scholarly journals Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment

2021 ◽  
Vol 11 ◽  
Author(s):  
Drishti Tiwari ◽  
Pawan Gupta
Keyword(s):  
Nuclear Receptors ◽  
Dietary Habits ◽  
Allergic Diseases ◽  
Living Standards ◽  
Metabolic Dysfunction ◽  
Genomic Changes ◽  
Physiological Processes ◽  
Gene Regulatory ◽  
Critical Requirement ◽  
Allergy And Asthma

The escalation in living standards and adoption of ‘Western lifestyle’ has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes. As a consequence of such promising attributes, nuclear receptors have historically been at the cutting edge of pharmacy world. This review discusses the recent findings that feature the cardinal importance of nuclear receptors and how they can be instrumental in modulating current asthma pharmacology. Further, it highlights a possible future employment of therapy involving dietary supplements and synthetic ligands that would engage NRs and aid in eliminating both asthma and linked comorbidities. Therefore, uncovering new and evolving roles through analysis of genomic changes would represent a feasible approach in both prevention and alleviation of asthma.

Transcriptional coregulator RIP140: an essential regulator of physiology

2017 ◽  
Vol 58 (3) ◽  
pp. R147-R158 ◽  
Author(s):  
Jaya Nautiyal
Keyword(s):  
Nuclear Receptors ◽  
Physiological Processes ◽  
Reproductive Axis ◽  
Transcriptional Coregulators ◽  
Transcriptional Coregulator ◽  
Gene Regulatory ◽  
Drive Gene ◽  
Regulatory Decisions ◽  
Regulatory Sites

Transcriptional coregulators drive gene regulatory decisions in the transcriptional space. Although transcription factors including all nuclear receptors provide a docking platform for coregulators to bind, these proteins bring enzymatic capabilities to the gene regulatory sites. RIP140 is a transcriptional coregulator essential for several physiological processes, and aberrations in its function may lead to diseased states. Unlike several other coregulators that are known either for their coactivating or corepressing roles, in gene regulation, RIP140 is capable of acting both as a coactivator and a corepressor. The role of RIP140 in female reproductive axis and recent findings of its role in carcinogenesis and adipose biology have been summarised.

scholarly journals Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021

2021 ◽  
pp. 1-16
Author(s):  
Ashley M. Queener ◽  
Sergio E. Chiarella ◽  
Lyda Cuervo-Pardo ◽  
Mackenzie E. Coden ◽  
Hiam Abdala-Valencia ◽  
...  
Keyword(s):  
Allergic Disease ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Allergic Diseases ◽  
Atopic Disease ◽  
Airway Disease ◽  
Epithelial Barrier ◽  
Metabolic Dysfunction ◽  
New Research

Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.

scholarly journals Effects of climatic changes and urban air pollution on the rising trends of respiratory allergy and asthma

2019 ◽  
Vol 6 ◽  
Author(s):  
Gennaro D'Amato
Keyword(s):  
Climate Change ◽  
Air Pollution ◽  
Urban Air Pollution ◽  
Allergic Diseases ◽  
Respiratory Allergy ◽  
Bronchial Obstruction ◽  
Urban Air ◽  
European Respiratory Society ◽  
Increased Risk ◽  
Allergy And Asthma

Over the past two decades there has been increasing interest in studies regarding effects on human health of climate changes and urban air pollution. Climate change induced by anthropogenic warming of the earth’s atmosphere is a daunt- ing problem and there are several observations about the role of urbanization, with its high levels of vehicle emissions and other pollutants, and westernized lifestyle with respect to the rising frequency of respiratory allergic diseases observed in most industrialized countries. There is also evidence that asthmatic subjects are at increased risk of developing exacerbations of bronchial obstruction with exposure to gaseous (ozone, nitrogen diox- ide, sulfur dioxide) and particulate inhalable components of air pollution. A change in the genetic predisposition is an unlikely cause of the increasing frequency in allergic diseases because genetic changes in a population require several generations. Consequently, environmental factors such as climate change and indoor and outdoor air pollution may contribute to explain the increasing frequency of respiratory allergy and asthma. Since concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increas- ing frequency of allergic respiratory diseases and bronchial asthma. Scientific societies such as the European Academy of Allergy and Clinical Immunology, European Respiratory Society and the World Allergy Organization have set up committees and task forces to produce documents to focalize attention on this topic, calling for prevention measures.  

