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Aflatoxin is a secondary metabolite secreted by Aspergillus flavus, parasitic Aspergillus, and other fungi through the polyketone pathway, and it can be detected in many foods. Aflatoxin has strong toxicity and carcinogenicity, and many studies have shown that aflatoxin is highly associated with liver cancer. In the present study, malignant transformation of L02 cells was induced by aflatoxin B1 (AFB1), and the gene expression, miRNA expression, and methylation level were detected by highthroughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1-treated group compared with the DMSO group. Among them, RSAD2 and SCIN were significantly upregulated, whereas TRAPPC3L and UBE2L6 were significantly downregulated. Has-miR-33b-3p was significantly upregulated, whereas Has-miR-3613-5p was significantly downregulated. The methylation results showed that 2832 CpG sites were methylated on the promoter or coding DNA sequence (CDS) of the gene, whereas the expression of DNMT3a and DNMT3b was significantly upregulated. Moreover, hypermethylation occurred in TRAPPC3L, CDH13, and SPINK13. The results of GO and KEGG pathway analyses showed that significantly changed genes and miRNAs were mainly involved in tumor formation, proliferation, invasion, and migration. The results of network map analysis showed that Hsa-miR-3613-5p, Hsa-miR-615-5p, Hsa-miR-615-3p, and Hsa-miR-3158-3p were the key miRNAs for malignant transformation of L02 cells induced by AFB1. In addition, the expression of ONECUT2, RAP1GAP2, and FSTL4 was regulated by DNA methylation and miRNAs. These results suggested that the gene expression network regulated by DNA methylation and miRNAs may play a vital role in AFB1-induced hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

The NanoString GeoMx digital spatial profiling is a new multiplexed platform that quantifies the abundance of tumor‐ and immune‐related proteins in a spatially resolved manner. We performed DSP for the simultaneous assessment of 52 analytes within spatially resolved tissue compartments defined by pan‐cytokeratin expression. We compared protein targets between 94 African American/Black and 65 European American/White cases, tumor and stromal tissue compartments, estrogen receptor alpha (ER)‐positive and ER‐negative cases, and explored potential biomarkers of survival. Of 33 analytes with robust signal for analysis, results were highly replicable. For a subset of markers, correlative analyses between DSP analytes and traditional immunohistochemistry scores revealed moderate to very strong associations between the two platforms. Similarly, DSP analytes and gene expression scores were concordant for 21 of 25 markers with overlap between the two datasets. Several analytes varied by ER status, and across the 25 immune markers surveyed, 14 had a significant inverse association with ER expression. B7 homolog 3 (B7‐H3; encoded by CD276) was the only analyte to show a significant difference by race, being lower in both the tumor and stromal compartments in Black women. DSP markers that were associated with survival included CD8, CD25, CD56, CD127, EpCAM, ER, Ki‐67, and STING. We conclude that DSP is an efficient tool for screening tumor‐ and immune‐related markers in a simultaneous fashion and yields results that are concordant with established immune profiling assays. DSP immune analytes were inversely associated with ER expression, in agreement with a substantial body of previous work that documents higher immune infiltration in ER‐negative breast cancers. This technology revealed that scores of the B7‐H3 protein were significantly lower in breast cancers from Black women compared with White women, an intriguing finding that requires replication in independent and racially diverse female populations. [ABSTRACT FROM AUTHOR]

Purpose: Secondary prevention of coronary artery disease, self‐management behavior, and blood pressure control are important to cardiovascular event prevention and promotion of quality of life (QOL), but they are underutilized. The purpose of this study was to investigate the effects of a self‐efficacy theory–based health information technology intervention implemented through blood control and patient self‐management. Design: A clinical randomized waitlist‐controlled trial. Methods: The study was conducted at a medical center in Taipei, Taiwan. A total of 60 subjects were randomly assigned to either the immediate intervention (experimental) group or the waitlist control group. The primary endpoint was systolic blood pressure at 3 months; secondary end points included self‐management behavior and QOL. Treatment for the immediate intervention group lasted 3 months, while the waitlist control group received routine care for the first 3 months, at which point they crossed over to the intervention arm and received the same intervention as the experimental group for another 3 months. Both groups were evaluated by questionnaires and physiological measurements at both 3 and 6 months postadmission. The results were analyzed using generalized estimating equations. Results: Systolic blood pressure significantly improved for the intervention group participants at 3 months, when there was also significant improvement in self‐management behavior and QOL. There was no significant or appreciable effect of time spent in the waitlist condition, with treatments in the two conditions being similarly effective. Conclusion: The use of a theory‐based health information technology treatment compared with usual care resulted in a significant improvement in systolic blood pressure, self‐management behavior, and QOL in patients with coronary artery disease. Clinical Relevance: This treatment would be a useful strategy for clinical care of cardiovascular disease patients, improving their disease self‐management. It also may help guide further digital health care strategies during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a lethal human malignancy and a leading cause of cancer‐related death worldwide. Patients with HCC are often diagnosed at an advanced stage, and the prognosis is usually poor. The multikinase inhibitor sorafenib is the first‐line treatment for patients with advanced HCC. However, cases of primary or acquired resistance to sorafenib have gradually increased, leading to a predicament in HCC therapy. Thus, it is critical to investigate the mechanism underlying sorafenib resistance. Transactivation response element RNA‐binding protein 2 (TARBP2) is a multifaceted miRNA biogenesis factor that regulates cancer stem cell (CSC) properties. The tumorigenicity and drug resistance of cancer cells are often enhanced due to the acquisition of CSC features. However, the role of TARBP2 in sorafenib resistance in HCC remains unknown. Our results demonstrate that TARBP2 is significantly downregulated in sorafenib‐resistant HCC cells. The TARBP2 protein was destabilized through autophagic–lysosomal proteolysis, thereby stabilizing the expression of the CSC marker protein Nanog, which facilitates sorafenib resistance in HCC cells. In summary, here we reveal a novel miRNA‐independent role of TARBP2 in regulating sorafenib resistance in HCC cells. Sorafenib is the first‐line treatment for patients with advanced hepatocellular carcinoma (HCC). The cases of sorafenib resistance have gradually increased, leading to a predicament HCC therapy. Our results demonstrate that transactivation response element RNA‐binding protein 2 (TARBP2) is downregulated in sorafenib‐resistant HCC cells. TARBP2 protein was destabilized through autophagic–lysosomal proteolysis, thereby stabilizing Nanog, which facilitates sorafenib resistance in HCC cells. [ABSTRACT FROM AUTHOR]

