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Bénédicte Ndeboko, Olivier Hantz, Guy Joseph Lemamy, Lucyna Cova
Alternative therapeutic approaches against chronic hepatitis B virus (HBV) infection need to be urgently developed because current therapies are only virostatic. In this context, cell penetration peptides (CPPs) and their Peptide Nucleic Acids (PNAs) cargoes appear as a promising novel class of biologically active compounds. In this review we summarize different in vitro and in vivo studies, exploring the potential of CPPs as vehicles for intracellular delivery of PNAs targeting hepadnaviral replication. Thus, studies conducted in the duck HBV (DHBV) infection model showed that conjugation of (D-Arg)₈ CPP to PNA targeting viral epsilon (ε) were able to efficiently inhibit viral replication in vivo following intravenous administration to ducklings...
July 16, 2018: Biomolecules
Linyuan Shen, Mailin Gan, Zhengdong Tan, Dongmei Jiang, Yanzhi Jiang, Mingzhou Li, Jinyong Wang, Xuewei Li, Shunhua Zhang, Li Zhu
tRNA-derived fragments (tRFs) are a new class of non-coding RNA that play an important role in regulating cellular RNA processing and protein translation. However, there is currently no study reporting the influence of tRFs on myocardial hypertrophy. In this study, we used an isoproterenol (ISO)-induced myocardial hypertrophy rat model. Small RNA (<40 nts) transcriptome sequencing was used to select differentially expressed tRFs. We also compared the tRFs expression pattern in F0 sperm and the hearts of F1 offspring between the myocardial hypertrophy group (Hyp) and the control group (Con)...
July 16, 2018: Biomolecules
Nabil A Bashir, Entesar S Ragab, Omar F Khabour, Basheer Y Khassawneh, Mahmoud A Alfaqih, Jafar A Momani
Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk...
July 13, 2018: Biomolecules
Hong Zhu, Jiali Yang, Yueming Jiang, Jun Zeng, Xuesong Zhou, Yanglin Hua, Bao Yang
Banana is a climacteric fruit with desirable palatability and high nutritional value. It ripens rapidly accompanied with metabolite changes during postharvest storage. In this work, morin was applied to treat banana to delay senescence. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor the changes of metabolite composition and levels in banana. The results showed that morin significantly delayed the changes of color and firmness. 1D and 2D NMR spectra reflected that the levels and composition of metabolites were changed with the senescence initiation...
July 12, 2018: Biomolecules
Shane R Stone, Tatjana Heinrich, Suzy M Juraja, Jiulia N Satiaputra, Clinton M Hall, Mark Anastasas, Anna D Mills, Christopher A Chamberlain, Scott Winslow, Kristin Priebatsch, Paula T Cunningham, Katrin Hoffmann, Nadia Milech
The ability of cell penetrating peptides (CPPs) to deliver biologically relevant cargos into cells is becoming more important as targets in the intracellular space continue to be explored. We have developed two assays based on CPP-dependent, intracellular delivery of TEM-1 β-lactamase enzyme, a functional biological molecule comparable in size to many protein therapeutics. The first assay focuses on the delivery of full-length β-lactamase to evaluate the internalization potential of a CPP sequence. The second assay uses a split-protein system where one component of β-lactamase is constitutively expressed in the cytoplasm of a stable cell line and the other component is delivered by a CPP...
July 11, 2018: Biomolecules
Jason K Allen, Dakota J Brock, Helena M Kondow-McConaghy, Jean-Philippe Pellois
Cell-penetrating peptides (CPPs) are typically prone to endocytic uptake into human cells. However, they are often inefficient at escaping from endosomes, which limits their ability to deliver cargos into cells. This review highlights the efforts that our laboratory has devoted toward developing CPPs that can mediate the leakage of endosomal membranes, and consequently gain better access to the intracellular milieu. In particular, we have identified a CPP named dimeric fluorescent TAT (dfTAT) with high endosomolytic activity...
July 11, 2018: Biomolecules
Bruno Leonardo Bozaquel-Morais, Leonie Vogt, Valentina D'Angelo, Raffael Schaffrath, Roland Klassen, Mónica Montero-Lomelí
The protein phosphatase Sit4 has been shown to be required for lipogenesis and resistance against the acetyl-CoA carboxylase inhibitor soraphen A. Since Sit4 is also required for biosynthesis of Elongator dependent tRNA modifications such as 5-methoxycarbonylmethyluridine (mcm⁵U), we investigated the relevance of tRNA modifications in lipogenesis and soraphen A response. While sit4 and Elongator ( elp3 ) mutants copy defects in mcm⁵U formation and stress sensitivity, they do not share soraphen A sensitivity and low lipid droplet (LD) phenotypes...
