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1.
The Effect of Inflammation on Bone.
Epsley, S, Tadros, S, Farid, A, Kargilis, D, Mehta, S, Rajapakse, CS
Frontiers in physiology. 2020;:511799
Abstract
Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.
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2.
β-Glucan Metabolic and Immunomodulatory Properties and Potential for Clinical Application.
Murphy, EJ, Rezoagli, E, Major, I, Rowan, NJ, Laffey, JG
Journal of fungi (Basel, Switzerland). 2020;(4)
Abstract
β-glucans are complex polysaccharides that are found in several plants and foods, including mushrooms. β-glucans display an array of potentially therapeutic properties. β-glucans have metabolic and gastro-intestinal effects, modulating the gut microbiome, altering lipid and glucose metabolism, reducing cholesterol, leading to their investigation as potential therapies for metabolic syndrome, obesity and diet regulation, gastrointestinal conditions such as irritable bowel, and to reduce cardiovascular and diabetes risk. β-glucans also have immune-modulating effects, leading to their investigation as adjuvant agents for cancers (solid and haematological malignancies), for immune-mediated conditions (e.g., allergic rhinitis, respiratory infections), and to enhance wound healing. The therapeutic potential of β-glucans is evidenced by the fact that two glucan isolates were licensed as drugs in Japan as immune-adjuvant therapy for cancer in 1980. Significant challenges exist to further clinical testing and translation of β-glucans. The diverse range of conditions for which β-glucans are in clinical testing underlines the incomplete understanding of the diverse mechanisms of action of β-glucans, a key knowledge gap. Furthermore, important differences appear to exist in the effects of apparently similar β-glucan preparations, which may be due to differences in sources and extraction procedures, another poorly understood issue. This review will describe the biology, potential mechanisms of action and key therapeutic targets being investigated in clinical trials of β-glucans and identify and discuss the key challenges to successful translation of this intriguing potential therapeutic.
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3.
Ramadan intermittent fasting and immunity: An important topic in the era of COVID-19.
Faris, MAE, Salem, ML, Jahrami, HA, Madkour, MI, BaHammam, AS
Annals of thoracic medicine. 2020;(3):125-133
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Abstract
WITH the growing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) infection, a parallel growing interest arose concerning potential preventive and adjunct therapies, dietary and lifestyle modifications, and remedies that may boost the immunity against SARS-CoV-2 infection. Furthermore, as Ramadan intermittent religious fasting that is practiced by about one and a half billion Muslims throughout the globe is coincide this year with COVID-19 pandemic, a growing debate rose concerning the expected impact of fasting during Ramadan month and the associated dietary and lifestyle behaviors on the body's immunity against the pandemic infection. Published literature was searched to find out how intermittent fasting (IF) and its model of Ramadan affect the various aspects related to the body's immunity against microbial infections. IF was found to impact immunity by changing different related elements, including oxidative stress and inflammation, metabolism, body weight, and body composition. Dietary and lifestyle modifications during Ramadan month and their impact on immunity, such as water intake and hydration status, sleep duration and timing, caloric intake and mealtime, and social and spirtual activities, were addressed. Further research is warranted to figure out how IF during ramadan affects immunity against SARS-CoV-2 infection.
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4.
Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer.
Kok, VC
Frontiers in oncology. 2020;:268
Abstract
Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D-cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.
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5.
What about glucocorticoids in primary Sjögren's syndrome?
Priori, R, Mastromanno, L, Izzo, R
Clinical and experimental rheumatology. 2020;(4):237-244
Abstract
Glucocorticoids (GCs) are involved in several physiological processes such as metabolism, water and electrolyte balance, growth, cardiovascular and cognitive functions, reproduction. Furthermore, they exert different effects on innate and adaptive immune cells. Due to their anti-inflammatory and immunosuppressive functions, these drugs are largely used for the treatment of inflammatory and autoimmune diseases. In comparison to other autoimmune rheumatic diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to date no reliable evidence is available for the use of systemic GCs in Sjögren's syndrome (SS), which is still based on case reports, case studies, retrospective or prospective studies and a small number of randomised controlled trials (RCTs). Despite this gap in our knowledge, GCs are commonly used in SS for glandular, joint, cutaneous, lung, haematological, renal, neurological involvement. More recently, some sets of recommendations for the management of SS have provided a few pieces of advice regarding the use of GCs in this condition. Future studies should not neglect the role of GCs, as this traditional therapeutic weapon can still have a role in the management of SS. Accordingly, this review will address and discuss the use of systemic GCs in isolated or primary SS.
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6.
Immune-Kynurenine Pathways and the Gut Microbiota-Brain Axis in Anxiety Disorders.