Ubiquitination and deubiquitination are important post-translational regulatory mechanisms responsible for fine tuning the antiviral signaling. In this study, we identified a deubiquitinase, the ubiquitin-specific peptidase 7/herpes virus associated ubiquitin-specific protease (USP7/HAUSP) as an important negative modulator of virus-induced signaling. Overexpression of USP7 suppressed Sendai virus and polyinosinic-polycytidylic acid and poly(deoxyadenylic-deoxythymidylic)-induced ISRE and IFN-ß activation, and enhanced virus replication. Knockdown or knockout of endogenous USP7 expression had the opposite effect. Coimmunoprecipitation assays showed that USP7 physically interacted with tripartite motif (TRIM)27. This interaction was enhanced after SeV infection. In addition, TNF receptor-associated factor family member-associated NF-kappa-B-binding kinase (TBK)-1 was pulled down in the TRIM27-USP7 complex. Overexpression of USP7 promoted the ubiquitination and degradation of TBK1 through promoting the stability of TRIM27. Knockout of endogenous USP7 led to enhanced TRIM27 degradation and reduced TBK1 ubiquitination and degradation, resulting in enhanced type I IFN signaling. Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1. [ABSTRACT FROM AUTHOR]

This work studies the power quality impacts of electric transportation charging including electric buses (EBs) and electric vehicles (EVs) on distribution systems. The stochastic harmonic models for EBs and EVs and the stochastic models for their usage scenarios are built utilising the measured charging data. Based on these models, a power quality analysis method considering the charging uncertainties of EBs and EVs is proposed in this study and then their impacts on distribution systems are investigated. The Monte Carlo simulation is integrated into the proposed method to study the under voltage, overcurrent, voltage unbalance, transformer overload, harmonic current, voltage etc. caused by the stochastic charging of EBs and EVs. An actual distribution system acquired from Taiwan Power Company is taken as an example to validate the practicability of the proposed method. The test results of the proposed stochastic model are compared with those of the conservative model. [ABSTRACT FROM AUTHOR]

"Shuangyou," a Vitis amurensis Rupr. variety, is widely cultivated in northeastern and western China. Its berries have high acidity and low sugar content. In this study, different proportions of sucrose were added to the must samples during fermentation to investigate the effect of sugar on the physicochemical properties and volatile compounds of "Shuangyou" wines. The addition of sucrose significantly improved yeast growth and alcohol production, altered the color qualities, and slightly decreased titratable acidity during fermentation. The highest tested proportion of added sucrose resulted in the highest maximum yeast counts and final ethanol concentrations. Moreover, 37 volatile compounds (esters, alcohols, fatty acids, ketones, and aldehydes) were identified and quantified by solid-phase microextraction with gas chromatography-mass spectrometry. The concentrations of these compounds were correlated with the addition of sucrose. Furthermore, the addition of 100 g/L sucrose was sufficient for improving the concentrations of the aromatic compounds. The increase in ester, alcohol, and fatty acid concentration led to a positive OAVs impact (odor activity value > 1) at the end of fermentation. [ABSTRACT FROM AUTHOR]

Combining ability estimates of lines to be used in breeding are useful for maize (Zea mays L.) breeders. The objectives of this study were to (i) evaluate combining ability of 25 improved exotic germplasm using different numbers of testers (1 to 3) from Suwan1, Reid, and non-Reid heterotic groups; (ii) study differences in combining ability estimates obtained with different number of testers from the same vs. different heterotic groups; and (iii) determine the appropriate segregating ('S') generation in which line selection should be done to obtain stable general combining ability (GCA) estimates of lines. The results showed that three testers (one from each of the three heterotic groups) were economically best for estimating GCA effects of lines, and if a tester from one of the three heterotic groups was missed, GCA estimates for some lines were biased when compared with GCA estimates with testers from all three heterotic groups. Second, the specific combining ability (SCA) effects of test-crosses were quite similar regardless of whether one or two testers were used from each of the three heterotic groups. Thus, to obtain reliable SCA estimates, at least one tester would need to be used from each of the heterotic groups. Third, the SCA effects were different among crosses between different lines and testers, and to obtain stable estimates of GCA effects for a line, S4 or S5 generation should be the earliest generation in which to begin selection. However, to select lines with diverse genetic backgrounds, S3 should be the key generation for selection. [ABSTRACT FROM AUTHOR]

Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER- breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER- cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 ( p = 7 × 10−5, gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 ( p = 1 × 10−4, corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes. [ABSTRACT FROM AUTHOR]

