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Orange Carotenoid Protein (OCP) is a water-soluble photoreceptor involved in photoprotection of cyanobacteria. The photoactive OCP contains a bound ketocarotenoid cofactor held in a protein matrix with a hydrogen bonding network. We have developed a system to replace essential residues of the photoactive OCP with non-canonical aromatic analogues that produce well-defined chemical or steric changes. Preliminary spectroscopic evaluation of the generated OCP variants demonstrates the potential of this "molecular surgery" to disentangle protein-chromophore interaction networks that are critical for photoreceptor function. In this way, the number and strength of key contacts with non-canonical amino acids could be controlled and manipulated. We have illustrated this principle here by replacing hydrogen bond donating residues with aromatic non-canonical amino acids that alter the state preference of OCP. • Orange Carotenoid Protein (OCP) is a water-soluble photoreceptor involved in photoprotection of cyanobacteria. • OCP contains a bound ketocarotenoid cofactor held in a protein matrix with a hydrogen bond network. • OCP expression with expanded genetic code enabled the study interactions between the ketocarotenoid and the protein matrix. • The number and strength of key contacts could be controlled and manipulated with non-canonical amino acids. • Replacement of hydrogen-bond donating residues by aromatic non-canonical amino acids changes state preference of OCP.. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common primary malignant brain tumor that is usually considered fatal even with treatment. This is often a result for tumor to develop resistance. Regarding the standard chemotherapy, the alkylating agent temozolomide is effective in disease control but the recurrence will still occur eventually. The mechanism of the resistance is various, and differs in terms of innate or acquired. To date, aberrations in O6-methylguanine-DNA methyltransferase are the clear factor that determines drug susceptibility. Alterations of the other DNA damage repair genes such as DNA mismatch repair genes are also known to affect the drug effect. Together these genes have roles in the innate resistance, but are not sufficient for explaining the mechanism leading to acquired resistance. Recent identification of specific cellular subsets with features of stem-like cells may have role in this process. The glioma stem-like cells are known for its superior ability in withstanding the drug-induced cytotoxicity, and giving the chance to repopulate the tumor. The mechanism is complicated to administrate cellular protection, such as the enhancing ability against reactive oxygen species and altering energy metabolism, the important steps to survive. In this review, we discuss the possible mechanism for these specific cellular subsets to evade cancer treatment, and the possible impact to the following treatment courses. In addition, we also discuss the possibility that can overcome this obstacle. [ABSTRACT FROM AUTHOR]

Integrin signaling may modulate several different functions involved in cell migration, invasion, proliferation and motility, and is a potential candidate biomarker for oral cancer. In the present study, a total of four integrin genes were evaluated as potential biomarkers of oral squamous cell carcinoma (OSCC). Gene expression was determined using the reverse transcription‑quantitative polymerase chain reaction in 55 OSCC and 55 matched normal oral tissues. The performance of individual and combined biomarkers was analyzed by receiver operating characteristic (ROC) analysis based on the relative mRNA expression (OSCC vs. matched oral tissue from the tumor‑free margin), which was calculated using the ΔΔCq value (ΔCq of OSCC‑ΔCq of oral tissue from the tumor‑free margin of the same patient). In the individual ROC analysis, the areas under the ROC curve (AUCs) of relative mRNA expression (ΔΔCq) of integrin subunit α3 (ITGA3), integrin subunit α5 (ITGA5), integrin subunit β1 (ITGB1) and integrin subunit β6 (ITGB6) in all tumor locations were 0.724, 0.698, 0.640 and 0.657, respectively. For locations 2 (tongue/mouth part) and 3 (edentulous ridge), their individual AUC values were 0.840, 0.765, 0.725 and 0.763, respectively. In the cumulative ROC analysis, ITGA3, ITGA5 and ITGB1 genes exhibited the highest combined AUC values (0.809 and 0.871 for all locations and locations 2 and 3 combined, respectively) compared with other biomarker combinations. In conclusion, the results of the present study identified that higher mRNA expressions of ITGA3, ITGA5, ITGB1 and ITGB6 genes are suitable for OSCC diagnosis biomarkers. Cumulative ROC analysis indicated an improved overall performance compared with the best individual integrin biomarker of OSCC. [ABSTRACT FROM AUTHOR]

To investigate using pre-germinated brown rice (PGBR) to treat metabolic syndrome, we fed one group of mice standard-regular-diet (SRD) for 20 weeks and another group of mice high-fat-diet (HFD) for 16 weeks. We subdivided them into HFD group and HFD + PGBR group whose dietary carbohydrate was replaced with PGBR for 4 weeks. The HFD group gained more weight, had higher blood pressure, heart rate, blood glucose and lipids, liver levels of TG, feces TG and bile acid, lower adipose levels of adipocytokine, lower skeletal muscle IR, IRS-1, IRS-2, PI3 K, Akt/PKB, GLUT-1, GLUT-4, GCK and PPAR-γ; higher liver SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α, and higher adipose SREBP-1, SCD-1, FAS, and lower adipose PPAR-α and adiponectin. The HFD + PGBR group had clearly improved blood pressure, biochemical parameters and above proteins expressions. PGBR successful treatment of metabolic syndrome was achieved through improvements in glucose and lipid synthesis and metabolism. PGBR treats HFD-induced metabolic syndrome through improving glucose and lipid synthesis and metabolism. [ABSTRACT FROM AUTHOR]

We have successfully mitigated the out-diffusion of Ge during molecular beam epitaxy of InGaAs on Ge by using a GaAsSb barrier layer as evidenced by secondary ion mass spectroscopy. Compared to GaAs, this GaAsSb barrier layer also results in a smoother surface morphology with its root-mean-square roughness of 0.7 nm due to the surfactant effect of Sb. Using a step-graded GaAsSb and AlGaAsSb metamorphic buffer layer, a 200-nm p-type In0.53Ga0.47As layer grown on Ge exhibits a hole mobility of 38 cm2 V−1 s−1 with a hole concentration of 2.6 × 1019 cm−3 at 300 K and 53 cm2 V−1 s−1 with a hole concentration of 1.2 × 1019 cm−3 at 77 K. [ABSTRACT FROM AUTHOR]

