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Treatment of eosinophlic esophagitis with swallowed topical corticosteroids.
Nennstiel, S, Schlag, C
World journal of gastroenterology. 2020;(36):5395-5407
Abstract
Eosinophilic esophagitis (EoE) is an emerging chronic local immune-mediated disease of the esophagus. Beside proton pump inhibitors and food-restriction-diets swallowed topical corticosteroids (STC) can be offered as a first line therapy according to current guidelines. This review describes the background and practical management of STCs in EoE. So far, mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications "off label". Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85% - an orodispersible tablet of budesonide has been approved as the first "in label" medication for EoE in Europe in June 2018. Whereas it was shown that disease remission induction of EoE by STCs is highly effective, there is still a lack of data regarding long-term and maintenance therapy. However, current studies on STC maintenance therapy add some movement into the game.
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A Cecal Mucormycosis Mass Mimicking Colon Cancer in a Patient with Renal Transplant: A Case Report and Literature Review.
Busbait, S, AlMusa, Z, Al Duhileb, M, Algarni, AA, Balhareth, A
The American journal of case reports. 2020;:e926325
Abstract
BACKGROUND Mucormycosis is a rare, invasive, and opportunistic fungal infection that occurs in the setting of neutropenia, immune deficiency, solid-organ transplant, and iron overload. The gastrointestinal system is a rare site of mucormycosis, and gastrointestinal mucormycosis is associated with high mortality and accounts for 4-7% of all cases. CASE REPORT We present the case of a 64-year-old hypertensive man with transfusion-dependent myelodysplastic syndrome who underwent renal transplant surgery 11 years ago. He also was taking maintenance Deferasirox for iron overload. He presented with a 2-day history of right lower-quadrant abdominal pain, nausea, vomiting, and non-bloody diarrhea. An abdominal examination revealed guarding and a 5×6 cm mass in the right iliac fossa. A CT scan of the abdomen showed signs of perforation of a cecal mass. As the patient was unstable, emergency right hemicolectomy and end ileostomy were performed. After the surgery, the patient was moved to the Intensive Care Unit (ICU) and a broad-spectrum antibiotic was administered. Histopathological examination results received on postoperative day 5 showed broad pauciseptate hyphae with substantial blood-vessel infiltration, suggestive of mucormycosis. Amphotericin B was started; however, on the same day, his condition deteriorated and he was moved back to the ICU. Despite maximum cardiorespiratory support, he had multiorgan failure and died. CONCLUSIONS Gastrointestinal mucormycosis presentation is non-specific, the diagnosis is often made late or is missed, and mortality remains high. High clinical suspicion, early diagnosis, and combined antifungal and surgical treatment is the best way to reduce mortality and improve survival.
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Nutraceuticals: An integrative approach to starve Parkinson's disease.
Lama, A, Pirozzi, C, Avagliano, C, Annunziata, C, Mollica, MP, Calignano, A, Meli, R, Mattace Raso, G
Brain, behavior, & immunity - health. 2020;:100037
Abstract
The therapeutic approach of multifactorial complex diseases is always a challenge; Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder triggered by genetic and environmental factors, contributing to its etiology. Indeed, several pathogenic mechanisms lead to selective dopaminergic neuronal injury, including oxidative stress, mitochondrial dysfunction, alteration of endoplasmic reticulum-to-Golgi protein trafficking, excitotoxicity, and neuroinflammation. Current treatment approaches include mainly dopamine replacement therapy or optimizing dopaminergic transmission; however, these strategies that do not counteract the pathogenic mechanisms underlying PD symptoms and often are less effective over time. Recently, there has been growing interest in the therapeutic use of nutraceuticals, that could represent an integrative approach to the pharmacological standard therapy and specifically affect one or more pathogenic pathways. The intake of nutraceuticals or nutritional modifications are generally safe and can be combined with current common drug therapy in most cases to improve the patient's quality of life and/or mitigate PD symptoms. The current review focuses on several key nutritional compounds and dietary modifications that are effective on several pathogenic pathways involved in PD onset and progression, and further highlights the rationale behind their potential use for the prevention and treatment of PD.
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Metabolism of Amino Acids in Cancer.