Pipeline construction can have considerable effects on agro-ecosystems. However, little research has documented pipeline installation disturbance on agricultural productivity. We sampled three sites in agricultural regions of West China in Gansu and Shaanxi provinces to study the effects of pipeline installation disturbance on crop productivity. Corn yield and five crop growth characteristics were measured and analyzed at six different distances on both sides of a pipeline at two sites: 0 (trench), 10 (piling or working zone), 20, 50, and 100 m. Crop productivity was assessed at a third site by sampling across pipelines at three different times after their construction (2, 6, and 8 yr). The results showed that agricultural productivity was mainly impaired inside the 20 m on both sides of the pipeline. The level of disturbance on agriculture productivity decreased as distance from pipeline increased. Crop productivity in the affected zones is expected to gradually improve over time. Pipeline installation had significant effect on soil organic matter, N content, and pH, and correlated with crop growth characteristics. Proper soil management practices, such as storing and backfilling topsoil separately from subsurface soil during the installation process, should be addressed to reduce the impacts of pipeline installation on crop productivity. [ABSTRACT FROM AUTHOR]

Background Early menarche is linked to higher incidence of adult asthma, suggesting that earlier puberty may influence type 2 immune response characteristics of allergic diseases. We examined the hypothesis that timing of breast and pubic hair development, which precede menarche, is associated with increased childhood atopic conditions. Methods Girls were enrolled at 6-8 yr of age (2004-2007) in the Breast Cancer and the Environment Research Program Puberty Study and were followed through 2011. Pubertal stages were assessed and atopic conditions were queried annually. Associations of age at pubertal stage 2 for breast or pubic hair development with atopic conditions were assessed using prevalence ratios ( PR) or odds ratios (OR) and 95% confidence intervals ( CI) from log-binomial regression and generalized estimating equation models, controlling for body mass index and other covariates. A total of 1055 girls with medical and pubertal stage data were included. Results Asthma (ever vs. never) was associated with younger pubarche (≤10 vs. >10 yr, PR = 1.15, CI: 1.04-1.28 adjusted for race/ethnicity and site; PR = 1.13, CI: 1.01-1.25 further adjusted for BMI), but not thelarche. In longitudinal models, risk of developing allergies increased with younger age at pubarche (adjusted OR = 1.60, CI: 1.10-2.34; ≤10 vs. >10 yr). Risks were highest among black girls with earlier pubarche (n = 248/326); for allergies, their fully adjusted OR was 2.35, CI: 1.06-5.19 for pubarche ≤10 vs. >10 yr. Conclusions Atopic conditions during childhood are associated with younger age at pubarche, independent of obesity, and these relationships may vary by racial/ethnic groups. [ABSTRACT FROM AUTHOR]

African American (AA) women are more likely than European American (EA) women to be diagnosed with breast cancer at younger ages and to develop poor prognosis tumors. However, these racial differences are largely unexplained. Folate and other methyl-group nutrients may be related to breast carcinogenesis, but few studies have examined these associations in AA populations. We examined the associations of dietary intake of these nutrients with breast cancer risk overall, by menopausal and estrogen receptor (ER) status among 1,582 AA (749 cases) and 1,434 EA (744 cases) women using data from a case-control study, the Women's Circle of Health Study. Unconditional multivariable logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each nutrient and breast cancer risk. In AA women, inverse associations were observed for natural food folate intake among premenopausal women (fourth vs. first quartile: OR = 0.57, 95% CI, 0.33-1.00; p for trend = 0.06) and for ER-positive tumors (fourth vs. first quartile: OR = 0.58, 95% CI, 0.36-0.93; p for trend = 0.03), whereas in EA women, a positive association was observed for intake of synthetic folate (fourth vs. first quartile: OR = 1.53, 95% CI, 1.06-2.21; p for trend = 0.03). Our findings suggest that natural food folate intake is inversely associated with breast cancer risk and that this association may vary by race, menopausal status or ER status. The finding of an increased risk observed among EA women with the highest intake of synthetic folate from fortified foods warrants further investigation. [ABSTRACT FROM AUTHOR]

Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA) and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA ( n = 335 cases) and 864 AA ( n = 458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1,307 EAs and 1,365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity ( IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity ( IL4R rs1801275), and T regulatory cell-mediated immunosuppression ( TGFB1 rs1800469) associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs ( P-trend = 0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER-positive breast cancers among EAs and marginally among AAs. Only among AA women, IL15 rs10833 and IL15RA rs2296135 were associated with ER-positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER-negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status. [ABSTRACT FROM AUTHOR]

CdSe nanocrystals (NCs) with different morphologies have been synthesized and applied as the acceptor in the active layer of the organic photovoltaic (OPV) devices. CdSe tetrapod (TP)/nanorod (NR) with zinc-blended seeds and wurtzite arms is prepared by seed growth method and mixed with poly(3-hexylthiophene) (P3HT): [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). When the concentrations of CdSe in P3HT: PCBM system are 50 wt% optimally, the efficiency can be promoted about 4.3%, suggesting that an enhancement of 13.2% can be obtained and the addition of anisotropic CdSe NCs content in the active layer can be beneficial for the transport of electrons and light absorption in the OPV devices. [ABSTRACT FROM AUTHOR]