July 11, 2018: Biomolecules
Weili Ma, Geun-Woo Jin, Paul M Gehret, Neil C Chada, Won Hyuk Suh
Retinoic acid (RA) is a bioactive lipid that has been shown to promote neural stem cell differentiation. However, the highly hydrophobic molecule needs to first solubilize and translocate across the cell membrane in order to exert a biological response. The cell entry of RA can be aided by cell penetrating peptides (CPPs), which are short amino acid sequences that are able to carry bioactive cargo past the cell membrane. In this work, a novel cell penetrating peptide was developed to deliver RA to human neural stem cells and, subsequently, promote neuronal differentiation...
July 9, 2018: Biomolecules
Sandeep Kumar Mathur, Pradeep Tiwari, Sonal Gupta, Nidhi Gupta, Surendra Nimesh, Krishna Mohan Medicherla, Prashanth Suravajhala
Understanding phenotypes and their genetic determinants for metabolic syndrome (MetS) has been quite challenging. With the advent of systems genomic approaches, there is a need to decipher methods for identification and evaluating the functional role of phenotypic traits associated with complex diseases, such as MetS. The monogenic syndromes of lipodystrophy are well understood, but the molecular pathophysiology of insulin resistance (IR) underpinning the obesity, diabetes mellitus, and dyslipidemia is not well deciphered...
July 6, 2018: Biomolecules
Gianmarco Di Mauro, Ambra Dondi, Giovanni Giangreco, Alexander Hogrebe, Elja Louer, Elisa Magistrati, Meeli Mullari, Gemma Turon, Wouter Verdurmen, Helena Xicoy Cortada, Sanja Zivanovic
The European Academy for Biomedical Science (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European Research Institutes (Institute for Research in Biomedicine&mdash;IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences&mdash;RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research&mdash;NNF CPR, Denmark; European School of Molecular Medicine&mdash;SEMM, Italy) and an innovative science communication agency (Scienseed)...
July 6, 2018: Biomolecules
Manuel Giménez-Andrés, Alenka Čopič, Bruno Antonny
Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar⁻apolar interfaces such as the lipid surfaces of cellular organelles. Using various examples, we discuss here how variations within this general scheme impart membrane-interacting AHs with different interfacial properties. Among the key parameters are: (i) the size of hydrophobic residues and their density per helical turn; (ii) the nature, the charge, and the distribution of polar residues; and (iii) the length of the AH...
July 5, 2018: Biomolecules
Rubayat Islam Khan, Saif Shahriar Rahman Nirzhor, Raushanara Akter
Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide⁺ (NAD⁺) dependent enzyme and stress response protein that has sparked the curiosity of many researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in multiple different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses, and more. Only in recent times, however, did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles, and structure Frye (2000)...
June 29, 2018: Biomolecules
Tanja Zeller, Alev Altay, Christoph Waldeyer, Sebastian Appelbaum, Francisco Ojeda, Julia Ruhe, Renate B Schnabel, Karl J Lackner, Stefan Blankenberg, Mahir Karakas
Iron is essential in terms of oxygen utilization and mitochondrial function. The liver-derived peptide hepcidin has been recognized as a key regulator of iron homeostasis. Since iron metabolism is crucially linked to cardiovascular health, and low hepcidin was proposed as potential new marker of iron metabolism, we aimed to evaluate the prognostic value of hepcidin in a large cohort of patients with coronary heart disease (CHD). Serum levels of hepcidin were determined at baseline in patients with angiographically documented CHD...
June 28, 2018: Biomolecules
Ewa A Grzybowska
Calcium is one of the most important second messengers and its intracellular signaling regulates many aspects of cell physiology. Calcium ions, like phosphate ions, are highly charged and thus are able to alter protein conformation upon binding; thereby they constitute key factors in signal transduction. One of the most common calcium-binding structural motifs is the EF-hand, a well-defined helix-loop-helix structural domain, present in many calcium-binding proteins (CBPs). Nonetheless, some CBPs contain non-canonical, disordered motifs, which usually bind calcium with high capacity and low affinity, and which represent a subset of proteins with specific functions, but these functions rarely involve signaling...
