vHDvDB 2.0: Database and Group Comparison Server for Hepatitis Delta Virus.

The hepatitis delta virus (HDV) is a unique pathogen with significant global health implications, affecting individuals who are coinfected with the hepatitis B virus (HBV). HDV infection has profound clinical consequences, manifesting either as coinfection with HBV, resulting in acute hepatitis and potential liver failure, or as superinfection in chronic HBV cases, substantially increasing the risk of cirrhosis and hepatocellular carcinoma. Given the complex dynamics of HDV infection and the urgent need for advanced research tools, this article introduces vHDvDB 2.0, a comprehensive HDV full-length sequence database. This innovative platform integrates data preprocessing, secondary structure prediction, and epidemiological research tools. The primary goal of vHDvDB 2.0 is to consolidate HDV sequence data into a user-friendly repository, thereby facilitating access for researchers and enhancing the broader scientific understanding of HDV. The significance of this database lies in its potential to streamline HDV research by providing a centralized resource for analyzing viral sequences and exploring genotype-specific characteristics. It will also enable more in-depth research within the HDV sequence domains.

Arginine Methylation of DDX3 by PRMT1 Mediates Mitochondrial Homeostasis to Promote Breast Cancer Metastasis.

Dysregulated mitochondrial dynamics and metabolism play important roles in tumorigenesis. Metastasizing tumor cells predominantly utilize mitochondrial metabolism, and regulators of metabolic reprogramming may provide reliable biomarkers for diagnosing cancer metastasis. Here, we identified a type I arginine methyltransferase-DEAD-box polypeptide 3, X-linked (PRMT1-DDX3) axis that promotes breast cancer metastasis by coordinating mitochondrial biogenesis and mitophagy to ensure mitochondrial quality control. Mechanistically, PRMT1 induces arginine methylation of DDX3, which enhances its protein stability and prevents proteasomal degradation. DDX3 mediates mitochondrial homeostasis by translocating to mitochondria where it facilitates phosphatase and tensin homology-induced kinase 1 translation in response to mitochondrial stress. Inhibition of DDX3 suppresses mitochondrial biogenesis and mitophagy, resulting in diminished cancer stemness and metastatic properties. Overall, this study uncovers a mechanism by which the PRMT1-DDX3 axis regulates mitochondrial homeostasis to support breast cancer metastasis, suggesting strategies for targeting metabolic vulnerabilities to treat metastatic breast cancer. Significance: DDX3 is stabilized by PRMT1-mediated arginine methylation and coordinates mitophagy and mitochondrial biogenesis by upregulating PINK1 to facilitate breast cancer progression.

Anti-obesity and anti-diabetic bioactive peptides: A comprehensive review of their sources, properties, and techno-functional challenges.

The scourge of obesity arising from obesogens and poor dieting still ravages our planet as half of the global population may be overweight and obese by 2035. This metabolic disorder is intertwined with type 2 diabetes (T2D), both of which warrant alternative therapeutic options other than clinically approved drugs like orlistat with their tendency of abuse and side effects. In this review, we comprehensively describe the global obesity problem and its connection to T2D. Obesity, overconsumption of fats, the mechanism of fat digestion, obesogenic gut microbiota, inhibition of fat digestion, and natural anti-obesity compounds are discussed. Similar discussions are made for diabetes with regard to glucose regulation, the diabetic gut microbiota, and insulinotropic compounds. The sources and production of anti-obesity bioactive peptides (AOBPs) and anti-diabetic bioactive peptides (ADBPs) are also described while explaining their structure-function relationships, gastrointestinal behaviors, and action mechanisms. Finally, the techno-functional applications of AOBPs and ADBPs are highlighted.

Techno-Functions and Safety Concerns of Plant-Based Peptides in Food Matrices.