Cellular components and signaling pathways are required for the proper growth of blood vessels. Here, we report for the first time that a teleost-specific gene ftr82 (finTRIM family, member 82) plays a critical role in vasculature during zebrafish development. To date, there has been no description of tripartite motif proteins (TRIM) in vascular development, and the role of ftr82 is unknown. In this study, we found that ftr82 mRNA is expressed during the development of vessels, and loss of ftr82 by morpholino (MO) knockdown impairs the growth of intersegmental vessels (ISV) and caudal vein plexus (CVP), suggesting that ftr82 plays a critical role in promoting ISV and CVP growth. We showed the specificity of ftr82 MO by analyzing ftr82 expression products and expressing ftr82 mRNA to rescue ftr82 morphants. We further showed that the knockdown of ftr82 reduced ISV cell numbers, suggesting that the growth impairment of vessels is likely due to a decrease of cell proliferation and migration, but not cell death. In addition, loss of ftr82 affects the expression of vascular markers, which is consistent with the defect of vascular growth. Finally, we showed that ftr82 likely interacts with vascular endothelial growth factor (VEGF) and Notch signaling. Together, we identify teleost-specific ftr82 as a vascular gene that plays an important role for vascular development in zebrafish. [ABSTRACT FROM AUTHOR]

PurposeRadiation combined with natural products may improve the radiosensitivity of cancer cells. This study investigated the potential of a combined modality treatment with Ultraviolet C (UVC; wavelength range 200–280 nm) and our previously identified anti-oral cancer agent (methanolic extracts ofCryptocarya concinnaroots; MECCrt) in oral cancer cells. Materials and methodsThe mechanism of the possible synergy of UVC and MECCrt was explored in terms of cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), and DNA damage analyses. ResultsIn cell viability (%) at 24 h treatment, the low doses of UVC (14 J/m2) and MECCrt (10μg/ml) resulted in slight damage to human oral cancer Ca9-22 cells (83.2 and 80.4) but was less harmful to human oral normal HGF-1 cells (93.4 and 91.8, respectively). The combined treatment of UVC and MECCrt (UVC/MECCrt) had a lower viability (54.5%) than UVC or MECCrt alone in Ca9-22 cells but no showed significant change in HGF-1 cells. In Ca9-22 cells, the expression of flow cytometry-based apoptosis (sub-G1 phase, annexin V, and pancaspase assays) was significantly higher in UVC/MECCrt than in UVC or MECCrt alone (p< 0.0001). Using flow cytometry, intracellular ROS levels of UVC/MECCrt and MECCrt alone were higher than for UVC alone. MitoMP change and H2A histone family member X (γH2AX; H2AFX)-based DNA damage were synergistically inhibited and induced by MECCrt/UVC compared to its single treatment in Ca9-22 cells, respectively. ConclusionUVC plus MECCrt treatment had selective killing and synergistic anti-proliferative effects against oral cancer cells involving apoptosis, oxidative stress, and DNA damage. This combination therapy appears to have a great clinical potential against oral cancer cells. [ABSTRACT FROM PUBLISHER]

Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 μM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Preclinical Research In this study the effects of low ‐ dose aspirin (5 mg/kg) on adhesion molecule and chemokine expression in a hyperlipidemic rat model. Six ‐ week ‐ old Sprague ‐ Dawley (SD) rats were assigned to two control groups receiving either a regular diet or high ‐ fat diet (HFD) and a treatment group fed HFD with 5 mg/kg aspirin for a 10 ‐ week period. Compared with the regular diet control group, the HFD control group had higher body weight, lower levels of high ‐ density lipoprotein, higher concentrations of insulin, triglyceride, total cholesterol, and low ‐ density lipoprotein, but no differences in blood glucose and glycated hemoglobin. The prothrombin time (PT) and activated partial thromboplastin time (aPTT) were clearly shortened in the HFD group. That group also had increased expression of intercellular adhesion molecule ‐ 1 (ICAM ‐ 1), ICAM ‐ 2, ICAM ‐ 3, vascular cell adhesion molecule (VCAM), platelet endothelial cell adhesion molecule (PECAM) and P ‐ selectin in platelets and vascular adhesion protein ‐ 1 in lymphocyte and in aorta increased expressions of ICAM ‐ 1, ICAM ‐ 2, ICAM ‐ 3, VCAM, PECAM, E ‐ selectin, monocyte chemoattractant protein ‐ 1 (MCP ‐ 1) and CCR2. The HFD rats also had increased PKCα, IκB kinase α (IKKα), p65, mitogen ‐ activated protein kinases (MAPKs) (p38, c ‐ Jun N ‐ terminal kinases 1, extracellular signal ‐ regulated kinase 1/2), and their phosphorylated forms. Low ‐ dose aspirin improved HFD ‐ induced hyperinsulinemia and hyperlipidemia, recovered PT and aPTT, inhibited upregulation of adhesion molecules and chemokines and reduced expression of PKCα, IKKα, p65, and MAPKs. Low ‐ dose aspirin ameliorates HFD ‐ induced hyperlipidemia and hyperinsulinemia, and prevents HFD ‐ induced expression of adhesion molecules and chemokine formation. [ABSTRACT FROM AUTHOR]

Apoptosis is a key mechanism for enhanced cellular radiosensitivity in radiation therapy. Studies suggest that Akt signaling may play a role in apoptosis and radioresistance. This study evaluates the possible modulating role of amiloride, an antihypertensive agent with a modulating effect to alternative splicing for regulating apoptosis, in the antiproliferative effects induced by ionizing radiation (IR) in glioblastoma multiforme (GBM) 8401 cells. Analysis of cell viability showed that amiloride treatment significantly inhibited cell proliferation in irradiated GBM8401 cells ( p<0.05) in a time-dependent manner, especially in cells treated with amiloride with IR post-treatment. In comparison with GBM8401 cells treated with amiloride alone, with GBM8401 cells treated with IR alone, and with human embryonic lung fibroblast control cells (HEL 299), GBM8401 cells treated with IR combined with amiloride showed increased overexpression of phosphorylated Akt, regardless of whether IR treatment was performed before or after amiloride administration. The alternative splicing pattern of apoptotic protease-activating factor-1 ( APAF1) in cells treated with amiloride alone, IR alone, and combined amiloride-IR treatments showed more consistent cell proliferation compared to that in other apoptosis-related genes such as baculoviral IAP repeat containing 5 ( BIRC5), Bcl-X, and homeodomain interacting protein kinase-3 ( HIPK3). In GBM8401 cells treated with amiloride with IR post-treatment, the ratio of prosurvival (-XL,-LC) to proapoptotic (-LN,-S) splice variants of APAF1 was lower than that seen in cells treated with amiloride with IR pretreatment, suggesting that proapoptotic splice variants of APAF1 ( APAF1-LN,-S) were higher in the glioblastoma cells treated with amiloride with IR post-treatment, as compared to glioblastoma cells and fibroblast control cells that had received other treatments. Together, these results suggest that amiloride modulates cell radiosensitivity involving the Akt phosphorylation and the alternative splicing of APAF1, especially for the cells treated with amiloride with IR post-treatment. Therefore, amiloride may improve the effectiveness of radiation therapy for GBMs. Treatment of irradiated GBM tumors with amiloride inhibited cell proliferation in a time-dependent manner. Drug treatment alone showed increased expression of pAkt. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to examine the association of lead exposure with cardiac conduction disturbance among lead-exposed and non-exposed workers in Taiwan. Methods: The participants comprised 312 lead workers and 329 referents who had no known occupational lead exposure. During their annual health examination, they were invited to take part in the survey. Standard resting 12-lead electrocardiograms were obtained and the electrocardiographic features studied were related to blood lead levels (BLLs). Results: The mean BLLs were 26.05 (SD = 13.98) and 2.62 (SD = 1.42) µg/dL in lead-exposed and reference groups, respectively. Compared with the referents, lead workers had significantly shorter PR interval and longer QTc interval. Especially, workers with BLL > 30 µg/dL had the highest risk after adjusting for age, sex, body mass index, and other potential confounders. Conclusion: The data suggest that lead exposure is positively associated with prolonged QTc interval. [ABSTRACT FROM AUTHOR]

