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https://www.readbyqxmd.com/read/29149530/proteases-and-protease-inhibitors-in-infectious-diseases
#1
REVIEW
Ayodeji A Agbowuro, Wilhelmina M Huston, Allan B Gamble, Joel D A Tyndall
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy...
November 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29149412/the-translationally-controlled-tumor-protein-and-the-cellular-response-to-ionizing-radiation-induced-dna-damage
#2
Jie Zhang, Grace Shim, Sonia M de Toledo, Edouard I Azzam
The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate (137)Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29148817/specific-recognition-of-g-quadruplexes-over-duplex-dna-by-a-macromolecular-nir-two-photon-fluorescent-probe
#3
Marco Deiana, Bastien Mettra, Lara Martinez-Fernandez, Leszek Mateusz Mazur, Krzysztof Pawlik, Chantal Andraud, Marek Samoc, Roberto Improta, Cyrille Monnereau, Katarzyna Matczyszyn
The implication of guanine-rich DNA sequences in biologically important roles such as telomerase dysfunction and the regulation of gene expression has prompted the search for structure-specific G-quadruplex agents for targeted diagnostic and therapeutic applications. To date, the number of two-photon absorbing fluorogenic dyes with intrinsically large two-photon absorption (TPA) cross-section (σ2) and quantum yield (φf), capable of specific detection of G-motifs over duplex DNAs is still limited. Herein, we report on a NIR two-photon poly(cationic) anthracene-based macromolecule able to selectively target G-quadruplexes (G4s) over genomic double-stranded DNA...
November 17, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/29148219/breaking-free-from-vascular-confinement-status-and-prospects-for-submicron-ultrasound-contrast-agents
#4
REVIEW
Carly Pellow, David E Goertz, Gang Zheng
The development of encapsulated microbubbles (~1-6 μm) has expanded the utility of ultrasound from soft tissue anatomical imaging to not only functional intravascular imaging, but therapeutic interventions, with compelling studies of elicited biological effects. The large diameter of these bubbles has confined their utility to the vasculature, but converging interdisciplinary research pathways are giving rise to new submicron ultrasound contrast agents capable of extending their effects beyond the vascular compartment...
November 17, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29147885/proceedings-of-the-2017-isev-symposium-on-hiv-neurohiv-drug-abuse-evs
#5
Guoku Hu, Sowmya Yelamanchili, Fatah Kashanchi, Norman Haughey, Vincent C Bond, Kenneth W Witwer, Lynn Pulliam, Shilpa Buch
Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND...
November 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29147792/characterization-of-a-novel-single-stranded-rna-mycovirus-related-to-invertebrate-viruses-from-the-plant-pathogen-verticillium-dahliae
#6
M Carmen Cañizares, Francisco J López-Escudero, Encarnación Pérez-Artés, María D García-Pedrajas
Fungal viruses, also known as mycoviruses, are widespread in all major groups of fungi. Mycoviruses from plant pathogens can reduce the virulence of their host fungus and have therefore potential as biological control agents. This has spurred the identification of novel mycoviruses in plant pathogens, research which is greatly contributing to our understanding of these organisms. In this work, we report the characterization of a novel monopartite mycovirus from Verticillium dahliae, the main causal agent of Verticillium wilt...
November 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29147559/factors-affecting-the-physical-stability-aggregation-of-peptide-therapeutics
#7
REVIEW
Karolina L Zapadka, Frederik J Becher, A L Gomes Dos Santos, Sophie E Jackson
The number of biological therapeutic agents in the clinic and development pipeline has increased dramatically over the last decade and the number will undoubtedly continue to increase in the coming years. Despite this fact, there are considerable challenges in the development, production and formulation of such biologics particularly with respect to their physical stabilities. There are many cases where self-association to form either amorphous aggregates or highly structured fibrillar species limits their use...
December 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/29147032/emptying-the-stores-lysosomal-diseases-and-therapeutic-strategies
#8
REVIEW
Frances M Platt
Lysosomal storage disorders (LSDs) - designated as 'orphan' diseases - are inborn errors of metabolism caused by defects in genes that encode proteins involved in various aspects of lysosomal homeostasis. For many years, LSDs were viewed as unattractive targets for the development of therapies owing to their low prevalence. However, the development and success of the first commercial biologic therapy for an LSD - enzyme replacement therapy for type 1 Gaucher disease - coupled with regulatory incentives rapidly catalysed commercial interest in therapeutically targeting LSDs...