Plant-based peptides (PBPs) benefit functional food development and environmental sustainability. Proteolysis remains the primary method of peptide production because it is a mild and nontoxic technique. However, potential safety concerns still emanate from toxic or allergenic sequences, amino acid racemization, iso-peptide bond formation, Maillard reaction, dose usage, and frequency. The main aim of this review is to investigate the techno-functions of PBPs in food matrices, as well as their safety concerns. The distinctive characteristics of PBPs exhibit their techno-functions for improving food quality and functionality by contributing to several crucial food formulations and processing. The techno-functions of PBPs include solubility, hydrophobicity, bitterness, foaming, oil-binding, and water-holding capacities, which subsequently affect food matrices. The safety and quality of foodstuff containing PBPs depend on the proper source of plant proteins, the selection of processing approaches, and compliance with legal regulations for allergen labeling and safety evaluations. The safety concerns in allergenicity and toxicity were discussed. The conclusion is that food technologists must apply safe limits and consider potential allergenic components generated during the development of food products with PBPs. Therefore, functional food products containing PBPs can be a promising strategy to provide consumers with wholesome health benefits.

Downregulation of TAZ elicits a mitochondrial redox imbalance and ferroptosis in lung epithelial cells exposed to diesel exhaust particles.

Mitochondrial dysfunction was reported to be involved in the development of lung diseases including chronic obstructive pulmonary disease (COPD). However, molecular regulation underlying metabolic disorders in the airway epithelia exposed to air pollution remains unclear. In the present study, lung bronchial epithelial BEAS-2B and alveolar epithelial A549 cells were treated with diesel exhaust particles (DEPs), the primary representative of ambient particle matter. This treatment elicited cell death accompanied by induction of lipid reactive oxygen species (ROS) production and ferroptosis. Lipidomics analyses revealed that DEPs increased glycerophospholipid contents. Accordingly, DEPs upregulated expression of the electron transport chain (ETC) complex and induced mitochondrial ROS production. Mechanistically, DEP exposure downregulated the Hippo transducer transcriptional co-activator with PDZ-binding motif (TAZ), which was further identified to be crucial for the ferroptosis-associated antioxidant system, including glutathione peroxidase 4 (GPX4), the glutamate-cysteine ligase catalytic subunit (GCLC), and glutathione-disulfide reductase (GSR). Moreover, immunohistochemistry confirmed downregulation of GPX4 and upregulation of lipid peroxidation in the bronchial epithelium of COPD patients and Sprague-Dawley rats exposed to air pollution. Finally, proteomics analyses confirmed alterations of ETC-related proteins in bronchoalveolar lavage from COPD patients compared to healthy subjects. Together, our study discovered that involvement of mitochondrial redox dysregulation plays a vital role in pulmonary epithelial cell destruction after exposure to air pollution.

Metal-binding peptides and their potential to enhance the absorption and bioavailability of minerals.

Minerals including calcium, iron, zinc, magnesium, and copper have several human nutritional functions due to their metabolic activities. Body tissues require sufficient levels of a variety of micronutrients to maintain their health. To achieve these micronutrient needs, dietary consumption must be adequate. Dietary proteins may regulate the biological functions of the body in addition to acting as nutrients. Some peptides encoded in the native protein sequences are primarily responsible for the absorption and bioavailability of minerals in physiological functions. Metal-binding peptides (MBPs) were discovered as potential agents for mineral supplements. Nevertheless, sufficient studies on how MBPs affect the biological functions of minerals are lacking. The hypothesis is that the absorption and bioavailability of minerals are significantly influenced by peptides, and these properties are further enhanced by the configuration and attribute of the metal-peptide complex. In this review, the production of MBPs is discussed using various key parameters such as the protein sources and amino acid residues, enzymatic hydrolysis, purification, sequencing and synthesis and in silico analysis of MBPs. The mechanisms of metal-peptide complexes as functional food ingredients are elucidated, including metal-peptide ratio, precursors and ligands, complexation reaction, absorbability and bioavailability. Finally, the characteristics and application of different metal-peptide complexes are also described.

Metabolomics analysis reveals changes related to pseudocyst formation induced by iron depletion in Trichomonas vaginalis.