Wei, Z, Liu, X, Cheng, C, Yu, W, Yi, P
Frontiers in cell and developmental biology. 2020;:603837
Abstract
Metabolic reprogramming has been widely recognized as a hallmark of malignancy. The uptake and metabolism of amino acids are aberrantly upregulated in many cancers that display addiction to particular amino acids. Amino acids facilitate the survival and proliferation of cancer cells under genotoxic, oxidative, and nutritional stress. Thus, targeting amino acid metabolism is becoming a potential therapeutic strategy for cancer patients. In this review, we will systematically summarize the recent progress of amino acid metabolism in malignancy and discuss their interconnection with mammalian target of rapamycin complex 1 (mTORC1) signaling, epigenetic modification, tumor growth and immunity, and ferroptosis. Finally, we will highlight the potential therapeutic applications.
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Role of Zinc in Mucosal Health and Disease: A Review of Physiological, Biochemical, and Molecular Processes.
Hassan, A, Sada, KK, Ketheeswaran, S, Dubey, AK, Bhat, MS
Cureus. 2020;(5):e8197
Abstract
Zinc is an essential trace element of all highly proliferating cells in the human body. It is essential to the development and growth of all organisms. Zinc plays a critical role in modulating resistance to infectious agents and reduces the duration, severity, and risk of diarrheal disease via improved regeneration of intestinal epithelium, improved absorption of water and electrolytes, increased levels of brush border enzymes, and, possibly, an enhancement in the immune response allowing better clearance of pathogens. On the cellular level, zinc finger motifs play various roles including diverse functions that involve specific gene expression for ion channels throughout the body. It maintains the function and the structure of the membrane barrier by contributing to host defense, which is particularly crucial in the intestines due to the continuous exposure to noxious agents and pathogens. Zinc deficiency is characterized by impaired immune function, loss of appetite, and growth retardation. More severe cases cause diarrhea, delayed sexual maturation, hair loss, eye and skin lesions, impotence and hypogonadism in males, as well as weight loss, taste abnormalities, delayed healing of wounds, and mental lethargy. The objective of this study is a critical review of the molecular and genetic regulation of zinc in various cellular processes and organs, the association between zinc and diarrheal disease, the recommended dietary zinc intake, and the effects of zinc deficiency on the human body.
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Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.
Al-Horani, RA, Kar, S
Viruses. 2020;12(10)
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The covid-19 pandemic has required the identification of therapies to prevent infection and limit severity. A previous paper by the same authors reviewed therapies that block the virus in the early stages of its lifecycle. This very large review of over 300 papers aimed to summarise therapeutics which are aimed at blocking the lifecycle of the virus after it has entered the body’s cells. The authors began by reviewing the lifecycle of the covid-19 virus explaining how it enters the body’s cells, replicates inside and then is released to infect new cells. Several antivirals, antimalarials and natural products were then reviewed. Of note, Remdesivir is being trialled in covid-19 patients, with mixed results, however, is being recommended in the US for the treatment of hospitalised covid-19 patients with severe disease. Ribavirin, which is being trialled in combination with other antivirals is also showing promising results in shortening hospitalisation times in covid-19 patients. It was concluded that any stage of the covid-19 lifecycle could be a target for therapeutics and combining therapies is likely to be more successful than monotherapy. This paper could be used by health care professionals to understand the most recent therapeutic research for covid-19.
Abstract
The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.
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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.
Khadke, S, Ahmed, N, Ahmed, N, Ratts, R, Raju, S, Gallogly, M, de Lima, M, Sohail, MR
Virology journal. 2020;17(1):154
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Severe manifestations of COVID-19 infection and mortality are associated with a cytokine storm. This is an excessive inflammatory response to the infection leading to an overproduction of pro-inflammatory signalling molecules, which consequently contributes to tissue and organ damage. This literature review summarised current knowledge, as of June 2020, about virus-associated cytokine storm, virus-host interactions and immunological mechanism, to gain a better understanding of the phenomena observed in COVID-19 infections and devise better treatment strategies. The review briefly outlines the epidemiology of COVID-19, predictors of severity of disease, mode of transmission, testing, viral structure, mechanism of invasion of the host cell, replication and immune invasion and the progression of the four stages of the cytokine storm. The second part of the review discusses antiviral therapeutics of interest with a table summarising drugs, mechanism and available data. This article may be of interest to those who like to delve further into the mechanisms and immune components involved in a cytokine storm and gain an oversight of the pathways targeted by allopathic agents that have been put forward as treatment options.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.