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29146731/organic-anion-transporting-polypeptide-1b3-as-a-dual-reporter-gene-for-fluorescence-and-magnetic-resonance-imaging
#9
Menq-Rong Wu, Hon-Man Liu, Chen-Wen Lu, Way-Hone Shen, I-Jou Lin, Li-Wen Liao, Yi-You Huang, Ming-Jium Shieh, Jong-Kai Hsiao
Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole-body levels. Transmembrane transporters recognizing specific molecular domains are of particular interest because they enable the migration of signal-source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion-transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual-modality reporter in MRI and noninvasive in vivo imaging system (IVIS)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146569/found-in-translation-how-preclinical-research-is-guiding-the-clinical-development-of-the-bcl2-selective-inhibitor-venetoclax
#10
REVIEW
Joel D Leverson, Deepak Sampath, Andrew J Souers, Saul H Rosenberg, Wayne J Fairbrother, Martine Amiot, Marina Konopleva, Anthony Letai
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax...
November 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29146308/-molecular-habituation-as-a-potential-mechanism-of-gradual-homeostatic-loss-with-age
#11
Alvaro Martinez Guimera, Ciaran M Welsh, Carole J Proctor, Anne McArdle, Daryl P Shanley
The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals implies another perspective in the study of sustained oxidative stress. This is a perspective of studying oxidative stress as a constitutive signal within the cell. In this work, we adopt a theoretical perspective as an exploratory and explanatory approach to examine how chronic oxidative stress can interfere with signal processing by redox signalling pathways in the cell...
November 13, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29146136/identification-of-highly-potent-btk-and-jak3-dual-inhibitors-with-improved-activity-for-the-treatment-of-b-cell-lymphoma
#12
Yang Ge, Changyuan Wang, Shijie Song, Jiaxin Huang, Zhihao Liu, Yongming Li, Qiang Meng, Jianbin Zhang, Jihong Yao, Kexin Liu, Xiaodong Ma, Xiuli Sun
The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas. Here we report the identification of several classes of pyrimidine derivatives as potent BTK and JAK3 dual inhibitors. Among these molecules, approximately two thirds displayed strong inhibitory capacity at less than 10 nM concentration, and four compounds (7e, 7g, 7m and 7n) could significantly inhibit the phosphorylation of BTK and JAK3 enzymes at concentrations lower than 1 nM...
November 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29146018/biological-treatments-in-giant-cell-arteritis-takayasu-arteritis
#13
Maxime Samson, Georgina Espígol-Frigolé, Nekane Terrades-García, Sergio Prieto-González, Marc Corbera-Bellalta, Roser Alba-Rovira, José Hernández-Rodríguez, Sylvain Audia, Bernard Bonnotte, Maria C Cid
Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main large vessel vasculitides. They share some similarities regarding their clinical, radiological and histological presentations but some pathogenic processes in GCA and TAK are activated differently, thus explaining their different sensitivity to biological therapies. The treatment of GCA and TAK essentially relies on glucocorticoids. However, thanks to major progress in our understanding of their pathogenesis, the role of biological therapies in the treatment of these two vasculitides is expanding, especially in relapsing or refractory diseases...
November 13, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/29145976/not-only-p-glycoprotein-amplification-of-the-abcb1-containing-chromosome-region-7q21-confers-multidrug-resistance-upon-cancer-cells-by-coordinated-overexpression-of-an-assortment-of-resistance-related-proteins
#14
Ilaria Genovese, Andrea Ilari, Yehuda G Assaraf, Francesco Fazi, Gianni Colotti
The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145791/impact-of-novel-n-aryl-piperamide-no-donors-on-nf-%C3%AE%C2%BAb-translocation-in-neuroinflammation-rational-drug-designing-synthesis-and-biological-evaluation
#15
Sajad Shahbazi, Jagdeep Kaur, Shikha Singh, K Gopinath Achary, Sameena Wani, Sobhagyalaxmi Jema, Jabed Akhtar, Ranbir Chander Sobti
NO donor drugs showed a significant therapeutic effect in the treatment of many diseases, such as arteriopathies, various acute and chronic inflammatory conditions, and several degenerative diseases. NO-releasing anti-inflammatory drugs are the prototypes of a novel class of compounds, combining the pharmacological activities of anti-inflammatory and anti-nociceptive of drugs with those of NO, thus possessing potential therapeutic applications in a great variety of diseases. In this study, we designed and predicted biological activity by targeting cyclooxygenase type 2 (COX-2) and NF-κB subunits and pharmacological profiling along with toxicity predictions of various N-aryl piperamides linked via an ester bond to a spacer that is bound to a NO-releasing moiety (-ONO2)...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29145607/phenology-of-the-dalmatian-toadflax-biological-control-agent-mecinus-janthiniformis-coleoptera-curculionidae-in-utah
#16
Samantha A Willden, Edward W Evans
The phenology of the stem-mining weevil Mecinus janthiniformis Toševski and Caldara (Coleoptera: Curculionidae) as adults attacking Dalmatian toadflax, Linaria dalmatica (L.) Miller (Plantaginaceae), was studied in 2014-2015 at two low elevation sites in northern Utah. The seasonal pattern of adult weevil abundance on the host plant at the two sites was most similar between years when described by degree-day accumulation, versus calendar date. Repeated censusing over the growing season revealed that males appeared first and subsequently peaked in abundance on the host plant earlier than females did, such that the adult population was dominated by males early in the season and by females late in the season...
