scholarly journals AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives

2020 ◽  
Vol 38 (4) ◽  
pp. 343-354 ◽  
Author(s):  
Waldemar A. Turski ◽  
Artur Wnorowski ◽  
Gabrielle N. Turski ◽  
Christopher A. Turski ◽  
Lechoslaw Turski
Keyword(s):  
Physical Exercise ◽  
Signaling Pathway ◽  
Clinical Symptoms ◽  
Epidemiological Studies ◽  
Multiple Organ ◽  
Aryl Hydrocarbon ◽  
Downstream Effectors ◽  
Ahr Gene ◽  
Parasitic Pathogens ◽  
Activation Syndrome

Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a “Systemic AhR Activation Syndrome” (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.

VALUE OF COMBINATION OF HAP SCORE AND BISAP SCORE IN PREDICTING SEVERITY IN PATIENTS OF ACUTE PANCREATITIS

2019 ◽  
pp. 96-100
Author(s):  
Thi Ngoc Suong Le ◽  
Pham Chi Tran ◽  
Van Huy Tran
Keyword(s):  
Acute Pancreatitis ◽  
Positive Predictive Value ◽  
Roc Curve ◽  
Predictive Value ◽  
Prognostic Value ◽  
Acute Inflammation ◽  
Clinical Symptoms ◽  
Mortality Rates ◽  
Multiple Organ ◽  
Central Hospital

Acute pancreatitis (AP) is an acute inflammation of the pancreas, usually occurs suddenly with a variety of clinical symptoms, complications of multiple organ failure and high mortality rates. Objectives: To determine the value of combination of HAP score and BISAP score in predicting the severity of acute pancreatitis of the Atlanta 2012 Classification. Patients and Methods: 75 patients of acute pancreatitis hospitalized at Hue Central Hospital between March 2017 and July 2018; HAP and BISHAP score is calculated within the first 24 hours. The severity of AP was classified by the revised Atlanta criteria 2012. Results: When combining the HAP and BISAP scores in predicting the severity of acute pancreatitis, the area under the ROC curve was 0,923 with sensitivity value was 66.7%, specificity value was 97.1%; positive predictive value was 66.7%, negative predictive value was 97.1%. Conclusion: The combination of HAP and BISAP scores increased the sensitivity, predictive value, and prognostic value in predicting the severity of acute pancreatitis of the revised Atlanta 2012 classification in compare to each single scores. Key words: HAPscore, BiSAP score, acute pancreatitis, predicting severity

Tapinarof-induced folliculitis: the paradigm of activation of the aryl hydrocarbon signaling pathway

2021 ◽  
Author(s):  
Maria Polina Konstantinou ◽  
Fatma Jendoubi ◽  
Salama Hegazy ◽  
Amel Bouznad ◽  
Marie Tauber ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Aryl Hydrocarbon

scholarly journals AHR-dependent genes and response to MTX therapy in rheumatoid arthritis patients

2021 ◽  
Author(s):  
Anna Wajda ◽  
Ewa Walczuk ◽  
Barbara Stypińska ◽  
Jakub Lach ◽  
Danat Yermakovich ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymphoblastic Leukemia ◽  
Mrna Level ◽  
Poor Response ◽  
Evolutionary Analysis ◽  
First Line ◽  
Aryl Hydrocarbon ◽  
First Line Therapy ◽  
Genes Expression ◽  
Ahr Gene

AbstractMethotrexate (MTX) is the first-line therapy for rheumatoid arthritis. Nevertheless, MTX resistance is quite a common issue in clinical practice. There are some premises that aryl hydrocarbon receptor (AhR) gene battery may take part in MTX metabolism. In the present retrospective study, we analyzed genes expression of AHR genes battery associated with MTX metabolism in whole blood of RA patients with good and poor response to MTX treatment. Additionally, sequencing, genotyping and bioinformatics analysis of AHR repressor gene (AHRR) c.565C > G (rs2292596) and c.1933G > C (rs34453673) have been performed. Theoretically, both changes may have an impact on H3K36me3 and H3K27me3. Evolutionary analysis revealed that rs2292596 may be possibly damaging. Allele G in rs2292596 and DAS28 seems to be associated with a higher risk of poor response to MTX treatment in RA. RA patients with poor response to MTX treatment revealed upregulated AhR and SLC19A1 mRNA level. Treatment with IL-6 inhibitor may be helpful to overcome the low-dose MTX resistance. Analysis of gene expression revealed possible another cause of poor response to MTX treatment which is different from that observed in the case of acute lymphoblastic leukemia.

scholarly journals A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

2017 ◽  
Vol 27 (2) ◽  
pp. 57-69 ◽  
Author(s):  
Alexey V. Polonikov ◽  
Olga Yu. Bushueva ◽  
Irina V. Bulgakova ◽  
Maxim B. Freidin ◽  
Mikhail I. Churnosov ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway

Electroacupuncture inhibits the corneal ROS/TXNIP/NLRP3 signaling pathway in a rat model of dry eye syndrome

2021 ◽  
pp. 096452842110392
Author(s):  
Yanting Yang ◽  
Dan Zhang ◽  
Lijie Wu ◽  
Ji Zhang ◽  
Danyan Wu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Dry Eye ◽  
Clinical Symptoms ◽  
Dry Eye Syndrome ◽  
Receptor Protein ◽  
Sprague Dawley ◽  
Corneal Injury ◽  
Caspase 1 ◽  
Des Model

