Omics Approaches to Identify Potential Biomarkers of Inflammatory Diseases in the Focal Adhesion Complex

Inflammatory diseases such as inflammatory bowel disease(IBD) require recurrent invasive tests, including blood tests, radiology, and endoscopic evaluation both to diagnose and assess disease activity, and to determine optimal therapeutic strategies. Simple ‘bedside' biomarkers could be used in all phases of patient management to avoid unnecessary investigation and guide further management. The focal adhesion complex(FAC) has been implicated in the pathogenesis of multiple inflammatory diseases, including IBD, rheumatoid arthritis, and multiple sclerosis. Utilizing omics technologies has proven to be an efficient approach to identify biomarkers from within the FAC in the field of cancer medicine. Predictive biomarkers are paving the way for the success of precision medicine for cancer patients, but inflammatory diseases have lagged behind in this respect. This review explores the current status of biomarker prediction for inflammatory diseases from within the FAC using omics technologies and highlights the benefits of future potential biomarker identification approaches.     

NMR spectroscopy and mass spectrometry in metabolomics analysis of <Emphasis Type="Italic">Salvia</Emphasis>

The interest in using the ‘-omics’ approach for nutrition, agriculture, food science and human health have seen an explosive growth in the last years. Particularly, metabolomics analysis is becoming an integral part of a system biological approach for investigating organisms. In this review, the limitations and advantages of NMR spectroscopy and mass spectrometry were discussed in details using the study reported in the literature on different Salvia species (S. hispanica, S. miltiorrhiza, S. officinalis, S. runcinata and S. stenophylla). Both approaches identify and quantify several classes of compounds but not the complete metabolite profile of the plant. A combined approach of these two powerful techniques provides better results allowing to determine both primary and secondary metabolites.     

马属动物全基因组高通量测序研究进展

马属(Equus)动物的祖先大约在5500万年前出现,经过持续分化形成现今的马、驴和斑马,统称马属动物。马作为家畜中的重要一员,是推动人类文明发展的载体,在人类的饮食、战争、农耕、运输和娱乐等领域做出了巨大贡献。然而,人类为了满足需求,或多或少影响着马的进化方向,从而在长时间自然和人工选择过程中形成了多种独具特色性状的不同马种。驴和骡在全球的存栏量也较多,在人类的生产和生活中起到的作用同样不可忽视,不但为人类提供了生产力而且还提供了食物和营养保健品。可见,马属动物对人类的重要性。近年来,高通量测序技术和生物信息学分析方法被广泛运用于家畜的遗传学研究。人们利用高通量测序手段探索马属动物在进化过程中的种群变化历史,解析形成独特性状的分子机制,为其育种工作提供有效的数据支持。本文综述了马属动物全基因组高通量测序的研究进展,以及利用该技术在马属动物的进化历史和功能基因挖掘研究领域所取得的成就,以期今后对马属动物的深入研究、产业开发和利用等方面提供参考信息。     

Identification of Household Bacterial Community and Analysis of Species Shared with Human Microbiome

Microbial populations in indoor environments, where we live and eat, are important for public health. Various bacterial species reside in the kitchen, and refrigerators, the major means of food storage within kitchens, can be a direct source of food borne illness. Therefore, the monitoring of microbiota in the refrigerator is important for food safety. We investigated and compared bacterial communities that reside in the vegetable compartment of the refrigerator and on the seat of the toilet, which is recognized as highly colonized by microorganisms, in ten houses using high-throughput sequencing. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were predominant in refrigerator and toilet samples. However, Proteobacteria was more abundant in the refrigerator, and Firmicutes was more abundant in the toilet. These household bacterial communities were compared with those of human skin and gut to identify potential sources of household bacteria. Bacterial communities from refrigerators and toilets shared more species in common with human skin than gut. Opportunistic pathogens, including Propionibacterium acnes, Bacteroides vulgatus, and Staphylococcus epidermidis, were identified as species shared with human skin and gut microbiota. This approach can provide a general background of the household microbiota and a potential method of source-tracking for public health purposes.     

