Oncoproteomics: current trends and future perspectives

Oncoproteomics is the application of proteomics technologies in oncology. Functional proteomics is a promising technique for the rational identification of biomarkers and novel therapeutic targets for cancers. Recent progress in proteomics has opened new avenues for tumor-associated biomarker discovery. With the advent of new and improved proteomics technologies, such as the development of quantitative proteomic methods, high-resolution, -speed and -sensitivity mass spectrometry and protein arrays, as well as advanced bioinformatics for data handling and interpretation, it is now possible to discover biomarkers that can reliably and accurately predict outcomes during cancer management and treatment. However, there are several difficulties in the study of proteins/peptides that are not inherent in the study of nucleic acids. New challenges arise in large-scale proteomic profiling when dealing with complex biological mixtures. Nevertheless, oncoproteomics offers great promise for unveiling the complex molecular events of tumorigenesis, as well as those that control clinically important tumor behaviors, such as metastasis, invasion and resistance to therapy. In this review, the development and advancement of oncoproteomics technologies for cancer research in recent years are expounded.     

Super-SILAC: current trends and future perspectives

Stable isotope labeling with amino acids in cell culture (SILAC) has risen as a powerful quantification technique in mass spectrometry (MS)–based proteomics in classical and modified forms. Previously, SILAC was limited to cultured cells because of the requirement of active protein synthesis; however, in recent years, it was expanded to model organisms and tissue samples. Specifically, the super-SILAC technique uses a mixture of SILAC-labeled cells as a spike-in standard for accurate quantification of unlabeled samples, thereby enabling quantification of human tissue samples. Here, we highlight the recent developments in super-SILAC and its application to the study of clinical samples, secretomes, post-translational modifications and organelle proteomes. Finally, we propose super-SILAC as a robust and accurate method that can be commercialized and applied to basic and clinical research.     

Oncoproteomics: current trends and future perspectives

Oncoproteomics is the application of proteomics technologies in oncology. Functional proteomics is a promising technique for the rational identification of biomarkers and novel therapeutic targets for cancers. Recent progress in proteomics has opened new avenues for tumor-associated biomarker discovery. With the advent of new and improved proteomics technologies, such as the development of quantitative proteomic methods, high-resolution, -speed and -sensitivity mass spectrometry and protein arrays, as well as advanced bioinformatics for data handling and interpretation, it is now possible to discover biomarkers that can reliably and accurately predict outcomes during cancer management and treatment. However, there are several difficulties in the study of proteins/peptides that are not inherent in the study of nucleic acids. New challenges arise in large-scale proteomic profiling when dealing with complex biological mixtures. Nevertheless, oncoproteomics offers great promise for unveiling the complex molecular events of tumorigenesis, as well as those that control clinically important tumor behaviors, such as metastasis, invasion and resistance to therapy. In this review, the development and advancement of oncoproteomics technologies for cancer research in recent years are expounded.     

Targeted protein degradation: current and future challenges

Traditional approaches in the development of small-molecule drugs typically aim to inhibit the biochemical activity of functional protein domains. In contrast, targeted protein degradation aims to reduce overall levels of disease-relevant proteins. Mechanistically, this can be achieved via chemical ligands that induce molecular proximity between an E3 ubiquitin ligase and a protein of interest, leading to ubiquitination and degradation of the protein of interest. This paradigm-shifting pharmacology promises to address several limitations inherent to conventional inhibitor design. Most notably, targeted protein degradation has the potential not only to expand the druggable proteome beyond the reach of traditional competitive inhibitors but also to develop therapeutic strategies of unmatched selectivity. This review briefly summarizes key challenges that remain to be addressed to deliver on these promises and to realize the full therapeutic potential of pharmacologic modulation of protein degradation pathways.     

蛋白质功能研究:历史、现状和将来

蛋白质是生命活动的直接执行者,参与生命的几乎所有过程,如遗传、发育、繁殖、物质和能量的代谢、应激等等。揭示生物体内成千上万种蛋白质的具体功能、完成功能的机制等是蛋白质研究的核心内容,是后基因组时代生命科学研究极富挑战的领域之一。本文就蛋白质功能研究的历史、现状和未来进行简要的讨论。希望能够帮助读者,特别是那些并不从事蛋白质研究的读者,更好地认识我国中长期科学与技术发展规划中制定“蛋白质研究”重大科学计划的必要性。     

Therapeutic peptides: Historical perspectives,current development trends,and future directions

Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts. We maintain a comprehensive dataset on peptides that have entered human clinical studies that includes over 150 peptides in active development today. Here we provide an overview of the peptide therapeutic landscape, including historical perspectives, molecular characteristics, regulatory benchmarks, and a therapeutic area breakdown.     

