siRNA alleviated UVB-induced cellular senescence. HSF4 directly bound to the p21cip1 promoter and increased H3K27m3 levels at the p21cip1 proximal promoter region by recruiting the methyltransferase EZH2. In animal models, p21cip1 was gradually upregulated in wild-type mouse lenses with increasing age, while Hsf4 levels decreased. We generated a Hsf4 mutant mice line (Hsf4del-42) which displayed obvious congenital cataract phenotype. The expression of p21cip1 and senescence-associated cytokines were induced in the cataractous lenses of Hsf4del-42 mice. H3K27m3 and EZH2 levels decreased in p21cip1 promoters in the lenses of Hsf4del-42 mice. The SA-β-Gal activities were positive in lens epithelia of aged Hsf4null zebrafish compared to wild-type lenses. p21cip1 and senescence-associated cytokines levels were also upregulated in lenses of Hsf4null zebrafish. Accordingly, we propose that HSF4 plays a protective role in lens epithelial cells against cellular senescence during lens development and aging, partly by fine-tuning p21cip1 expression.

Axial stress monitoring in arbitrary cross sections is a challenging task. Stringers are the main axial load carrying components of aircraft skin structures and have typical complex cross sections. This paper investigates the strategy of axial stress monitoring in an arbitrary cross section based on acoustoelastic guided waves using piezoelectric lead zirconate titanate (PZT) sensors. To select appropriate guided wave frequencies and modes sensitive for axial stress monitoring in an arbitrary cross section, the feature guided waves are investigated using acoustoelastic theory combined with the semianalytical finite element method. The mode shapes are derived, which show that these longitudinal-like modes are more sensitive to axial stress. A PZT transducer array is also considered to maximize desired modes. Piezoelectric sensors are used to excite and detect the guided waves in the experiments. Results from acoustoelastic measurements on a T-type stringer are presented, showing the feasibility of this method for axial stress monitoring.

To explore the effect of low intensity pulsed ultrasound (LIPUS) on TGF-β1/Smad 2, 3 signal pathway during the dentin injury and repair. Methods: Among 25 Sprague-Dawley rats, 5 rats served as a blank control group without treatment. The remaining 20 rats received modified caries preparation inbilateral maxillary first molars to establish a model of dentin-pulp injury and repair. The right maxillary first molars served as a LIPUS group, which received LIPUS irradiation (frequency: 1.5 MHz, pulse width: 200 μs, pulse repetition frequency: 1 kHz, spatial averaged temporal averaged intensity: 30 mW/cm2, 20 min/d), and the left maxillary first molars served as a cavity-prepared group, which received fake LIPUS irradiation. The rats were sacrificed at 1, 3, 5, 7 and 14 days after LIPUS irradiation. Immunohistochemical staining and Image-pro plus 6.0 were applied to detect the expression and distribution of transforming growth factor-beta1 (TGF-β1) and small mothers against decapentaplegic 2/3(Smad 2 and Smad 3). Results: Immunohistochemical staining showed that the expression of TGF-β1 and Smad 2, 3 were low innormal pulp, but they were increased in different degree after dentin injury. The result of image analysis showed that the expression of TGF-β1 in the cavity-prepared group gradually increased at the first day and peaked at day 5, and then it returned to normal level at day 14. However, the expression of TGF-β1 in the LIPUS group were significantly higher than that in the cavity-prepared group at day 3 and 5 (both P0.05). The expressions of Smad 2,3 in both the LIPUS group and the cavity-prepared group were consistently increased all the way, but the expressions in the LIPUS group were higher compared with that in the cavity-prepared group (P0.05). Conclusion: The TGF-β1/Smad 2, 3 signal pathway can be activated during the dentin injury and repair. LIPUS can up-regulate the expression of TGF-β1 and Smad 2, 3 in the early period, which may take part in the dentin-pulp complex injury and repair process.目的：观察低强度脉冲超声(low intensity pulsed ultrasound，LIPUS)对牙本质牙髓复合体损伤修复模型中TGF-β1/Smads信号通路的影响。方法：25只Sprague-Dawley大鼠随机选择5只大鼠作为空白对照组，不予任何处理。剩余20只于双侧上颌第一磨牙采用改良备洞法备洞，建立牙本质牙髓损伤修复模型，右侧为LIPUS组，予以LIPUS辐照(强度为30 mW/cm2，频率为1.5 MHz，调制信号波宽为200 μs，重复率为1 kHz，20 min/d)；左侧为备洞组，予以超声假照处理。分别在辐照1，3，5，7，14 d后处死大鼠，运用免疫组织化学法及图像分析技术检测TGF-β1，Smad 2和3在牙髓组织中的动态表达和定位情况。结果：TGF-β1，Smad 2，3蛋白在正常牙髓组织中均呈弱阳性表达，而在牙本质损伤后出现不同程度的表达增加。备洞组TGF-β1蛋白表达在1 d时增加，在5 d时TGF-β1表达最强，在14 d时表达减弱接近正常水平；与备洞组相比，LIPUS组在3和5 d时表达明显升高(均P0.05)。Smad 2，3在LIPUS组及备洞组牙髓中表达均呈现逐步升高的基本变化，其中LIPUS组升高更明显(P0.05)。结论：TGF-β1/Smad 2，3信号通路可能参与了牙本质损伤的修复过程，LIPUS在牙本质损伤修复早期可上调TGF-β1，Smad 2，3的表达，可能参与并促进了牙本质牙髓复合体的损伤修复过程。.

