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Alternatives to Biologics in Management of Knee Osteoarthritis: A Systematic Review.
Hassan, F, Murrell, WD, Refalo, A, Maffulli, N
Sports medicine and arthroscopy review. 2018;(2):79-85
Abstract
BACKGROUND Knee osteoarthritis (KOA) is a common condition encountered by physicians. KOA is addressed by a wide array of modalities including a number of nonbiological treatments. METHODS PubMed, ISI Web of Science, and SPORTDiscus were searched for level 1 to 4 studies published from inception to August 2017. RESULTS A total of 18 studies were evaluated and results demonstrated moderate supporting evidence for prolotherapy and limited evidence for botulinum toxin type A, sodium bicarbonate and calcium gluconate, and low-molecular weight fraction of 5% human serum albumin. Evidence for local anesthetic agents was conflicting. CONCLUSION There is moderate supportive evidence for the effectiveness of prolotherapy in improving pain and function in both, short-term and long-term. Limited supporting evidence found for botulinum toxin type A, sodium bicarbonate and calcium gluconate, and low-molecular weight fraction of 5% human serum albumin in improving pain and function. There is conflicting evidence for the use of local anesthetic agents in patients with KOA.
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Biological therapies for eosinophilic gastrointestinal diseases.
Wechsler, JB, Hirano, I
The Journal of allergy and clinical immunology. 2018;(1):24-31.e2
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Abstract
The scientific basis and the clinical application of mAb therapies that target specific immunologic pathways for eosinophilic gastrointestinal diseases are areas of active interest. There is a growing recognition of a subset of patients with eosinophilic esophagitis whose disease does not respond well to topical steroids or elimination diets. In addition, long-term use of corticosteroids presents possible risks that are currently being evaluated. Systemic therapy with a biologic agent offers potential advantages as a global approach that could limit the need for multiple, locally active medical therapies and allergen avoidance. The identification of novel biologic strategies is ongoing, and the recent validation of instruments and outcome measures to assess disease activity has proved essential in demonstrating efficacy. Studies using biologics that target IL-13 pathways in the treatment of eosinophilic esophagitis have demonstrated substantial promise.
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Rieske non-heme iron-dependent oxygenases catalyse diverse reactions in natural product biosynthesis.
Perry, C, de Los Santos, ELC, Alkhalaf, LM, Challis, GL
Natural product reports. 2018;(7):622-632
Abstract
Covering: up to the end of 2017 The roles played by Rieske non-heme iron-dependent oxygenases in natural product biosynthesis are reviewed, with particular focus on experimentally characterised examples. Enzymes belonging to this class are known to catalyse a range of transformations, including oxidative carbocyclisation, N-oxygenation, C-hydroxylation and C-C desaturation. Examples of such enzymes that have yet to be experimentally investigated are also briefly described and their likely functions are discussed.
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MAPPs for the identification of immunogenic hotspots of biotherapeutics; an overview of the technology and its application to the biopharmaceutical arena.
Quarmby, V, Phung, QT, Lill, JR
Expert review of proteomics. 2018;(9):733-748
Abstract
Anti-drug antibody (ADA) responses are becoming an increasing concern as more highly engineered and sophisticated biotherapeutics enter the clinic. An arsenal of tools has been developed to identify potential T cell epitopes that may drive unwanted immunological responses to protein therapeutics; one such tool is termed 'Major Histocompatibility Complex-Associated Peptide Proteomics' (MAPPs). This review highlights the evolution of this MHC II profiling technology, its technological advantages and limitations, and its utility in helping to de-risk the immunogenicity of biotherapeutics. Areas covered: A comprehensive literature review was performed along with discussions with key leaders in the field of MAPPs to summarize the importance of monitoring potential immunogenicity of clinical molecules. Herein we also describe how MAPPs has been applied specifically for monitoring MHC II peptides derived from biotherapeutics. Expert commentary: Given the importance of this growing field we discuss the complementary tools used in conjunction with MAPPs and review case studies where this approach has informed clinical studies and in some cases allowed re-engineering of the biotherapeutic moiety to a less immunogenic format.