scholarly journals Membrane progesterone receptor induces meiosis in Xenopus oocytes through endocytosis into signaling endosomes and interaction with APPL1 and Akt2

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000901
Author(s):  
Nancy Nader ◽  
Maya Dib ◽  
Rawad Hodeify ◽  
Raphael Courjaret ◽  
Asha Elmi ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Xenopus Oocytes ◽  
Steroid Hormone ◽  
Adaptor Protein ◽  
G Protein Coupled Receptors ◽  
Adiponectin Receptors ◽  
Physiological Processes ◽  
Oocyte Meiosis ◽  
Membrane Progesterone Receptor ◽  
G Protein Coupled

The steroid hormone progesterone (P4) mediates many physiological processes through either nuclear receptors that modulate gene expression or membrane P4 receptors (mPRs) that mediate nongenomic signaling. mPR signaling remains poorly understood. Here we show that the topology of mPRβ is similar to adiponectin receptors and opposite to that of G-protein-coupled receptors (GPCRs). Using Xenopus oocyte meiosis as a well-established physiological readout of nongenomic P4 signaling, we demonstrate that mPRβ signaling requires the adaptor protein APPL1 and the kinase Akt2. We further show that P4 induces clathrin-dependent endocytosis of mPRβ into signaling endosome, where mPR interacts transiently with APPL1 and Akt2 to induce meiosis. Our findings outline the early steps involved in mPR signaling and expand the spectrum of mPR signaling through the multitude of pathways involving APPL1.

scholarly journals Hepatocyte-Specific Mutation Establishes Retinoid X Receptor α as a Heterodimeric Integrator of Multiple Physiological Processes in the Liver

2000 ◽  
Vol 20 (12) ◽  
pp. 4436-4444 ◽  
Author(s):  
Yu-Jui Yvonne Wan ◽  
Dahsing An ◽  
Yan Cai ◽  
Joyce J. Repa ◽  
Tim Hung-Po Chen ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Metabolic Pathways ◽  
Biochemical Parameters ◽  
Xenobiotic Metabolism ◽  
Retinoid X Receptor ◽  
Adult Liver ◽  
Retinoid X Receptors ◽  
Physiological Processes ◽  
Physiological Pathways ◽  
X Receptors

ABSTRACT A large number of physiological processes in the adult liver are regulated by nuclear receptors that require heterodimerization with retinoid X receptors (RXRs). In this study, we have usedcre-mediated recombination to disrupt the mouse RXRα gene specifically in hepatocytes. Although such mice are viable, molecular and biochemical parameters indicate that every one of the examined metabolic pathways in the liver (mediated by RXR heterodimerization with PPARα, CARβ, PXR, LXR, and FXR) is compromised in the absence of RXRα. These data demonstrate the presence of a complex circuitry in which RXRα is integrated into a number of diverse physiological pathways as a common regulatory component of cholesterol, fatty acid, bile acid, steroid, and xenobiotic metabolism and homeostasis.

scholarly journals Prioritizing Research Challenges and Funding for Allergy and Asthma and the Need for Translational Research — The European Strategic Forum on Allergic Diseases

2020 ◽  
Vol 16 (5) ◽  
pp. 281-295
Author(s):  
I. Agache ◽  
I. Annesi-Maesano ◽  
A. Bonertz ◽  
F. Branca ◽  
A. Cant ◽  
...  
Keyword(s):  
Clinical Immunology ◽  
Allergic Diseases ◽  
White Paper ◽  
Decision Makers ◽  
Special Focus ◽  
European Academy ◽  
Open Debate ◽  
Regulatory Bodies ◽  
Global Access ◽  
Allergy And Asthma