Objective The objective of this study was to evaluate the outcome and feasibility of concurrent chemotherapy with paclitaxel plus carboplatin and radiotherapy (RT) in patients with high-risk or advanced endometrial cancer. Methods A retrospective analysis of patients treated between January 2003 and December 2009 was conducted. Adjuvant therapy consisted of external beam radiation to the pelvis (45–48.6 Gy) and weekly administration of paclitaxel (40 mg/m2) plus carboplatin with an area under the curve of 2 administered intravenously during RT. Two further cycles of paclitaxel (175 mg/m2) and carboplatin (area under the curve, 5), separated by 4 weeks, were administered at the end of RT for advanced stage disease. Para-aortic RT and/or vault brachytherapy were added at the discretion of the physicians. Results A total of 31 patients with a median age of 56 years (31–69 years) were evaluated. The majority had stage III disease (58%), and the most common histology was endometrioid adenocarcinoma (78%). All patients completed the planned RT. The median follow-up time was 64 months (12–86 months). Five patients’ conditions progressed, and all 5 died of the disease. Most of the 5 patients were with serous histologic type and advanced stage disease. There was no local recurrence. The 2-, 3-, and 5-year progression-free survival rates were 87%, 84%, and 79%, respectively. The 2-, 3-, and 5-year overall survival rates were 94%, 87%, and 83%, respectively. Toxicity included grade 3/4 neutropenia in 45.2% of patients, gastrointestinal toxicity in 32.3% of patients, and grade 1/2 sensory neuropathy in 38.7% of patients. Conclusions Concomitant paclitaxel plus carboplatin and radiation was feasible and well tolerated and resulted in excellent local-regional control. However, distant metastases continued to occur in more advanced-stage patients. This regimen appears reasonable to be tested for efficacy in randomized studies.

To investigate the root and canal morphology of permanent mandibular anterior teeth in a Chongqing population using cone-beam computed tomography (CBCT).CBCT images of 1,725 patients in a Chongqing population were selected, and a total of 9,646 mandibular anterior teeth were analyzed. The number of root canals and the canal configurations were investigated.In total, 0.3% (11/3,257) of lateral incisors and 0.8% (26/3,014) of canines had double roots, and 3.8% (127/3,375) of central incisors, 10.6% (345/3,257) of lateral incisors, and 4.2% (127/3,014) of canines had multi-root canals. The difference in the incidence of multi-canals in lateral incisors between female and male was statistically significant. The frequency of multi-canals in the different age groups was 5.0% for central incisors for ages 21-30 years, 14.7% for lateral incisors for ages 41-50 years, and 8.1% for canines for ages 41-50 years.With the limitations of the current study, we found that a high percentage of mandibular anterior teeth had multiple canals in the studied Chinese Chongqing population. The current data may provide clinicians practicing in Chongqing with a more thorough understanding of root canal morphology.