Abstract: RNA A-to-I editing is the most common single-base editing in the animal kingdom. Dysregulations of RNA A-to-I editing are associated with developmental defects in mouse and human diseases. Mouse knockout models deficient in ADAR activities show lethal phenotypes associated with defects in nervous system, failure of hematopoiesis and reduced tolerance to stress. While several methods of identifying RNA A-to-I editing sites are currently available, most of the critical editing targets responsible for the important biological functions of ADARs remain unknown. Here we report a method to systematically analyze RNA A-to-I editing targets by combining I-specific cleavage and exon array analysis. Our results show that I-specific cleavage on editing sites causes more than twofold signal reductions in edited exons of known targets such as Gria2, Htr2c, Gabra3 and Cyfip2 in mice. This method provides an experimental approach for genome-wide analysis of RNA A-to-I editing targets with exon-level resolution. We believe this method will help expedite inquiry into the roles of RNA A-to-I editing in various biological processes and diseases. [Copyright &y& Elsevier]

An essential task in a genomic analysis of a human disease is limiting the number of strongly associated genes when studying susceptibility to the disease. The goal of this study was to compare computational tools with and without feature selection for predicting osteoporosis outcome in Taiwanese women based on genetic factors such as single nucleotide polymorphisms (SNPs). To elucidate relationships between osteoporosis and SNPs in this population, three classification algorithms were applied: multilayer feedforward neural network (MFNN), naive Bayes, and logistic regression. A wrapper-based feature selection method was also used to identify a subset of major SNPs. Experimental results showed that the MFNN model with the wrapper-based approach was the best predictive model for inferring disease susceptibility based on the complex relationship between osteoporosis and SNPs in Taiwanese women. The findings suggest that patients and doctors can use the proposed tool to enhance decision making based on clinical factors such as SNP genotyping data. [ABSTRACT FROM AUTHOR]

Accurate prediction of operons can improve the functional annotation and application of genes within operons in prokaryotes. Here, we review several features: (i) intergenic distance, (ii) metabolic pathways, (iii) homologous genes, (iv) promoters and terminators, (v) gene order conservation, (vi) microarray, (vii) clusters of orthologous groups, (viii) gene length ratio, (ix) phylogenetic profiles, (x) operon length/size and (xi) STRING database scores, as well as some other features, which have been applied in recent operon prediction methods in prokaryotes in the literature. Based on a comparison of the prediction performances of these features, we conclude that other, as yet undiscovered features, or feature selection with a receiver operating characteristic analysis before algorithm processing can improve operon prediction in prokaryotes. [ABSTRACT FROM AUTHOR]

Background: Complete mitochondrial (mt) genome sequencing is becoming increasingly common for phylogenetic reconstruction and as a model for genome evolution. For long template sequencing, i.e., like the entire mtDNA, it is essential to design primers for Polymerase Chain Reaction (PCR) amplicons which are partly overlapping each other. The presented chromosome walking strategy provides the overlapping design to solve the problem for unreliable sequencing data at the 59 end and provides the effective sequencing. However, current algorithms and tools are mostly focused on the primer design for a local region in the genomic sequence. Accordingly, it is still challenging to provide the primer sets for the entire mtDNA. Methodology/Principal Findings: The purpose of this study is to develop an integrated primer design algorithm for entire mt genome in general, and for the common primer sets for closely-related species in particular. We introduce ClustalW to generate the multiple sequence alignment needed to find the conserved sequences in closely-related species. These conserved sequences are suitable for designing the common primers for the entire mtDNA. Using a heuristic algorithm particle swarm optimization (PSO), all the designed primers were computationally validated to fit the common primer design constraints, such as the melting temperature, primer length and GC content, PCR product length, secondary structure, specificity, and terminal limitation. The overlap requirement for PCR amplicons in the entire mtDNA is satisfied by defining the overlapping region with the sliding window technology. Finally, primer sets were designed within the overlapping region. The primer sets for the entire mtDNA sequences were successfully demonstrated in the example of two closely-related fish species. The pseudo code for the primer design algorithm is provided. Conclusions/Significance: In conclusion, it can be said that our proposed sliding window-based PSO algorithm provides the necessary primer sets for the entire mt genome amplification and sequencing. [ABSTRACT FROM AUTHOR]

Abstract: Sequences of the partial 293-bp nuclear Z-chromosome-linked chromo-helicase binding protein (CHD-Z) and 729-bp mitochondrial cytochrome b (cyt b) genes were obtained from two species of the same family Pycnonotidae of Pycnonotus sinensis (P. sinensis, Chinese Bulbul) and Pycnonotus taivanus (P. taivanus, Taiwan Bulbul) distributed in Taiwan. A panel of 10 individuals (n =5 for each) with unknown relationship was used to characterize single nucleotide polymorphisms (SNPs) of these genes. We identified 2 and 10 SNPs in CHD-Z and cyt b loci, respectively. Frequency of SNPs was 10 per every 1465- and 729-bp on average. Pairwise nucleotide divergences of CHD-Z and cyt b genes among 10 specimens ranged from 0 to 0.0034 and 0 to 0.0055, respectively. Phylogenetic analysis suggested that the P. taivanus group assignment based on the CHD-Z and cyt b sequences is obviously very similar to P. sinensis. [Copyright &y& Elsevier]