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision‐makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy’s output with the perspective offered by EAACI’s partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real‐world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients’ organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.

scholarly journals Abbott FreeStyle Libre Versus Dexcom G6: Detecting Disorders of Carbohydrate Metabolism in a Youthful Non-Diabetic Cohort Pilot Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A449-A450
Author(s):  
Florence Comite ◽  
Madeleine Heard ◽  
Aalin Izhar
Keyword(s):  
Glycemic Control ◽  
Carbohydrate Metabolism ◽  
Dietary Habits ◽  
Glucose Monitoring ◽  
Screening Tools ◽  
Metabolic Dysfunction ◽  
Freestyle Libre ◽  
Device Placement ◽  
The Mean ◽  
Fasting Hypoglycemia

Abstract Objective: Disorders of aging develop decades prior to emerging according to evidence in the literature. Early detection and actionable intervention have tremendous potential to prevent, delay, or even reverse the onset of disease. Individual carbohydrate metabolism data inform interventions to address the progression of underlying disorders of carbohydrate metabolism. Continuous glucose monitoring (CGM) devices can be harnessed to reveal suboptimal glycemic control. In the present study, two CGM devices were used to screen for carbohydrate metabolic dysfunction in 14 individuals without a history of type 2 diabetes. Methods: The two CGM devices used in this prospective cohort study were the Abbott FreeStyle Libre and Dexcom G6. Participants concurrently wore both devices for 30 days and were instructed to maintain their usual dietary habits for the duration of the study. The optimal glucose range was defined as 70–120 mg/dL. Glucose data were compiled and analyzed to screen for metabolic abnormalities. Results: 14 non-diabetic individuals were enrolled in this study. The cohort was 50% female with ages ranging from 22–46 years (mean=31.4 years). Out of the 14 participants, 100% showed glycemic abnormalities, including hypoglycemia and hyperglycemia. Across the cohort, the Abbott FreeStyle Libre and Dexcom G6 detected fasting and postprandial values between 40–237 mg/dL and 40–279 mg/dL, respectively. Both CGM devices detected glucose values <70 mg/dL and >120 mg/dL in all 14 participants. The amount of time each participant spent outside the optimal glucose range was variable. Using the Abbott FreeStyle Libre, the mean percent of time that participant glucose values measured <70 mg/dL and >120 mg/dL were 9.1% and 4.8%, respectively. Using the Dexcom G6, the mean percent of time that participant glucose values measured <70 mg/dL and >120 mg/dL were 1.4% and 19.2%, respectively. Discussion: Using CGM devices, we discovered that these 14 non-diabetic individuals exhibit suboptimal glycemic control, as demonstrated by blood glucose measurements falling outside 70–120 mg/dL for all participants. In addition, the Abbott FreeStyle Libre detected fasting hypoglycemia and reactive hypoglycemic responses more often than the Dexcom G6, while the Dexcom G6 detected more postprandial hyperglycemia than the Abbott FreeStyle Libre. It is plausible that the recommended device placement contributed to these differences, with the Abbott FreeStyle Libre on the tricep and Dexcom G6 on the abdomen. These findings support the utility of CGM devices as screening tools to detect and predict disorders of carbohydrate metabolism and warrant further investigation into the variation between CGM device measurements.

scholarly journals Post-Coronavirus Era: Should We Expect a Surge in Allergic Diseases and Asthma?