BACKGROUND: Iron is an essential element for cellular functions, such as energy metabolism. Trichomonas vaginalis, a human urogenital tract pathogen, is capable of surviving in the environment without sufficient iron supplementation. Pseudocysts (cyst-like structures) are an environmentally tolerated stage of this parasite while encountering undesired conditions, including iron deficiency. We previously demonstrated that iron deficiency induces more active glycolysis but a drastic downregulation of hydrogenosomal energy metabolic enzymes. Therefore, the metabolic direction of the end product of glycolysis is still controversial. METHODS: In the present work, we conducted an LC‒MS-based metabolomics analysis to obtain accurate insights into the enzymatic events of T. vaginalis under iron-depleted (ID) conditions. RESULTS: First, we showed the possible digestion of glycogen, cellulose polymerization, and accumulation of raffinose family oligosaccharides (RFOs). Second, a medium-chain fatty acid (MCFA), capric acid, was elevated, whereas most detected C18 fatty acids were reduced significantly. Third, amino acids were mostly reduced, especially alanine, glutamate, and serine. Thirty-three dipeptides showed significant accumulation in ID cells, which was probably associated with the decrease in amino acids. Our results indicated that glycogen was metabolized as the carbon source, and the structural component cellulose was synthesized at same time. The decrease in C18 fatty acids implied possible incorporation in the membranous compartment for pseudocyst formation. The decrease in amino acids accompanied by an increase in dipeptides implied incomplete proteolysis. These enzymatic reactions (alanine dehydrogenase, glutamate dehydrogenase, and threonine dehydratase) were likely involved in ammonia release. CONCLUSION: These findings highlighted the possible glycogen utilization, cellulose biosynthesis, and fatty acid incorporation in pseudocyst formation as well as NO precursor ammonia production induced by iron-depleted stress.

Protein cysteine S-nitrosylation provides reducing power by enhancing lactate dehydrogenase activity in Trichomonas vaginalis under iron deficiency.

BACKGROUND: Iron plays essential roles in the pathogenesis and proliferation of Trichomonas vaginalis, the causative agent of the most prevalent non-viral human sexually transmitted infection. We previously demonstrated that under iron deficiency, the endogenous nitric oxide (NO) is accumulated and capable of regulating the survival of T. vaginalis. Herein, we aim to explore the influence of NO on the activity of the pyruvate-reducing enzyme lactate dehydrogenase in T. vaginalis (TvLDH). METHODS: Levels of lactate and pyruvate were detected for determining glycolysis activity in T. vaginalis under iron deficiency. Quantitative PCR was performed to determine the expression of TvLDH. S-nitrosylated (SNO) proteomics was conducted to identify the NO-modified proteins. The activities of glyceraldehyde-3-phosphate dehydrogenase (TvGAPDH) and TvLDH were measured after sodium nitrate treatment. The effects of protein nitrosylation on the production of cellular reducing power were examined by measuring the amount of nicotinamide adenine dinucleotide (NAD) and the ratio of the NAD redox pair (NAD+/NADH). RESULTS: We found that although the glycolytic pathway was activated in cells under iron depletion, the level of pyruvate was decreased due to the increased level of TvLDH. By analyzing the SNO proteome of T. vaginalis upon iron deficiency, we found that TvLDH is one of the glycolytic enzymes modified by SNO. The production of pyruvate was significantly reduced after nitrate treatment, indicating that protein nitrosylation accelerated the consumption of pyruvate by increasing TvLDH activity. Nitrate treatment also induced NAD oxidation, suggesting that protein nitrosylation was the key posttranslational modification controlling cellular redox status. CONCLUSIONS: We demonstrated that NO-mediated protein nitrosylation plays pivotal roles in the regulation of glycolysis, pyruvate metabolism, and the activity of TvLDH. The recycling of oxidized NAD catalyzed by TvLDH provided the reducing power that allowed T. vaginalis to adapt to the iron-deficient environment.

CoMutPlotter: a web tool for visual summary of mutations in cancer cohorts.