Glucocorticoids are stress-responsive neuroendocrine mediators and play an important role in malignant progression, especially in solid tumours. We demonstrate a novel mechanism by which glucocorticoids modulate p53-dependent miR-145 expression in HPV-positive cervical cancer cells through induction of E6 proteins. We found that expression of miR-145 was reduced in cervical cancer tissues. Cortisol induced HPV-E6 expression and suppressed p53 and miR-145 in cervical cancer cells. MiR-145 expression in cervical cancer cells was wild-type p53-dependent, and cortisol-induced down-regulation of miR-145 expression prevented chemotherapy-induced apoptosis, whereas over-expression of miR-145 enhanced sensitivity to mitomycin and reversed the chemoresistance induced by glucocorticoids. We also show that miR-145 augments the effects of p53 by suppressing the inhibitors of p53 in cervical cancer cells, suggesting that miR-145 plays a role in p53 tumour suppression. Finally, we demonstrate that miR-145 inhibits both the motility and invasion of cervical cancer cells. Our findings identify a novel pathway through which the neuroendocrine macroenvironment affects cervical tumour growth, invasion and therapy resistance and show that miR-145 may serve as a target for cervical cancer therapy. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Lamb waves play an important role in structure health monitoring (SHM) systems. The excitation of Lamb waves has been discussed for a long time with absorbing results. However, little effort has been made towards the precise characterization of Lamb wave excitation by various transducer models with mathematical foundation. In this paper, the excitation of plane Lamb waves with plane strain assumption in isotropic plate structures under applied surface loading is solved with the Hamiltonian system. The response of the Lamb modes excited by applied loading is expressed analytically. The effect of applied loading is divided into the product of two parts as the effect of direction and the effect of distribution, which can be changed by selecting different types of transducer and the corresponding transducer configurations. The direction of loading determines the corresponding displacement of each mode. The effect of applied loading on the in-plane and normal directions depends on the in-plane and normal displacements at the surface respectively. The effect of the surface loading distribution on the Lamb mode amplitudes is mainly reflected by amplitude versus frequency or wavenumber. The frequencies at which the maxima and minima of the S0 or A0 mode response occur depend on the distribution of surface loading. The numerical results of simulations conducted on an infinite aluminum plate verify the theoretical prediction of not only the direction but also the distribution of applied loading. A pure S0 or A0 mode can be excited by selecting the appropriate direction and distribution at the corresponding frequency.

OBJECTIVE To evaluate the applicability of combined therapy and the prognostic factors in patients with carcinoma of the cervical stump (CCS). METHODS The clinical records of 60 CCS patients who underwent combined treatment in our hospital during a period from January 2000 to December 2007, were collected and retrospectively analyzed. The prognostic factors were studied using univariate analysis. Analytical evaluation of the independent prognostic factors was performed using COX proportional-hazards regression model. RESULTS The 1-, 3- and 5-year survival rates of the 60 patients were 95%, 78% and 68%, respectively, with a median survival time of 32 months. Univariate survival analysis showed that these independent prognostic factors included positive pelvic lymph nodes ( P = 0.001), lymphovascular tumor embolus ( P = 0.001), and adjuvant chemotherapy ( P = 0.011). In the 60 cases, postoperative local recurrence in the pelvic cavity occurred in 1 and distant metastasis in 3. Related complications, such as radiocystitis, recto-vaginal fi stula and vesico-vaginal fi stula were found in 6 of the total cases (10%). The serum levels of squamous epithelium antigen detected before and after treatment were significantly different ( P = 0.000). The incidence of CCS is low; however, the disease is diffi cult to cure due to the high incidence of complications and to the frequency of distant metastasis. Therefore, individualized treatment is needed. Complications from subtotal hysterectomy (STH) should be treated and controlled aggressively. Careful follow-up as well as close monitoring and observation for signifi cant symptoms in the postoperative course will enhance clinical outcome. CONCLUSION Cancer of the cervical stump has a low morbidity and severe complications, and most recurrences are distant metastases. Because it is difficult to cure, there is a need to design a treatment regimen for each individual patient based on the factors deemed as high risk. The surgical indications for subtotal uterine resection should be followed and close follow-up after surgery should be maintained.

