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1.
Amino Acid Metabolism in Cancer Drug Resistance.
Yoo, HC, Han, JM
Cells. 2022;(1)
Abstract
Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.
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2.
Zinc finger proteins: insights into the transcriptional and post transcriptional regulation of immune response.
Rakhra, G, Rakhra, G
Molecular biology reports. 2021;(7):5735-5743
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Abstract
BACKGROUND Zinc finger proteins encompass one of the unique and large families of proteins with diversified biological functions in the human body. These proteins are primarily considered to be DNA binding transcription factors; however, owing to the diverse array of zinc-finger domains, they are able to interact with molecules other than DNA like RNA, proteins, lipids and PAR (poly-ADP-ribose). Evidences from recent scientific studies have provided an insight into the potential functions of zinc finger proteins in immune system regulation both at the transcriptional and post transcriptional level. However, the mechanism and importance of zinc finger proteins in the regulation of immune response is not very well defined and understood. This review highlights in detail the importance of zinc finger proteins in the regulation of immune system at transcriptional and post transcriptional level. CONCLUSION Different types of zinc finger proteins are involved in immune system regulation and their mechanism of regulation is discussed herewith.
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Sustaining efficient immune functions with regular physical exercise in the COVID-19 era and beyond.
Furtado, GE, Letieri, RV, Caldo-Silva, A, Sardão, VA, Teixeira, AM, de Barros, MP, Vieira, RP, Bachi, ALL
European journal of clinical investigation. 2021;(5):e13485
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Abstract
The new coronavirus (SARS-CoV-2) appearance in Wuhan, China, did rise the new virus disease (COVID-19), which spread globally in a short time, leading the World Health Organization to declare a new global pandemic. To contain and mitigate the spread of SARS-CoV-2, specific public health procedures were implemented in virtually all countries, with a significant impact on society, making it difficult to keep the regular practice of physical activity. It is widely accepted that an active lifestyle contributes to the improvement of general health and preservation of cardiovascular, respiratory, osteo-muscular and immune system capacities. The positive effects of regular physical activity on the immune system have emerged as a pivotal trigger of general health, underlying the beneficial effects of physical activity on multiple physiological systems. Accordingly, recent studies have already pointed out the negative impact of physical inactivity caused by the social isolation imposed by the public sanitary authorities due to COVID-19. Nevertheless, there are still no current narrative reviews evaluating the real impact of COVID-19 on active lifestyle or even discussing the possible beneficial effects of exercise-promoted immune upgrade against the severity or progression of COVID-19. Based on the consensus in the scientific literature, in this review, we discuss how an exercise adherence could adequately improve immune responses in times of the 'COVID-19 Era and beyond'.
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The Role of Oat Nutrients in the Immune System: A Narrative Review.
Chen, O, Mah, E, Dioum, E, Marwaha, A, Shanmugam, S, Malleshi, N, Sudha, V, Gayathri, R, Unnikrishnan, R, Anjana, RM, et al
Nutrients. 2021;(4)
Abstract
Optimal nutrition is the foundation for the development and maintenance of a healthy immune system. An optimal supply of nutrients is required for biosynthesis of immune factors and immune cell proliferation. Nutrient deficiency/inadequacy and hidden hunger, which manifests as depleted nutrients reserves, increase the risk of infectious diseases and aggravate disease severity. Therefore, an adequate and balanced diet containing an abundant diversity of foods, nutrients, and non-nutrient chemicals is paramount for an optimal immune defense against infectious diseases, including cold/flu and non-communicable diseases. Some nutrients and foods play a larger role than others in the support of the immune system. Oats are a nutritious whole grain and contain several immunomodulating nutrients. In this narrative review, we discuss the contribution of oat nutrients, including dietary fiber (β-glucans), copper, iron, selenium, and zinc, polyphenolics (ferulic acid and avenanthramides), and proteins (glutamine) in optimizing the innate and adaptive immune system's response to infections directly by modulating the innate and adaptive immunity and indirectly by eliciting changes in the gut microbiota and related metabolites.
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The Influence of Nutritional Factors on Immunological Outcomes.
Tourkochristou, E, Triantos, C, Mouzaki, A
Frontiers in immunology. 2021;:665968
Abstract
Through food intake, humans obtain a variety of nutrients that are essential for growth, cellular function, tissue development, energy, and immune defense. A special interaction between nutrients and gut-associated lymphoid tissue occurs in the intestinal tract. Enterocytes of the intestinal barrier act as sensors for antigens from nutrients and the intestinal microbiota, which they deliver to the underlying immune system of the lamina propria, triggering an immune response. Studies investigating the mechanism of influence of nutrition on immunological outcomes have highlighted an important role of macronutrients (proteins, carbohydrates, fatty acids) and micronutrients (vitamins, minerals, phytochemicals, antioxidants, probiotics) in modulating immune homeostasis. Nutrients exert their role in innate immunity and inflammation by regulating the expression of TLRs, pro- and anti-inflammatory cytokines, thus interfering with immune cell crosstalk and signaling. Chemical substrates derived from nutrient metabolism may act as cofactors or blockers of enzymatic activity, influencing molecular pathways and chemical reactions associated with microbial killing, inflammation, and oxidative stress. Immune cell function appears to be influenced by certain nutrients that form parts of the cell membrane structure and are involved in energy production and prevention of cytotoxicity. Nutrients also contribute to the initiation and regulation of adaptive immune responses by modulating B and T lymphocyte differentiation, proliferation and activation, and antibody production. The purpose of this review is to present the available data from the field of nutritional immunology to elucidate the complex and dynamic relationship between nutrients and the immune system, the delineation of which will lead to optimized nutritional regimens for disease prevention and patient care.