A damant colony optimization (D-ACO) analysis of the overall stability of high arch dams on complicated foundations is presented in this paper. A modified ant colony optimization (ACO) model is proposed for obtaining dam concrete and rock mechanical parameters. A typical damparameter feedback problem is proposed for nonlinear back-analysis numerical model based on field monitoring deformation and ACO. The basic principle of the proposed model is the establishment of the objective function of optimizing real concrete and rock mechanical parameter. The feedback analysis is then implemented with a modified ant colony algorithm. The algorithm performance is satisfactory, and the accuracy is verified. The m groups of feedback parameters, used to run a nonlinear FEM code, and the displacement and stress distribution are discussed. A feedback analysis of the deformation of the Lijiaxia arch dam and based on the modified ant colony optimization method is also conducted. By considering various material parameters obtained using different analysismethods, comparative analyses were conducted on damdisplacements, stress distribution characteristics, and overall dam stability. The comparison results show that the proposal model can effectively solve for feedbackmultiple parameters of damconcrete and rock material and basically satisfy assessment requirements for geotechnical structural engineering discipline. [ABSTRACT FROM AUTHOR]

As semiconductor technology scales into the nanometer regime, intermittent faults have become an increasing threat. This paper focuses on the effects of intermittent faults on NET versus REG on one hand and the implications for dependability strategy on the other. First, the vulnerability characteristics of representative units in OpenSPARC T2 are revealed, and in particular, the highly sensitive modules are identified. Second, an arch-level dependability enhancement strategy is proposed, showing that events such as core/strand running status and core-memory interface events can be candidates of detectable symptoms. A simple watchdog can be deployed to detect application running status (IEXE event). Then SDC (silent data corruption) rate is evaluated demonstrating its potential. Third and last, the effects of traditional protection schemes in the target CMT to intermittent faults are quantitatively studied on behalf of the contribution of each trap type, demonstrating the necessity of taking this factor into account for the strategy. [ABSTRACT FROM AUTHOR]

CI inhibitor (C1INH) plays an important role in the classical pathway of the complement system. Mutations in C1INH gene cause quantitative or qualitative deficiencies in C1INH, which can lead to hereditary angioedema (HAE) type I or II. Here, we identified a novel frame-shift mutation C.1391-1445del55 (p.v464fsx556) in exon 8 in a large Chinese family with HAE type I. This 55 base pairs deletion abolishes the original stop codon and introduces a new stop codon 220 bp downstream of the original one, and leads to mutated C1INH protein prolonged from 500 to 556 amino acids. The levels of C4 and C1INH as well as C1INH activity in serum were significantly reduced in affected individuals. This is the first report of a novel mutation abolishing the physiological stop codon of C1INH gene in a large Chinese family with HAE type I. [ABSTRACT FROM AUTHOR]

Objective. The effects of low-intensity 630 nm semiconductor laser irradiation at 3.6 J/cm² (LISL) on wound healing in diabetic rats were studied in this paper. Methods. 36 diabetic rats with dorsal cutaneous excisional wounds were divided into three LISL groups and a control group randomly. The three LISL groups were irradiated with LISL at 5, 10, and 20mW/cm² five times a week for two weeks, respectively. The process of wound healing was assessed by assessing blood glucose, calculating percentage of wound closure, histopathological evaluation, and immunohistochemical quantification. Results. Blood glucose of all groups remained at similar levels throughout the experiment. LISL could obviously promote wound contraction, fibroblasts proliferation, and collagen synthesis, alter bFGF and TGF-β1 expression, and reduce inflammatory reaction in the early and middle phases of chronic wound-healing process. However, LISL could not shorten cicatrization time, and the treatment effects were not sensitive to illuminate parameters in the later phase of the experiment. Conclusions. LISL might have auxiliary effects in the early and middle phases of wound healing in STZ-induced diabetic rats, but the reciprocity rule might not hold. The wound-healing process of early-phase diabetes rats shows typical characteristics of self-limited disease. [ABSTRACT FROM AUTHOR]

The human bacterial pathogen Helicobacter pylori forms biofilms. However, the constituents of the biofilm have not been extensively investigated. In this study, we analyzed the carbohydrate and protein components of biofilm formed by H. pylori strain ATCC 43504 (NCTC 11637). Development of H. pylori biofilm was analyzed using scanning electron microscopy (SEM) and quantified using crystal violet staining. The extracted extracellular polysaccharide (EPS) matrix was analyzed using GC-MS and nuclear magnetic resonance (NMR) analyses. Proteomic profiles of biofilms were examined by SDS-PAGE while deletion mutants of upregulated biofilm proteins were constructed and characterized. Formation of H. pylori biofilm is time dependent as shown by crystal violet staining assay and SEM. NMR reveals the prevalence of 1,4-mannosyl linkages in both developing and mature biofilms. Proteomic analysis of the biofilm indicates the upregulation of neutrophil-activating protein A (NapA) and several stress-induced proteins. Interestingly, the isogenic mutant napA revealed a different biofilm phenotype that showed reduced aggregated colonial structure when compared to the wild type. This in vitro study shows that mannose-related proteoglycans (proteomannans) are involved in the process of H. pylori biofilm formation while the presence of upregulated NapA in the biofilm implies the potency to increase adhesiveness of H. pylori biofilm. Being a complex matrix of proteins and carbohydrates, which are probably interdependent, the H. pylori biofilm could possibly offer a protective haven for the survival of this gastric bacterial pathogen in the extragastric environments. [ABSTRACT FROM AUTHOR]