Background: PCR-restriction fragment length polymorphism (RFLP) assay is a cost-effective method for SNP genotyping and mutation detection, but the manual mining for restriction enzyme sites is challenging and cumbersome. Three years after we constructed SNP-RFLPing, a freely accessible database and analysis tool for restriction enzyme mining of SNPs, significant improvements over the 2006 version have been made and incorporated into the latest version, SNP-RFLPing 2. Results: The primary aim of SNP-RFLPing 2 is to provide comprehensive PCR-RFLP information with multiple functionality about SNPs, such as SNP retrieval to multiple species, different polymorphism types (bi-allelic, tri-allelic, tetra-allelic or indels), gene-centric searching, HapMap tagSNPs, gene ontology-based searching, miRNAs, and SNP500Cancer. The RFLP restriction enzymes and the corresponding PCR primers for the natural and mutagenic types of each SNP are simultaneously analyzed. All the RFLP restriction enzyme prices are also provided to aid selection. Furthermore, the previously encountered updating problems for most SNP related databases are resolved by an on-line retrieval system. Conclusions: The user interfaces for functional SNP analyses have been substantially improved and integrated. SNP-RFLPing 2 offers a new and user-friendly interface for RFLP genotyping that can be used in association studies and is freely available at http://bio.kuas.edu.tw/snp-rflping2. [ABSTRACT FROM AUTHOR]

Protoapigenone, isolated from the native fern plant Thelypteris torresiana, has anticancer activity against some cancer cells. However, the toxicological mechanism for protoapigenone is still unknown. Here, we investigated the anticancer effect of protoapigenone on human lung cancer cell lines. The comet assay showed that DNA damage induced by protoapigenone is dose-dependent. Trypan blue exclusion showed that the cell killing by protoapigenone is both time and dose dependent. The IC50 of protoapigenone for 12, 24, and 48 h in H1299 cells is 6.11, 2.74, and 1.49 μM, respectively. Flow cytometry showed cell cycle perturbation such as sub-G1 accumulation (at 1.57 μM for 48 h and at 3.57 μM for 12 and 24 h) and G2/M arrest (at 3.57 μM for 12 and 24 h) for protoapigenone. The sub-G1 accumulation phenomena in the 3.57 μM for 24 h sample were shown to be apoptosis using Annexin V-immunofluorescence/propidium iodide staining. These results suggest protoapigenone is a potential chemotherapeutic agent for lung cancers. [ABSTRACT FROM AUTHOR]

Abstract: Background: High-throughput single nucleotide polymorphism (SNP) genotyping generates a huge amount of SNP data in genome-wide association studies. Simultaneous analyses for multiple SNP interactions associated with many diseases and cancers are essential; however, these analyses are still computationally challenging. Methods: In this study, we propose an odds ratio-based binary particle swarm optimization (OR-BPSO) method to evaluate the risk of breast cancer. Results: BPSO provides the combinational SNPs with their corresponding genotype, called SNP barcodes, with the maximal difference of occurrence between the control and breast cancer groups. A specific SNP barcode with an optimized fitness value was identified among seven SNP combinations within the space of one minute. The identified SNP barcodes with the best performance between control and breast cancer groups were found to be control-dominant, suggesting that these SNP barcodes may prove protective against breast cancer. After statistical analysis, these control-dominant SNP barcodes were processed for odds ratio analysis for quantitative measurement with regard to the risk of breast cancer. Conclusion: This study proposes an effective high-speed method to analyze the SNP–SNP interactions for breast cancer association study. [Copyright &y& Elsevier]

AbstractMany sequence-alignment tools were developed to discover single nucleotide polymorphisms (SNPs) derived from resequencing in genomic regions. Whether an identified SNP is indeed a novel SNP or is already contained in dbSNP is often difficult to answer. Here, we describe a freely available software, Seq-SNPing, which is a Java-based software for SNP discovery, and ID identification and editing and visualizating of sequence alignments. It is easy to use, fast, and provides an accurate method for searching and organizing SNP IDs from multiple sequence inputs, thereby greatly facilitating genetic studies. Seq-SNPing provides SNP identification by selecting any range of unaligned or aligned sequences in sequences that are similar. SNP IDs in the National Center for Biotechnology Information (NCBI) or user-defined SNPs within a selected sequence can be identified by Seq-SNPing. Information needed for SNP-RFLP (restriction fragment length polymorphism) genotyping is provided, such as SNP-REs (restriction enzymes), the sequence trimmer, sequence finder, BLAST (Basic Local Alignment Search Tool), SNP-BLAST, UCSC BLAT (BLAST-like alignment tool), RE mining, antisequencer (Anti-seq), and Tm(melting temperature)/GC of selected sequence. The thresholds for SNP calling are adjustable by selecting the height of the peak for each nucleotide representative curve in the chromatogram. Therefore, Seq-SNPing can discover SNPs and identify SNP IDs in both sequence text and chromatogram files in a fast and reliable way. The software is fully compatible with Microsoft®Windows. The program and user manual are available at http://bio.kuas.edu.tw/Seq-SNPing for download. [ABSTRACT FROM AUTHOR]

Abstract: Structural properties of GaN epilayers on wet-etched protruding and recess-patterned sapphire substrates (PSSs) have been investigated in detail using high-resolution double-crystal X-ray diffraction (DCXRD) and etch-pit density methods. The DCXRD results reveal various dislocation configurations on both types of PSSs. The etch pits of GaN on the recess PSS exhibit a regular distribution, i.e. less etch pits or threading dislocation density (TDD) onto the recess area than those onto the sapphire mesas. On the contrary, an irregular distribution is observed for the etch pits of GaN on the protruding PSS. A higher crystal quality of the GaN epilayer grown onto the recess PSS can be achieved as compared with that onto the protruding PSS. These data reflect that the GaN epilayer on the recess PSS could be a better template for the second epitaxial lateral overgrowth (ELOG) of GaN. As a result, the GaN epilayers after the ELOG process display the TDDs of around ∼106 cm−2. [Copyright &y& Elsevier]