BACKGROUND: CoMut plot is widely used in cancer research publications as a visual summary of mutational landscapes in cancer cohorts. This summary plot can inspect gene mutation rate and sample mutation burden with their relevant clinical details, which is a common first step for analyzing the recurrence and co-occurrence of gene mutations across samples. The cBioPortal and iCoMut are two web-based tools that allow users to create intricate visualizations from pre-loaded TCGA and ICGC data. For custom data analysis, only limited command-line packages are available now, making the production of CoMut plots difficult to achieve, especially for researchers without advanced bioinformatics skills. To address the needs for custom data and TCGA/ICGC data comparison, we have created CoMutPlotter, a web-based tool for the production of publication-quality graphs in an easy-of-use and automatic manner. RESULTS: We introduce a web-based tool named CoMutPlotter to lower the barriers between complex cancer genomic data and researchers, providing intuitive access to mutational profiles from TCGA/ICGC projects as well as custom cohort studies. A wide variety of file formats are supported by CoMutPlotter to translate cancer mutation profiles into biological insights and clinical applications, which include Mutation Annotation Format (MAF), Tab-separated values (TSV) and Variant Call Format (VCF) files. CONCLUSIONS: In summary, CoMutPlotter is the first tool of its kind that supports VCF file, the most widely used file format, as its input material. CoMutPlotter also provides the most-wanted function for comparing mutation patterns between custom cohort and TCGA/ICGC project. Contributions of COSMIC mutational signatures in individual samples are also included in the summary plot, which is a unique feature of our tool. CoMutPlotter is freely available at http://tardis.cgu.edu.tw/comutplotter .

VAReporter: variant reporter for cancer research of massive parallel sequencing.

BACKGROUND: High throughput sequencing technologies have been an increasingly critical aspect of precision medicine owing to a better identification of disease targets, which contributes to improved health care cost and clinical outcomes. In particular, disease-oriented targeted enrichment sequencing is becoming a widely-accepted application for diagnostic purposes, which can interrogate known diagnostic variants as well as identify novel biomarkers from panels of entire human coding exome or disease-associated genes. RESULTS: We introduce a workflow named VAReporter to facilitate the management of variant assessment in disease-targeted sequencing, the identification of pathogenic variants, the interpretation of biological effects and the prioritization of clinically actionable targets. State-of-art algorithms that account for mutation phenotypes are used to rank the importance of mutated genes through visual analytic strategies. We established an extensive annotation source by integrating a wide variety of biomedical databases and followed the American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation and reporting of sequence variations. CONCLUSIONS: In summary, VAReporter is the first web server designed to provide a "one-stop" resource for individual's diagnosis and large-scale cohort studies, and is freely available at http://rnd.cgu.edu.tw/vareporter .

mSignatureDB: a database for deciphering mutational signatures in human cancers.

Cancer is a genetic disease caused by somatic mutations; however, the understanding of the causative biological processes generating these mutations is limited. A cancer genome bears the cumulative effects of mutational processes during tumor development. Deciphering mutational signatures in cancer is a new topic in cancer research. The Wellcome Trust Sanger Institute (WTSI) has categorized 30 reference signatures in the COSMIC database based on the analyses of ∼10 000 sequencing datasets from TCGA and ICGC. Large cohorts and bioinformatics skills are required to perform the same analysis as WTSI. The quantification of known signatures in custom cohorts is not possible under the current framework of the COSMIC database, which motivates us to construct a database for mutational signatures in cancers and make such analyses more accessible to general researchers. mSignatureDB (http://tardis.cgu.edu.tw/msignaturedb) integrates R packages and in-house scripts to determine the contributions of the published signatures in 15 780 individual tumors from 73 TCGA/ICGC cancer projects, making comparison of signature patterns within and between projects become possible. mSignatureDB also allows users to perform signature analysis on their own datasets, quantifying contributions of signatures at sample resolution, which is a unique feature of mSignatureDB not available in other related databases.

APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.

Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B -/-:89A3B +/-:27A3B +/+), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.

CMPD: cancer mutant proteome database.