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Dissecting the interaction between COVID-19 and diabetes mellitus.
Chee, YJ, Tan, SK, Yeoh, E
Journal of diabetes investigation. 2020;11(5):1104-1114
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Several countries have reported higher death rates and more severe cases of covid-19 amongst individuals with chronic diseases such as type 2 diabetes. This review of 100 papers aimed to investigate the interconnecting factors which may contribute to poorer prognosis in individuals with covid-19 and type 2 diabetes. Although the evidence suggests that patients with type 2 diabetes have poorer outcomes after contracting covid-19, they are not more susceptible to infection. The paper reported that mechanisms which may increase severity in type 2 diabetics are abnormal immune function, increased susceptibility to inflammation, the increased adherence of the virus to target cells and reduced ability to fight infection. It is important to manage blood sugars when suffering from covid-19. The paper reviewed the use of several medications such as metformin, dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide-1 agonists and insulin in the context of individuals suffering from covid-19, with insulin being the treatment of choice in the acutely ill patient. Current treatments of covid-19 were also reviewed such as chloroquine and hydroxychloroquine, Lopinavir-ritonavir, IL-6 receptor agonists, type 1 interferon and remdesivir. It was concluded that clinicians should be aware of the risks in patients with type 2 diabetes and covid-19. However as new data is made available, the chronic and long-term implications will become clearer. This study could be used by health care professionals to ensure that patients with type 2 diabetes do everything they can to avoid covid-19 infection and that if contracted these patients are closely monitored for severe disease.
Abstract
Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.
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Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?
Menegazzi, M, Campagnari, R, Bertoldi, M, Crupi, R, Di Paola, R, Cuzzocrea, S
International journal of molecular sciences. 2020;21(14)
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Some individuals who have contracted Covid-19 experience an extreme inflammatory reaction known as cytokine storm syndrome. This review paper of 129 studies aimed to review the use of epigallocatechin 3-gallate (EGCG), a green tea derived chemical reported to reduce inflammation with a view to be used in individuals with Covid-19. Conventional therapies used in diseases known to induce extreme inflammation were discussed focusing on steroid based drugs. However, results in Covid-19 patients have shown increased mortality and decreased viral clearance. Several other drugs are being trialled in Covid-19. The use of EGCG and green tea extract (GTE) in several diseases such as rheumatoid arthritis, Sjogrens syndrome, multiple sclerosis, human immunodeficiency virus, dengue virus and inflammatory bowel disease was discussed and beneficial effects such as being anti-inflammatory, antiviral, antimicrobial, and having anti-cancer properties were outlined. The possible mechanisms involved were extensively discussed. The use of EGCG and GTE in a clinical setting was reported to have favourable outcomes and be a potentially safe natural supplement. It was concluded that given the safety and many benefits shown by EGCG in viruses and inflammatory diseases, EGCG/GTE may be effective in Covid-19, and clinical trials are needed. This study could be used by healthcare professionals to justify the recommendation of EGCG/GTE in individuals with Covid-19 and many other inflammatory and viral diseases.
Abstract
Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.
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Can Natural Polyphenols Help in Reducing Cytokine Storm in COVID-19 Patients?
Giovinazzo, G, Gerardi, C, Uberti-Foppa, C, Lopalco, L
Molecules (Basel, Switzerland). 2020;25(24)
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During covid-19 infection the body experiences a hyper-immune reaction resulting in an extreme inflammatory response known as cytokine release syndrome (CRS), which correlates with poor prognosis and severe illness. There are no effective treatments for CRS, although there are ongoing trials. The use of natural plant chemicals known as polyphenols have been shown in previous trials to improve inflammation This review of over 90 studies aimed to summarise the use of polyphenols to fight severe covid-19 infection. The paper began by reviewing current drug therapies, which have been shown in studies to be of benefit to inflammation, with tocilizumab being heavily reviewed. The authors then reviewed several plant polyphenols and reviewed how they can modulate inflammation through inhibiting inflammatory molecules and viral activity. It was concluded that human studies are lacking data and so phytochemicals may be promising for the treatment of covid-19. This study could be used by health care professionals to understand the importance of recommending a whole food, plant rich diet with many different coloured foods for individuals who are suffering from covid-19.
Abstract
SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.