Objective: The aim of this meta-analysis was to assess the methylene tetrahydrofolate reductase (MTHFR) gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. Materials and Methods: The databases of PubMed, MEDLINE, Wanfang, and CNIK was electronic searched to find the case–control or cohort study about the relationship between MTHFR gene C677T polymorphisms and esophageal cancer susceptibility in Chinese Han population. The odds ratio (OR) was used to assess the relationship between CC, CT, and TT genotype and esophageal cancer risk. The data were pooled using Stata 11.0 software. Results: Eight articles included 1752 esophageal cancer and 2363 controls were found and included in this meta-analysis. The pooled OR was 1.86 with its 95% confidence interval of 1.21–2.86 and 1.62 with its 95% confidence interval of 1.15–2.27 for TT versus CC and CT versus CC model which indicated that people with TT OR CT genotype significant increase the risk of developing esophageal cancer. Conclusion: Esophageal cancer risk was significantly increased in people with TT/CT genotype of MTHFR gene.

Background Our previous studies show that β2-adrenergic receptor (β2-AR) is highly expressed in most Her2-overexpressing breast cancers. However, the mechanisms underlying upregulation of the β2-AR expression in Her2-overexpressing breast cancer cells are not fully understood. The clinical significance of the β2-AR overexpression in breast cancer is unclear. Methods Human breast cancer cells MCF-7 and MCF-7/Her2 were transfected with the let-7 mimics or inhibitors. The expression of β2-AR was analyzed by Western blot. The β2-AR status in primary and metastatic sites of breast cancer and the human breast cancer tissue microarrays containing 49 primary tumors and 50 metastatic lymph node tissues was analyzed by immunohistochemistry. The correlation of lymph node metastasis with the β2-AR level was determined in 59 primary tumor tissues from the patients with Her2-positive breast cancer. The clinical prognostic significance of the β2-AR overexpression in the patients with Her2-positive breast cancers was evaluated by a retrospective study. Results The let-7f level in Her2-overexpressing breast cancer cells SKBR3 and BT474 was significantly lower than that in MCF-7 cells, which express low level of Her2. Ectopic expression of Her2 in MCF-7 cells (MCF-7/Her2) represses the expression of microRNA let-7f, which is previously identified to regulate baseline β2-AR expression. The treatment with MEK1/2 inhibitors PD98059 or PD184352 effectively restored the let-7f level, suggesting that Her2-overexpression-mediated ERK constitutive activation inhibited let-7f, leading to the upregulation of the β2-AR expression. The transfection with the let-7f mimics markedly downregulated the β2-AR level, whereas the let-7 inhibitor significantly upregulated the β2-AR expression in both parental MCF-7 and MCF-7/Her2 cells. In addition, treatment of MCF-7/Her2 cells with isoproterenol resulted in a concentration-dependent reduction of the let-7f expression, demonstrating that the inhibitory effect of Her2 overexpression on let-7f can be reinforced by agonist-triggered β2-AR activation. We further demonstrate that high level of β2-AR associates with lymph node metastasis and poor outcome in the patients with Her2-positive breast cancer. Conclusions The mutual and reciprocal interaction between Her2, β2-AR, and let-7f may maintain a high level of β2-AR in breast cancer cells. Our data suggest that β2-AR may be a new useful biomarker for predicting prognosis in Her2-positive breast cancer and may also be a promising selective therapeutic target for the aggressive subtype of breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1869-6) contains supplementary material, which is available to authorized users.

Patients and Tumor Characteristics. (DOC 47 kb)

Total RNA from 10 cases of ovarian cancer and from normal ovarian tissues were extracted by a single step method. The cDNA was retro-transcribed from an equal quantity of mRNA derived from the 10 cases of ovarian carcinoma and normal ovarian tissues, followed by labeling the cDNA strands with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BiostarH 8464 dot human somatic cell genes. Fluorescence signals were assessed by a ScanArray 4000 laser scanner and the images analyzed by Gene Pix Pro 3.0 software with a digital computer. By applying the cDNA microarray we found a total of 185 genes for which expression levels differed more than 5 times comparing human ovarian carcinoma with normal ovarian epithelium. Among these genes 86 were up-regulated > 5 times and 99 were down regulated

