Inherited Cardiomyopathies: Genetics and Clinical Genetic Testing

Inherited cardiomyopathies are major causes of morbidity and mortality and include a group of cardiac disorders such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), left ventricular noncompaction (LVNC), and restrictive cardiomyopathy (RCM). These diseases have a substantial genetic component and predispose to sudden cardiac death. Since the first gene was identified as a disease-causing gene for HCM over two decades ago, more than eighty genes have been identified to be associated with inherited cardiomyopathies and genetic testing has become prevalent in making clinical diagnosis. With the advent of next-generation sequencing technology, genetic panel testing of inherited cardiomyopathies has become feasible and cost efficient. In this review, we summarize the individual cardiomyopathies with the emphasis on cardiomyopathy genetics and genetic testing

The Serum microRNA Profile of Intrahepatic Cholestasis of Pregnancy: Identification of Novel Noninvasive Biomarkers

Background/Aims: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease that significantly increases the risk of fetal complications. Here, we measured serum miRNA levels in ICP patients to identify candidate biomarkers for ICP. Methods: We used the Agilent miRNA array followed by reverse transcription-polymerase chain reaction assays to identify and validate the serum miRNA profiles of 40 pregnant women with ICP and 40 healthy pregnant controls. We used bioinformatics to identify metabolic processes related to differentially expressed miRNAs. Results: The expression levels of three miRNAs (miR-371a- 5p, miR-6865-5p, and miR-1182) were significantly increased in ICP patients compared to controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.771, 0.811, and 0.798, respectively. Multiple logistic regression analysis showed that a combination of the levels of the three miRNAs afforded a greater AUC (0.845), thus more reliably diagnosing ICP. The levels of all three miRNAs were positively associated with that of total bile acids. Furthermore, bioinformatics analysis indicated that the three miRNAs principally affected lipid phosphorylation, apoptosis, and the MAPK signaling pathway. Conclusion: This preliminary work improves our understanding of serum miRNA changes in pregnant women with ICP. The three miRNAs may serve as novel noninvasive biomarkers of ICP

Peptide-based Supramolecular Colloids

Peptide-based supramolecular colloids are assembled systems based on weak interactions between peptides (such as hydrogen bonding, electrostatic forces, hydrophobic effects, pi-pi interactions, and van der Waals forces), spontaneously formed in a bottom-up manner. Peptide-based supramolecular colloids have ordered molecular arrangements and regular structures, with characteristics of both traditional colloids and supramolecular systems. Constructing functional supramolecular colloids via weak intermolecular interactions assists in understanding the process of biomolecular self-assembly in vivo and provides an effective strategy for designing supramolecular materials with excellent performance. Peptides, consisting of several amino acids, are elegant building blocks in supramolecular chemistry as well as colloid and interface chemistry because of their biological origin, clear composition, low immunogenicity, structural programmability, excellent biosafety, and high biodegradability. Based on the approach of supramolecular self-assembly, peptides can be manipulated to form multiscale and multifunctional colloidal systems, which have widespread applications in medicine, catalysis, energy, nanotechnology, and other fields. However, the realization of precise control of the structures and functions of these supramolecular colloids through peptide design and intermolecular interactions regulation remains an important issue to be addressed. To study the assembly process and physicochemical mechanism of supramolecular colloids at the molecular scale, and to explore the relationship between colloidal structure and function, the construction and functionalization of supramolecular colloids must be achieved. This work is a systematic summary of the assembly mechanism, structures, and functions as well as the state of the art of peptide-based supramolecular colloids with emphasis on the regulation of intermolecular interactions and structure-function relationships. The research progress of peptide-based supramolecular colloids in the following fields is summarized herein: i) biomimetic photosynthesis, including light capture and charge separation; and ii) tumor phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT). Currently, it is feasible to induce functional enhancement of peptide colloids via supramolecular assembly. The most important aspect is to design the primary structure of the peptide building block, to precisely control the weak interactions between peptide molecules and rationally optimize the self-assembly process, and control the size and structure of the assemblies. Followup studies should focus on the design of molecular precursors, the combination of basic research and practical application of peptide-based supramolecular colloids will be essential. The advantages of peptide-based supramolecular colloids, including their ordered organization, flexible structures, and versatile functions, will open up novel avenues for various applications of supramolecular colloids in fields such as green energy and medicine. It is hoped that this review will provide inspiration and broaden ideas to further drive the development and application of supramolecular colloids

Self-assembled injectable biomolecular hydrogels towards phototherapy

Biomolecular hydrogels assembled from biomolecules, such as proteins, peptides, and polysaccharides, are promising candidates for facilitating biomedical applications due to their advantages of high biocompatibility, adjustable mechanical properties, functional diversity, and good degradability. This review focuses on current progress in the field of supramolecular injectable biomolecular hydrogels and their applications in antitumor photodynamic therapy (PDT), photothermal therapy (PTT), combined PDT and PTT, and antibacterial phototherapy with emphasis on biomolecular hydrogelators, injectable behaviors, phototherapeutic functions, and the remaining challenges. We hope that this review can provide useful inspiration for the construction and biological applications of novel photo-functional hydrogels as well as phototherapies

Nanodrugs based on peptide-modulated self-assembly: Design, delivery and tumor therapy

