Our study showed that S-methylisothiourea (SMT) had anti-inflammatory effects in treating herpes simplex encephalitis in mice, and SMT also induced apoptosis of herpes simplex virus (HSV-1)-infected microglial cells. Both animal and cell models were employed in this study. Both models included the following five groups: a normal control group, a virus group (HSV-1 infected), an SMT group (HSV-1-infected + SMT (0.1 mg/10 g)), a dexamethasone group (HSV-1 infected + dexamethasone (2 mug/10 g)), and an APS group (HSV-1-infected + APS (0.8 mg/10 g)). ELISA was used to measure tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-10, and Greiss method was used for measuring nitric oxide (NO) secretion. HE staining was performed for detecting changes in mice brain. Flow cytometry assay for caspase-3, caspase-8, caspase-9, and caspase-12 expressions was also carried out to assess apoptosis. Expressions of TNF-alpha, IL-1beta, and NO were significantly elevated after stimulation of microglial cells with HSV-1. Following SMT intervention, TNF-alpha, IL-1beta, and NO levels were significantly decreased. The inflammatory changes in HSV-1-infected murine brain tissues were also reduced. SMT induction of apoptosis of HSV-stimulated microglia seemed to be through three pathways: the death receptor, mitochondrially gated, and endoplasmic reticulum. SMT can reduce HSV-induced inflammatory insult to the brain. Its mechanism of action is most probably due to the induction of microglial cell apoptosis.

To better understand the role of PRL-3 in progression and metastasis of colorectal cancer (CRC), we searched for PRL-3 associated proteins using proteomic methods. We identified 39 proteins regulated by PRL-3 based on proteomic strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines and CRC tissues indicated that PRL-3 could interact with stathmin. And, both stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells. Moreover, Gain-of-function and loss-of-function analyses revealed that stathmin promoted proliferation, motility and migration of human CRC cells. Immunohistochemical analysis of 149 colorectal tumor samples showed that overexpression of stathmin was strongly correlated with tumor differentiation (P=0.035), tumor invasion (P=0.024), lymph node status (P<0.001), Dukes classification (P<0.001) and TNM staging (P<0.001) of CRC patients. Univariate and multivariate survival analyses further supported that over-expression of stathmin protein was a potential independent poor prognostic factor for CRC. Our results reveal many PRL-3 associated proteins for the first time. The oncoprotein stathmin playes a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC.

The sensitivity encoding (SENSE) reconstruction reconstruction of parallel imaging can suffer from amplified noise at high reduction factors due to the ill-conditioned system matrix. Regularization alleviates this problem by imposing priors on the reconstructed image. These priors typically introduce both intrastructure smoothness and interstructure smoothness. The former mainly reduces noise, while the latter can also decrease intensity changes between different structures and cause structure loss. In this study, coherence regularization was proposed to impose only intrastructure smoothness in order to enhance the preservation of the image structure. Its energy functional was formed by examining the connection between regularization and the diffusion equation of adaptive image filtering. The coherence regularization extracts image structure information directly from the noisy data by adapting diffusion equation-related image-filtering methods. In this study, a nonlocal operator derived from the nonlocal mean filter was used for structure detection. Based on this structure information, only intrastructure intensity changes are penalized while the interstructure intensity changes are preserved. Both phantom simulation and in vivo experiments demonstrate that the coherence regularization would be able to effectively suppress noise in SENSE reconstruction at high reduction factors while suffering from much less image degradation, compared to Tikhonov and total variation methods. Magn Reson Med, 2010. (c) 2010 Wiley-Liss, Inc.