Food security and marine capture fisheries: characteristics, trends, drivers and future perspectives

World population is expected to grow from the present 6.8 billion people to about 9 billion by 2050. The growing need for nutritious and healthy food will increase the demand for fisheries products from marine sources, whose productivity is already highly stressed by excessive fishing pressure, growing organic pollution, toxic contamination, coastal degradation and climate change. Looking towards 2050, the question is how fisheries governance, and the national and international policy and legal frameworks within which it is nested, will ensure a sustainable harvest, maintain biodiversity and ecosystem functions, and adapt to climate change. This paper looks at global fisheries production, the state of resources, contribution to food security and governance. It describes the main changes affecting the sector, including geographical expansion, fishing capacity-building, natural variability, environmental degradation and climate change. It identifies drivers and future challenges, while suggesting how new science, policies and interventions could best address those challenges.     

Bio-ontologies: current trends and future directions

In recent years, as a knowledge-based discipline, bioinformatics has been made more computationally amenable. After its beginnings as a technology advocated by computer scientists to overcome problems of heterogeneity, ontology has been taken up by biologists themselves as a means to consistently annotate features from genotype to phenotype. In medical informatics, artifacts called ontologies have been used for a longer period of time to produce controlled lexicons for coding schemes. In this article, we review the current position in ontologies and how they have become institutionalized within biomedicine. As the field has matured, the much older philosophical aspects of ontology have come into play. With this and the institutionalization of ontology has come greater formality. We review this trend and what benefits it might bring to ontologies and their use within biomedicine.     

Noninvasive preimplantation genetic testing in assisted reproductive technology: current state and future perspectives

Invasive genetic screening of pre-implantation embryos via biopsied trophectoderm (TE) cells has been in use for more than 20 years, while its benefits in selecting euploid embryos remain controversial. Recent advances in the ability to process embryonic cell-free DNA (cfDNA) from blastocoel fluid (BF) and spent culture media (SCM) of blastocysts in a manner similar to that of a biopsied TE sample provide a potential alternative holding great promise for obtaining cytogenetic information of the embryos without intrusive biopsy of traditional biopsy-based pre-implantation genetic testing (PGT). Several studies have reported even higher diagnostic accuracy in non-invasive PGT (ni-PGT) than conventional PGT. However, there are still several technical challenges to be overcome before ni-PGT can be accepted as a reliable genomic information source of embryo. In this review, we have summarized the emergence and current state of ni-PGT, and discussed our own perspectives on their limitations and future prospect. There is still a long way to go before truly wide clinical application of ni-PGT.     

Helicobacter pylori chromosomal DNA replication: current status and future perspectives

Helicobacter pylori causes gastritis, gastric ulcer and gastric cancer. Though DNA replication and its control are central to bacterial proliferation, pathogenesis, virulence and/or dormancy, our knowledge of DNA synthesis in slow growing pathogenic bacteria like H. pylori is still preliminary. Here, we review the current understanding of DNA replication, replication restart and recombinational repair in H. pylori. Several differences have been identified between the H. pylori and Escherichia coli replication machineries including the absence of DnaC, the helicase loader usually conserved in gram-negative bacteria. These differences suggest different mechanisms of DNA replication at initiation and restart of stalled forks in H. pylori.     

LC-MS for protein characterization: current capabilities and future trends

With advances in ionization methods and instrumentation, liquid chromatography (LC)/mass spectrometry (MS) has become a powerful technology for protein characterization. This review article will describe the general approaches on LC-MS analysis in protein characterization, including bottom-up and top-down strategies. Discussions will be given on characterization of recombinant proteins, and post-translational and protein modifications such as disulfide bonds, glycosylation and phosphorylation using LC-MS. New research directions in this area will also be presented to illustrate future prospects of LC-MS in protein characterization, including application to proteomics.     