// Zhengyan Yang 1,* , Liang Guo 1,* , Dan Liu 1 , Limin Sun 1 , Hongyu Chen 1 , Que Deng 1 , Yanjun Liu 2 , Ming Yu 1 , Yuanfang Ma 2 , Ning Guo 1 and Ming Shi 1 1 Institute of Basic Medical Sciences, Beijing, P.R. China 2 Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng, P.R. China * These authors contributed equally to this work Correspondence: Ming Shi, email: // Ning Guo, email: // Keywords : trastuzumab, gastric cancer, STAT3, Notch Received : September 29, 2014 Accepted : December 27, 2014 Published : December 31, 2014 Abstract In the present study, we demonstrate that prolonged treatment by trastuzumab induced resistance of NCI-N87 gastric cancer cells to trastuzumab. The resistant cells possessed typical characteristics of epithelial to mesenchymal transition (EMT)/cancer stem cells and acquired more invasive and metastatic potentials both in vitro and in vivo . Long term treatment with trastuzumab dramatically inhibited the phosphorylation of Akt, but triggered the activation of STAT3. The level of IL-6 was remarkably increased, implicating that the release of IL-6 that drives the STAT3 activation initiates the survival signaling transition. Furthermore, the Notch activities were significantly enhanced in the resistant cells, companied by upregulation of the Notch ligand Jagged-1 and the Notch responsive genes Hey1 and Hey2. Inhibiting the endogenous Notch pathway reduced the IL-6 expression and restored the sensitivities of the resistant cells to trastuzumab. Blocking of the STAT3 signaling abrogated IL-6-induced Jagged-1 expression, effectively inhibited the growth of the trastuzumab resistant cells, and enhanced the anti-tumor activities of trastuzumab in the resistant cells. These findings implicate that the IL-6/STAT3/Jagged-1/Notch axis may be a useful target and that combination of the Notch or STAT3 inhibitors with trastuzumab may prevent or delay clinical resistance and improve the efficacy of trastuzumab in gastric cancer.

Angiogenesis is an important factor in invasive tumor growth, progression, and metastasis. Multiple proangiogenic mechanisms are involved in tumor angiogenesis. In this study, we showed that the neurotransmitter norepinephrine upregulated VEGF (VEGFA) expression in breast cancer cells and that the culture supernatant from norepinephrine-treated breast cancer cells promoted the formation of the capillary-like network of endothelial cells. However, the effects of norepinephrine were further enhanced when the endothelial cells were cocultured with breast cancer cells, indicating a critical role of tumor cell-endothelial cell contacts in norepinephrine-induced tumor angiogenesis. Interestingly, norepinephrine dramatically induced the activation of the Notch pathway, which is a cell-contact-mediated intercellular signaling pathway and tightly linked to tumor cell-stromal cell interaction and angiogenesis, in the endothelial cells that had been cocultured with breast cancer cells. Furthermore, the expression of the Notch ligand Jagged 1 was significantly upregulated by norepinephrine at both mRNA and protein levels in breast cancer cells. Inhibitors of β2-adrenergic receptor (β2-AR), protein kinase A (PKA), and mTOR could reverse norepinephrine-induced Jagged 1 upregulation, indicating that the β2-AR-PKA-mTOR pathway participates in this process. Knockdown of Jagged 1 expression in breast cancer cells not only repressed norepinephrine-induced activation of the Notch pathway in cocultured endothelial cells but also evidently impaired the effects of norepinephrine on capillary-like sprout formation. These data demonstrate that tumor angiogenesis mediated by the Jagged 1/Notch intercellular signaling is governed by the norepinephrine-activated β2-AR-PKA-mTOR pathway.

To investigate the remineralization efficacy of different types of toothpastes on initial enamel lesions in vitro.Artificial initial lesions were created on 150 enamel discs from freshly extracted bovine incisors. These enamel discs were divided into five groups. The test treatment consisted of undiluted Colgate Sensitive Pro-Relief Toothpaste containing 8.0% arginine, calcium carbonate and 1,450 ppm fluoride that was applied on the enamel surface under a pH-cycling including 4 x 3-minute application daily for 12 days and soaked in remineralizing solution during the untreated periods. The two other test products were commercial products: Crest Cavity Protection Toothpaste, containing 0.11% fluoride and GC Tooth Mousse, a professional remineralizing treatment paste (the active ingredients: casein phosphopeptide - amorphous calcium phosphate, fluoride). NaF solution (0.14% fluoride) was used as the positive control, while double distilled water (ddH2O) was used as the negative control. The remineralization of enamel discs was evaluated using Knoop hardness test, confocal laser scanning microscopy (CLSM) and polarized light microscopy (PLM), and the caries lesion depth was quantified using an image analyzer. The data were analyzed by ANOVA.All test products showed a recovery of the Knoop Hardness Number (KHN) after remineralization cycling treatment. The recovery of enamel KHN for Colgate Sensitive Pro-Relief, GC Mousse, Crest toothpasteand NaF groups were 44.53 +/- 6.72%, 35.00 +/- 7.83%, 24.56 +/- 5.95% and 42.51 +/- 6.74% respectively, while the recovery of negative control group was 18.99 +/- 4.98%. PLM results indicated the lesion depth recovery of 49.63 +/- 8.06%, 35.08 +/- 2.19%, 22.60 +/- 7.30% and 53.20 +/- 1.48% respectively, which were also significantly greater than that of the negative group (20.51 +/- 4.80%). CLSM analysis showed a reduction of average area, and total and average dye fluorescence of the lesions after treatment. The Colgate Sensitive Pro-Relief group presented significantly greater remineralization than the other toothpaste groups, while the Crest toothpaste group showed the lowest remineralization ability.