Whole-exome sequencing, which centres on the protein coding regions of disease/cancer associated genes, represents the most cost-effective method to-date for deciphering the association between genetic alterations and diseases. Large-scale whole exome/genome sequencing projects have been launched by various institutions, such as NCI, Broad Institute and TCGA, to provide a comprehensive catalogue of coding variants in diverse tissue samples and cell lines. Further functional and clinical interrogation of these sequence variations must rely on extensive cross-platforms integration of sequencing information and a proteome database that explicitly and comprehensively archives the corresponding mutated peptide sequences. While such data resource is a critical for the mass spectrometry-based proteomic analysis of exomic variants, no database is currently available for the collection of mutant protein sequences that correspond to recent large-scale genomic data. To address this issue and serve as bridge to integrate genomic and proteomics datasets, CMPD (http://cgbc.cgu.edu.tw/cmpd) collected over 2 millions genetic alterations, which not only facilitates the confirmation and examination of potential cancer biomarkers but also provides an invaluable resource for translational medicine research and opportunities to identify mutated proteins encoded by mutated genes.

Vanno: a visualization-aided variant annotation tool.

Next-generation sequencing (NGS) technologies have revolutionized the field of genetics and are trending toward clinical diagnostics. Exome and targeted sequencing in a disease context represent a major NGS clinical application, considering its utility and cost-effectiveness. With the ongoing discovery of disease-associated genes, various gene panels have been launched for both basic research and diagnostic tests. However, the fundamental inconsistencies among the diverse annotation sources, software packages, and data formats have complicated the subsequent analysis. To manage disease-associated NGS data, we developed Vanno, a Web-based application for in-depth analysis and rapid evaluation of disease-causative genome sequence alterations. Vanno integrates information from biomedical databases, functional predictions from available evaluation models, and mutation landscapes from TCGA cancer types. A highly integrated framework that incorporates filtering, sorting, clustering, and visual analytic modules is provided to facilitate exploration of oncogenomics datasets at different levels, such as gene, variant, protein domain, or three-dimensional structure. Such design is crucial for the extraction of knowledge from sequence alterations and translating biological insights into clinical applications. Taken together, Vanno supports almost all disease-associated gene tests and exome sequencing panels designed for NGS, providing a complete solution for targeted and exome sequencing analysis. Vanno is freely available at http://cgts.cgu.edu.tw/vanno.

ChIPseek, a web-based analysis tool for ChIP data.

BACKGROUND: Chromatin is a dynamic but highly regulated structure. DNA-binding proteins such as transcription factors, epigenetic and chromatin modifiers are responsible for regulating specific gene expression pattern and may result in different phenotypes. To reveal the identity of the proteins associated with the specific region on DNA, chromatin immunoprecipitation (ChIP) is the most widely used technique. ChIP assay followed by next generation sequencing (ChIP-seq) or microarray (ChIP-chip) is often used to study patterns of protein-binding profiles in different cell types and in cancer samples on a genome-wide scale. However, only a limited number of bioinformatics tools are available for ChIP datasets analysis. RESULTS: We present ChIPseek, a web-based tool for ChIP data analysis providing summary statistics in graphs and offering several commonly demanded analyses. ChIPseek can provide statistical summary of the dataset including histogram of peak length distribution, histogram of distances to the nearest transcription start site (TSS), and pie chart (or bar chart) of genomic locations for users to have a comprehensive view on the dataset for further analysis. For examining the potential functions of peaks, ChIPseek provides peak annotation, visualization of peak genomic location, motif identification, sequence extraction, and comparison between datasets. Beyond that, ChIPseek also offers users the flexibility to filter peaks and re-analyze the filtered subset of peaks. ChIPseek supports 20 different genome assemblies for 12 model organisms including human, mouse, rat, worm, fly, frog, zebrafish, chicken, yeast, fission yeast, Arabidopsis, and rice. We use demo datasets to demonstrate the usage and intuitive user interface of ChIPseek. CONCLUSIONS: ChIPseek provides a user-friendly interface for biologists to analyze large-scale ChIP data without requiring any programing skills. All the results and figures produced by ChIPseek can be downloaded for further analysis. The analysis tools built into ChIPseek, especially the ones for selecting and examine a subset of peaks from ChIP data, provides invaluable helps for exploring the high through-put data from either ChIP-seq or ChIP-chip. ChIPseek is freely available at http://chipseek.cgu.edu.tw.