Abstract: Traditional mitochondrial 16S rRNA is commonly used in many species identification studies. However, it is difficult to apply to the phylogenetic studies among the Oncorhynchus subspecies, which is a crucial need for management purposes for Oncorhynchus masou formosanus, Taiwan salmon. In this study, we have developed an improved species identification method for Taiwan salmon distinguished with other Oncorhynchus subspecies tested by exploiting PCR for growth hormone (GH) 1 gene. By comparing DNA sequences for GH1 from 11 species of Oncorhynchus subspecies we designed novel PCR primers that exploit differences between Taiwan salmon and other Oncorhynchus subspecies. Therefore, the technique is an important tool in the management of populations of the endangered land-locked Taiwan salmon preventing from their possible hybrids with other Oncorhynchus subspecies once tested. [Copyright &y& Elsevier]

Abstract: Genome-wide association analysis involved many single-nucleotide polymorphisms (SNPs) data is challenging mathematically and computationally. Hence, we propose the odds ratio-based discrete binary particle swarm optimization (OR-DBPSO) method that uses the OR as a new quantitative measure of disease risk among many SNP combinations with genotypes called “SNP barcode”. DBPSO are applied to generate SNP barcode, which computes the maximal difference of occurrence between the case and control groups, to predict disease susceptibility such as osteoporosis. Different SNP barcode patterns may occur several times in either low or high bone mineral density (BMD) groups. Our results showed that a DBPSO can effectively identify a specific SNP barcode with an optimized fitness value. SNP barcodes with a low fitness value will naturally be discarded from the population. A representative SNP barcode with a variable number of SNPs is processed to OR analysis to determine the maximum difference between the low and high BMD groups in statistics manner. Therefore, this paper introduces a powerful procedure to analyze disease-associated SNP–SNP interaction in genome-wide genes. [Copyright &y& Elsevier]

Introduction: Radiation dosimetry assessment often begins with measuring pharmaceutical biodistribution in rodents. The traditional approach to dosimetry in rodents involves a radioassay ex vivo of harvested organs at different time points following administration of the radiopharmaceutical. The emergence of small-animal positron emission tomography (PET) presents the opportunity for an alternative method for making radiodosimetry estimates previously employed only in humans and large animals. In the current manuscript, normal-tissue absorbed dose estimates for the 18F-labeled chemotherapy agent [18F]5-fluorouracil ([18F]5-FU) were derived by PET imaging- and by tissue harvesting-based methods in rats.Methods: Small-animal PET data were acquired dynamically for up to 2 h after injection of [18F]5-FU in anesthetized rats (n=16). Combined polynomial and exponential functions were used to model the harvesting-based and imaging-based time-activity data. The measured time-activity data were extrapolated to modeled (i.e., Standard Man) human organs and human absorbed doses calculated.Results: Organ activities derived by imaging-based and by harvesting-based methods were highly correlated (r>0.999) as were the projected human dosimetry estimates across organs (r=0.998) obtained with each method. The tissues calculated to receive highest radiation dose by both methods were related to routes of excretion (bladder wall, liver, and intestines). The harvesting-based and imaging-based methods yielded effective dose (ED) of 2.94E-2 and 2.97E-2 mSv/MBq, respectively.Conclusions: Small-animal PET presents an opportunity for providing radiation dose estimates with statistical and logistical advantages over traditional tissue harvesting-based methods. [ABSTRACT FROM AUTHOR]

The phosphoinositide-3-kinase (PI3K) pathway has widely been considered as a potential therapeutic target for head and neck cancer (HNC); however, the application of PI3K inhibitors is often overshadowed by the induction of drug resistance with unknown mechanisms. In this study, PII3K inhibitor resistant cancer cells were developed by prolonged culturing of cell lines with BEZ235, a dual PI3K and mammalian target of rapamycin (mTOR) inhibitor. The drug resistant HNC cells showed higher IC50 of the proliferation to inhibitors specifically targeting PI3K and/or mTOR, as compared to their parental cells. These cells also showed profound resistance to drugs of other classes. Molecular analysis revealed persistent activation of phosphorylated AKT at threonine 308 in the drug resistant cells and increased expression of markers for tumor-initiating cells. Interestingly, increased intra-cellular ROS levels were observed in the drug resistant cells. Among anti-oxidant molecules, the expression of SOD2 was increased and was associated with the ALDH-positive tumor-initiating cell features. Co-incubation of SOD inhibitors and BEZ235 decreased the stemness feature of the cells in vitro, as shown by results of the spheroid formation assay. In conclusion, dysregulation of SOD2 might contribute to the profound resistance to PI3K inhibitors and the other drugs in HNC cells. [ABSTRACT FROM AUTHOR]

The mechanism of particle separation in a small hydrocyclone is analyzed in this study. The separation efficiency of particles is affected by two major effects, the centrifugal and underflow effects. The fundamentals of these effects on the selectivity curve are derived from the theories of hydrodynamics. Three JIS particulate samples are separated in a 10-mm hydrocyclone. The proposed mechanism can be demonstrated by the available data. An increase in split ratio leads to an increase in the separation efficiency only for fine particles; consequently, a decrease in the separation sharpness results in a remarkable fishhook phenomenon. When the feed rate is increased by increasing the pressure drop through the hydrocyclone, the entire partial separation efficiency will be improved, but the separation sharpness and fishhook depth have no substantial varieties. The proposed mechanism can be used for explaining these phenomena, for the selection of optimum operating conditions, and for the hydrocyclone design. [ABSTRACT FROM AUTHOR]

Abstract: Eagles are sexually monomorphic and therefore it is difficult to determine their gender, which is a crucial need for management purposes. In this study, we have developed an improved gender identification method by exploiting length differences between the Chromo-Helicase-DNA binding protein (CHD)-Z and CHD-W genes of Spilornis cheela hoya. By comparing DNA sequences for CHD-W and CHD-Z from 10 species of Falconiformes eagles we designed universal gender identification PCR primers that exploit differences in product size. Standard agarose gels were shown to easily distinguish between the 148-bp CHD-ZW and the 258-bp CHD-W PCR products. When used with 28 samples of S. cheela hoya, our improved universal primers provided a fast and precise gender identification assay. [Copyright &y& Elsevier]