Objective: To study the gene expression of high metastatic human ovarian carcinoma cell line (HO-8910PM) and to screen for novel metastasis- associated genes by cDNA microarray. Methods: The cDNA was retro-transcribed from equal quantity mRNA derived from tissues of highly metastatic ovarian carcinoma cell line and normal ovarian, and was labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BioDoor 4096 double dot human whole gene chip. The chip was scanned by scanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results: By applying the cDNA microarray we found: A total of 323 genes whose expression level were 3 times higher or lower in HO-8910PM cell than normal ovarian epithelium cell were screened out, with 71 higher and 252 lower respectively. Among these 10 were new genes. 67 genes showed expression difference bigger than 6 times between HO-8910PM cell and normal ovarian epithelium cell, among these genes 12 were higher, 55 lower, and two new genes were found. Conclusion: cDNA microarray technique is effective in screening the differentially expressed genes between human ovarian cancer cell line (HO-8910PM) and normal ovarian epithelium cell. Using the cDNA microarray to analyze of human ovarian cancer cell line gene expression profile difference will help the gene diagnosis, treatment and protection.

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

Erbin is ubiquitously expressed in normal epithelial tissues and constitutively associates with Her2 at the basolateral membranes in epithelial cells. The inhibitory role of Erbin in ERK signaling has been demonstrated. However, whether the expression of Erbin is altered in Her2-overexpressing breast cancer is unclear. There is little information regarding the function of Erbin in cancer progression. In the present study, we demonstrate that the level of Erbin is significantly downregulated or lost in breast cancer tissues. Erbin deficiency resulted in a dramatic enhancement in heregulin-induced AKT activation and overexpression of Erbin not only significantly decreased the intensity of heregulin-induced AKT phosphorylation but also shortened its duration in Her2-overexpressing breast cancer cells. Knockdown of Erbin remarkably promotes cell migration, induces invasive phenotype of breast cancer cells and antagonized the anti-proliferative effect of therapeutic antibody trastuzumab. Treatment with AKT inhibitor GDC0941 dramatically reversed the effects of Erbin knockdown on the cell migration and trastuzumab resistance, which is mainly mediated by aberrant activation of AKT. The data reveal that Erbin is a negative regulator of AKT activation and suggest that Erbin may play a role in breast cancer progression.

Tetracentron sinense (Trochodendraceae) is a Tertiary relict endemic to East Asia. Microsatellite markers were developed and characterized to investigate the population genetics of the species.Microsatellite markers were isolated from the genome of T. sinense using the protocol of Fast Isolation by AFLP of Sequences COntaining repeats (FIASCO). Eight polymorphic microsatellite markers were assessed in 44 samples collected from three wild populations. The number of alleles observed for each locus ranged from two to five. The observed and expected heterozygosities ranged from 0.0000 to 0.9375 and 0.0000 to 0.7681, respectively.The microsatellite markers will be helpful in further studies of the population genetics and phylogeography of T. sinense.