The hemocompatibility of La2O3-doped TiO2 films with different concentration prepared by radio frequency (RF) sputtering was studied. The microstructures and blood compatibility of TiO2 films were investigated by scan electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and UV-visible optical absorption spectroscopy, respectively. With the increasing of the La2O3 concentrations, the TiO2 films become smooth, and the grain size becomes smaller. Meanwhile, the band gap of the samples increases from 2.85 to 3.3 eV with increasing of the La2O3 content in TiO2 films from 0 to 3.64%. La2O3-doped TiO2 films exhibit n-type semiconductor properties due to the existence of Ti2+ and Ti3+. The mechanism of hemocompatibility of TiO2 film doped with La2O3 was analyzed and discussed. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo. Experimental Dermatology 2010; : 958-964. Malignant melanoma (MM) is characterized by aggressive metastasis and high mortality rate. Microtubule-associated proteins 2 (MAP2) is expressed abundantly in majority of melanocytic nevi and primary melanomas, but absent in metastatic melanomas. To determine whether MAP2 correlates with tumor progression of MM, we investigated the effects of MAP2 inhibition on the biological behaviour of metastatic melanoma in vitro and in vivo. Our results demonstrated that adenovirus-mediated MAP2 induced apoptotic cell death and cell cycle arrest in metastatic human and mouse melanoma cell lines in vitro, and substantially inhibited the growth of melanomas in nude mice in vivo. In addition, intracellular expression of MAP2 was found to induce the morphologic alteration, suppress the migration and invasion and affect the assembly, stabilization and bundling of microtubules in melanoma cells. This is the first study that MAP2 expression significantly inhibits the growth of MM in vivo. Our results suggest that MAP2 may serve as a promising molecular target for therapy and chemoprevention of MM in humans. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSC) are the primary cell type mediating hepatic fibrosis. Although known for its antiviral effects, the inhibitory effects of interferon-beta (IFN-β) on HSC treatment have not yet been established. Both human and rat activated HSC cell lines were incubated with increasing concentrations of recombinant human IFN-β1a (rhIFN-β1a) for 24, 48 or 72 h. The effects of rhIFN-β1a on α-smooth muscle actin (α-SMA), collagen types I and III, transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), and mothers against decapentaplegic homolog (Smad4, Smad7) expression in HSC were examined using Western blotting and immunocytochemistry. Proliferation of HSC was evaluated via bromodeoxyuridine assay. rhIFN-β1a treatment had a dose-dependent, inhibitory effect on α-SMA and collagen type I protein expression. In addition, rhIFN-β1a decreased the expression of collagen type III, TGF-β1, PDGF-BB and Smad4 protein expression in HSC compared with untreated cells. We also observed increased Smad7 protein expression and decreased proliferation in rhIFN-β1a-treated HSC. Our data suggest that rhIFN-β1a treatment decreased α-SMA and collagen expression and inhibited the activation of HSC through the inhibition of the TGF-β and PDGF pathways. [ABSTRACT FROM AUTHOR]

Background: Extramammary Paget's disease (EMPD) is a rare neoplasm of apocrine gland-bearing skin. It is known that over-expression of survivin and human telomerase reverse transcriptase (hTERT) correlates with malignancies. We investigated the expression of hTERT and survivin by Paget's cells and their role in the tissue invasion and recurrence of EMPD. Method: Forty-two patients were enrolled into the study. Expression of survivin and hTERT were analyzed by immunohistochemistry and in situ hybridization techniques. The variables including the expression level of survivin and hTERT, gender, age, lesion location, invasion level and number of surgeries were statistically analyzed using Fisher's exact test. Results: Survivin was positively stained in 18 of 22 cases (81.8%), and hTERT in 18 of 29 cases (62.1%). Significantly higher level of survivin expression was detected in patients with multiple surgeries than those with single one (p = 0.0458). Expression of hTERT was significantly higher in the patients with micro-invasive and invasive lesions than those with non-invasive lesions (p = 0.0478). Conclusions: Over-expression of survivin and hTERT correlated strongly with recurrence and local invasion of EMPD lesions. EMPD has male gender predominance in Oriental population. Shan S-J, Zhang N, Geng S-L, Zhou Z, Chen X, Nie T, Guo Z, Li C, Liu Q, Guo Y, Wei H, Chen H-D. Expression of survivin and human telomerase reverse transcriptase in extramammary Paget's disease. [ABSTRACT FROM AUTHOR]