Toxin immunosensors and sensor arrays for food quality control

The global efforts to improve consumer protection and public health lead to an increasing number of analytical approaches applicable to food analysis and process control. Biosensor systems are efficient analytical tools to monitor production processes or storage of nutrition and to control contamination outbreaks as they are easy-to-use, fast, and with minimal effort on sample preparation. Relevant targets of immunosensors implemented to food safety are prevalent bacterial toxins (staphylococcal enterotoxins and clostridial toxins), plant toxins (Ricin), mycotoxins (aflatoxins and ochratoxin A), marine toxins, and other pathogenic bacterial contaminations (Listeria, Salmonella, Staphylococcus aureus, or Escherichia coli). These cause acute intoxication and also chronic diseases in humans consuming contaminated food. Promising approaches for the determination of different types of toxins in food matrices will be outlined. The corresponding sensor systems use immunological receptor units such as antibodies or antigens and include optical (fluorescence and surface plasmon resonance), electrochemical, or acoustical readout methods. This review is focused on recent developments of sensor formats devoted to food safety control and is structured according to the type of toxin or contaminant that is recognized. It is intended to give an overview on emerging sensor technologies and their potential applications for the rapid analysis of the most important food poisoning agents.     

香菇加工技术研究现状及应用展望

香菇是一种营养丰富的食用真菌,具有较好的营养及药用保健价值,是一种对人体健康非常有益的菌类食物。叙述了香菇的营养成分及功效、药理及药用价值,对香菇的加工技术及产品进行了总结,对加工现状及应用前景进行了论述,探讨了香菇加工存在的问题及发展方向。     

Nutrition in the life cycle assessment of foods—function or impact?

Purpose

This work provides an unambiguous conceptual framework for inclusion of nutrition in Life Cycle Assessments (LCAs) of food that enables the distinction between two different roles of nutrition, namely serving as the basis of food comparisons via the functional unit and as an impact pathway that links food ingestion with human health effects.

Methods

We compare how nutritional aspects have been considered in the functional unit of published LCAs of food with the procedural requirements for ensuring comparability of the functional units. We consider the relevance of nutrient profiling models for assessing food- and diet-related health damages and benefits in the context of LCAs of food. We finally recommend a method that will enable a systematic, comparative, and holistic assessment of the marginal health effect of food products on human health.

Results and discussion

Satiety is proposed as a central attribute for comparisons of food products, while weighted measures of nutrient content are suggested to be largely misplaced as part of the functional unit. In contrast, nutritional measures have a large role to play in assessing the human health impacts of the marginal ingestion of specific food products. Such measures should enable a direct quantification of human health effect and benefits and should take advantage of robust epidemiological evidence.

Conclusions

Nutritional measures enter into both the functional unit in the form of satiety measures and into the calculation of impacts in the form of the marginal influence of the specific food item on the human health impact of the overall diet. To enhance the differentiation of health impacts at the level of individual food items, it is recommended to combine the nutrient balance indicator with the DALY Nutritional Index (DANI) in each specific dietary context.

     

A review of LC–MS techniques and high-throughput approaches used to investigate drug metabolism by cytochrome P450s

One of the major challenges facing the pharmaceutical industry today is finding new ways to increase productivity, decrease costs whilst still ultimately developing new therapies that enhance human health. To help address these challenges the utilisation of analytical technologies and high-throughput automated platforms has been employed; in order to perform more experiments in a shorter time frame with increased data quality. One of the main in vitro techniques to assess new chemical entities in a discovery setting has been the use of recombinant liver enzymes, microsomes and hepatocytes. These techniques can help predict in vivo metabolism, clearance and potential drug–drug interactions of these new compounds by cytochrome P450s (the major drug metabolising enzymes). This in vitro methodology has been totally transformed in recent times by the use of automated liquid handling and HPLC tandem mass spectrometry detection techniques (LC–MS/MS). This review aims looking at recent advances in the methodology used to investigate drug metabolism by cytochrome P450s; including an up to date summary of high-throughput platforms including the use of automation and LC–MS/MS to facilitate greater throughput, chromatographic resolution and data quality.     

Foodomics for human health: current status and perspectives

Introduction: In the post-genomic era, the opportunity to combine and integrate cutting-edge analytical platforms and data processing systems allowed the birth of foodomics, ‘a discipline that studies the Food and Nutrition domains through the application of advanced omics technologies to improve consumer’s well-being, health, and confidence’. Since then, this discipline has rapidly evolved and researchers are now facing the daunting tasks to meet consumers’ needs in terms of food traceability, sustainability, quality, safety and integrity. Most importantly, today it is imperative to provide solid evidence of the mechanisms through which food can promote human health and well-being.

Areas covered: In this review, the complex relationships connecting food, nutrition and human health will be discussed, with emphasis on the relapses for the development of functional foods and nutraceuticals, personalized nutrition approaches, and the study of the interplay among gut microbiota, diet and health/diseases.

Expert commentary: Evidence has been provided supporting the role of various omic platforms in studying the health-promoting effects of food and customized dietary interventions. However, although associated to major analytical challenges, only the proper integration of multi-omics studies and the implementation of bioinformatics tools and databases will help translate findings from clinical practice into effective personalized treatment strategies.     