ABSTRACTGenome-wide association analysis involving many single nucleotide polymorphisms (SNPs) data is challenging mathematically and computationally. It is time consuming to classify the combination of multilocus genotypes into high- and low-risk groups without false positive and negative errors. Hence, we propose the odds ratio-based genetic algorithms (OR-GA) method that uses the odds ratio as a new quantitative measure of disease risk among many SNP combinations. Genetic algorithms (GA) are applied to generate SNP barcodes of genotypes, which propose the maximal difference of occurrence between the case and control groups, to predict disease susceptibility (e.g., osteoporosis). When individuals are grouped into a low and high bone mass density (BMD) range, different SNP barcode patterns may occur several times in each of these two groups. Our results showed that a GA can effectively identify a specific SNP barcode with an optimized fitness value. SNP barcodes with a low fitness value will naturally be discarded from the population. A representative SNP barcode with a variable number of SNPs is processed by odds ratio analysis to determine the maximum difference between the low and high BMD groups in a statistical manner. Therefore, this paper introduces a powerful procedure for analysis of disease-associated SNP barcode in genome-wide genes. [ABSTRACT FROM AUTHOR]

Abstract: Gene expression profiles, which represent the state of a cell at a molecular level, have great potential as a medical diagnosis tool. Compared to the number of genes involved, available training data sets generally have a fairly small sample size in cancer type classification. These training data limitations constitute a challenge to certain classification methodologies. A reliable selection method for genes relevant for sample classification is needed in order to speed up the processing rate, decrease the predictive error rate, and to avoid incomprehensibility due to the large number of genes investigated. Improved binary particle swarm optimization (IBPSO) is used in this study to implement feature selection, and the K-nearest neighbor (K-NN) method serves as an evaluator of the IBPSO for gene expression data classification problems. Experimental results show that this method effectively simplifies feature selection and reduces the total number of features needed. The classification accuracy obtained by the proposed method has the highest classification accuracy in nine of the 11 gene expression data test problems, and is comparative to the classification accuracy of the two other test problems, as compared to the best results previously published. [Copyright &y& Elsevier]

Background: Combination of CHD (chromo-helicase-DNA binding protein)-specific polymerase chain reaction (PCR) with electrophoresis (PCR/electrophoresis) is the most common avian molecular sexing technique but it is lab-intensive and gel-required. Gender determination often fails when the difference in length between the PCR products of CHD-Z and CHD-W genes is too short to be resolved. Results: Here, we are the first to introduce a PCR-melting curve analysis (PCR/MCA) to identify the gender of birds by genomic DNA, which is gel-free, quick, and inexpensive. Spilornis cheela hoya (S. c. hoya) and Pycnonotus sinensis (P. sinensis) were used to illustrate this novel molecular sexing technique. The difference in the length of CHD genes in S. c. hoya and P. sinensis is 13-, and 52-bp, respectively. Using Griffiths' P2/P8 primers, molecular sexing failed both in PCR/electrophoresis of S. c. hoya and in PCR/MCA of S. c. hoya and P. sinensis. In contrast, we redesigned sex-specific primers to yield 185- and 112-bp PCR products for the CHD-Z and CHD-W genes of S. c. hoya, respectively, using PCR/MCA. Using this specific primer set, at least 13 samples of S. c. hoya were examined simultaneously and the Tm peaks of CHD-Z and CHD-W PCR products were distinguished. Conclusion: In this study, we introduced a high-throughput avian molecular sexing technique and successfully applied it to two species. This new method holds a great potential for use in high throughput sexing of other avian species, as well. [ABSTRACT FROM AUTHOR]

Abstract: Lipoma is a benign neoplasm of normal fat cells that appears as a soft, movable swelling, often with a slight yellowish coloration. Human mesenchymal stem cells (MSCs) that have been isolated from bone marrow, blood, and other adult tissues including adipose tissue have the potential to be useful candidates for therapy. No literature had reported about stem cells from lipoma tissue. Here, a new cell culture method is described and utilized to greatly accelerate the growth rate and prolong the lifespan of lipoma-derived MSCs. Cells produced in early cultures display characteristics similar to those previously reported for multipotential stem cells, including a high frequency of anchorage-independent growth in soft agar and a lack of gap junctional intercellular communication in cell types with serpiginous morphology. These cells can differentiate into adipocytes, osteoblasts, and chondrocytes after induction. In conclusion, lipoma-derived stem cells possessing the characteristics of MSCs are described for the first time. [Copyright &y& Elsevier]

Background: Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. Methods: Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). Results: We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. Conclusions: These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity. [Copyright &y& Elsevier]

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease with autosomal dominant transmission characterized by the presence of malformations of the big toes and of postnatal progressive heterotopic endochondral osteogenesis. We report the case of 3-year-old girl with dysplasia of the first metatarsal bones and progressive heterotopic ossificans of the right thigh due to previous diphtheria–tetanus–pertussis immunizations and several inappropriate surgical interventions. Direct sequence analysis identified a 617G–A nucleotide mutation in the patient but not in her parents or brother. Pedigree analysis suggests that a de novo mutation in the ACVR1 gene is responsible for the disease in this family. This is the first report of the results of a mutation analysis in a sporadic case of FOP in a Taiwanese patient. [ABSTRACT FROM AUTHOR]

Background: The restriction fragment length polymorphism (RFLP) is a common laboratory method for the genotyping of single nucleotide polymorphisms (SNPs). Here, we describe a webbased software, named SNP-RFLPing, which provides the restriction enzyme for RFLP assays on a batch of SNPs and genes from the human, rat, and mouse genomes. Results: Three user-friendly inputs are included: 1) NCBI dbSNP "rs" or "ss" IDs; 2) NCBI Entrez gene ID and HUGO gene name; 3) any formats of SNP-in-sequence, are allowed to perform the SNP-RFLPing assay. These inputs are auto-programmed to SNP-containing sequences and their complementary sequences for the selection of restriction enzymes. All SNPs with available RFLP restriction enzymes of each input genes are provided even if many SNPs exist. The SNP-RFLPing analysis provides the SNP contig position, heterozygosity, function, protein residue, and amino acid position for cSNPs, as well as commercial and non-commercial restriction enzymes. Conclusion: This web-based software solves the input format problems in similar softwares and greatly simplifies the procedure for providing the RFLP enzyme. Mixed free forms of input data are friendly to users who perform the SNP-RFLPing assay. SNP-RFLPing offers a time-saving application for association studies in personalized medicine and is freely available at http://bio.kuas.edu.tw/snprflp/. [ABSTRACT FROM AUTHOR]

Objectives. To explore whether local growth factors concentration, including vascular endothelial growth factor (VEGF) and transforming growth factor beta one (TGF-β 1 ), influence the formation of coronary collaterals. Design. Thirty-six patients scheduled for coronary angiography received a 6F Goodale-Lubin catheterization to collect blood from the coronary sinus (CS) and right atrium (RA). Results. Patients with coronary collaterals had a higher number of diseased vessels (2.6±0.2 vs. 1.4±0.3, p = 0.005), higher percentage of severity of stenosis (93±2 vs. 48±8, P [ABSTRACT FROM AUTHOR]

Highlights the importance of the trustworthiness of salespeople as a determinant of the development of quality buyer-seller relationships in the business market. Emphasis on how various personal, situational and organizational factors affect the components of trustworthiness; Impact of idealism, situational factors of extrinsic motivation and intrinsic motivation on trustworthiness; Effects of the organizational factors of culture and salesforce control system.