2021 ◽  
Vol 14 (1) ◽  
pp. 291-293
Author(s):  
Entezar Mehrabi Nasab ◽  
Seyyed Shamsadin Athari
Keyword(s):  
Allergic Diseases ◽  
The Body ◽  
Personal Hygiene ◽  
Infectious Agents ◽  
Th2 Response ◽  
Th2 Responses ◽  
Immune Imbalance ◽  
Th1 And Th2 Responses ◽  
Th1 Immune Responses ◽  
Allergy And Asthma

Some infectious agents by priming the immune system promote protection against allergy and asthma. During infections, Th1 immune responses are dominant, while in allergic conditions, Th2 responses are more pronounced. Th1 immune response protects the body against infections, and Th2 response leads to allergy and asthma. For maintaining health, the balance between Th1 and Th2 responses is necessary. The COVID-19 infection augments Th1 and also eosinophilic responses. On the other hand, the main protocols to control the COVID-19 pandemic require adherence to health standards, maintaining personal hygiene, frequent disinfecting of hands, using face masks, etc. In the post-COVID-19 era, this sterile condition may relinquish, and the Th1/Th2 immune imbalance may lead to an increase in the incidence of allergy and asthma. Therefore, focus on the COVID-19 infection should not deter us from foreseeing a surge in asthma and other post-coronavirus problems.

scholarly journals Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Ahmad Alatshan ◽  
Szilvia Benkő
Keyword(s):  
Immune Responses ◽  
Nuclear Receptors ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Inflammatory Conditions ◽  
Physiological Processes ◽  
Nlrp3 Inflammasome Activation ◽  
Wide Range ◽  
Multiple Levels ◽  
Approved Drugs

Nuclear receptors are important bridges between lipid signaling molecules and transcription responses. Beside their role in several developmental and physiological processes, many of these receptors have been shown to regulate and determine the fate of immune cells, and the outcome of immune responses under physiological and pathological conditions. While NLRP3 inflammasome is assumed as key regulator for innate and adaptive immune responses, and has been associated with various pathological events, the precise impact of the nuclear receptors on the function of inflammasome is hardly investigated. A wide variety of factors and conditions have been identified as modulators of NLRP3 inflammasome activation, and at the same time, many of the nuclear receptors are known to regulate, and interact with these factors, including cellular metabolism and various signaling pathways. Nuclear receptors are in the focus of many researches, as these receptors are easy to manipulate by lipid soluble molecules. Importantly, nuclear receptors mediate regulatory mechanisms at multiple levels: not only at transcription level, but also in the cytosol via non-genomic effects. Their importance is also reflected by the numerous approved drugs that have been developed in the past decade to specifically target nuclear receptors subtypes. Researches aiming to delineate mechanisms that regulate NLRP3 inflammasome activation draw a wide range of attention due to their unquestionable importance in infectious and sterile inflammatory conditions. In this review, we provide an overview of current reports and knowledge about NLRP3 inflammasome regulation from the perspective of nuclear receptors, in order to bring new insight to the potentially therapeutic aspect in targeting NLRP3 inflammasome and NLRP3 inflammasome-associated diseases.

scholarly journals Histamine and its Effects Mediated via H3 Receptor – Potential Clinical Applications of H3 Antagonists

2013 ◽  
Vol 13 (Supplement-1) ◽  
pp. 28-36
Author(s):  
E. Hanuskova ◽  
J. Plevkova
Keyword(s):  
First Generation ◽  
Inflammatory Diseases ◽  
Receptor Potential ◽  
Allergic Diseases ◽  
Histamine Receptor ◽  
Clinical Applications ◽  
Receptor Antagonists ◽  
Physiological Processes ◽  
Inflammatory Drugs

Abstract Histamine is one of the most important biogenic amines and it mediates numbers of physiological processes. It is also involved in majority of inflammatory diseases via its receptors H1, H2, H3 and H4. The role of histamine had been recognized as substantial in many allergic diseases including bronchial asthma, thus the histamine receptor antagonists (H1) are frequently used in the clinical practice as potent anti-allergic and anti-inflammatory drugs. However, first generation of antihistamines have also adverse effects, predominantly sedation, changes in appetite and many more, and they are still not fully effective in all patients. Attention is now focused mainly on H3 and H4 receptor antagonists and their potential clinical applications. This review focuses basically on the H3 receptor, its expression pattern and some effects which are mediated by H3, discussing its clinical relevance

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