A Multilayer Network Approach for Guiding Drug Repositioning in Neglected Diseases

Drug development for neglected diseases has been historically hampered due to lack of market incentives. The advent of public domain resources containing chemical information from high throughput screenings is changing the landscape of drug discovery for these diseases. In this work we took advantage of data from extensively studied organisms like human, mouse, E. coli and yeast, among others, to develop a novel integrative network model to prioritize and identify candidate drug targets in neglected pathogen proteomes, and bioactive drug-like molecules. We modeled genomic (proteins) and chemical (bioactive compounds) data as a multilayer weighted network graph that takes advantage of bioactivity data across 221 species, chemical similarities between 1.7 10⁵ compounds and several functional relations among 1.67 10⁵ proteins. These relations comprised orthology, sharing of protein domains, and shared participation in defined biochemical pathways. We showcase the application of this network graph to the problem of prioritization of new candidate targets, based on the information available in the graph for known compound-target associations. We validated this strategy by performing a cross validation procedure for known mouse and Trypanosoma cruzi targets and showed that our approach outperforms classic alignment-based approaches. Moreover, our model provides additional flexibility as two different network definitions could be considered, finding in both cases qualitatively different but sensible candidate targets. We also showcase the application of the network to suggest targets for orphan compounds that are active against Plasmodium falciparum in high-throughput screens. In this case our approach provided a reduced prioritization list of target proteins for the query molecules and showed the ability to propose new testable hypotheses for each compound. Moreover, we found that some predictions highlighted by our network model were supported by independent experimental validations as found post-facto in the literature.     

A life cycle assessment framework combining nutritional and environmental health impacts of diet: a case study on milk

Purpose

While there has been considerable effort to understand the environmental impact of a food or diet, nutritional effects are not usually included in food-related life cycle assessment (LCA).

Methods

We developed a novel Combined Nutritional and Environmental Life Cycle Assessment (CONE-LCA) framework that evaluates and compares in parallel the environmental and nutritional effects of foods or diets. We applied this framework to assess human health impacts, expressed in Disability Adjusted Life Years (DALYs), in a proof-of-concept case study that investigated the environmental and nutritional human health effects associated with the addition of one serving of fluid milk to the present average adult US diet. Epidemiology-based nutritional impacts and benefits linked to milk intake, such as colorectal cancer, stroke, and prostate cancer, were compared to selected environmental impacts traditionally considered in LCA (global warming and particulate matter) carried to a human health endpoint.

Results and discussion

Considering potential human health effects related to global warming, particulate matter, and nutrition, within the context of this study, findings suggest that adding one serving of milk to the current average diet could result in a health benefit for American adults, assuming that existing foods associated with substantial health benefits are not substituted, such as fruits and vegetables. The net health benefit is further increased when considering an iso-caloric substitution of less healthy foods (sugar-sweetened beverages). Further studies are needed to test whether this conclusion holds within a more comprehensive assessment of environmental and nutritional health impacts.

Conclusions

This case study provides the first quantitative epidemiology-based estimate of the complements and trade-offs between nutrition and environment human health burden expressed in DALYs, pioneering the infancy of a new approach in LCA. We recommend further testing of this CONE-LCA approach for other food items and diets, especially when making recommendations about sustainable diets and food choices.

     

Unique Functional and Structural Properties of the LRRK2 Protein ATP-binding Pocket

Pathogenic mutations in the LRRK2 gene can cause late-onset Parkinson disease. The most common mutation, G2019S, resides in the kinase domain and enhances activity. LRRK2 possesses the unique property of cis-autophosphorylation of its own GTPase domain. Because high-resolution structures of the human LRRK2 kinase domain are not available, we used novel high-throughput assays that measured both cis-autophosphorylation and trans-peptide phosphorylation to probe the ATP-binding pocket. We disclose hundreds of commercially available activity-selective LRRK2 kinase inhibitors. Some compounds inhibit cis-autophosphorylation more strongly than trans-peptide phosphorylation, and other compounds inhibit G2019S-LRRK2 more strongly than WT-LRRK2. Through exploitation of structure-activity relationships revealed through high-throughput analyses, we identified a useful probe inhibitor, SRI-29132 (11). SRI-29132 is exquisitely selective for LRRK2 kinase activity and is effective in attenuating proinflammatory responses in macrophages and rescuing neurite retraction phenotypes in neurons. Furthermore, the compound demonstrates excellent potency, is highly blood-brain barrier-permeant, but suffers from rapid first-pass metabolism. Despite the observed selectivity of SRI-29132, docking models highlighted critical interactions with residues conserved in many protein kinases, implying a unique structural configuration for the LRRK2 ATP-binding pocket. Although the human LRRK2 kinase domain is unstable and insoluble, we demonstrate that the LRRK2 homolog from ameba can be mutated to approximate some aspects of the human LRRK2 ATP-binding pocket. Our results provide a rich resource for LRRK2 small molecule inhibitor development. More broadly, our results provide a precedent for the functional interrogation of ATP-binding pockets when traditional approaches to ascertain structure prove difficult.     

