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Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
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Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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Nutrition amid the COVID-19 pandemic: a multi-level framework for action.
Naja, F, Hamadeh, R
European journal of clinical nutrition. 2020;74(8):1117-1121
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This Lebanese articled provides a commentary on the evolving COVID-19 pandemic and aims to give a framework for Nutritional action to help the physical and mental health of individuals, communities, and nations. At an individual level the focus is on the link between diet and immunity and the profound effect diet has on people’s immune system and disease susceptibility. An adequate intake of iron, zinc, and vitamins A, E, B6, and B12 is predominantly vital for the maintenance of immune function. Individuals should aim to eat as healthily as possible, including a wide range of fruits and vegetables, limit snacking, take regular exercise and get an adequate amount of sleep to support their health. Single foods promising cures or prevention of infection are unfounded claims which can give a false sense of security. The focus for communities is on food availability, for nations its food security and on a global level it is about food trade agreements. Its important to protect against hoarding and panic buying to ensure enough food for everyone. National economic instability during COVID-19 can lead to a risk of food security so governments are advised to support local agricultural produce and reduce their reliance on imported goods. Global supply chains and agreements need to be respected to lessen the impact further down the supply chain. The health of each individual has a direct impact on the community and nation and is a direct consequence of their dietary awareness and choices.
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Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic.
Gasmi, A, Noor, S, Tippairote, T, Dadar, M, Menzel, A, Bjørklund, G
Clinical immunology (Orlando, Fla.). 2020;215:108409
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With the continuing spread of COVID-19 and lack of any approved treatments, this paper examines possible strategies for prevention. The data emerging so far highlights that individual health status plays a critical role in determining clinical severity of COVID-19 symptoms ranging from asymptomatic, mild, moderate, to death. Metabolic status, as determined by a patient’s diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors can therefore be considered preventative strategies to improve the severity of COVID-19 outcomes. Social distancing and personal hygiene are stated as the most effective strategies to prevent or slow spread of the disease. However individual health status, age and the presence of pre-existing comorbidities influences outcomes, as shown by global data highlighting a prevalence in older, males with metabolic conditions; hypertension in 23.7% patients and diabetes in 16.2% of patients. Older males appear more prone to infectious diseases with high pro-inflammatory immune responses and low adaptive immune responses than an older woman. Diet and healthy intestinal and respiratory tract microbiota may also influence immune system competence. Numerous micronutrients are essential for immunocompetence, particularly vitamin A, C, D, E, Bs, iron, selenium, and zinc. A balanced diet, high in colourful fruits and vegetables with a variation of prebiotic fibres, probiotics, and plant polyphenols and phytonutrients, help promote a healthy, diverse microbiota. Oral probiotics may also be beneficial to vulnerable individuals. Vitamin D supplementation is also proving helpful in prevention of acute respiratory tract infections. Other lifestyle factors such as smoking and exposure to environmental toxins should also be considered. Together these preventative measures may reduce personal risk of getting the disease.
Abstract
It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.
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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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A systematic review on COVID-19 pandemic with special emphasis on curative potentials of Nigeria based medicinal plants.
Oladele, JO, Ajayi, EI, Oyeleke, OM, Oladele, OT, Olowookere, BD, Adeniyi, BM, Oyewole, OI, Oladiji, AT
Heliyon. 2020;6(9):e04897
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At the time of writing, there were no known vaccines or treatments for Covid-19. This systematic review article aimed to investigate how Covid-19 works in the body and any Nigerian based medicinal plants that could mitigate this. The paper first began by discussing that the highly contagious nature and susceptibility of the population has ensured that Covid-19 has spread to all continents and that men may be more susceptible than women. How the virus enters the body’s cells, and the extreme inflammatory reaction it causes was extensively discussed. The paper went on to explain that Covid-19 had a higher infectivity and was more easily transmitted but a lower death rate in comparison to other coronaviruses such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). The authors then go on to extensively review plants that may be of benefit to individuals with Covid-19 due to their anti-inflammatory, anti-viral, antioxidant, and cell membrane and immune boosting properties. Finally, plants used in the treatment of other respiratory infections such as cold and flu were reviewed. It was concluded that although plants have been effective in the treatment of symptoms of Covid-19, research is needed to prove their abilities and that combining plants as a treatment regimen may be more effective. This study could be used by healthcare professionals to understand the mode of action of Covid-19 and how natural therapies could be included in a treatment plan.