Development of a human dihydroorotate dehydrogenase (hDHODH) pharma-similarity index approach with scaffold-hopping strategy for the design of novel potential inhibitors.

Human dihydroorotate dehydrogenase (hDHODH) is a class-2 dihydroorotate dehydrogenase. Because it is extensively used by proliferating cells, its inhibition in autoimmune and inflammatory diseases, cancers, and multiple sclerosis is of substantial clinical importance. In this study, we had two aims. The first was to develop an hDHODH pharma-similarity index approach (PhSIA) using integrated molecular dynamics calculations, pharmacophore hypothesis, and comparative molecular similarity index analysis (CoMSIA) contour information techniques. The approach, for the discovery and design of novel inhibitors, was based on 25 diverse known hDHODH inhibitors. Three statistical methods were used to verify the performance of hDHODH PhSIA. Fischer's cross-validation test provided a 98% confidence level and the goodness of hit (GH) test score was 0.61. The q(2), r(2), and predictive r(2) values were 0.55, 0.97, and 0.92, respectively, for a partial least squares validation method. In our approach, each diverse inhibitor structure could easily be aligned with contour information, and common substructures were unnecessary. For our second aim, we used the proposed approach to design 13 novel hDHODH inhibitors using a scaffold-hopping strategy. Chemical features of the approach were divided into two groups, and the Vitas-M Laboratory fragment was used to create de novo inhibitors. This approach provides a useful tool for the discovery and design of potential inhibitors of hDHODH, and does not require docking analysis; thus, our method can assist medicinal chemists in their efforts to identify novel inhibitors.

CPAP: Cancer Panel Analysis Pipeline.

Targeted sequencing using next-generation sequencing technologies is currently being rapidly adopted for clinical sequencing and cancer marker tests. However, no existing bioinformatics tool is available for the analysis and visualization of multiple targeted sequencing datasets. In the present study, we use cancer panel targeted sequencing datasets generated by the Life Technologies Ion Personal Genome Machine Sequencer as an example to illustrate how to develop an automated pipeline for the comparative analyses of multiple datasets. Cancer Panel Analysis Pipeline (CPAP) uses standard output files from variant calling software to generate a distribution map of SNPs among all of the samples in a circular diagram generated by Circos. The diagram is hyperlinked to a dynamic HTML table that allows the users to identify target SNPs by using different filters. CPAP also integrates additional information about the identified SNPs by linking to an integrated SQL database compiled from SNP-related databases, including dbSNP, 1000 Genomes Project, COSMIC, and dbNSFP. CPAP only takes 17 min to complete a comparative analysis of 500 datasets. CPAP not only provides an automated platform for the analysis of multiple cancer panel datasets but can also serve as a model for any customized targeted sequencing project.

Construction and analysis of a plant non-specific lipid transfer protein database (nsLTPDB).