Diversity of the intestinal microbiota in different patterns of feeding infants by Illumina high-throughput sequencing

The gastrointestinal microbiota plays a crucial role in the health and disease of the host through its impact on nutrition. Gut microbial composition is related to different diets, but an association of microbiota with different diets in infant has not yet been shown. In this work, we compared the fecal microbiota of breast-fed (BF) and formula-fed infants (FF). By using Illumina high-throughput sequencing and biochemical analyses, we found differences in gut microbiota between the two groups. BF infants showed a significant enrichment of Actinobacteria and Firmicutes and depletion of Proteobacteria (P < 0.05), the abundance of Bacteroidetes in the two groups was very low (P > 0.05). Enterobacteriaceae (Proteobacteria) were the dominant bacteria in FF infant fecal microbiota, and Veillonellaceae (Firmicutes) and Enterobacteriaceae (Proteobacteria) were the dominant bacteria in the BF infant fecal microbiota. The number of genera (percentage of sequences >0.1 %) in BF and FF infants was 17 and 15 respectively, and Streptococcus was the dominant bacterial genus in both groups.     

Towards a systems level analysis of health and nutrition

Although theoretical systems analysis has been available for over half a century, the recent advent of omic high-throughput analytical platforms along with the integration of individual tools and technologies has given rise to the field of modern systems biology. Coupled with information technology, bioinformatics, knowledge management and powerful mathematical models, systems biology has opened up new vistas in our understanding of complex biological systems. Currently there are two distinct approaches that include the inductively driven computational systems biology (bottom-up approach) and the deductive data-driven top-down analysis. Such approaches offer enormous potential in the elucidation of disease as well as defining key pathways and networks involved in optimal human health and nutrition. The tools and technologies now available in systems biology analyses offer exciting opportunities to develop the emerging areas of personalized medicine and individual nutritional profiling.     

RNA-interference in the nematode Caenorhabditis elegans is effective using paraformaldehyde-inactivated E. coli HT115 bacteria as a food source

The nematode Caenorhabditis elegans is a widely used research model for the investigation of metabolism, aging and age-associated diseases. However, when investigating the impact of natural compounds or drugs on those topics, a major confounder is the metabolism of these test substances by live E. coli bacteria, the standard food source of C. elegans. Using paraformaldehyde instead of heat to inactivate E. coli, which allows for high-throughput technologies and better food availability, it is shown here that RNA-interference works equally well, thus demonstrating the absence of considerable interfering modifications of paraformaldehyde with nucleic acids.     

Food-Pharma Convergence in Medical Nutrition– Best of Both Worlds?

At present, industries within the health and life science sector are moving towards one another resulting in new industries such as the medical nutrition industry. Medical nutrition products are specific nutritional compositions for intervention in disease progression and symptom alleviation. Industry convergence, described as the blurring of boundaries between industries, plays a crucial role in the shaping of new markets and industries. Assuming that the medical nutrition industry has emerged from the convergence between the food and pharma industries, it is crucial to research how and which distinct industry domains have contributed to establish this relatively new industry. The first two stages of industry convergence (knowledge diffusion and consolidation) are measured by means of patent analysis. First, the extent of knowledge diffusion within the medical nutrition industry is graphed in a patent citation interrelations network. Subsequently the consolidation based on technological convergence is determined by means of patent co-classification. Furthermore, the medical nutrition core domain and technology interrelations are measured by means of a cross impact analysis. This study proves that the medical nutrition industry is a result of food and pharma convergence. It is therefore crucial for medical nutrition companies to effectively monitor technological developments within as well as across industry boundaries. This study further reveals that although the medical nutrition industry’s core technology domain is food, technological development is mainly driven by pharmaceutical/pharmacological technologies Additionally, the results indicate that the industry has surpassed the knowledge diffusion stage of convergence, and is currently in the consolidation phase of industry convergence. Nevertheless, while the medical nutrition can be classified as an industry in an advanced phase of convergence, one cannot predict that the pharma and food industry segments will completely converge or whether the medical industry will become an individual successful industry.