PURPOSE: The cytokines present in the aqueous humor and serum of C3H/HeN mice with endotoxin-induced acute anterior uveitis were analyzed, and the potential role of the cytokines in the pathogenesis of the disease was investigated. METHODS: One hundred and eighty C3H/HeN mice were divided into an experimental group (n=150) and a control group (n=30). The mice in the experimental group were footpad-injected with 200 mug Vibro cholerae endotoxin (classical biotype, serotype Ogawa). The mice were then executed 4 h, 8 h, 16 h, 24 h, and 48 h after the injection of endotoxin. Aqueous humor and peripheral blood samples were collected using a microinjector. Ten samples were pooled together for analysis and centrifuged at 705x g, at 4 degrees C, for 3 min. The supernatant was collected and stored at -80 degrees C. The concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-gamma (IFN-gamma) in the samples were measured using a Cytometric Bead Array (CBA). RESULTS: Acute anterior uveitis was successfully induced in C3H/HeN mice. At roughly 16 h post-injection, the concentrations of both IL-1 and IL-6 reached peak levels, and were significantly different from the control group (p=0.001 and p=0.001, respectively). At 24 h post-injection, the concentrations of IFN-gamma and IL-10 in the aqueous humor reached peak levels, and were significantly different from the control group (p=0.022 and p=0.003). The concentrations of IFN-gamma in serum at 4 and 24 hours were significantly different from the control group (p=0.033 and p=0.032). The concentration of IL-10 in serum, at 24 h post-injection, was also found to be significantly different from the control group (p=0.003). The cytokine expression levels in the aqueous humor were consistent with what would be expected during the process of inflammation. CONCLUSIONS: Both IL-1 and IL-6 appear to play an important role in acute anterior uveitis; furthermore, the severity of inflammation may be associated with the dynamic balance of IFN-gamma and IL-10. Our results suggest that the cytokine network might be a useful therapeutic target in the treatment of acute anterior uveitis.

3-O-alpha-D-ribofuranosyl epothilone A (epothiloneoside A) is a major component of glycosylated epothilones in Sorangium cellulosum strain So0157-2. The production and glycosylation ratios of epothiloneoside A in both solid and liquid culture conditions with various pH values and carbon sources were studied. The results showed that glycosylation occurs whenever epothilones are produced, regardless of changes in pH values, production time curves, and different carbon sources. We suggest that glycosylation is a stable process, paralleling the biosynthesis of epothilones in the So0157-2 strain.

BACKGROUND: -Studies on the incidence and predictors of heart failure (HF) are often restricted to elderly persons, or identify only inpatient cases. METHODS AND RESULTS: -We determined the incidence and predictors of new HF diagnosed in either outpatient or inpatient settings, among 359,947 women and men (age >/= 18 years) insured by Kaiser Permanente Georgia at any time during calendar years 2000-2005. Subjects were free of HF at baseline, and incident HF was identified with ICD-9 codes (one inpatient or two outpatient HF visits). We developed multivariable Cox models to assess the association of antecedent factors (coronary heart disease, hypertension, diabetes mellitus, atrial fibrillation, and valvular heart disease) with incident HF. Separate models were created for each sex, and for newly diagnosed HF in outpatient or inpatient settings. There were 4,001 incident HF cases (50% women, and 48% in subjects < 65 years old), during 1,015,794 person-years follow-up. The incidence rate of HF was greater in men than in women (4.24 versus 3.68 per 1,000 person-years), but was stable across the study interval in both sexes. Two-thirds of incident HF cases from this population occurred in outpatients. These five antecedent factors and age yielded excellent discrimination for incident HF in both outpatients and inpatients, and in both sexes (C>0.85 in all models). CONCLUSIONS: -Common, modifiable risk factors accurately discriminate women and men at risk for HF diagnosed in either outpatient or inpatient settings. Approximately two-thirds of new HF cases in our insured population were diagnosed in outpatients; more research is needed to characterize these subjects and their prognosis.

Summary. With the proliferation of spatially oriented time-to-event data, spatial modeling in the survival context has received increased recent attention. A traditional way to capture a spatial pattern is to introduce frailty terms in the linear predictor of a semiparametric model, such as proportional hazards or accelerated failure time. We propose a new methodology to capture the spatial pattern by assuming a prior based on a mixture of spatially dependent Polya trees for the baseline survival in the proportional hazards model. Thanks to modern Markov chain Monte Carlo (MCMC) methods, this approach remains computationally feasible in a fully hierarchical Bayesian framework. We compare the spatially dependent mixture of Polya trees (MPT) approach to the traditional spatial frailty approach, and illustrate the usefulness of this method with an analysis of Iowan breast cancer survival data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. Our method provides better goodness of fit over the traditional alternatives as measured by log pseudo marginal likelihood (LPML), the deviance information criterion (DIC), and full sample score (FSS) statistics.

