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https://www.readbyqxmd.com/read/28440276/next-generation-probiotics-the-spectrum-from-probiotics-to-live-biotherapeutics
#1
Paul W O'Toole, Julian R Marchesi, Colin Hill
The leading probiotics currently available to consumers are generally drawn from a narrow range of organisms. Knowledge of the gut microbiota and its constituent actors is changing this paradigm, particularly given the phylogenetic range and relatively unknown characteristics of the organisms under investigation as novel therapeutics. For this reason, and because their development is likely to be more amenable to a pharmaceutical than a food delivery route, these organisms are often operationally referred to as next-generation probiotics, a concept that overlaps with the emerging concept of live biotherapeutic products...
April 25, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28436240/biotherapeutic-potential-and-mechanisms-of-action-of-colchicine
#2
Kashyap Kumar Dubey, Punit Kumar, Nikolaos E Labrou, Pratyoosh Shukla
Cancer is a clinical situation caused by uncontrolled cell division and is responsible for a large number of deaths worldwide. Colchicine is a classical antimitotic, tubulin-binding agent (TBA) which is being explored for its antitumor activities, although its tubulin-binding ability leads to some toxicity toward normal cells proliferation. Colchicine derivatives are considered as potent antitumor compounds with less toxicity compared to colchicine. Derivatives with substituted functional groups at A-ring (methoxy), B-ring (acetamide) or C-ring (methoxy) have been synthesized via chemical and microbial routes and show modified bioactivities and altered tropolonic functionality...
April 23, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28435459/aptamer-internalization-via-endocytosis-inducing-s-phase-arrest-and-priming-maver-1-lymphoma-cells-for-cytarabine-chemotherapy
#3
Huan Li, Shuanghui Yang, Ge Yu, Liangfang Shen, Jia Fan, Ling Xu, Hedong Zhang, Nianxi Zhao, Zihua Zeng, Tony Hu, Jianguo Wen, Youli Zu
The goal of precision therapy is to efficiently treat cancer without side effects. Aptamers are a class of small ligands composed of single-stranded oligonucleotides that bind to their targets with high affinity and specificity. In this study, we identified an ssDNA aptamer specifically targeting Maver-1 lymphoma cells with high binding affinity (Kd = 70±8 pmol/L). Interestingly, cellular cycle studies revealed that exposure of Maver-1 cells to synthetic aptamers triggered S-phase arrest of 40% of the cells (vs...
2017: Theranostics
https://www.readbyqxmd.com/read/28425960/studying-lactoferrin-n-glycosylation
#4
REVIEW
Sercan Karav, J Bruce German, Camille Rouquié, Annabelle Le Parc, Daniela Barile
Lactoferrin is a multifunctional glycoprotein found in the milk of most mammals. In addition to its well-known role of binding iron, lactoferrin carries many important biological functions, including the promotion of cell proliferation and differentiation, and as an anti-bacterial, anti-viral, and anti-parasitic protein. These functions differ among lactoferrin homologs in mammals. Although considerable attention has been given to the many functions of lactoferrin, its primary nutritional contribution is presumed to be related to its iron-binding characteristics, whereas the role of glycosylation has been neglected...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421849/infliximab-crystal-structures-reveal-insights-into-self-association
#5
Thomas F Lerch, Penelope Sharpe, Stephen J Mayclin, Thomas E Edwards, Eunhee Lee, Hugh D Conlon, Sharon Polleck, Jason C Rouse, Yin Luo, Qin Zou
Aggregation and self-association in protein-based biotherapeutics are critical quality attributes that are tightly controlled by the manufacturing process. Aggregates have the potential to elicit immune reactions, including neutralizing anti-drug antibodies, which can diminish the drug's efficacy upon subsequent dosing. The structural basis of reversible self-association, a form of non-covalent aggregation in the native state, is only beginning to emerge for many biologics and is often unique to a given molecule...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28419935/identification-of-a-host-cell-protein-impurity-in-therapeutic-protein-p1
#6
Deepti Ahluwalia, Harbhajan Dhillon, Thomas Slaney, Hangtian Song, Heather Boux, Sheetal Mehta, Lei Zhang, Anulfo Valdeza, Girija Krishnamurthy
Residual host cell proteins (HCPs) are process-related impurities present in biotherapeutics that can pose safety health risks to patients. An adequate control of HCP levels in the final product, and demonstration of HCP clearance throughout a product manufacturing process is critical for all biotherapeutic products. Developing effective downstream purification processes can be challenging as HCPs and product proteins may possess an affinity for each other or have similar physicochemical properties, resulting in co-purification...