Background: Allelic imbalance (AI), the loss or gain of chromosomal regions, is found in many cancers. AI can be detected in genomic tumor DNA released into the blood after necrosis or apoptosis. We evaluated plasma DNA concentration, allelic status in plasma DNA, and serum CA 125 level as screening tests for ovarian and other cancers. Methods: Plasma samples were obtained from 330 women (44 normal healthy control individuals, 122 patients with various cancers, and 164 control patients with non-neoplastic diseases). Plasma DNA concentration was determined in all samples. Allelic status was determined by digital single nucleotide polymorphism (SNP) analysis with eight SNP markers in plasma DNA from 54 patients with ovarian cancer and 31 control patients. CA 125 was determined in 63 samples. Receiver-operating characteristic (ROC) curves were plotted, and the areas under the ROC curves—a measure of the overall ability of a diagnostic test with multiple cutoffs to distinguish between diseased and nondiseased individuals— were determined. Results: The area under the ROC curve for plasma DNA concentration was 0.90 for patients with neoplastic disease versus healthy control individuals and 0.74 for patients with neoplastic diseases versus control patients with non-neoplastic diseases. For control subjects given a specificity of 100% (95% confidence interval [CI] = 92% to 100%), the highest sensitivity achieved was 57% (95% CI = 49% to 67%). AI in at least one SNP was found in 87% (95% CI = 60% to 98%) of patients with stage I/II ovarian cancer and 95% (95% CI = 83% to 99%) of patients with stage III/IV ovarian cancer, but AI was not found in 31 patients with non-neoplastic diseases (specificity = 100%, 95% CI = 89% to 100%). The area under the ROC curve assessing AI was 0.95. Combining the serum CA 125 level with the plasma DNA concentration increased the area under the ROC curve from 0.78 (CA 125 alone) to 0.84. Conclusion: Plasma DNA concentration may... [ABSTRACT FROM AUTHOR]

This study presents a fluorescence-based microbial sensor for the detection of metal ions as a novel analytical tool for environmental applications. Our results demonstrate the effectiveness of whole-cell sensors in the selective detection of gold ions. Two heavy-metal-tolerant proteobacteria, Cupriavidus metallidurans and Ralstonia eutropha, were examined and showed great specificity. This work highlights the potential of employing engineered microbial strains as robust analytical tools. [ABSTRACT FROM AUTHOR]

In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNAPyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants have been developed during the last decade, enabling a substantial genetic code expansion, mainly with aliphatic pyrrolysine analogs. However, comparatively less progress has been made to expand the substrate range of MmPylRS towards aromatic amino acid residues. Therefore, we set to further expand the substrate scope of orthogonal translation by a semi-rational approach; redesigning the MmPylRS efficiency. Based on the randomization of residues from the binding pocket and tRNA binding domain, we identify three positions (V401, W417 and S193) crucial for ncAA specificity and enzyme activity. Their systematic mutagenesis enabled us to generate MmPylRS variants dedicated to tryptophan (such as β-(1-Azulenyl)-l-alanine or 1-methyl-l-tryptophan) and tyrosine (mainly halogenated) analogs. Moreover, our strategy also significantly improves the orthogonal translation efficiency with the previously activated analog 3-benzothienyl-l-alanine. Our study revealed the engineering of both first shell and distant residues to modify substrate specificity as an important strategy to further expand our ability to discover and recruit new ncAAs for orthogonal translation [ABSTRACT FROM AUTHOR]

. (J Card Surg 2011;26:214-216) [ABSTRACT FROM AUTHOR]

Multilayer Ag/[Ag2Se(t)/FePt(1nm)]10 (thickness t = 0.1-0.4 nm) were alternately deposited on a glass substrate and subsequently annealed by rapid thermal process (RTP) at 800 °C for 3 min. After RTP, the interface between FePt and Ag2Se was intermixed to form particulate films. The grains size of the L10 FePt decreased from 9.8 to 7.7 nm when the total thickness of Ag2Se intermediate layer increases to 1 nm. The Ag/(Ag2Se/FePt)10 particulate film showed perpendicular magnetization and a slight increase in out-of-plane coercivity over that of the original thickness of Ag2Se. The Ag2Se atoms were immiscible with FePt phase but the FePt grains were refined and separated well from the Ag2Se phase. Compared with Ag/FePt bilayer, the grains of the FePt were refined and uniformly separated in the Ag/[Ag2Se(t)/FePt]10 multilayer with t = 0.1 nm. [ABSTRACT FROM AUTHOR]

Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis–miRNA–exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases. [ABSTRACT FROM AUTHOR]

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 μg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2′-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) involvement is a rare disease with poor prognosis. This study aimed to evaluate the outcome of HCC patients receiving radiotherapy (RT) to IVC tumor thrombus.Methods: A total of 42 consecutive HCC patients treated with RT to IVC tumor thrombus between September 2007 and October 2018 were enrolled. Overall survival (OS), the response of IVC thrombus, prognostic factors and failure pattern were assessed.Results: The median follow-up time was 4.4 months. The median RT equivalent dose in 2-Gy fractions was 48.75 Gy (range, 3.25-67.10). The objective response rate of IVC thrombus was 47.6% (95% confidence interval [CI], 33.3-64.3%). The OS rate at 1 year was 30.0%, with a median OS of 6.6 months (95% CI, 3.7-9.5) from the start of RT. On multivariate analysis, Child-Pugh class, lymph node metastasis, lung metastasis and objective response of IVC thrombus were independent predictors for OS. Lung was the most common site of first progression in 14 (33.3%) patients. For 32 patients without lung metastasis before RT, use of systemic treatment concurrent with and/or after RT was associated with a significantly longer lung metastasis-free survival (5.9 vs. 1.5 months, p = 0.0033).Conclusions: RT is effective for IVC tumor thrombus of HCC with acceptable adverse effects. RT might be a treatment option incorporated into combination therapy for HCC involving IVC. [ABSTRACT FROM AUTHOR]