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Skin cancers are by far the most common human malignancies. Retinoids have shown promising preventive and therapeutic effects against a variety of human malignancies. The aim of this study was to investigate the apoptosis-inducing effect of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells. We found that acitretin preferentially inhibited the growth of SCL-1 cells in a dose- and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells. This inhibition appeared to be due to induction of apoptosis as revealed by enzyme-linked immunosorbent assay. AnnexinV/propidium iodide assay and morphological observation confirmed the pro-apoptotic effect of acitretin on SCL-1 cells. We further demonstrated that apoptosis was induced within 1–2 days and involved activation of caspases-8, -9, -3 and poly (ADP-ribose) polymerase (PARP). Caspase-8 inhibitor effectively suppressed acitretin-induced apoptosis whereas caspase-9 inhibitor did not. Acitretin increased the levels of CD95 (Fas), CD95-ligand and Fas-associated death domain. Neutralizing ZB4 anti-Fas antibody significantly inhibited the apoptosis in SCL-1 cells induced by acitretin. These results suggest that acitretin is able to induce apoptosis in skin cancer cells possibly via death receptor CD95 apoptosis pathway without affecting the viability of normal keratinocyte. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the role of spinal neuronal nicotinic acetylcholine receptors in the analgesic effects of isoflurane. After having established the mice model of analgesia by intraperitoneally injecting (i.p.) appropriate doses of isoflurane, nicotine, a neuronal nicotinic acetylcholine receptor agonist was intrathecally injected. The effects of isoflurane and nicotine on paw licking times and formalin-induced c-fos expression in the spinal cord dorsal horn were examined. Our correlative studies have shown that isoflurane can decrease the paw licking times and simultaneously suppress c-fos expression after injection of formalin in the mice. Nicotine can partially antagonize the effects induced by isoflurane above. Spinal neuronal nicotinic acetylcholine receptors may be important targets for the analgesic effects of isoflurane in formalin pain. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate whether the sunscreen-containing 2–5% green tea extracts (GTEs) protect ultraviolet irradiation (UVR)-induced photoaging and photoimmunosuppression. Materials and methods: Twenty volunteers were exposed to repetitive solar-simulated UVR (ssUVR) on the upper back at a dosage of 1.5 minimal erythema doses (MED) per day for four consecutive days. Thirty minutes before each UVR and 6, 24, and 48 h after the last UV exposure, the products containing vehicle, and 2–5% GTEs were applied onto five sites on the dorsal skin, respectively. The skin biopsies were obtained 72 h after the last UVR. The thickness of the stratum corneum and epidermis was measured under the microscope and the expression of cytokeratins (CK)-5/6, CK16, metalloproteinases (MMP)-2, MMP-9, and the CD1a+ Langerhans cells (LCs) were determined using immunohistochemistry. Results: Our results showed that UVR substantially induced cutaneous erythema, thickening of the epidermis, overexpression of CK5/6, CK16, MMP-2, MMP-9, and depletion of CD1a+ LCs. The sunscreens containing different concentrations of GTEs conferred significant protection against the photoaging and photoimmunology-related biological events. Interestingly, the protective effects were not parallel to the concentrations of GTEs, with 2% and 3% GTEs showing the most efficacious photoprotection. Conclusions: GTEs-containing sunscreens have potential photoprotective effects on UVR-induced photoaging and photoimmunosuppression. [ABSTRACT FROM AUTHOR]

The article describes the crystal structure of 5-(4,5-ethylenedithio-1,3-dithiol-2-yl-idene)-1,3,4,6-tetrathiapentalen-2-one (EDTO-TTP) and 5-[4,5-(ethene-1,2-diyldithio)-1,3-dithiol-2-ylidene]-1,3,4,6-tetrathiapentalen-2-one (VDTO-TTP). It shows the planar conformation adopted by EDTO-TTP molecule as well as the similarity of the bond characteristics of both compounds. Also reported is the intermolecular interactions exhibited by the EDTO-TTP crystal structure, including transverse and longitudinal interactions, and hydrogen bonding.

Geranyl diphosphate (GDP) is the precursor of monoterpenes, which are the major floral scent compounds in Phalaenopsis bellina. The cDNA of P. bellina GDP synthase ( PbGDPS) was cloned, and its sequence corresponds to the second Asp-rich motif (SARM), but not to any aspartate-rich (Asp-rich) motif. The recombinant PbGDPS enzyme exhibits dual prenyltransferase activity, producing both GDP and farnesyl diphosphate (FDP), and a yeast two-hybrid assay and gel filtration revealed that PbGDPS was able to form a homodimer. Spatial and temporal expression analyses showed that the expression of PbGDPS was flower specific, and that maximal PbGDPS expression was concomitant with maximal emission of monoterpenes on day 5 post-anthesis. Homology modelling of PbGDPS indicated that the Glu-rich motif might provide a binding site for Mg2+ and catalyze the formation of prenyl products in a similar way to SARM. Replacement of the key Glu residues with alanine totally abolished enzyme activity, whereas their mutation to Asp resulted in a mutant with two-thirds of the activity of the wild-type protein. Phylogenetic analysis indicated that plant GDPS proteins formed four clades: members of both GDPS-a and GDPS-b clades contain Asp-rich motifs, and function as homodimers. In contrast, proteins in the GDPS-c and GDPS-d clades do not contain Asp-rich motifs, but although members of the GDPS-c clade function as heterodimers, PbGDPS, which is more closely related to the GDPS-c clade proteins than to GDPS-a and GDPS-b proteins, and is currently the sole member of the GDPS-d clade, functions as a homodimer. [ABSTRACT FROM AUTHOR]

Three new species of the subgenus Parapenthecia of the genus Apenthecia are reported from the Oriental Region: A. ( P.) heterochaeta Chen and Toda, sp. nov. from Indonesia, and A. ( P.) hispida Chen and Toda, sp. nov. and A. ( P.) litongi Cao and Chen, sp. nov. from south China. Interestingly, the last species lacks a very peculiar character, the swollen or scale-like orbital setae, which are commonly seen in all other species of the genus Apenthecia. A key to all species of the subgenus Parapenthecia is provided. [ABSTRACT FROM AUTHOR]

Background Matrine is a traditional Chinese medicine with significant inhibitory activity against malignant tumors. Its effects on the invasiveness and metastasis of malignant tumors have rarely been reported. Aim To investigate whether matrine can inhibit the metastasis-related activities of the human malignant melanoma cell line A375 in vitro. Methods 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin-V–fluorescein isothiocyanate/propidium iodide (Annexin-V-FITC/PI) affinity assay were used to examine the effects of matrine on the proliferation and apoptosis induction of A375 cells. The morphologic changes of A375 cells were observed by light and electron microscopy. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to evaluate the expression of heparanase mRNA and protein. The effect of matrine on the adhesion ability and invasiveness of treated A375 cells was tested by cell–Matrigel adhesion assay and Matrigel invasion assay, respectively. Results Matrine showed significant inhibition of the proliferation of A375 cells in a dose- and time-dependent manner. It also induced apoptosis in a dose-dependent manner. Compared with the control group, the levels of heparanase mRNA and protein expression of A375 cells treated with different concentrations of matrine were decreased significantly, as were their adhesion ability and invasiveness. Conclusions These findings indicate that matrine inhibits the invasiveness and metastasis of A375 cells in vitro. The mechanisms may be linked to the inhibition of cellular proliferation, induction of apoptosis, and downregulation of heparanase mRNA and protein expression. [ABSTRACT FROM AUTHOR]