November 14, 2017: Environmental Entomology
https://www.readbyqxmd.com/read/29144774/strategies-for-enhanced-crop-resistance-to-insect-pests
#17
Angela E Douglas
Insect pests are responsible for substantial crop losses worldwide through direct damage and transmission of plant diseases, and novel approaches that complement or replace broad-spectrum chemical insecticides will facilitate the sustainable intensification of food production in the coming decades. Multiple strategies for improved crop resistance to insect pests, especially strategies relating to plant secondary metabolism and immunity and microbiome science, are becoming available. Recent advances in metabolic engineering of plant secondary chemistry offer the promise of specific toxicity or deterrence to insect pests; improved understanding of plant immunity against insects provides routes to optimize plant defenses against insects; and the microbiomes of insect pests can be exploited, either as a target or as a vehicle for delivery of insecticidal agents...
November 16, 2017: Annual Review of Plant Biology
https://www.readbyqxmd.com/read/29144748/chemical-modification-for-proteolytic-stabilization-of-the-selective-%C3%AE-v%C3%AE-3-integrin-rgdechi-peptide-in-vitro-and-in-vivo-activities-on-malignant-melanoma-cells
#18
Daniela Comegna, Antonella Zannetti, Annarita Del Gatto, Ivan de Paola, Luigi Russo, Sonia Di Gaetano, Annamaria Liguoro, Domenica Capasso, Michele Saviano, Laura Zaccaro
Herein we report the synthesis and biological characterization of the novel peptide ψRGDechi as the first step towards novel targeted theranostics in melanoma. This pseudo-peptide is designed from our previously reported RGDechi peptide, known to bind selectively αvβ3 integrin, and differs for a modified amide bond at the main protease cleavage site. This chemical modification drastically reduces the enzymatic degradation in serum, compared to its parental peptide, resulting in an overall magnification of the biological activity on a highly expressing αvβ3 human metastatic melanoma cell line...
November 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29144594/on-the-origin-of-obesity-identifying-the-biological-environmental-and-cultural-drivers-of-genetic-risk-among-human-populations
#19
REVIEW
A Qasim, M Turcotte, R J de Souza, M C Samaan, D Champredon, J Dushoff, J R Speakman, D Meyre
Genetic predisposition to obesity presents a paradox: how do genetic variants with a detrimental impact on human health persist through evolutionary time? Numerous hypotheses, such as the thrifty genotype hypothesis, attempt to explain this phenomenon yet fail to provide a justification for the modern obesity epidemic. In this critical review, we appraise existing theories explaining the evolutionary origins of obesity and explore novel biological and sociocultural agents of evolutionary change to help explain the modern-day distribution of obesity-predisposing variants...
November 16, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29144411/nucleic-acid-aptamers-emerging-applications-in-medical-imaging-nanotechnology-neurosciences-and-drug-delivery
#20
REVIEW
Pascal Röthlisberger, Cécile Gasse, Marcel Hollenstein
Recent progresses in organic chemistry and molecular biology have allowed the emergence of numerous new applications of nucleic acids that markedly deviate from their natural functions. Particularly, DNA and RNA molecules-coined aptamers-can be brought to bind to specific targets with high affinity and selectivity. While aptamers are mainly applied as biosensors, diagnostic agents, tools in proteomics and biotechnology, and as targeted therapeutics, these chemical antibodies slowly begin to be used in other fields...
November 16, 2017: International Journal of Molecular Sciences
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