Computational Tactics for Precision Cancer Network Biology

Network biology has garnered tremendous attention in understanding complex systems of cancer, because the mechanisms underlying cancer involve the perturbations in the specific function of molecular networks, rather than a disorder of a single gene. In this article, we review the various computational tactics for gene regulatory network analysis, focused especially on personalized anti-cancer therapy. This paper covers three major topics: (1) cell line’s (or patient’s) cancer characteristics specific gene regulatory network estimation, which enables us to reveal molecular interplays under varying conditions of cancer characteristics of cell lines (or patient); (2) computational approaches to interpret the multitudinous and massive networks; (3) network-based application to uncover molecular mechanisms of cancer and related marker identification. We expect that this review will help readers understand personalized computational network biology that plays a significant role in precision cancer medicine.     

Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine

Indole-containing compounds demonstrate an array of biological activities relevant to numerous human diseases. The biological activities of diverse indole-based agents are driven by molecular interactions between indole agent and critical therapeutic target. The chemical inventory of medicinally useful or promising indole compounds spans the entire structural spectrum, from simple synthetic indoles to highly complex indole alkaloids. In an analogous fashion, the chemistry behind the indole heterocycle is unique and provides rich opportunities for extensive synthetic chemistry, enabling the construction and development of novel indole compounds to explore chemical space. This review will present heterocyclic chemistry of the indole nucleus, indole compounds of clinical use, complex indole alkaloids and indole-inspired discovery efforts by multiple research groups interested in using novel indole-containing small molecules to drive discoveries in human biology and medicine.     

Towards Precision Medicine for Osteoarthritis: Focus on the Synovial Fluid Proteome

Osteoarthritis (OA) is a joint degenerative disease that most affects old age. The study of proteomics in synovial fluid (SF) has the task of providing additional elements to diagnose and predict the progress of OA. This review aims to identify the most significant biomarkers in the study of OA and to stimulate their routine use. Some of the major components of the ECM, such as proteoglycan aggrecan and decorin, were found considerably reduced in OA. Some biomarkers have proved useful for staging the temporality of OA: Periostin was found to be increased in early OA, while CRTA1 and MMPs were found to be increased in late OA. In its natural attempt at tissue regeneration, Collagen III was found to be increased in early OA while decreased in late OA. Some molecules studied in other areas, such as ZHX3 (oncological marker), LYVE1, and VEGF (lymph and angiogenesis markers), also have been found to be altered in OA. It also has been recorded that alteration of the hormonal pathway, using a dosage of PPAR-γ and RETN, can influence the evolution of OA. IL-1, one of the most investigated biomarkers in OA-SF, is not as reliable as a target of OA in recent studies. The study of biomarkers in SF appears to be, in combination with the clinical and radiological aspects, an additional weapon to address the diagnosis and staging of OA. Therefore, it can guide us more appropriately towards the indication of arthroplasty in patients with OA.     

Perfluorocarbons in Chemical Biology

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, and ¹⁹F NMR studies in complex environments. Herein, we describe how the unique properties of perfluorocarbons have been employed to understand and manipulate biological systems.     

几种化学药剂对水绵的生物活性测定

简要介绍了水绵的生物学特性及发生情况。室内初步研究了硫酸铜、三苯基醋酸锡及两者薯瘟锡混剂对水绵的生物活性。结果表明,三苯基醋酸锡对水绵的防除效果最好,在70ga．i．／hm^2剂量下对水绵的防效可达90％,其次是三苯基醋酸锡与硫酸铜混剂,再次是硫酸铜。     

磁性纳米粒子在生物学及医学领域的应用

磁性纳米粒子由于其生物相客性和低毒性而广泛应用于生物医学领域.阐述了近年来磁性纳米粒子在生物分离、生物检测、靶向药物输送、磁共振成像、肿瘤磁感应热疗等生物学和医学领域中的应用进展,并指出其主要发展方向和亟待解决的问题.     