We compared the frequency and spectra of p53 mutations in skin tumors from UVB-irradiated and benzo(a)pyrene-UVA-treated SKH-1 mice. Analysis of p53 mutations using a combination of polymerase chain reaction, denaturing high-performance liquid chromatography, and sequencing shows that the frequency and spectrum of p53 mutations in BaP-UVA-induced tumors are quite different from those in UVB-induced tumors. SKH-1 mice were treated with BaP-UVA or UVB for 30 weeks after which skin tumors were collected for analysis of p53 mutations. Among the 11 BaP-UVA-induced tumors with diameters of 5–10 mm, two displayed mutations in exon 8 yielding a mutation frequency of 18.2%. In contrast, the mutation frequency among BaP-UVA-induced tumors was 10.5%. In UVB-induced tumors, the mutation frequency in exon 8 was highly correlated with tumor size. A total of 77.8% of tumors with diameters larger than 10 mm contained p53 mutations. The overall mutation frequency among UVB-induced tumors was 17.9% in exon 8 and only 3.8% in exon 5. Hotspots for p53 mutation in UVB-induced tumors were found at codons 128 and 149 (exon 5), and at codons 268, 270, 271 and 273–276 (exon 8). In addition to widely recognized C→T missense mutations, there were also tandem CC→AG changes coupled with either an insertion of T, a C→G substitution or G→C/T mutations. All of the mutations were found at tri- or tetra-pyrimidine sites. Thirty-nine per cent of all p53 mutations occurred at codons 274 and 275; 53% occurred at codons 268–271. Two multiple mutation clusters were located at codons 268–271 and 274–276. Both BaP-UVA and UVB caused C→T transitions at codon 275 in exon 8. A C→T mutation at codon 294 was induced only by BaP-UVA treatment. In contrast to UVB treatment, BaP-UVA treatment did not induce any mutations in exon 5. We show that individually subcarcinogenic levels of BaP and UVA synergistically induce a novel p53-mutation fingerprint. This fingerprint could serve as a prognostic indicator for the development of BaP-UVA-induced skin tumors. [ABSTRACT FROM AUTHOR]

Cyclooxygenase (COX)-2 inhibitors are known to be used as chemopreventative agents against certain malignancies. Thus far, there has been very limited information on whether COX-2 inhibitors protect against chronic narrow-band UVB (NB-UVB)-induced immunosuppression. The present study investigated the effect of nonselective and specific COX-2 inhibitors, indomethacin and celecoxib, on epidermal Ia+ Langerhans cells (LCs) and Thy-1+ dendritic epidermal T cells (DETCs) in mice irradiated with NB-UVB. Sixty female BALB/c mice were divided randomly into the control group (sham) and the experimental groups (irradiated with NB-UVB for 17 weeks, further divided into five groups according to the diets containing different concentrations of either COX-2 inhibitors). Alterations in the density and morphology of epidermal Ia+ LCs and Thy-1+ DETCs in mice were documented using fluorescence microscopy. Chronic NB-UVB irradiation substantially decreased the density and altered the morphology of the epidermal Ia+ LCs and Thy-1+ DETCs in control mice. The dietary supplementation of both COX-2 inhibitors displayed a dosage-dependent protective effect on the murine dendritic cells irradiated by NB-UVB. In conclusion, COX-2 inhibitors protected against chronic NB–UVB-induced density and morphologic changes in epidermal Ia+ LCs and Thy-1+ DETCs in mice. [ABSTRACT FROM AUTHOR]

A practical stereoselective synthesis of (S)-bakuchiol (1) and its enantiomer is reported. The important intermediate, (R)-configured β-siloxy aldehyde 5, was obtained in three steps from the easily available material geraniol (2) via the key step of Yamamoto's rearrangement of epoxy silyl ethers. (S)-Bakuchiol (1) and its enantiomer, (R)-bakuchiol (17), were finally obtained in different synthetic sequences with overall yields of 51% (ten steps) and 40% (nine steps) from geraniol (2), respectively. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of hepatitis B virus X ( HBx) gene on apoptosis and cell cycle in hepatocyte line HL-7702 and to discuss the possible mechanisms in the pathway. Methods: The recombinant plasmid pcDNA3-X and vector pcDNA3 were transfected into HL-7702 cells and selected by G418 to construct two new cell lines, which were named HL-7702-HBx and HL-7702-con, respectively. Reverse transcription polymerase chain reaction (RT–PCR) and western blot analysis were used to confirm that HBx gene was expressed steadily in the HL-7702-HBx cells. Then apoptosis and cell cycle of the two cells were detected by DNA ladder, flow cytometric analysis, and electronic microscope observation. Apoptosis and cell cycle gene expressions in the two cells were subsequently evaluated by using gene arrays. Some of results were further confirmed by real-time PCR and western blot analysis. Results: RT–PCR and the western blot analysis showed that HL-7702-HBx expressed the HBx gene steadily. Comparedwith the HL-7702-con cells, there was increased apoptosis and accumulation of the S phase in the HL-7702-HBx cells. The gene array analysis indicated that some DNA repair genes ( XRCC1, DDB1, etc.) and DNA damage checkpoint-related genes ( Cdc47, RAD17, etc.) played roles in the HBx-mediated imbalance of apoptosis and cell cycle. Both cDNA array analysis and real-time RT–PCR showed that mRNA of XRCC1, Cdc47 and RAD17 were upregulated by HBx. Unexpectedly, the western blot analysis revealed that HBx inhibited their protein expression. Conclusion: The expression of HBx in HL-7702 cells promoted apoptosis and accumulation of the S phase through the inhibition of DNA repair and checkpoints via post-transcriptional mechanisms. [ABSTRACT FROM AUTHOR]