April 9, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28402755/distribution-of-fcrn-across-species-and-tissues
#7
Sari Latvala, Bjoern Jacobsen, Michael B Otteneder, Annika Herrmann, Sven Kronenberg
The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I type molecule that binds to, transports, and recycles immunoglobulin G (IgG) and albumin, thereby protecting them from lysosomal degradation. Therefore, besides the knowledge of FcRn affinity, FcRn protein expression is critical in understanding the pharmacokinetic behavior of Fc-containing biotherapeutics such as monoclonal antibodies. The goal of this investigation was to achieve for the first time a comparative assessment of FcRn distribution across a variety of tissues and species...
April 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28384050/tilt-biotherapeutics
#8
Akseli Hemminki
No abstract text is available yet for this article.
March 1, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28378257/new-doxorubicin-nanocarriers-based-on-cyclodextrins
#9
Maurizio Viale, Valentina Giglio, Massimiliano Monticone, Irena Maric, Giovanni Lentini, Mattia Rocco, Graziella Vecchio
Polymeric nanoparticles and fibrin gels (FBGs) are attractive biomaterials for local delivery of a variety of biotherapeutic agents, from drugs to proteins. We combined these different drug delivery approaches by preparing nanoparticle-loaded FBGs characterized by their intrinsic features of drug delivery rate and antiproliferative/apoptotic activities. Inclusion complexes of doxorubicin (DOXO) with oligomeric β-cyclodextrins (oCyD) functionalized with different functional groups were studied. These nanocarriers were able to interact with FBGs as shown by a decreased release rate of DOXO...
April 4, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28374318/erratum-to-systematic-verification-of-bioanalytical-similarity-between-a-biosimilar-and-a-reference-biotherapeutic-committee-recommendations-for-the-development-and-validation-of-a-single-ligand-binding-assay-to-support-pharmacokinetic-assessments
#10
Joseph C Marini, Michael Anderson, Xiao-Yan Cai, John Chappell, Todd Coffey, Dominique Gouty, Aparna Kasinath, Vera Koppenburg, Philip Oldfield, Shannon Rebarchak, Ronald R Bowsher
No abstract text is available yet for this article.
April 3, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28373031/isolation-and-quantification-of-antimalarial-n-alkylamides-from-flower-head-derived-in%C3%A2-vitro-callus-cultures-of-spilanthes-paniculata
#11
Radhika Rajendran, Balaji Sitthu Narashimman, Vishal Trivedi, Rakhi Chaturvedi
This is the pioneer work reporting on simple procedure for synchronized determination and quantification of two biologically active N-alkylamides, (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol) and (2E,4Z)-N-isobutyl-2,4-undecadiene-8,10-diynamide (UDA), using in vitro callus cultures from flower-heads of Spilanthes paniculata. The extracts were purified using preparative thin layer chromatography (TLC) and finest separation of compounds was optimized using high performance liquid chromatography (HPLC)...
March 31, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28371718/comparability-study-of-rituximab-originator-and-follow-on-biopharmaceutical
#12
Othman Montacir, Houda Montacir, Murat Eravci, Andreas Springer, Stephan Hinderlich, Amirhossein Saadati, Maria Kristina Parr
Immunglobolin G (IgG)-based biopharmaceuticals are emerging on the pharmaceuticals market due to their high target selectivity in different diseases. In parallel, a growing interest by other companies to produce similar or highly similar follow-on biologics exits, once the patent of blockbuster biotherapeutics is about to expire. In correlation to their complex structure, an analytical challenge is facing the approval of these biosimilars. Health authorities (e.g. FDA and EMA) have issued several guidelines to define critical quality attributes during manufacturing process changes...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28366475/biological-therapies-of-immunologic-diseases-strategies-for-immunologic-interventions
#13
REVIEW
Brooke I Polk, Lanny J Rosenwasser
The immune system possesses a vast number of potential targets for therapeutic intervention. Although therapies for many pathways have been pursued, only few have yielded significant success. Hindrances in altering biologic pathways include the potential for unwanted downstream effects, ineffectiveness owing to biological redundancy, recognition of a therapeutic molecule as foreign by the body's innate immune system, and the risks of subsequent malignancy and/or autoimmunity. This article covers currently available biotherapeutic agent classes as well as potential direction for future therapy...
May 2017: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/28356427/microbiota-gut-brain-axis-modulator-of-host-metabolism-and-appetite
#14
REVIEW
Marcel van de Wouw, Harriët Schellekens, Timothy G Dinan, John F Cryan
The gut harbors an enormous diversity of microbes that are essential for the maintenance of homeostasis in health and disease. A growing body of evidence supports the role of this microbiota in influencing host appetite and food intake. Individual species within the gut microbiota are under selective pressure arising from nutrients available and other bacterial species present. Each bacterial species within the gut aims to increase its own fitness, habitat, and survival via specific fermentation of dietary nutrients and secretion of metabolites, many of which can influence host appetite and eating behavior by directly affecting nutrient sensing and appetite and satiety-regulating systems...