In this review we consider assembled nanodrugs as a type of nanoscale drugs formed by molecular self-assembly and associated with precise organization of multiple non-covalent interactions. Their typical feature is that the drug itself is considered as one of the building blocks with flexibly interplaying interaction for supramolecular assembly and nanostructure formation with robust stability and high loading efficiency in a controlled and tunable way. The super stability with retained function results from the "hydrophobic effect" of supramolecular self assembly of peptides and drugs. It is the hydrophobic effect responsible for both colloidal stability and circulation stability in body against dilution and blood-flow shearing. The assembled nanodrugs are distinguished from conventional ones with encapsulation of the drugs in delivery nanocarriers. We will focus on how peptides and peptide-conjugates can be designed for controlling and mediating the formation of the assembled nanodrugs. Emphasis will be put on the rational design of intermolecular interactions between drugs and peptides, in vitro and in vivo drug delivery and antitumor therapeutic effects. Finally, we will discuss the key challenges and promising perspectives of such kind of peptide-mediated assembled nanodrugs for both technical advances and potential clinical translation. (C) 2017 Elsevier Ltd. All rights reserved

Methods and Interdisciplinarity

International audienceInterdisciplinarity research results from a growing need for multi-perspective methods and knowledge on complex and multifaceted objects of study. It is not simply scientific research that involves several disciplines but ultimately, the aim is confronting this knowledge and – if possible – articulating it coherently.Using specific examples, Methods and Interdisciplinarity categorizes the different modes of interdisciplinarity, and discusses the mechanisms of hybridization between them. On the one hand, the book shows how the same issue can be treated according to various points of view from several disciplines, which can give rise to complementary or even contradictory knowledge. On the other hand, it illustrates how methods from some disciplines make it possible to articulate the qualitative or quantitative approaches of others

High-tolerance crystalline hydrogels formed from self-assembling cyclic dipeptide

Peptide-based supramolecular hydrogels, as a new type of biological nanoarchitectonic structure, hold great promise for a wide range of biomedical and nanotechnological applications, such as tissue engineering, drug delivery, and electronic and photonic energy storage. In this work, a cyclic dipeptide (CDP) cyclo-(Trp-Tyr) (C-WY), which has exceptional structural rigidity and high stability, is selected as a hydrogelator for the formation of supramolecular hydrogels. The unique hydrogen bonding in C-WY endows a high propensity for self-assembly and the resulting hydrogels are revealed to be crystalline. The crystalline hydrogels possess excellent mechanical capacity and superior tolerance to various harsh conditions, including in the presence of charged biopolymers, extreme acid/base environments, and changing thermal conditions. Such high tolerance enables the crystalline hydrogels to be applied in the complex and harsh environments of electrochemistry. In addition, this study demonstrates that the self-assembly of cyclic dipeptides results in highly robust hydrogels which can be applied for electrochemical applications such as electrochemical supercapacitors

Prokaryotic expression of goldfish Tgf2 transposase with optimal codons and its enzyme activity

Tgf2 transposase (Tgf2-TPase), a hAT transposase from goldfish, plays an important role in fish transgenic applications. Previously, the production of the recombinant Tgf2-TPase protein required rigorous fermentation at low temperatures (22 °C) and early log phase induction (OD600 = 0.3–0.4) in Rosetta 1 (DE3) Escherichia coli lines. In order to better express the Tgf2-TPase and detect its enzyme activity, 83 rare codons in Tgf2-TPase were optimized and designated Tgf2-TPase83. The expression results showed that the soluble recombinant Tgf2-TPase83 was highly expressed at 30 °C and was inducible at an OD600 of 0.5–0.6 in the same prokaryotic expression system. After purification by affinity chromatography, Tgf2-TPase83 with codon optimization had higher enzyme activity than the Tgf2-TPase control. Comparison of different preservation methods (freeze-drying at −80 °C, storage in 20%-glycerol, 8%-sucrose, 4%-mannitol), revealed storage of Tgf2-TPase83 in glycerol helped to preserve its DNase digestion activity. Furthermore, size exclusion chromatography suggested that the purified Tgf2-TPase83 could recognize and bind to DNA probes containing a terminal inverted repeat (TIR) and a subterminal repeat (STR) sequence of the Tgf2 transposon. Overall, the results showed that optimizing the 83 codons of Tgf2 transposase can simplify the fermentation process and improve the enzyme activity. We propose that the production of the Tgf2-Tpase83 protein in a soluble and active form could provide an alternative tool for genetic modification of fish. Keywords: Codon optimization, Enzyme activity, Prokaryotic expression, Tgf2 transposas

Supramolecular Protein Nanodrugs with Coordination- and Heating-Enhanced Photothermal Effects for Antitumor Therapy

Supramolecular protein nanodrugs provide opportunities for improving antitumor therapeutic efficiency and lowering toxicity. However, protein nanodrugs that have robust structural stability and enhanced therapeutic efficiency are still in infancy. In this study, photothermal protein nanodrugs are constructed through a supramolecular approach along with heating by using proteins, photosensitizers, and metal ions as the building blocks. The metal coordination and heating improve not only the structural stability but also photothermal performance of the resulting nanodrugs. By virtue of the first integration of coordination- and heating-enhanced photothermal effects, the nanodrugs show superior photothermal conversion efficiency, enhanced tumor accumulation, and improved tumor inhibition. Metal coordination and heating are versatile to be applied for various protein nanodrugs. Hence, this study provides insights for the construction of highly efficient photothermal nanodrugs and thus will be beneficial to precision theranostics