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA2. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells. [ABSTRACT FROM AUTHOR]

Serum neutrophil-to-lymphocytes ratio (NLR) is a potential predictive and prognostic marker in head and neck cancers. This study aimed to determine the role of pretreatment serum NLR in patients with hypopharyngeal cancer (HPC) treated with definitive chemoradiotherapy. We retrospectively investigated the correlation between clinicopathological parameters and NLR status and analysed its impact on therapeutic response and survival. A total of 120 patients treated at a single institution between 2009 and 2015 were included. The median follow-up time was 24.1 months. High NLR (NLR ≥ 4) was associated with advanced T classification (p = 0.01*) and advanced stage (p = 0.02*) based on chi-square test. We also found that high pretreatment NLR was correlated with poor treatment response (HR = 2.42, 95% CI: 1.08-5.44, p = 0.03*). Pretreatment NLR was also an independent prognostic factor for progression-free survival (HR = 1.71, 95% CI: 1.01-2.90, p = 0.046*) and overall survival (HR = 1.99, 95% CI: 1.21-3.28, p = 0.01*) while correcting for known prognostic factors. Overall, these findings support that NLR is a potential biomarker for host response to tumour aggressiveness, therapeutic response to chemoradiotherapy and survival in HPC patients. This study is limited by its retrospective nature and further validation is warranted. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and can be divided into three major subsites: buccal mucosal SCC (BMSCC), tongue SCC (TSCC), and lip SCC (LSCC). The autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1(SQSTM1) are widely used proteins to evaluate autophagy in tumor tissues. However, the role of MAP1LC3B and SQSTM1 in OSCC is not fully understood, particularly in certain subsites. With a tissue microarray comprised of 498 OSCC patients, including 181 BMSCC, 244 TSCC, and 73 LSCC patients, we found that the expression levels of MAP1LC3B and cytoplasmic SQSTM1 were elevated in the tumor tissues of three subsites compared with those in adjacent normal tissues. MAP1LC3B was associated with a poor prognosis only in TSCC. SQSTM1 was associated with poor differentiation in three subsites, while the association with lymph node invasion was only observed in BMSCC. Interestingly, MAP1LC3B was positively correlated with SQSTM1 in the tumor tissues of BMSCC, whereas it showed no correlation with SQSTM1 in adjacent normal tissue. The coexpression of higher MAP1LC3B and SQSTM1 demonstrated a significantly worse disease-specific survival (DSS) and disease-free survival (DFS) in patients with BMSCC and LSCC, but not TSCC. The knockdown of MAP1LC3B and SQSTM1 reduced autophagy, cell proliferation, invasion and tumorspheres of BMSCC cells. Additionally, silencing both MAP1LC3B and SQSTM1 enhanced the cytotoxic effects of paclitaxel in the tumorspheres of BMSCC cells. Taken together, MAP1LC3B and SQSTM1 might modulate autophagy to facilitate tumorigenesis and chemoresistance in OSCC, particularly in BMSCC. [ABSTRACT FROM AUTHOR]

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow–Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells. [ABSTRACT FROM AUTHOR]

In this study, multistacked InAs submonolayer (SML) quantum dots (QDs) were sandwiched in an InGaAs/GaAsSb dot-in-a-double-well (DDwell) structure to enhance the crystal quality and optical properties of QDs. The photoluminescence (PL) intensity of the InAs SML QDs with the DDwell structure was 5.5 times higher than that of conventional InAs/GaAs SML QDs because of the reduced number of nonradiative recombination centers and the enhanced carrier hole confinement. The PL results of the DDwell structure exhibit two peaks that represent the carrier overflow from SML QDs to InGaAs quantum wells (QWs) and hence the radiative recombination in InGaAs QWs because of the shallow carrier confinement of SML QDs. Among the compared samples, the DDwell structure exhibited the highest activation energy of 101.8 meV. Furthermore, the carrier thermal escape was suppressed in these InAs SML QDs. High-resolution transmission electron microscopy revealed that the microstructures of the InAs SML QDs demonstrated larger dots for the DDwell structure, thus verifying that the emission wavelength elongated in the PL measurement. These improved optical properties of the InAs SML QDs with the DDwell structure were attributable to the improved crystal quality because of the use of Sb surfactants and additional volume for carrier recombination provided by the InGaAs quantum well. The DDwell structure can thus be applied in optoelectronic devices to obtain advanced performance. [ABSTRACT FROM AUTHOR]

Exosomes are cell-derived membranous structures primarily involved in the delivery of the payload to the recipient cells, and they play central roles in carcinogenesis and metastasis. Radiotherapy is a common cancer treatment that occasionally generates exosomal miRNA-associated modulation to regulate the therapeutic anticancer function and side effects. Combining radiotherapy and natural products may modulate the radioprotective and radiosensitizing responses of non-cancer and cancer cells, but there is a knowledge gap regarding the connection of this combined treatment with exosomal miRNAs and their downstream targets for radiation and exosome biogenesis. This review focuses on radioprotective natural products in terms of their impacts on exosomal miRNAs to target radiation-modulating and exosome biogenesis (secretion and assembly) genes. Several natural products have individually demonstrated radioprotective and miRNA-modulating effects. However, the impact of natural-product-modulated miRNAs on radiation response and exosome biogenesis remains unclear. In this review, by searching through PubMed/Google Scholar, available reports on potential functions that show radioprotection for non-cancer tissues and radiosensitization for cancer among these natural-product-modulated miRNAs were assessed. Next, by accessing the miRNA database (miRDB), the predicted targets of the radiation- and exosome biogenesis-modulating genes from the Gene Ontology database (MGI) were retrieved bioinformatically based on these miRNAs. Moreover, the target-centric analysis showed that several natural products share the same miRNAs and targets to regulate radiation response and exosome biogenesis. As a result, the miRNA–radiomodulation (radioprotection and radiosensitization)–exosome biogenesis axis in regard to natural-product-mediated radiotherapeutic effects is well organized. This review focuses on natural products and their regulating effects on miRNAs to assess the potential impacts of radiomodulation and exosome biogenesis for both the radiosensitization of cancer cells and the radioprotection of non-cancer cells. [ABSTRACT FROM AUTHOR]