Background Her2 and β2-adrenergic receptor (β2-AR) can form a heterocomplex in cardiomyocytes and agonists can induce Her2 transactivation, which is important for cardiovascular homeostasis. The scaffolding molecules that mediate β2-AR/Her2 interaction are currently unknown. Erbin, a PDZ domain-containing protein is a binding partner of Her2. The C-terminus of β2-AR harbors a PDZ domain-binding motif. Hypothesis of this study is that Erbin may organize the assembly of β2-AR/Her2 complex. Methods The interaction among β2-AR, Her2 and Erbin was investigated in COS-7, HEK-293 and H9c2 cells and rat brain and heart tissues by coimmunoprecipitation. The β2-AR binding region of Erbin was identified by utilizing the Erbin deletion mutants. The functional significance of Erbin in cardiomyocytes was determined by Erbin silencing, contraction frequency measurement and cellular apoptosis assays. Results Erbin was able to form a complex with both exogenous and endogenous β2-AR and Her2 in the presence of isoproterenol (ISO). Deletion of the Erbin LRR domain did not affect its binding to β2-AR and Her2, whereas lacking of the PDZ domain lost the ability of Erbin. Silencing of Erbin greatly abrogated ISO-induced activation of ERK. The treatment of H9c2 cells transfected with the Erbin siRNA with ISO caused severe cell apoptosis. Knock-down of Erbin expression in primary neonatal rat cardiomyocytes led to a remarkable reduction of the beating frequency after ISO stimulation. Conclusions Erbin mediates catecholamine-induced β2-AR/Her2 complexation and promotes catecholamine-induced activation of ERK signaling in cardiomyocytes, conferring protection of cardiomyocytes from apoptosis induced by chronic catecholamine stimulation.

Glucocorticoids are stress-responsive neuroendocrine mediators and play an important role in malignant progression, especially in solid tumours. We demonstrate a novel mechanism by which glucocorticoids modulate p53-dependent miR-145 expression in HPV-positive cervical cancer cells through induction of E6 proteins. We found that expression of miR-145 was reduced in cervical cancer tissues. Cortisol induced HPV-E6 expression and suppressed p53 and miR-145 in cervical cancer cells. MiR-145 expression in cervical cancer cells was wild-type p53-dependent, and cortisol-induced down-regulation of miR-145 expression prevented chemotherapy-induced apoptosis, whereas over-expression of miR-145 enhanced sensitivity to mitomycin and reversed the chemoresistance induced by glucocorticoids. We also show that miR-145 augments the effects of p53 by suppressing the inhibitors of p53 in cervical cancer cells, suggesting that miR-145 plays a role in p53 tumour suppression. Finally, we demonstrate that miR-145 inhibits both the motility and invasion of cervical cancer cells. Our findings identify a novel pathway through which the neuroendocrine macroenvironment affects cervical tumour growth, invasion and therapy resistance and show that miR-145 may serve as a target for cervical cancer therapy. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

When the body is intruded, there is a congenital immune process to find and reduce the damage as quickly as possible. This is an important recovery character for the biology immune system. A model that simulates the biology's congenital immunity is introduced in the computer immune system. It has two basal agents, Damage Detector Agent and Congenital Response Agent. Damage Detector Agent finds intrusion and releases dangerous signal to excited Congenital Response Agent. And it uses a Dynamic Semi-Active Replication technology to ensure the system can work. All this work can improve the system's robustness that it can supply the basic services when it's intruded.

To study the difference between gene expressions of high (H0-8910PM) and low (HO-8910) metastatic human ovarian carcinoma cell lines and screen novel associated genes by cDNA microarray.cDNA retro-transcribed from equal quantities of mRNA derived from high and low metastatic tumor cells or normal ovarian tissues were labeled with Cy5 and Cy3 fluorescein as probes. The mixed probe was hybridized with two pieces of BioDoor 4096 double dot human whole gene chip and scanned with a ScanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software.A total of 355 genes with expression levels more than 3 times larger were found by comparing the HO-8910 cell with normal ovarian epithelial cells. A total of 323 genes with expression levels more than 3 times larger in HO-8910PM cells compared to normal ovarian epithelium cells were also detected. A total of 165 genes whose expression levels were more than two times those of HO-8910PM cells compared to their mother cell line (HO-8910) were detected. Twenty-one genes with expression levels3 times were found from comparison of these two tumor cell lines.cDNA microarray techniques are effective in screening differential gene expression between two human ovarian cancer cell lines (H0-8910PM; HO-8910) and normal ovarian epithelial cells. These genes may be related to the genesis and development of ovarian carcinoma. Analysis of the human ovarian cancer gene expression profile with cDNA microarray may help in gene diagnosis, treatment and prevention.