June 19, 2018: Biomolecules
Xu Yang, Xin Wang, Xiao-Yu Chen, Hai-Yu Ji, Yan Zhang, An-Jun Liu
Pinocembrin is a natural flavonoid compound which is capable of antioxidant, antibacterial, anti-inflammatory, and antineoplastic activities. The present study aimed to enhance the solubility and antioxidant activities of pinocembrin by complex formation with lecithin. The physicochemical characteristics of pinocembrin⁻lecithin complex were analyzed by ultraviolet (UV), fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and solubility assay, and the antioxidant activities of pinocembrin⁻lecithin complex were evaluated via radical scavenging capacities for 2,2&prime;-diphenyl-1-picrylhydrazyl (DPPH), 2,2&prime;-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl, and superoxide-anion...
June 19, 2018: Biomolecules
Irene Traghella, Francesca Mastorci, Pepe Alessia, Alessandro Pingitore, Cristina Vassalle
The primary prevention of cardiovascular (CV) disease depends on the capacity to identify subjects at higher risk long before the occurrence of CV clinical manifestations. Traditional risk factors do not cover fully prediction of individual risk. Moreover, there is an area of gray for patients at intermediate CV risk, which offers wide margins of improvement. These observations highlight the need for new additive tools for a more accurate risk stratification. An increasing number of candidate biomarkers have been identified to predict CV risk and events, although they generally give only a moderate increase when added to currently available predictive scores...
June 15, 2018: Biomolecules
Lin Zhu, Jiansheng Guo, Zhongyou Ma, Jianfei Wang, Cheng Zhou
Induction of ethylene biosynthesis by aphids increases the susceptibility of several plant species to aphids. Recent studies have indicated that some MYB transcription factors regulate the phloem-based defense against aphid infestation by modulating ethylene (ET) signaling. Arabidopsis MYB102 has previously been shown to be induced by wound signaling and regulate defense response against chewing insects. However, it remains unclear whether Arabidopsis MYB102 takes part in the defense response of plants to aphids...
June 7, 2018: Biomolecules
Marianna Penzo, Lorenzo Montanaro
Ribosomal RNA (rRNA) is extensively edited through base methylation and acetylation, 2'-O-ribose methylation and uridine isomerization. In human rRNA, 95 uridines are predicted to by modified to pseudouridine by ribonucleoprotein complexes sharing four core proteins and differing for a RNA sequence guiding the complex to specific residues to be modified. Most pseudouridylation sites are placed within functionally important ribosomal domains and can influence ribosomal functional features. Information obtained so far only partially explained the degree of regulation and the consequences of pseudouridylation on ribosomal structure and function in different physiological and pathological conditions...
June 5, 2018: Biomolecules
Gi Yong Kim, Su-Jin Yeom, Sung-Chan Jang, Chang-Soo Lee, Changhyun Roh, Heon-Ho Jeong
Polydimethyl-siloxane (PDMS) is often applied to fabricate cell chips. In this study, we fabricated an adipocyte microcell pattern chips using PDMS to analyze the inhibition activity of lipid droplets in mouse embryo fibroblast cells (3T3-L1) with anti-obesity agents. To form the PDMS based micropattern, we applied the micro-contact printing technique using PDMS micro-stamps that had been fabricated by conventional soft lithography. This PDMS micro-pattern enabled the selective growth of 3T3-L1 cells onto the specific region by preventing cell adhesion on the PDMS region...
June 4, 2018: Biomolecules
Andrew Hill, Brad Niles, Andrew Cuyegkeng, Ted Powers
TOR is a serine/threonine protein kinase that assembles into distinct TOR Complexes 1 and 2 (TORC1 or TORC2) to regulate cell growth. In mammalian cells, a single mTOR incorporates stably into mTORC1 and mTORC2. By contrast, in Saccharomyces cerevisiae , two highly similar Tor1 and Tor2 proteins exist, where Tor1 assembles exclusively into TORC1 and Tor2 assembles preferentially into TORC2. To gain insight into TOR complex assembly, we used this bifurcation in yeast to identify structural elements within Tor1 and Tor2 that govern their complex specificity...
June 1, 2018: Biomolecules
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