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The Role of Creatine in the Development and Activation of Immune Responses.
Bredahl, EC, Eckerson, JM, Tracy, SM, McDonald, TL, Drescher, KM
Nutrients. 2021;(3)
Abstract
The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.
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Dietary Regulation of Immunity.
Lee, AH, Dixit, VD
Immunity. 2020;(3):510-523
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Abstract
Integrated immunometabolic responses link dietary intake, energy utilization, and storage to immune regulation of tissue function and is therefore essential for the maintenance and restoration of homeostasis. Adipose-resident leukocytes have non-traditional immunological functions that regulate organismal metabolism by controlling insulin action, lipolysis, and mitochondrial respiration to control the usage of substrates for production of heat versus ATP. Energetically expensive vital functions such as immunological responses might have thus evolved to respond accordingly to dietary surplus and deficit of macronutrient intake. Here, we review the interaction of dietary intake of macronutrients and their metabolism with the immune system. We discuss immunometabolic checkpoints that promote healthspan and highlight how dietary fate and regulation of glucose, fat, and protein metabolism might affect immunity.
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Rheumatologists' perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets.
Misra, DP, Agarwal, V, Gasparyan, AY, Zimba, O
Clinical rheumatology. 2020;(7):2055-2062
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Abstract
The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren's syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still's disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.Key Points• Patients with coronavirus disease 19 (COVID-19) may have features mimicking rheumatic diseases, such as arthralgias, acute interstitial pneumonia, myocarditis, leucopenia, lymphopenia, thrombocytopenia and cytokine storm with features akin to secondary hemophagocytic lymphohistiocytosis.• Although preliminary results may be encouraging, high-quality clinical trials are needed to better understand the role of drugs commonly used in rheumatology like hydroxychloroquine and tocilizumab in COVID-19.• Until further evidence emerges, it may be cautiously recommended to continue glucocorticoids and other disease-modifying antirheumatic drugs (DMARDs) in patients receiving these therapies, with discontinuation of DMARDs during infections as per standard practice.
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Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin.
Jiang, Y, Tsoi, LC, Billi, AC, Ward, NL, Harms, PW, Zeng, C, Maverakis, E, Kahlenberg, JM, Gudjonsson, JE
JCI insight. 2020;(20)
Abstract
The skin serves as the primary interface between our body and the external environment and acts as a barrier against entry of physical agents, chemicals, and microbes. Keratinocytes make up the main cellular constitute of the outermost layer of the skin, contributing to the formation of the epidermis, and they are crucial for maintaining the integrity of this barrier. Beyond serving as a physical barrier component, keratinocytes actively participate in maintaining tissue homeostasis, shaping, amplifying, and regulating immune responses in skin. Keratinocytes act as sentinels, continuously monitoring changes in the environment, and, through microbial sensing, stretch, or other physical stimuli, can initiate a broad range of inflammatory responses via secretion of various cytokines, chemokines, and growth factors. This diverse function of keratinocytes contributes to the highly variable clinical manifestation of skin immune responses. In this Review, we highlight the highly diverse functions of epidermal keratinocytes and their contribution to various immune-mediated skin diseases.
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The key role of zinc in elderly immunity: A possible approach in the COVID-19 crisis.
de Almeida Brasiel, PG
Clinical nutrition ESPEN. 2020;:65-66
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Abstract
BACKGROUND & AIMS The COVID-19 infection can lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affecting patients aged 60 and older. Preliminary data suggest that the nutritional status can change the course of the infection, and on the matter, zinc is crucial for growth, development, and the maintenance of immune function. In the absence of treatment for this virus, there is an urgent need to find alternative methods that can contribute to control of disease. The aim of this paper is to establish the relation between zinc and COVID-19. METHODS AND RESULTS From the prior scientific knowledge, we have performed a review of the literature and examine the role of zinc in immune function in the infection by COVID-19. Our findings are that the zinc as an anti-inflammatory agent may help to optimize immune function and reduce the risk of infection. CONCLUSIONS Zinc supplementation can be a useful strategy to reduce the global burden of infection in the elderly, there is a need the increased reporting to improve our understanding of COVID-19 and the care of affected patients.