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subsequent entry biologics

Silvio Danese, Stefanos Bonovas, Laurent Peyrin-Biroulet
Biologic agents have revolutionized the care management of many life-threatening and debilitating diseases. As patents for older biologic therapies have begun to expire, the market has opened to copy versions of the originators - commonly referred to as biosimilars, follow-on biologic agents or subsequent-entry biologic agents - which are expected to gain a portion of the market, reduce health-care spending and increase treatment access worldwide. Importantly for patients with IBD, CT-P13 was the first biosimilar to infliximab that obtained regulatory approval by the European Medicines Agency in September 2013 and by the FDA in April 2016...
October 12, 2016: Nature Reviews. Gastroenterology & Hepatology
Chia-Chun Tseng, Shun-Jen Chang, Wen-Chan Tsai, Tsan-Teng Ou, Cheng-Chin Wu, Wan-Yu Sung, Ming-Chia Hsieh, Jeng-Hsien Yen
OBJECTIVE: Past studies have shown common pathologic characteristics and shared immunologic features between polymyositis (PM) and amyotrophic lateral sclerosis (ALS). To explore the potential relationship between the two diseases, we performed a nationwide cohort study. METHODS: We identified all newly diagnosed PM from Taiwan's Registry of Catastrophic Illness Database between January 1, 1998 and December 31, 2011. Each PM patient was matched to at most 5 control patients from the National Health Insurance Research Database by sex, age, and entry date...
October 9, 2016: Arthritis Care & Research
Sulong Xiao, Qi Wang, Longlong Si, Xiaoshu Zhou, Yongmin Zhang, Lihe Zhang, Demin Zhou
Hepatitis C virus (HCV) entry is a key target for the treatment of chronic HCV infection. In our continuing efforts to identify novel potential anti-HCV entry inhibitors, a series of water-soluble triazole-bridged α-cyclodextrin-pentacyclic triterpene conjugates were easily synthesized with moderate to good yields. These novel compounds were fully identified and characterized by 1D and 2D NMR spectroscopy and ESI-HRMS. The anti-HCV entry activities were determined based on HCVpp/VSVGpp entry assays. The best results were found for compounds 15 and 18, which displayed the most promising anti-HCV entry activities with average IC50 values of 1...
August 12, 2016: European Journal of Medicinal Chemistry
Karolin Léger, Ann-Katrin Hopp, Monika Fey, Michael O Hottiger
ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli...
August 2, 2016: Cell Cycle
Xiaoyan Guo, Ping Chen, Xiaohu Hou, Wenjuan Xu, Dan Wang, Tian-Yan Wang, Liping Zhang, Gang Zheng, Zhi-Liang Gao, Cheng-Yi He, Boping Zhou, Zhi-Ying Chen
HBV covalently closed circular DNA (cccDNA) is drug-resistant and responsible for viral persistence. To facilitate the development of anti-cccDNA drugs, we developed a minicircle DNA vector (MC)-based technology to produce large quantity of recombined cccDNA (rcccDNA) resembling closely to its wild-type counterpart both in structure and function. The rcccDNA differed to the wild-type cccDNA (wtcccDNA) only in that it carried an extra 36-bp DNA recombinant product attR upstream of the preC/C gene. Using a procedure similar to standard plasmid production, milligrams of rcccDNA can be generated in common laboratories conveniently...
2016: Scientific Reports
Javier Fernandez-Chamorro, Gloria Lozano, Juan Antonio Garcia-Martin, Jorge Ramajo, Ivan Dotu, Peter Clote, Encarnacion Martinez-Salas
The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems...
2016: Scientific Reports
Catherine A Shaw, Gysell M Mortimer, Zhou J Deng, Edwin S Carter, Shea P Connell, Mark R Miller, Rodger Duffin, David E Newby, Patrick W F Hadoke, Rodney F Minchin
In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid. This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles...
September 2016: Nanotoxicology
Nagendra Kumar Singh
microRNA (miRNA) is an endogenous and evolutionary conserved non-coding RNA, involved in post-transcriptional process as gene repressor and mRNA cleavage through RNA-induced silencing complex (RISC) formation. In RISC, miRNA binds in complementary base pair with targeted mRNA along with Argonaut proteins complex, causes gene repression or endonucleolytic cleavage of mRNAs and results in many diseases and syndromes. After the discovery of miRNA lin-4 and let-7, subsequently large numbers of miRNAs were discovered by low-throughput and high-throughput experimental techniques along with computational process in various biological and metabolic processes...
March 28, 2016: Interdisciplinary Sciences, Computational Life Sciences
Jop Jans, Hicham elMoussaoui, Ronald de Groot, Marien I de Jonge, Gerben Ferwerda
BACKGROUND: Respiratory syncytial virus (RSV) can cause recurrent and severe respiratory tract infections. Cytoskeletal proteins are often involved during viral infections, either for cell entry or the initiation of the immune response. The importance of actin and clathrin dynamics for cell entry and the initiation of the cellular immune response against RSV in human immune cells is not known yet. The aim of this study was to investigate the role of actin and clathrin on cell entry of RSV and the subsequent effect on T cell activation and interferon gamma release in human immune cells...