Abstract
Despite the frightening mortality rate associated with COVID-19, there is no known approved drug to effectively combat the pandemic. COVID-19 clinical manifestations include fever, fatigue, cough, shortness of breath, and other complications. At present, there is no known effective treatment or vaccine that can mitigate/inhibit SARS-CoV-2. Available clinical intervention for COVID-19 is only palliative and limited to support. Thus, there is an exigent need for effective and non-invasive treatment. This article evaluates the possible mechanism of actions of SARS-CoV-2 and present Nigeria based medicinal plants which have pharmacological and biological activities that can mitigate the hallmarks of the pathogenesis of COVID-19. SARS-CoV-2 mode of actions includes hyper-inflammation characterized by a severe and fatal hyper-cytokinaemia with multi-organ failure; immunosuppression; reduction of angiotensin-converting enzyme 2 (ACE2) to enhance pulmonary vascular permeability causing damage to the alveoli; and further activated by open reading frame (ORF)3a, ORF3b, and ORF7a via c-Jun N- terminal kinase (JNK) pathway which induces lung damage. These mechanisms of action of SARS-CoV-2 can be mitigated by a combination therapy of medicinal herbs based on their pharmacological activities. Since the clinical manifestations of COVID-19 are multifactorial with co-morbidities, we strongly recommend the use of combined therapy such that two or more herbs with specific therapeutic actions are administered to combat the mediators of the disease.
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Vitamin C: an essential "stress hormone" during sepsis.
Marik, PE
Journal of thoracic disease. 2020;12(Suppl 1):S84-S88
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Most mammals can synthesise vitamin C, except humans, other primates and guinea pigs, who lost this ability through a mutation. It is estimated that goats produce 2-4g of vitamin C per day, but significantly more when stressed. Vitamin C is thought to play an important role in our stress response. This short review articles discusses the importance of vitamin C during stress, in particular the stress of sepsis. The adrenal glands, our “stress organs”, contain very high levels of vitamin C which is released when the hypothalamus-pituitary-adrenal (HPA) axis (which deals with our response to stressors) is stimulated. In animals, there is an inverse relationship between vitamin C internal manufacture and cortisol release under stress: the less vitamin C an animal can produce, the more cortisol they release. A number of vitamin C’s biological actions including antioxidant, anti-inflammatory, immune function, synthesis of the stress hormones adrenaline and noradrenaline and wound healing, may play an important role during a stress response. During sepsis vitamin C gets used up at alarming rate. Sepsis is a complex disease and vitamin C’s biological actions can affect many of the underlying pathophysiological processes. Preclinical and clinical studies have shown a beneficial effect of vitamin C in patients with sepsis and synergistic effects are seen with thiamine (vitamin B1), corticosteroids and antibiotics.
Abstract
The stress response is a preserved evolutionary response that functions to enhance the survival of the species. In mammals, the stress response is characterized by activation of the HPA axis and sympathoadrenal system (SAS) as well as the increased synthesis and secretion of vitamin C. Cortisol, catecholamines, and vitamin C act synergistically to increase hemodynamic reserve, maintain immune function and protect the host against excessive oxidant injury. Humans (and anthropoid apes) have lost the ability to synthesize vitamin C and therefore have an impaired stress response. The inability to produce vitamin C has serious implications in septic humans. Treatment with vitamin C appears to restore the stress response and improve the survival of stressed humans.
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Immediate and long-term consequences of COVID-19 infections for the development of neurological disease.
Heneka, MT, Golenbock, D, Latz, E, Morgan, D, Brown, R
Alzheimer's research & therapy. 2020;12(1):69
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Covid-19 may cause brain dysfunction evidenced by symptoms individuals experience once they have contracted the disease. Loss of smell, taste and confusion have all been reported by patients and a number of severe cases have reported incidences of stroke. These are all of concern, as Covid-19 can severely affect the elderly who ordinarily are the most likely to suffer from brain disorders. This small review paper of 27 studies stated that there are four possible ways in which Covid-19 may affect the brain, which put Covid-19 sufferers at an increased risk of long-term brain disorders. This was supported by findings, which showed one third of Covid-19 patients leave hospital with evidence of brain dysfunction. Inflammation was heavily reviewed by the authors as a possible causal factor. It was concluded that patients who survive Covid-19 infection are at an increased risk for developing brain disorders such as Alzheimer's disease, however it was acknowledged that further studies are required. Clinicians could use this study to understand the possible need for both short-term and long-term monitoring of brain function in individuals who have survived Covid-19, especially if they are elderly.
Abstract
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.