AIM: To evaluate the diagnostic value of cancer-testis antigen (CTA) mRNA in peripheral blood samples from hepatocellular carcinoma (HCC) patients. METHODS: Peripheral blood samples were taken from 90 patients with HCC before operation. Expression of melanoma antigen-1 (MAGE-1), synovial sarcoma X breakpoint-1 (SSX-1), and cancer-testis-associated protein of 11 kDa (CTp11) mRNA in peripheral blood mononuclear cells (PBMC) was tested by nested reverse transcripts-polymerase chain reaction (RT-PCR). Serum alpha-fetoprotein (AFP) in these patients was also determined. RESULTS: The positive rate of MAGE-1, SSX-1 and CTp11 transcripts was 37.7%, 34.4%, 31.1% in PBMC samples, and 74.4%, 73.3%, 62.2% in their resected tumor samples, respectively. The positive rate for at least one of the transcripts of three CTA genes was 66.7% in PBMC samples and 91.1% in their resected tumor samples. MAGE-1, SSX-1 and/or CTp11 mRNA were not detected in the PBMC of those patients from whom the resected tumor samples were MAGE-1, SSX-1 and/or CTp11 mRNA negative, nor in the PBMC samples from 20 healthy donors and 10 cirrhotic patients. Among the 90 patients, the serum AFP in 44 patients met the general diagnostic standard (AFP > 400 mug/L) for HCC, and was negative (AFP </= 20 mug/L) or positive with a low concentration (20 mug/L < AFP </= 400 mug/L) in the other patients. The positive rate for at least one of the transcripts of three CTA genes in PBMC samples from the AFP negative or positive patients with a low concentration was 69.2% and 45.0%, respectively. Of the 90 patients, 71 (78.9%) were diagnosed as HCC by nested RT-PCR and serum AFP. Although the positive rate for at least one of the transcripts of three CTA genes in PBMC samples from 53 patients at TNM stage III or IV was obviously higher than that in PBMC samples from 37 patients at stage I or II (77.9% vs 51.4%, P = 0.010), the CTA mRNA was detected in 41.7% and 56.0% of PBMC samples from HCC patients at stages I and II, respectively. CONCLUSION: Detecting MAGE-1, SSX-1 and CTp11 mRNA in PBMC improves the total diagnostic rate of HCC.

Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related synaptic structure alterations in different memory processes. We found that CTA training could induce increased postsynaptic density (PSD) length in insular cortex (IC), but not in basolateral amygdala (BLA) and prelimbic cortex (PrL) during short-term memory (STM) formation, whereas it led to increased PSD length and synapse density in both IC and PrL during long-term memory (LTM) formation. Inhibition of actin rearrangement in the IC, but not in the BLA and PrL, impaired memory acquisition. Furthermore, actin dynamics in the IC or PrL is necessary for memory consolidation. On the contrary, inhibition of actin dynamics in the IC, BLA, or PrL had no effect on CTA memory retrieval. Our results suggest temporal and regional-specific regulation of actin rearrangement-related synaptic structure in different phases of CTA memory.

PURPOSE: Radiation-induced pneumonitis (RP) is the most common dose-limiting complication in lung cancer patients treated with radiotherapy. Accumulating evidence indicates that P53 and the ataxia telangiectasia-mutated protein (ATM)-dependent signaling response cascade play a crucial role in radiation-induced diseases. Consistent with this, our previous study showed that a functional genetic ATM polymorphism was associated with increased RP risk. METHODS AND MATERIALS: To evaluate the role of genetic P53 polymorphism in RP, we analyzed the P53 Arg72Pro polymorphism in a cohort including 253 lung cancer patients receiving thoracic irradiation. RESULTS: We found that the P53 72Arg/Arg genotype was associated with increased RP risk compared with the 72Pro/Pro genotype. Furthermore, the P53 Arg72Pro and ATM -111G>A polymorphisms display an additive combination effect in intensifying the risk of developing RP. The cross-validation test showed that 63.2% of RP cases can be identified by P53 and ATM genotypes. CONCLUSIONS: These results indicate that genetic polymorphisms in the ATM-P53 pathway influence susceptibility to RP and genotyping P53 and ATM polymorphisms might help to identify patients susceptible to developing RP when receiving radiotherapy.

The decrease of erythrocyte deformability may be one of the predisposing factors for pulmonary hypertension and ascites in broiler chickens. In mammals, the cytoplasmic calcium is a major regulator of erythrocyte deformability. In this study, the erythrocyte deformability was measured, and the precise locations of Ca(2+) and Ca(2+)-ATPase in the erythrocytes were investigated in chickens with ascites syndrome induced by low ambient temperature. The results showed that ascitic broilers had higher filtration index of erythrocyte compared with control groups, indicating a decrease in erythrocyte deformability in ascitic broilers. The more calcium deposits were observed in the erythrocytes of ascitic broilers compared with those of the age-matched control birds. The Ca(2+)-ATPase reactive grains were significantly decreased on the erythrocyte membranes of ascitic broilers. Our data suggest that accumulation of intracellular calcium and inhibition of Ca(2+)-ATPase might be important factors for the reduced deformability of the erythrocytes of ascitic broilers.