2016: Virology Journal
András Spät, László Hunyady, Gergő Szanda
The major physiological stimuli of aldosterone secretion are angiotensin II (AII) and extracellular K(+), whereas cortisol production is primarily regulated by corticotropin (ACTH) in fasciculata cells. AII triggers Ca(2+) release from internal stores that is followed by store-operated and voltage-dependent Ca(2+) entry, whereas K(+)-evoked depolarization activates voltage-dependent Ca(2+) channels. ACTH acts primarily through the formation of cAMP and subsequent protein phosphorylation by protein kinase A...
2016: Frontiers in Endocrinology
Showkat Ahmad Dar, Anamika Thakur, Abid Qureshi, Manoj Kumar
Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs...
2016: Scientific Reports
Edward J Calabrese
In Part I, hormetic doses of a variety of agents stimulated adaptive responses that conditioned and protected cells against the subsequent toxicity resulting from a second, higher dose (called a challenging dose) of the same or different agents. Herein (Part II), the optimal conditioning (hormetic) doses of many agents are documented, cellular mechanisms and temporal profiles are examined from which the conditioning (hormetic) responses are elicited, and the optimal conditioning doses are compared to the levels at which optimal protection occurs in response to the toxic challenge dose...
August 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Andre A M Torricelli, Abirami Santhanam, Jiahui Wu, Vivek Singh, Steven E Wilson
The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts...
January 2016: Experimental Eye Research
Tiffany Baker, Simon Carpenter, Simon Gubbins, Richard Newton, Giovanni Lo Iacono, James Wood, Lara Ellen Harrup
BACKGROUND: Biting midges of the genus Culicoides Latreille, 1809 (Diptera: Ceratopogonidae) cause a significant biting nuisance to equines and are responsible for the biological transmission of African horse sickness virus (AHSV). While currently restricted in distribution to sub-Saharan Africa, AHSV has a history of emergence into southern Europe and causes one of the most lethal diseases of horses and other species of Equidae. In the event of an outbreak of AHSV, the use of insecticide treated nets (ITNs) to screen equine accomodation is recommended by competent authorities including the Office International des Épizooties (OIE) in order to reduce vector-host contact...
2015: Parasites & Vectors
Cassie S Mitchell, Ashlyn Cates, Renaid B Kim, Sabrina K Hollinger
Biocuration is a time-intensive process that involves extraction, transcription, and organization of biological or clinical data from disjointed data sets into a user-friendly database. Curated data is subsequently used primarily for text mining or informatics analysis (bioinformatics, neuroinformatics, health informatics, etc.) and secondarily as a researcher resource. Biocuration is traditionally considered a Ph.D. level task, but a massive shortage of curators to consolidate the ever-mounting biomedical "big data" opens the possibility of utilizing biocuration as a means to mine today's data while teaching students skill sets they can utilize in any career...
2015: Journal of Undergraduate Neuroscience Education: JUNE: a Publication of FUN, Faculty for Undergraduate Neuroscience
Rajiv Karbhal, Sangeeta Sawant, Urmila Kulkarni-Kale
BACKGROUND: Diverse types of biological data, primary as well as derived, are available in various formats and are stored in heterogeneous resources. Database-specific as well as integrated search engines are available for carrying out efficient searches of databases. These search engines however, do not support extraction of subsets of data with the same level of granularity that exists in typical database entries. In order to extract fine grained subsets of data, users are required to download complete or partial database entries and write scripts for parsing and extraction...
2015: BioData Mining
Christina I Swanson, Joy H Meserve, Patrick C McCarter, Alexis Thieme, Tony Mathew, Timothy C Elston, Robert J Duronio
In developing organisms, divergence from the canonical cell division cycle is often necessary to ensure the proper growth, differentiation, and physiological function of a variety of tissues. An important example is endoreplication, in which endocycling cells alternate between G and S phase without intervening mitosis or cytokinesis, resulting in polyploidy. Although significantly different from the canonical cell cycle, endocycles use regulatory pathways that also function in diploid cells, particularly those involved in S phase entry and progression...
December 15, 2015: Development
Noemi Cavaletto, Anna Luganini, Giorgio Gribaudo
UNLABELLED: The human cytomegalovirus (HCMV) US12 gene family includes a group of 10 contiguous genes (US12 to US21) encoding predicted seven-transmembrane-domain (7TMD) proteins that are nonessential for replication within cultured fibroblasts. Nevertheless, inactivation of some US12 family members affects virus replication in other cell types; e.g., deletion of US16 or US18 abrogates virus growth in endothelial and epithelial cells or in human gingival tissue, respectively, suggesting a role for some US12 proteins in HCMV cell tropism...
November 2015: Journal of Virology
Michał Pikuła, Paulina Langa, Paulina Kosikowska, Piotr Trzonkowski
Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells...
2015: Postȩpy Higieny i Medycyny Doświadczalnej
Hui Dong, Sicheng Song, Jingjing Li, Chunyun Xu, Haowei Zhang, Liang Ouyang
A facile method via 1,3-dipolar cycloaddition of substituted benzylidene-2-phenyloxazolone under mild conditions with azomethine ylides, which were generated in situ by a decarboxylative route from a common set of diverse isatins and amino acid derivatives was developed for a 15-membered library of regio- and stereoselective oxazolones-grafted spirooxindole-pyrrolidine, pyrrolizidines and pyrrolothiazoles. After screening their cytotoxic activities against a spectrum of cell-lines, compound 4h was identified as potent antitumor agent and inducing apoptosis...
September 1, 2015: Bioorganic & Medicinal Chemistry Letters
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