Aim: A rat model was used for the evaluation of collagen-coated and salt-modified polycaprolactone (PCL) scaffolds for bladder grafting after hemicystectomy. Methods: SD rats underwent partial cystectomy and cystoplasty with collagen-coated and salt-modified polycaprolactone scaffolds. The grafts of the regenerated bladder wall were harvested at different intervals and tissue regeneration was evaluated microscopically. Anatomic and functional characters were evaluated by cystography and urodynamics. Results: At harvesting, after 1 and 2 months, we found good preservation of the bladder shape and volume in all 16 rats receiving PCL cystorrhaphy. No stone formation was observed. Good epithelialization and ingrowth of smooth muscle cells were seen after 2 months grafting. Collagen-coated PCL scaffolds showed considerable encrustation, which appeared to be absorbed and disappear with time. The cystographic and urodynamic examinations revealed intact contour and a well-accommodated bladder with reservoir volume and contractility. Conclusions: In the rat model, we have successfully demonstrated the applicability of collagen coated and salt-modified PCL in reconstruction of the partial cystectomized bladder. [ABSTRACT FROM AUTHOR]

Eight species of the Amiota sinuata species group are reported from eastern Malaysia, including six new species, A. bispinula, A. cerata, A. curvibacula, A. lambirensis, A. parviserrata and A. quadrifoliolata spp. nov. A key to Asian species of the group is provided. [ABSTRACT FROM AUTHOR]

Avoparcin, a vancomycin analogue, was banned as a feed additive in Taiwan in 2000. A nationwide surveillance was conducted to study the prevalence of vancomycin-resistant enterococci (VRE) on chicken farms between 2000 and 2003. Among the 1021 E. faecalis and 967 E. faecium isolates studied, resistance to tetracycline, erythromycin, high-level aminoglycosides, ciprofloxacin and chloramphenicol either increased or remained high except vancomycin. The proportion of VRE decreased, between 2000 and 2003, from 13.7% (22/161) to 3.7% (11/299) for E. faecalis, and 3.4% (4/119) to 0% (0/300) for E. faecium. Only 8.8% (7/80) of the chicken farms surveyed harboured VRE in 2003 compared with 25% (15/60) in 2000. All VRE were resistant to tetracycline and erythromycin. All VRE possess the vanA gene but nearly all (79 of 83 isolates) were susceptible to teicoplanin, indicating VanB phenotype. Some clones were detected from different farms in various regions over the years. We conclude that the frequency of VRE in chicken farms decreased in association with a ban on avoparcin; and the continued presence of VRE may be due to the ability of some strains to persist in the farms, transfer of vancomycin resistance determinants or co-selection by the continued use of other antibiotics. [ABSTRACT FROM AUTHOR]

1. There is considerable controversy regarding the tolerance of diabetic hearts to ischaemia and the underlying mechanisms responsible for the increased heart tolerance to ischamia remain uncertain. In the present study, we observed, in vitro, type 1 diabetic heart responses to ischaemia and reperfusion at different degrees of hyperglycaemia. In addition, the possible role of increased osmolarity in cardioprotection due to hyperglycaemia was evaluated. 2. Hearts from 3 week streptozocin-induced diabetic rats were isolated and perfused in a Langendorff apparatus and subjected to 30 min ischaemia and 30 min reperfusion. Cardiac function and the electrocardiogram were recorded. Myocardial content of osmolarity associated heat shock protein (hsp) 90, heme oxygenase (HO)-1 and anti-oxidant enzymes were determined in diabetic or hyperosmotic solution-perfused hearts using western blot. The hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG; 2 × 10−7 mol/L) or the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (1 × 10−5 mol/L) was added to the perfusate to observe the effects of hsp90 inhibition and hsp90-associated endothelial NOS on ischaemic responses of diabetic hearts. 3. Compared with normal control rats, diabetic hearts with severe hyperglycaemia (blood glucose > 20 mmol/L) showed markedly improved postischaemic heart function with fewer reperfusion arrhythmias. Mild hyperglycaemia (< 12 mmol/L) exhibited no significant cardioprotection. 4. Elevated expression of hsp90 accompanied the enhanced resistance to ischaemia in diabetic hearts, which was abrogated by 17-AAG. In the presence of the NOS inhibitor, heart function was preserved, whereas reperfusion arrhythmias were increased in diabetes. Diabetic hearts also had markedly elevated HO-1 and catalase, with no significant change in superoxide dismutase. Hyperosmotic perfusion with glucose or mannitol also increased myocardial hsp90 and catalase. 5. The present findings reveal that heart resistance to ischaemia is increased in short-term type 1 diabetes with severe hyperglycaemia. Elevated osmolarity caused by significant hyperglycaemia may contribute to the enhanced myocardial activity against oxidative injury during ischaemia and reperfusion. [ABSTRACT FROM AUTHOR]