OBJECTIVE: To analyze the prevalence of malnutrition and its affected factors of poor rural infants under 2 years old in Guangxi Province. METHODS; Applying a three stages stratified cluster sampling method, a total of 653 subjects were sampled from 4 rural poor counties. The Z score standards recommended by NCHS/WHO were used to evaluate the nutrition and health condition of infants. Non-conditional multifactor logistic regression model was used to analyze the factors affecting nutritional status. RESULTS: The rates of low birth weight, growth retardation, under weight, emaciation and anemia of 653 infants under 2 years old were 8.7%, 39.7%, 42.1%,14.4% and 25.4% respectively. The non-conditional multifactor logistic regression model indicates that the age of infants, the caregivers and the time of their mothers working outside were the associated risk factors of growth retardation and under weight of the babies. CONCLUSION: The rate of low birth weight in part of rural poor areas in Guangxi Province was obviously higher than the expecting target (i. e. lower than 5%) at the year 2010. The rates of growth retardation, under weight, emaciation and anemia were still high.

Hepatocellular carcinoma (HCC) is the second most common malignancy in Asia, with a 5-year survival rate of less than 5% due to high recurrence after surgery and resistance to chemotherapy. A variety of therapeutic interventions to treat HCC, particularly gene therapy, have recently been investigated in tumor model systems to provide a more complete understanding of hepatocarcinogenesis and effectively design therapeutic strategies to treat this disease. In the present study, we constructed an adenoviral vector expressing small interfering RNA (siRNA) targeting a newly discovered gene named up-regulated gene 11 (URG11). We introduced this vector into HCC cells to investigate the role of URG11 in HCC carcinogenesis. We observed that upon URG11 knockdown, HCC cell proliferation was inhibited through downregulation of several G1-S phase related molecules including cyclin D1 and apoptosis was induced as a result of Bcl-2 downregulation. Besides decreased expression of cyclin D1, CDK4, pRb and Bcl-2, URG11 also suppressed several other proteins including CAPN9, which was identified by cDNA microarray and 2-D gel electrophoresis. Moreover, Ad-URG11-siRNA significantly suppressed HCC tumor growth in nude mice. In conclusion, Ad-URG11-siRNA can significantly suppress HCC tumor growth in vitro and in vivo by silencing the URG11 gene, and the use of this vector for gene therapy may represent a novel strategy to treat human HCC.

BACKGROUND: The clinical value of postoperative radiotherapy (PORT) in stage N2 nonsmall-cell lung cancer (NSCLC) is controversy. The aim of this study is to analyze the efficacy of PORT in subgroup of stage N2 NSCLC, which can help clinicians to choose proper patients for PORT. METHODS: Clinical data of 359 patients with stage N2 NSCLC treated with radical surgery between Mar. 2000 and Jul. 2005 were retrospectively reviewed. Two hundred and seven patients received adjuvant chemotherapy and one hundred and four patients received adjuvant radiotherapy. First, the group of patients were analyzed to evaluate the factors affecting the overall survival. The all patients were divided based on tumor size and the number of lymph node metastasis station (single station or multiple station) so as to evaluate the role of PORT. The endpoint was overall survival (OS) and local recurrence-free survival (LRFS). Kaplan-Meier method was used to calculate the OS, LRFS and Log-rank was used to compare the difference in OS and LRFS between different groups. RESULTS: The median duration of follow-up was 2.3 years. 224 patients died. The median survival was 1.5 years and 1, 3, 5-year survival were 78%, 38% and 26%. Univariate analysis showed tumor size, the number of lymph node metastasis station and PORT were correlated with OS. Among patients, 5-year survival rates in PORT and non-PORT were 29% and 24% (P=0.047) respectively. In subgroups, PORT was related with high survival in patients with multiple station N2 compared to non-PORT: 36% vs 20% (P=0.013) and 33% vs 15% (P=0.002) in patients in patients with tumor size>3 cm. Also, it was related with low local recurrence compared to non-PORT: 65% vs 48% (P=0.006) and 62% vs 48% (P=0.033). CONCLUSIONS: PORT can improve overall survival for N2 NSCLC, especially the patients with the factors as follows: tumor size>3 cm and multiple station N2 can benefit from PORT more or less.