浅谈化学生物学课程教学的探索与实践

化学生物学课程作为一门重要的专业课,在教学过程中面临着教材难选、不易讲授、教学效果难衡量等困难。结合自身的教学实践,文章从教学内容,教学方式及成绩考核三方面总结了一些经验,探索了一些行之有效的具体教学措施,以期更好地激发学生的学习兴趣、培养专业思维模式、提高学习效率,从而获得更好的教学效果。     

Advances and Opportunities in Epigenetic Chemical Biology

The study of epigenetics has greatly benefited from the development and application of various chemical biology approaches. In this review, we highlight the key targets for modulation and recent methods developed to enact such modulation. We discuss various chemical biology techniques to study DNA methylation and the post-translational modification of histones as well as their effect on gene expression. Additionally, we address the wealth of protein synthesis approaches to yield histones and nucleosomes bearing epigenetic modifications. Throughout, we highlight targets that present opportunities for the chemical biology community, as well as exciting new approaches that will provide additional insight into the roles of epigenetic marks.     

Chemical Translational Biology: Redefining Druggability of Protein-Protein Interactions

Chemical biologists use chemical tools to answer biological questions. The translational application of these principles has led to an explosion in the discovery and druggability of new protein targets, including protein-protein interactions (PPIs). Proteins tend to interact with other macromolecules using relatively large and featureless binding surfaces, which has hampered traditional drug discovery efforts, particularly for interactions with weaker affinity. In this article, I discuss several emerging strategies for targeting PPIs, including computational and structural methods and novel screening approaches. In particular, I focus on hijacking intrinsic protein allosteric pathways for the discovery and design of small-molecule and peptide ligands.     

A Personal Perspective on Chemical Biology: Before the Beginning

This perspective represents a brief personal account of early days before “chemical biology” emerged as a field of inquiry. Imagine a time when oligomers of DNA could not be synthesized and the order of the TACG letters in DNA could not be sequenced. Even the high resolution structure of the DNA double helix was not yet determined. 1975 was a time when there was a deep chasm between chemistry and biology. Chemists with precise knowledge of all the atoms in natural product architectures looked with dismay at the imprecise messy world of biology. Water was to be avoided! My view was that the power of synthetic organic chemistry should be used to create function, synthesis with a purpose. Our organic group at Caltech would embrace molecular recognition of biologics in water as a frontier for chemistry. We dreamed of inventing small molecules that would control the activity of macromolecules such as DNA, proteins and carbohydrates in living cells. We chemists would sky dive into the messy world of biology.     

EFMC,Medicinal Chemistry and Chemical Biology in Europe

This article is a reflection on the development of medicinal chemistry and chemical biology in Europe, and how the European Federation for Medicinal Chemistry (EFMC) helps the scientific community address its changing scope in a proactive manner. Networking, knowledge exchange and representation, as well as the acceptance and integration of novel scientific developments, are keys to a healthy and dynamic scientific community. This article also reviews some of the forces that shape the medicinal chemistry and chemical biology continuum, including cross-fertilization, digitalization, and the outsourcing of synthetic and characterization work to focus on productivity and scientific excellence.     

miRNAs as Biomarkers in Diabetes: Moving towards Precision Medicine

Diabetes mellitus (DM) is a complex metabolic disease with many specifically related complications. Early diagnosis of this disease could prevent the progression to overt disease and its related complications. There are several limitations to using existing biomarkers, and between 24% and 62% of people with diabetes remain undiagnosed and untreated, suggesting a large gap in current diagnostic practices. Early detection of the percentage of insulin-producing cells preceding loss of function would allow for effective therapeutic interventions that could delay or slow down the onset of diabetes. MicroRNAs (miRNAs) could be used for early diagnosis, as well as for following the progression and the severity of the disease, due to the fact of their pancreatic specific expression and stability in various body fluids. Thus, many studies have focused on the identification and validation of such groups or “signatures of miRNAs” that may prove useful in diagnosing or treating patients. Here, we summarize the findings on miRNAs as biomarkers in diabetes and those associated with direct cellular reprogramming strategies, as well as the relevance of miRNAs that act as a bidirectional switch for cell therapy of damaged pancreatic tissue and the studies that have measured and tracked miRNAs as biomarkers in insulin resistance are addressed.     