Background: Electroacupuncture (EA) treatment has been found to ameliorate clinical symptoms in patients with dry eye, but its mechanisms are still not entirely clear. Objective: To study the regulation of EA on ocular surface function and the corneal reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/Nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in dry eye syndrome (DES) model rats. Methods: Male Sprague-Dawley (SD) rats were randomly divided into five groups: Normal, Model, Model + EA, Model + NAC (N-actetylcysteine) and Model + NS (normal saline). The DES model was developed by subcutaneous injection of scopolamine hydrobromide with exposure to an air draft in the latter four groups. After intervention, the Schirmer I test (SIT), tear film break-up time (BUT) and ROS content were measured, the histopathological changes of corneal tissues were observed, and the mRNA and protein expression levels of TXNIP, NLRP3, apoptosis-associated Speck-like protein containing CARD (ASC), caspase-1, interleukin (IL)-1β and IL-18 were detected. Results: Compared with the Model group, the SIT and BUT increased significantly in the Model + EA group after intervention (p < 0.05), and the corneal injury was improved. Corneal ROS content declined in both Model + EA and Model + NAC groups (p < 0.05), and mRNA expression of TXNIP, NLRP3, ASC and caspase-1 also decreased (p < 0.01). Corneal protein expression of TXNIP, NLRP3, IL-1β and IL-18 decreased significantly in the Model + EA group (p < 0.01). Conclusion: Inhibiting the ROS/TXNIP/NLRP3 signaling pathway may be the mechanism underlying the role of EA in improving corneal injury in DES model rats.

scholarly journals The Relevance of a Physical Active Lifestyle and Physical Fitness on Immune Defense: Mitigating Disease Burden, With Focus on COVID-19 Consequences

2021 ◽  
Vol 12 ◽  
Author(s):  
Tayrine Ordonio Filgueira ◽  
Angela Castoldi ◽  
Lucas Eduardo R. Santos ◽  
Geraldo José de Amorim ◽  
Matheus Santos de Sousa Fernandes ◽  
...  
Keyword(s):  
Physical Activity ◽  
Physical Exercise ◽  
Physical Fitness ◽  
Bed Rest ◽  
Multiple Organ ◽  
Immune Defense ◽  
Sitting Time ◽  
Low Grade ◽  
Home Based ◽  
Effective Therapeutic Strategy

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a fast spreading virus leading to the development of Coronavirus Disease-2019 (COVID-19). Severe and critical cases are characterized by damage to the respiratory system, endothelial inflammation, and multiple organ failure triggered by an excessive production of proinflammatory cytokines, culminating in the high number of deaths all over the world. Sedentarism induces worse, continuous, and progressive consequences to health. On the other hand, physical activity provides benefits to health and improves low-grade systemic inflammation. The aim of this review is to elucidate the effects of physical activity in physical fitness, immune defense, and its contribution to mitigate the severe inflammatory response mediated by SARS-CoV-2. Physical exercise is an effective therapeutic strategy to mitigate the consequences of SARS-CoV-2 infection. In this sense, studies have shown that acute physical exercise induces the production of myokines that are secreted in tissues and into the bloodstream, supporting its systemic modulatory effect. Therefore, maintaining physical activity influence balance the immune system and increases immune vigilance, and also might promote potent effects against the consequences of infectious diseases and chronic diseases associated with the development of severe forms of COVID-19. Protocols to maintain exercise practice are suggested and have been strongly established, such as home-based exercise (HBE) and outdoor-based exercise (OBE). In this regard, HBE might help to reduce levels of physical inactivity, bed rest, and sitting time, impacting on adherence to physical activity, promoting all the benefits related to exercise, and attracting patients in different stages of treatment for COVID-19. In parallel, OBE must improve health, but also prevent and mitigate COVID-19 severe outcomes in all populations. In conclusion, HBE or OBE models can be a potent strategy to mitigate the progress of infection, and a coadjutant therapy for COVID-19 at all ages and different chronic conditions.

Otorhinolaryngological manifestations of COVID-19

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jarosław Wysocki
Keyword(s):  
Respiratory Tract ◽  
Distress Syndrome ◽  
Clinical Symptoms ◽  
Wide Spectrum ◽  
Multiple Organ ◽  
Upper Respiratory Tract ◽  
Equilibrium System ◽  
Similar Frequency ◽  
Upper Respiratory ◽  
Loss Of Strength

COVID-19 manifests itself in a wide spectrum of clinical symptoms, both in terms of their variety and severity. It can be asymptomatic or abortive, mild, moderate, severe and lightning, as septic with multiple organ failure and shock Typical leading symptoms of COVID-19 are: high fever poorly responding to drugs, severe loss of strength, chest pain, dyspnoea, pain headaches, bone and joint pain and muscle pain, until the onset of acute respiratory distress syndrome (ARDS). However, many publications mention among the possible symptoms also others, not related to the involvement of the lower respiratory tract. These are gastrointestinal disorders, damage to the central and peripheral nervous system, catarrh of the upper respiratory tract and dysfunctions of the sensory organs. The aim of this literature review was to determine the frequency of various head and neck dysfunctions that are part of COVID-19. Symptoms of conjunctivitis, nasal mucosa, pharynx and larynx are reported by about of patients, but they do not always occur at the same time, as in infections caused, for example, by rhinoviruses. Anosmi / hyposmia or ageusia / hypogeusia occur with a similar frequency. Symptoms of damage to the equilibrium system, such as dizziness, are reported by approx. 1/3, vertigo and hearing loss approx. 5-6%, tinnitus approx. 10% of patients. Reports of coexistence with COVID-19 of peripheral paresis of the facial nerve are so far relatively few and often included in the neurological disorders, the frequency of which is also about 1/3 of COVID-19 cases. Importantly, both catarrhal symptoms and the others listed here may precede, co-occur or follow the appearance of the leading symptoms of COVID-19. They can also be the only symptoms of this disease. This should prompt otorhinolaryngologists to be particularly vigilant in this regard

Sign in / Sign up

Export Citation Format

Share Document