Polymers for gene delivery: current status and future perspectives

Gene therapy is a hope for curing many diseases and pathological conditions which are relatively difficult to treat. However lack of proper gene delivery vehicle is the main limiting step in this direction. Though viral vectors still lead as the major vehicle used in gene therapy clinical trials, their immunogenicity and low capacity restrict their wide use. Hence there is a need for developing non-viral vectors which can really be used for clinical applications. Polymers are a versatile group of molecules which can be modified and designed or engineered according to the end needs of the applications. The objective of this review is to summarize the recent advances in the development of polymeric vectors for gene delivery applications reported in patents and scientific journals.     

Cancer metabolism: current perspectives and future directions

Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation'' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles'' heel''. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells.     

LC-MS for protein characterization: current capabilities and future trends

With advances in ionization methods and instrumentation, liquid chromatography (LC)/mass spectrometry (MS) has become a powerful technology for protein characterization. This review article will describe the general approaches on LC-MS analysis in protein characterization, including bottom-up and top-down strategies. Discussions will be given on characterization of recombinant proteins, and post-translational and protein modifications such as disulfide bonds, glycosylation and phosphorylation using LC-MS. New research directions in this area will also be presented to illustrate future prospects of LC-MS in protein characterization, including application to proteomics.     

Liquid chromatographic and spectrofluorimetric assays of empagliflozin: Applied to degradation kinetic study and content uniformity testing

Stability‐indicating high‐performance liquid chromatography (HPLC) and spectrofluorimetric methods were developed for determination of empagliflozin (EGF). EGF was subjected to oxidation, wet heat, photo‐degradation, acid hydrolysis and alkali hydrolysis. The alkaline degradation pathway was subjected to a kinetics study as the major product obtained after stress conditions. Arrhenius plots were constructed and the activation energies of the degradation process were calculated. HPLC was used for the kinetic study as it enabled simultaneous determination of EGF and the degradation product while the spectrofluorimetric assay was applied to content uniformity testing due to its higher sensitivity and lower limit of detection (LOD). Isocratic chromatographic elution was attained for HPLC on a Intersil® C₁₈ column (150 mm × 4 mm, 5 μm), using a mobile phase of acetonitrile–potassium dihydrogen phosphate buffer pH 4, (50:50, v/v) at a flow rate of 1 ml/min with ultraviolet (UV) detection at 225 nm. The relative fluorescence intensity was recorded by spectrofluorimeter applying synchronous mode using ?λ = 70 nm at 297.6 nm. Linearity ranges were found to be 5–50 μg/ml and 50–1000 ng/ml for HPLC and spectrofluorimetric methods, respectively.     

聚乙烯塑料生物降解研究进展

聚乙烯(polyethylene,PE)塑料是全球通用合成树脂中产量最丰富的品种,也是最难降解的塑料之一,其在环境中大量积累已造成严重的生态污染。传统的垃圾填埋、堆肥和焚烧处理技术难以满足生态环境的保护要求,生物降解是解决塑料污染问题的一种生态友好、成本低廉、前景可期的方法。本文对PE塑料的化学结构、降解微生物的种类、降解酶和代谢途径等方面进行了综述,结合国内外PE塑料生物降解的前沿和热点问题,建议重点开展高效降解菌株筛选、人工合成菌群构建、降解酶的挖掘与改造等方面的研究,为PE塑料生物降解研究提供路径选择和理论借鉴。     

Cryo-electron microscopy for structural biology:current status and future perspectives

Recently, significant technical breakthroughs in both hardware equipment and software algorithms have enabled cryo-electron microscopy(cryo-EM) to become one of the most important techniques in biological structural analysis. The technical aspects of cryo-EM define its unique advantages and the direction of development. As a rapidly emerging field, cryo-EM has benefitted from highly interdisciplinary research efforts. Here we review the current status of cryo-EM in the context of structural biology and discuss the technical challenges. It may eventually merge structural and cell biology at multiple scales.     

Engineering plants for aphid resistance: current status and future perspectives

Key message

The current status of development of transgenic plants for improved aphid resistance, and the pros and cons of different strategies are reviewed and future perspectives are proposed.