Chemical Biology Tools To Investigate Malaria Parasites

Parasitic diseases like malaria tropica have been shaping human evolution and history since the beginning of mankind. After infection, the response of the human host ranges from asymptomatic to severe and may culminate in death. Therefore, proper examination of the parasite's biology is pivotal to deciphering unique molecular, biochemical and cell biological processes, which in turn ensure the identification of treatment strategies, such as potent drug targets and vaccine candidates. However, implementing molecular biology methods for genetic manipulation proves to be difficult for many parasite model organisms. The development of fast and straightforward applicable alternatives, for instance small-molecule probes from the field of chemical biology, is essential. In this review, we will recapitulate the highlights of previous molecular and chemical biology approaches that have already created insight and understanding of the malaria parasite Plasmodium falciparum. We discuss current developments from the field of chemical biology and explore how their application could advance research into this parasite in the future. We anticipate that the described approaches will help to close knowledge gaps in the biology of P. falciparum and we hope that researchers will be inspired to use these methods to gain knowledge – with the aim of ending this devastating disease.     

Asthma in the Precision Medicine Era: Biologics and Probiotics

Asthma is a major global health issue. Over 300 million people worldwide suffer from this chronic inflammatory airway disease. Typical clinical symptoms of asthma are characterized by a recurrent wheezy cough, chest tightness, and shortness of breath. The main goals of asthma management are to alleviate asthma symptoms, reduce the risk of asthma exacerbations, and minimize long-term medicinal adverse effects. However, currently available type 2 T helper cells (Th2)-directed treatments are often ineffective due to the heterogeneity of the asthma subgroups, which manifests clinically with variable and poor treatment responses. Personalized precision therapy of asthma according to individualized clinical characteristics (phenotype) and laboratory biomarkers (endotype) is the future prospect. This mini review discusses the molecular mechanisms underlying asthma pathogenesis, including the hot sought-after topic of microbiota, add-on therapies and the potential application of probiotics in the management of asthma.     

Engineering the Next Generation of Matched Models for Chemical Translational Biology

In order to achieve patient personalization and translate compounds through the discovery phase into the clinic, high throughput test models should be designed to be as closely matched to the patient as possible. Engineering high throughput and physiologically relevant biological models is the idealized scenario for testing next generation modulators. I present here a cautionary example of a misaligned model as well as my viewpoint on how overcoming this bottleneck is one of the next frontiers in chemical biology.     

Molecular Landscape and Therapeutic Strategies in Cholangiocarcinoma: An Integrated Translational Approach towards Precision Medicine

Cholangiocarcinomas (CCAs) are heterogeneous biliary tract malignancies with dismal prognosis, mainly due to tumor aggressiveness, late diagnosis, and poor response to current therapeutic options. High-throughput technologies have been used as a fundamental tool in unveiling CCA molecular landscape, and several molecular classifications have been proposed, leading to various targeted therapy trials. In this review, we aim to analyze the critical issues concerning the status of precision medicine in CCA, discussing molecular signatures and clusters, related to both anatomical classification and different etiopathogenesis, and the latest therapeutic strategies. Furthermore, we propose an integrated approach comprising the CCA molecular mechanism, pathobiology, clinical and histological findings, and treatment perspectives for the ultimate purpose of improving the methods of patient allocations in clinical trials and the response to personalized therapies.     

Neuroinflammation and Precision Medicine in Pediatric Neurocritical Care: Multi-Modal Monitoring of Immunometabolic Dysfunction

The understanding of molecular biology in neurocritical care (NCC) is expanding rapidly and recognizing the important contribution of neuroinflammation, specifically changes in immunometabolism, towards pathological disease processes encountered across all illnesses in the NCC. Additionally, the importance of individualized inflammatory responses has been emphasized, acknowledging that not all individuals have the same mechanisms contributing towards their presentation. By understanding cellular processes that drive disease, we can make better personalized therapy decisions to improve patient outcomes. While the understanding of these cellular processes is evolving, the ability to measure such cellular responses at bedside to make acute care decisions is lacking. In this overview, we review cellular mechanisms involved in pathological neuroinflammation with a focus on immunometabolic dysfunction and review non-invasive bedside tools that have the potential to measure indirect and direct markers of shifts in cellular metabolism related to neuroinflammation. These tools include near-infrared spectroscopy, transcranial doppler, elastography, electroencephalography, magnetic resonance imaging and spectroscopy, and cytokine analysis. Additionally, we review the importance of genetic testing in providing information about unique metabolic profiles to guide individualized interpretation of bedside data. Together in tandem, these modalities have the potential to provide real time information and guide more informed treatment decisions.