BACKGROUND: Plant non-specific lipid transfer proteins (nsLTPs) are small and basic proteins. Recently, nsLTPs have been reported involved in many physiological functions such as mediating phospholipid transfer, participating in plant defence activity against bacterial and fungal pathogens, and enhancing cell wall extension in tobacco. However, the lipid transfer mechanism of nsLTPs is still unclear, and comprehensive information of nsLTPs is difficult to obtain. METHODS: In this study, we identified 595 nsLTPs from 121 different species and constructed an nsLTPs database--nsLTPDB--which comprises the sequence information, structures, relevant literatures, and biological data of all plant nsLTPs http://nsltpdb.life.nthu.edu.tw/. RESULTS: Meanwhile, bioinformatics and statistics methods were implemented to develop a classification method for nsLTPs based on the patterns of the eight highly-conserved cysteine residues, and to suggest strict Prosite-styled patterns for Type I and Type II nsLTPs. The pattern of Type I is C X2 V X5-7 C [V, L, I] × Y [L, A, V] X8-13 CC × G X12 D × [Q, K, R] X2 CXC X16-21 P X2 C X13-15C, and that of Type II is C X4 L X2 C X9-11 P [S, T] X2 CC X5 Q X2-4 C[L, F]C X2 [A, L, I] × [D, N] P X10-12 [K, R] X4-5 C X3-4 P X0-2 C. Moreover, we referred the Prosite-styled patterns to the experimental mutagenesis data that previously established by our group, and found that the residues with higher conservation played an important role in the structural stability or lipid binding ability of nsLTPs. CONCLUSIONS: Taken together, this research has suggested potential residues that might be essential to modulate the structural and functional properties of plant nsLTPs. Finally, we proposed some biologically important sites of the nsLTPs, which are described by using a new Prosite-styled pattern that we defined.

Antioxidant and semicarbazide-sensitive amine oxidase inhibitory activities of glucuronic acid hydroxamate.

The antioxidant and inhibitory activities of glucuronic acid (GluA) and its synthesized 1-methoxyl-6-glucuronic acid hydroxamate (GluA-NHOH) against semicarbazide-sensitive amine oxidase (SSAO) were investigated. The scavenging activities of GluA-NHOH against 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radicals (half-inhibition concentration [IC50], 152µM) and hydroxyl radicals (IC50, 70nM) were determined. The protective activities of GluA-NHOH against hydroxyl radical-mediated calf thymus DNA damage and peroxynitrite-mediated dihydrorhodamine oxidation were also investigated. GluA-NHOH, but not GluA, exhibited dose-dependent protective activities. GluA-NHOH, but not GluA, effectively inhibited bovine SSAO activities in a dose-dependent manner, and was further confirmed by AO activity stains on an acrylamide gel. GluA-NHOH showed mixed noncompetitive inhibition of bovine SSAO with respect to benzylamine (substrate) and benzylamine-SSAO (substrate-enzyme complex). The Vmax' and Km' values were reduced in the presence of GluA-NHOH (0.04mM).

Antioxidant and nitric oxide production inhibitory activities of galacturonyl hydroxamic acid.

The self-prepared pectin hydroxamic acid has been reported to have antioxidant activities [Yang, S. S., Cheng, K. D., Lin, Y. S., Liu, Y. W., & Hou, W. C. (2004). Pectin hydroxamic acids exhibit antioxidant activities in vitro. Journal of Agricultural and Food Chemistry, 52, 4270-4273]. In this study, the galacturonic acid (GalA), the monomer unit of the pectin polymer, was esterified with acidic methanol (1N HCl) at 4°C with gentle stirring for 5days to get galacturonic acid methyl ester which was further reacted with alkaline hydroxylamine to get galacturonyl hydroxamic acid (GalA-NHOH). The GalA-NHOH was used to test the antioxidant and antiradical activities in the comparison with GalA. The scavenging activities of GalA-NHOH against DPPH radicals (half-inhibition concentration, IC50, was 82µM), hydroxyl radicals detected by electron spin resonance (IC50 was 0.227nM in the comparison with Trolox of 0.433µM), superoxide radicals (IC50 was 830µM) were determined. The protection activities of GalA-NHOH against hydroxyl radicals-mediated calf thymus DNA damages, linoleic acid peroxidation and peroxynitrite-mediated dihydrorhodamine 123 oxidations were also investigated. It was found that the GalA-NHOH exhibited dose-dependently antioxidant activity and few or none was found in GalA. The GalA-NHOH was used to evaluate the suppressed activity of nitric oxide (NO) productions of RAW264.7 cells in the presence of lipopolysaccharide (LPS, 100ng/ml) as inducers. It was found that GalA-NHOH (0.02-0.1mg/ml) could dose-dependently suppress the NO productions (expressed as nitrite concentrations) in RAW264.7 cells without significant cytotoxicity.