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Beetroot juice ingestion during prolonged moderate-intensity exercise attenuates progressive rise in O2 uptake.
Tan, R, Wylie, LJ, Thompson, C, Blackwell, JR, Bailey, SJ, Vanhatalo, A, Jones, AM
Journal of applied physiology (Bethesda, Md. : 1985). 2018;(5):1254-1263
Abstract
Nitrate-rich beetroot juice (BR) supplementation has been shown to increase biomarkers of nitric oxide availability with implications for the physiological responses to exercise. We hypothesized that BR supplementation before and during prolonged moderate-intensity exercise would maintain an elevated plasma nitrite concentration ([[Formula: see text]]), attenuate the expected progressive increase in V̇o2 over time, and improve performance in a subsequent time trial (TT). In a double-blind, randomized, crossover design, 12 men completed 2 h of moderate-intensity cycle exercise followed by a 100-kJ TT in three conditions: 1) BR before and 1 h into exercise (BR + BR); 2) BR before and placebo (PL) 1 h into exercise (BR + PL); and 3) PL before and 1 h into exercise (PL + PL). During the 2-h moderate-intensity exercise bout, plasma [[Formula: see text]] declined by ~17% in BR + PL but increased by ~8% in BR + BR such that, at 2 h, plasma [[Formula: see text]] was greater in BR + BR than both BR + PL and PL + PL ( P < 0.05). V̇o2 was not different among conditions over the first 90 min of exercise but was lower at 120 min in BR + BR (1.73 ± 0.24 l/min) compared with BR + PL (1.80 ± 0.21 l/min; P = 0.08) and PL + PL (1.83 ± 0.27 l/min; P < 0.01). The decline in muscle glycogen concentration over the 2-h exercise bout was attenuated in BR + BR (~28% decline) compared with BR + PL (~44% decline) and PL + PL (~44% decline; n = 9, P < 0.05). TT performance was not different among conditions ( P > 0.05). BR supplementation before and during prolonged moderate-intensity exercise attenuated the progressive rise in V̇o2 over time and appeared to reduce muscle glycogen depletion but did not enhance subsequent TT performance. NEW & NOTEWORTHY We show for the first time that ingestion of nitrate during exercise preserves elevated plasma [nitrite] and negates the progressive rise in O2 uptake during prolonged moderate-intensity exercise.
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Recent examples of α-ketoglutarate-dependent mononuclear non-haem iron enzymes in natural product biosyntheses.
Gao, SS, Naowarojna, N, Cheng, R, Liu, X, Liu, P
Natural product reports. 2018;(8):792-837
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Abstract
Covering: up to 2018 α-Ketoglutarate (αKG, also known as 2-oxoglutarate)-dependent mononuclear non-haem iron (αKG-NHFe) enzymes catalyze a wide range of biochemical reactions, including hydroxylation, ring fragmentation, C-C bond cleavage, epimerization, desaturation, endoperoxidation and heterocycle formation. These enzymes utilize iron(ii) as the metallo-cofactor and αKG as the co-substrate. Herein, we summarize several novel αKG-NHFe enzymes involved in natural product biosyntheses discovered in recent years, including halogenation reactions, amino acid modifications and tailoring reactions in the biosynthesis of terpenes, lipids, fatty acids and phosphonates. We also conducted a survey of the currently available structures of αKG-NHFe enzymes, in which αKG binds to the metallo-centre bidentately through either a proximal- or distal-type binding mode. Future structure-function and structure-reactivity relationship investigations will provide crucial information regarding how activities in this large class of enzymes have been fine-tuned in nature.
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Spirulina platensis effectively ameliorates anthropometric measurements and obesity-related metabolic disorders in obese or overweight healthy individuals: A randomized controlled trial.