March 29, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28346883/identification-and-characterization-of-a-thermally-cleaved-fragment-of-monoclonal-antibody-a-detected-by-sodium-dodecyl-sulfate-capillary-gel-electrophoresis
#15
Kei Kubota, Naoki Kobayashi, Masayuki Yabuta, Motomu Ohara, Toyohiro Naito, Takuya Kubo, Koji Otsuka
This report describes a novel, comprehensive approach to identifying a fragment peak of monoclonal antibody-A (mAb-A), detected by sodium dodecyl sulfate-capillary gel electrophoresis (SDS-cGE). The fragment migrated close to the internal standard (10kDa marker) of SDS-cGE and increased about 0.5% under a 25°C condition for 6 months. Generally, identification of fragments observed in SDS-cGE is challenging to carry out due to the difficulty of collecting analytical amounts of fractionations from the capillary...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28342833/a-high-density-cho-s-transient-transfection-system-comparison-of-expicho-and-expi293
#16
Nina K Jain, Susan Barkowski-Clark, Richard Altman, Krista Johnson, Fang Sun, Jonathan Zmuda, Chao Yan Liu, Adriana Kita, Ryan Schulz, Alyssa Neill, Robert Ballinger, Rekha Patel, Jian Liu, Alinafe Mpanda, Brian Huta, Henry Chiou, Walter Voegtli, Tadas Panavas
Chinese Hamster Ovary (CHO) cells are the principal mammalian host used for stable cell line generation and biotherapeutic protein production. Until recently, production of milligrams to grams of protein in CHO transient systems was challenging. As such, Human Embryonic Kidney (HEK293) cells are the most common mammalian cell type used for transient transfection. The post-translational modifications (PTMs) of a protein are dictated in part by the cell line used for expression, and changes in PTMs have been shown to affect both the activity and biophysical properties of proteins...
March 23, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28342222/the-h3-loop-of-antibodies-shows-unique-structural-characteristics
#17
Cristian Regep, Guy Georges, Jiye Shi, Bojana Popovic, Charlotte M Deane
The H3 loop in the Complementary Determining Region (CDR) of antibodies plays a key role in their ability to bind the diverse space of potential antigens. It is also exceptionally difficult to model computationally causing a significant hurdle for in-silico development of antibody biotherapeutics. In this paper we show that most H3s have unique structural characteristics which may explain why they are so challenging to model. We found that over 75% of H3 loops do not have a sub-Angstrom structural neighbour in the non-antibody world...
March 25, 2017: Proteins
https://www.readbyqxmd.com/read/28328036/use-of-a-stable-isotope-labeled-reporter-peptide-and-antioxidants-for-reliable-quantification-of-methionine-oxidation-in-a-monoclonal-antibody-by-liquid-chromatography-mass-spectrometry
#18
Pilsoo Kang, Tanya Mezhebovsky, Wei Chen, James A McCardle, Sheng Zhang, Eric P Sullivan, Philip M Sass, Eric Routhier
RATIONALE: Accurate quantification of methionine oxidation in therapeutic proteins by liquid chromatography/mass spectrometry (LC/MS) is challenging due to the potential artifacts introduced during sample preparation and analysis in the peptide mapping workflow. In this study, a systematic approach for optimization of the peptide mapping procedure to achieve reliable quantification of endogenous methionine oxidation in monoclonal antibodies was developed. METHODS: The approach is based on usage of a stable-isotope-labeled reporter peptide, identical in sequence to the tryptic peptide of an IgG1 monoclonal antibody containing the methionine residue most prone to oxidation...
July 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28289128/characterizing-the-overall-derivatization-of-conjugated-oligomeric-proteins
#19
Michaela Wendeler, Wei Zhao, Christopher Thompson, Manuel Baca, Dhanesh Gadre, Xiangyang Wang, Harry Yang
The analysis and accurate quantitation of bioconjugations proves challenging in the case of oligomeric proteins, especially when the size of the molecule or the nature of the conjugate do not allow the analysis of the intact protein under native conditions. In this case, analytical methods are frequently applied that result in a dissociation of non-covalently linked subunits. This limits the analysis to a description of individual subunits, thereby obscuring the accurate characterization of the overall functionalization...
March 13, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28267992/clostridium-difficile-disease-diagnosis-pathogenesis-and-treatment-update
#20
REVIEW
Lena M Napolitano, Charles E Edmiston
Clostridium difficile infections are the leading cause of health care-associated infectious diarrhea, posing a significant risk for both medical and surgical patients. Because of the significant morbidity and mortality associated with C difficile infections, knowledge of the epidemiology of C difficile in combination with a high index of suspicion and susceptible patient populations (including surgical, postcolectomy, and inflammatory bowel disease patients) is warranted. C difficile infections present with a wide spectrum of disease, ranging from mild diarrhea to fulminant colitis or small bowel enteritis and recurrent C difficile infections...
March 3, 2017: Surgery
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