Abstract

Aphids are major agricultural pests that cause significant yield losses of crop plants each year. Excessive dependence on insecticides for aphid control is undesirable because of the development of insecticide resistance, the potential negative effects on non-target organisms and environmental pollution. Transgenic plants engineered for resistance to aphids via a non-toxic mode of action could be an efficient alternative strategy. In this review, the distribution of major aphid species and their damages on crop plants, the so far isolated aphid-resistance genes and their applications in developments of transgenic plants for improved aphid resistance, and the pros and cons of these strategies are reviewed and future perspectives are proposed. Although the transgenic plants developed through expressing aphid-resistant genes, manipulating plant secondary metabolism and plant-mediated RNAi strategy have been demonstrated to confer improved aphid resistance to some degree. So far, no aphid-resistant transgenic crop plants have ever been commercialized. This commentary is intended to be a helpful insight into the generation and future commercialization of aphid-resistant transgenic crops in a global context.     

An eco‐friendly direct spectrofluorimetric method for the determination of irreversible tyrosine kinase inhibitors,neratinib and pelitinib: application to stability studies

A new rapid and simple stability‐indicating spectrofluorimetric method has been developed for the determination of two irreversible tyrosine kinase inhibitors (TKIs), neratinib (NER) and pelitinib (PEL). The method is based upon measurement of the native fluorescence intensity of both drugs at λ_ex 270 nm in aqueous borate buffer solutions (pH 10.5). The fluorescence intensity recorded at 545 nm (NER) and 465 nm (PEL) were rectilinear over the concentration range of 0.1–10 μg/mL for both drugs with a high correlation coefficient (r > 0.999). The proposed method provided low limits of detection and of quantitation of 0.07, 0.11 μg/mL (NER) and 0.02, 0.05 μg/mL (PEL), respectively. The method was successfully applied for the determination of NER and PEL in bulk powder. The proposed methods were fully validated as per the International Conference on Harmonisation (ICH) guidelines. The application of the method was extended to stability studies of both NER and PEL under different forced‐degradation conditions (acidic‐induced, base‐induced, oxidative, wet heat, and photolytic degradation). Moreover, the kinetics of the base‐induced and oxidative degradation of both drugs was investigated and the pseudo‐first‐order rate constants and half‐lives were estimated at different temperatures. Also, an Arrhenius plot was applied to predict the stability behaviour of the two drugs at room temperature. Copyright © 2016 John Wiley & Sons, Ltd.     

Sources of reactive nitrogen affecting ecosystems in Latin America and the Caribbean: current trends and future perspectives

While the amount of reactive nitrogen circulating at the global level has increased markedly in the last century, the effects of this increase are largely seen at the regional level due to interacting ecological and socio-economic factors. In contrast with most other regions of the world, Latin America and the Caribbean (LA-Ca) stand out due to the fact that the major input of reactive nitrogen (Nr) still occurs naturally via biological nitrogen fixation (BNF) in natural ecosystems as opposed to anthropogenic inputs of synthetic fertilizer, fossil fuel combustion and cropping with leguminous species. Largely due to economic reasons, the consumption of fertilizer N in the LA-Ca region is still low in comparison with the average consumption of the world. However, the fertilizer N consumption is increasing at a much faster rate than that in developed regions of the world, like USA and Canada. The Nr production through BNF in cultivated plants that fix nitrogen (C-BNF) is 5 times lower than that occurring naturally in Latin America, but is still equivalent to 16% of the world C-BNF. The cultivation of nitrogen-fixing crop species in the LA-Ca region is also increasing, almost entirely due to the expansion of soybean fields in the central and northern regions of Brazil and the Pampa region of Argentina. Other anthropogenic activities in the region that contribute to an increase in the circulation of reactive nitrogen include the impact of biomass burning and urbanization. In the last decade, an average of 47,000 km² per year of forests was burned in the LA-Ca region. The environmental impact of urban centers in the LA-Ca region has become very important, since an intense urbanization process is occurring in this region, at an intensity that far exceeds urban development in the northern hemisphere. The consequences of increased urbanization include increased emissions of NO _x to the atmosphere due to the fossil fuel combustion, and the lack of sewage treatment facilities in most cities of the LA-Ca result in a large volume of untreated sewage discharged into surface waters, creating serious environmental problems. The combination of rapid urbanization and agricultural intensification in this region suggest that concern is warranted for the potential for increase in the circulation of reactive nitrogen in the very near future. At the same time, the opportunity still exists to mitigate some of the consequences of human impact on the nitrogen cycle in a region that still maintains a large fraction of its natural ecosystems intact.