BACKGROUND: Postoperative radiotherapy (PORT) after complete resection of non-small cell lung cancer (NSCLC) has been introduced in order to reduce locoregional recurrence, but it remains controversy whether PORT can improve survival. Therefore, we want to investigate the effect of PORT and the relationship between failure patterns and primarily location of stage IIIA (N2) in NSCLC. METHODS: This retrospective analysis included 233 patients who underwent resection of NSCLC, first recurrence involving a local-regional site. It illustrated the factors affecting local recurrence and the sites of failure on the basis of lobe of primary tumor. RESULTS: Multivariable analysis demonstrated the number of positive lymph nodes (P=0.003), T stage (P<0.001), histological type (P=0.038), modus operandi (P=0.013) and the number of mediastinal lymph node stations involved (P=0.018) were the independent factors. For all patients, the most common site of failure was the bronchial stump/staple line, which was present more often in those who had a wedge resection than in those who had a more radical procedure (P<0.001). The local-region frequency of squamous was higher than adenocarcinoma carcinoma (P=0.025). The recurrence frequency of mediastinal lymph node among T1 and T2-3 were 36.4%, 62.0% (P=0.009) respectively. The localregion recurrence among primarily tumor location were different. CONCLUSIONS: The number of positive lymph nodes, T stage, histological type, modus operations and the number of mediastinal lymph node stations involved were the independent factors in IIIA (N2) NSCLC.

BACKGROUND: The recurrence, metastasis and multidrug resistance (MDR) in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. METHODS: The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. RESULTS: The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1*10(6) and 1.5*10(6) cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2 CONCLUSIONS: The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it's a good experimental model for lung cancer research.

We demonstrate an eight-channel reconfigurable optical filter on a silicon chip. It consists of cascaded microring resonators and integrated compact heaters. With an embedded Mach-Zehnder (MZ) arm coupling to a microring resonator, the important parameters of a filter such as center frequency, extinction ratio and bandwidth can be controlled simultaneously for purposes of filtering, routing and spectral shaping. Thus our device could potentially be useful in dense wavelength division multiplexing (DWDM) and radio frequency arbitrary waveform generation (RFAWG). Multichannel filter response was successfully tuned to match the International Telecommunication Unit (ITU) grid with 50, 100 and 200GHz in channel spacing. Programmable channel selectivity was demonstrated by heating the MZ arm, and continuous adjustment of through-port extinction ratio from 0dB to 27dB was achieved. Meanwhile, the 3dB bandwidth in the drop port changed from 0.12nm to 0.16nm. The device had an ultra-compact footprint (1200mumx100mum) excluding the metal leads and contact pads, making it suitable for large scale integration.

We report on dissipative soliton (DS) generation in an Yb-doped (YDF) fiber laser passively mode locked with the nonlinear polarization rotation (NPR) technique. We found that even without the insertion of a physical bandpass filter in the cavity, not only could DSs be automatically formed in the laser but also the formed DSs have a spectral bandwidth that is far narrower than the Yb-fiber gain bandwidth. Numerical simulations well reproduced the experimental observations. Our results suggest that a physical intracavity bandpass filter is not a crucial component for the generation of DSs in all-normal-dispersion YDF lasers mode locked with the NPR technique.

Poly(ethyleneglycol)-b-poly(4-vinylpyridine) (PEG-b-P4VP) and zinc meso-5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin (ZnTPPS) form complex micelles based on electrostatic interactions. The complex micelles have a core-shell structure that can effectively prevent the demetallization and aggregation of ZnTPPS in acidic aqueous solutions (pH < 4.0).

To explore the structure and property features of complex aggregates assembled by polymer and organic dye molecules in microcosmic soft confined space, a three-dimensional microconfinement is constructed by W/O inverse emulsion as the site for the complex aggregation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP). It is found that porphyrin molecules exist in emulsion droplets mainly as the deprotonated monomer form, even though the pH of the water phase is much lower than the pK(a) of TPPS in bulk (pK(a) approximately 4.7). In spatially confined circumstances, upon blending of the single-component emulsions, complex aggregates are formed due to the thermodynamic collision of emulsion droplets and the subsequent electrostatic interaction between TPPS and polymer. The resultant novel complexes possess a relatively precise structure and homogenous core consisting of a porphyrin and P4VP block. Upon emulsion-breaking, the metastable complex kinetic intermediates generated in original acidic emulsion droplets display a remarkable trend of reaggregation within a certain period of time followed by a disassociation and redispersion. Complex aggregates with some novel morphologies are observed. The final product has a core-shell structure with the electrostatic complex of deprotonized porphyrin molecules homogenously dispersing in the P4VP clew as the core and the soluble PEG as the shell. However, those complexes produced in basic emulsion droplets exhibit a relatively higher stability against further aggregation after breakage of emulsion.