Evrensel, A, Ünsalver, BÖ, Ceylan, ME
Advances in experimental medicine and biology. 2020;:155-167
Abstract
Anxiety disorders are a complex set of illnesses in which genetic factors, particularly stress, play a role in the etiopathogenesis. In recent years, inflammation and intestinal microbiota have also been included in this complex network of relationships. The functions associated with tryptophan catabolism and serotonin biosynthesis have long been associated with anxiety disorders. Tryptophan catabolism progresses toward the path of the kynurenine in the presence of stress and inflammation. The catabolism of kynurenine is a pathway in which many enzymes play a role and a large number of catabolites with neuroactive properties occur. The body's serotonin biosynthesis is primarily performed by enterochromaffin cells located in the intestines. A change in the intestinal microbiota composition (dysbiosis) directly affects the serotonin biosynthesis. Stress, unhealthy nutrition, and the use of antibiotics cause dysbiosis. In the light of this new perspective, the role of dysbiosis-induced inflammation and kynurenine pathway catabolites activated sequentially come into prominence in the etiopathogenesis of anxiety disorders.
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7.
Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer's Disease.
Borsom, EM, Lee, K, Cope, EK
Brain sciences. 2020;(11)
Abstract
The human microbiota is composed of trillions of microbial cells inhabiting the oral cavity, skin, gastrointestinal (GI) tract, airways, and reproductive organs. The gut microbiota is composed of dynamic communities of microorganisms that communicate bidirectionally with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites, known as the gut microbiota-brain axis. The gut microbiota-brain axis is suspected to be involved in the development of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease, and Autism Spectrum Disorder. AD is an irreversible, neurodegenerative disease of the central nervous system (CNS), characterized by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Microglia and astrocytes, the resident immune cells of the CNS, play an integral role in AD development, as neuroinflammation is a driving factor of disease severity. The gut microbiota-brain axis is a novel target for Alzheimer's disease therapeutics to modulate critical neuroimmune and metabolic pathways. Potential therapeutics include probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. This review summarizes our current understanding of the role of the gut microbiota-brain axis and neuroinflammation in the onset and development of Alzheimer's disease, limitations of current research, and potential for gut microbiota-brain axis targeted therapies.
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8.
γ-Aminobutyric acid and related amino acids in plant immune responses: Emerging mechanisms of action.
Tarkowski, ŁP, Signorelli, S, Höfte, M
Plant, cell & environment. 2020;(5):1103-1116
Abstract
The entanglement between primary metabolism regulation and stress responses is a puzzling and fascinating theme in plant sciences. Among the major metabolites found in plants, γ-aminobutyric acid (GABA) fulfils important roles in connecting C and N metabolic fluxes through the GABA shunt. Activation of GABA metabolism is known since long to occur in plant tissues following biotic stresses, where GABA appears to have substantially different modes of action towards different categories of pathogens and pests. While it can harm insects thanks to its inhibitory effect on the neuronal transmission, its capacity to modulate the hypersensitive response in attacked host cells was proven to be crucial for host defences in several pathosystems. In this review, we discuss how plants can employ GABA's versatility to effectively deal with all the major biotic stressors, and how GABA can shape plant immune responses against pathogens by modulating reactive oxygen species balance in invaded plant tissues. Finally, we discuss the connections between GABA and other stress-related amino acids such as BABA (β-aminobutyric acid), glutamate and proline.
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9.
An Overview of Ozone Therapy for Treating Foot Ulcers in Patients With Diabetes.
Wen, Q, Chen, Q
The American journal of the medical sciences. 2020;(2):112-119
Abstract
Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes mellitus, which is becoming increasingly prevalent throughout the world, with high mortality and morbidity. Because of the complex pathophysiological processes involved, DFU is difficult to treat effectively with traditional therapies. Ozone therapy, an emerging method, has been reported as potentially beneficial for closure of DFUs and may gradually move to the forefront of clinical practice. Possible mechanisms of action include antioxidant capacity, pathogen inactivation, vascular and endogenous growth factor modulation, and immune system activation. However, some researchers are skeptical about its safety, and clinical trials are lacking. This article reviews the current research and application of ozone therapy for DFUs.
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10.
Omega-3 Fatty Acids for Sport Performance-Are They Equally Beneficial for Athletes and Amateurs? A Narrative Review.
Thielecke, F, Blannin, A
Nutrients. 2020;(12)
Abstract
Omega-3 fatty acids, specifically eicosapentanoic acid (EPA, 20:5n-3) and docosahexanoic acid (DHA, 22:6n-3) are receiving increasing attention in sports nutrition. While the usual focus is that of athletes, questions remain if the different training status between athletes and amateurs influences the response to EPA/DHA, and as to whether amateurs would benefit from EPA/DHA supplementation. We critically examine the efficacy of EPA/DHA on performance, recovery and injury/reduced risk of illness in athletes as well as amateurs. Relevant studies conducted in amateurs will not only broaden the body of evidence but shed more light on the effects of EPA/DHA in professionally trained vs. amateur populations. Overall, studies of EPA/DHA supplementation in sport performance are few and research designs rather diverse. Several studies suggest a potentially beneficial effect of EPA/DHA on performance by improved endurance capacity and delayed onset of muscle soreness, as well as on markers related to enhanced recovery and immune modulation. The majority of these studies are conducted in amateurs. While the evidence seems to broadly support beneficial effects of EPA/DHA supplementation for athletes and more so in amateurs, strong conclusions and clear recommendations about the use of EPA/DHA supplementation are currently hampered by inconsistent translation into clinical endpoints.