Yousefi, R, Mottaghi, A, Saidpour, A
Complementary therapies in medicine. 2018;:106-112
Abstract
AIMS: Novel alternative treatments such as food supplements may be an effective approach to weight management. The aim of the present study was to investigate the possible effects of Spirulina Platensis (SP) on anthropometric measures, appetite and metabolic parameters in obese or overweight individuals. MATERIAL AND METHODS A total of fifty-two obese and overweight subjects (25 kg/m2 ≤ body mass index (BMI) <40 kg/m2) were randomly selected to be allocated to SP (4 × 500 mg daily tablets along with restricted calorie diet (RCD)) or placebo (placebo tablets along with RCD) for 12 weeks of intervention. Anthropometric measurements and appetite score were assessed at baseline, weeks 6 and 12. Biochemical assessments were performed at baseline and week 12. RESULTS Thirty-eight participants completed the intervention. Body weight, waist circumference, body fat and BMI significantly reduced in the SP group compared to the placebo group (p < 0.001, p = 0.049, p = 0.049 and p = 0.02, respectively). In the SP group, the reduction triglycerides (TG) and high sensitivity C-reactive protein levels was considerably significant compared to the placebo group (p = 0.03, p = 0.02, respectively). Appetite score was significantly reduced in the SP group compared to the baseline (p < 0.001). CONCLUSIONS This study suggests that spirulina platensis, as a complementary therapy may have beneficial effects on adherence to RCD, management of weight loss and also reduction in TG levels through possible modulatory effects on anti-inflammatory pathways.
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Microbial production of small medicinal molecules and biologics: From nature to synthetic pathways.
Zhang, R, Li, C, Wang, J, Yang, Y, Yan, Y
Biotechnology advances. 2018;(8):2219-2231
Abstract
Natural products are promising chemicals due to their structural diversity and bioactivities. Over the decades, a vast variety of gene clusters encoding natural products have been identified and overexpressed in microbes. Recently, the development of metabolic engineering, synthetic biology and bioinformatics strategies have facilitated target discovery and design. Microbial cells have been therefore constantly engineered for product accumulation. This review summarizes approaches of domesticating microbial hosts in producing major classes of natural products, with an emphasis on recent advances.
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Towards a sustainable bio-based economy: Redirecting primary metabolism to new products with plant synthetic biology.
Shih, PM
Plant science : an international journal of experimental plant biology. 2018;:84-91
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Abstract
Humans have domesticated many plant species as indispensable sources of food, materials, and medicines. The dawning era of synthetic biology represents a means to further refine, redesign, and engineer crops to meet various societal and industrial needs. Current and future endeavors will utilize plants as the foundation of a bio-based economy through the photosynthetic production of carbohydrate feedstocks for the microbial fermentation of biofuels and bioproducts, with the end goal of decreasing our dependence on petrochemicals. As our technological capabilities improve, metabolic engineering efforts may expand the utility of plants beyond sugar feedstocks through the direct production of target compounds, including pharmaceuticals, renewable fuels, and commodity chemicals. However, relatively little work has been done to fully realize the potential in redirecting central carbon metabolism in plants for the engineering of novel bioproducts. Although our ability to rationally engineer and manipulate plant metabolism is in its infancy, I highlight some of the opportunities and challenges in applying synthetic biology towards engineering plant primary metabolism.
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Natural Products for Promoting Joint Health and Managing Osteoarthritis.
Henrotin, Y, Mobasheri, A
Current rheumatology reports. 2018;(11):72
Abstract
PURPOSE OF REVIEW Osteoarthritis, the most common joint disease, is associated with substantial medical costs, lost productivity, and reduced quality of life. However, available pharmaceutical treatments have limitations in terms of efficacy and long-term safety. RECENT FINDINGS In vitro evidence suggests that some natural products may possess anti-inflammatory and anti-oxidative properties and may inhibit the release of key osteoarthritis-related cytokines. There is, therefore, ongoing interest in identifying natural products that safely promote joint health and treat osteoarthritis. Numerous plant extracts, including curcumin, Boswellia extract, and pycnogenol, have shown effect sizes (ES) for reducing pain and functional disability larger than those observed with analgesics and products such as glucosamine and chondroitin. The ES for methylsulfonylmethane and avocado/soybean unsaponifiables are also considered to be clinically relevant. Data from a small number of studies using natural products for treating osteoarthritis are promising but require confirmation in further well-designed clinical trials.