scholarly journals Minireview: Estrogen Receptor-β: Mechanistic Insights from Recent Studies

2010 ◽  
Vol 24 (9) ◽  
pp. 1703-1714 ◽  
Author(s):  
Bonnie J. Deroo ◽  
Adrian V. Buensuceso
Keyword(s):  
Estrogen Receptor ◽  
Immune System ◽  
Molecular Mechanisms ◽  
The Body ◽  
Estrogen Receptor Β ◽  
Biological Functions ◽  
Significant Progress ◽  
Estrogen Action ◽  
Organ Systems

Abstract The discovery of estrogen receptor-β (ERβ) in 1996 stimulated great interest in the physiological roles and molecular mechanisms of ERβ action. We now know that ERβ plays a major role in mediating estrogen action in several tissues and organ systems, including the ovary, cardiovascular system, brain, and the immune system, and that ERβ and ERα generally play distinct physiological roles in the body. Although significant progress has been made toward understanding the molecular mechanisms of ERβ action, particularly in vitro, there remains a large gap in our understanding of the mechanisms by which ERβ elicits its biological functions in a true physiological context.

scholarly journals Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food

2021 ◽  
Vol 18 (7) ◽  
pp. 3332
Author(s):  
Olga V. Naidenko ◽  
David Q. Andrews ◽  
Alexis M. Temkin ◽  
Tasha Stoiber ◽  
Uloma Igara Uche ◽  
...  
Keyword(s):  
Immune System ◽  
High Throughput ◽  
Environmental Protection Agency ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Specific Activity ◽  
Laboratory Animals ◽  
In Vitro Assays ◽  
Toxicological Studies

The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

scholarly journals Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Susanne Schüler-Toprak ◽  
Julia Häring ◽  
Elisabeth C. Inwald ◽  
Christoph Moehle ◽  
Olaf Ortmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Estrogen Receptor Β

scholarly journals Systemic Lupus Erythematosus Disease: An Overview of the Clinical Approach to Pathogenesis, Diagnosis, and Treatment

2021 ◽  
Vol 4 (2) ◽  
pp. 91-98
Author(s):  
Saurabh Nimesh ◽  
Md. Iftekhar Ahmad ◽  
Shikhka Dhama ◽  
Pradeep Kumar ◽  
Muhammad Akram ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Chronic Disease ◽  
Lupus Erythematosus ◽  
The Body ◽  
Clinical Approach ◽  
Systemic Lupus Erythematosus Disease ◽  
Systemic Lupus ◽  
Organ Systems ◽  
Novel Approaches

The systemic lupus erythematosus (SLE), commonly known as Lupus, is a rare and complex multisystem autoimmune disease where one’s immune system is overactive, and the body attacks its organ systems. SLE is a historically old disease described already in antiquity; it is an example of a chronic disease with physical, psychological, financial, and social implications for individuals diagnosed. It has inspired medical and basic biological scientists that focus on molecular biology, basic immunology, immunopathology, clinical science, genetics, and epidemiology. The syndrome is real in its existence-although hidden behind obstacles, cumbersome for patients and clinicians, and rebellious for scientists. There is currently no cure for SLE. The goal of treatment is to ease symptoms. This article will review information on the general approach to SLE therapy, focusing on currently approved therapies and novel approaches that might be used in the future.

scholarly journals Inflammatory complications of CGRP monoclonal antibodies: a case series

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jason C. Ray ◽  
Penelope Allen ◽  
Ann Bacsi ◽  
Julian J. Bosco ◽  
Luke Chen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Case Series ◽  
Preventive Treatment ◽  
The Body ◽  
Temporal Association ◽  
Organ Systems ◽  
Calcitonin Gene ◽  
Close Proximity ◽  
The Central Nervous System

Abstract Background Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. Cases We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. Conclusion This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

Physical plasma and leukocytes – immune or reactive?

2018 ◽  
Vol 400 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Sander Bekeschus ◽  
Christian Seebauer ◽  
Kristian Wende ◽  
Anke Schmidt
Keyword(s):  
Wound Healing ◽  
Immune System ◽  
Plasma Treatment ◽  
Immune Cells ◽  
The Body ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Physical Plasma

AbstractLeukocytes are professionals in recognizing and removing pathogenic or unwanted material. They are present in virtually all tissues, and highly motile to enter or leave specific sites throughout the body. Less than a decade ago, physical plasmas entered the field of medicine to deliver their delicate mix of reactive species and other physical agents for mainly dermatological or oncological therapy. Plasma treatment thus affects leukocytes via direct or indirect means: immune cells are either present in tissues during treatment, or infiltrate or exfiltrate plasma-treated areas. The immune system is crucial for human health and resolution of many types of diseases. It is therefore vital to study the response of leukocytes after plasma treatmentin vitroandin vivo. This review gathers together the major themes in the plasma treatment of innate and adaptive immune cells, and puts these into the context of wound healing and oncology, the two major topics in plasma medicine.

scholarly journals The Rise of Retinal Organoids for Vision Research

2020 ◽  
Vol 21 (22) ◽  
pp. 8484 ◽  
Author(s):  
Kritika Sharma ◽  
Tim U. Krohne ◽  
Volker Busskamp
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Retinal Cell ◽  
Retinal Diseases ◽  
Organ Systems ◽  
Cell Sources ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases lead to irreversible blindness. Decades of research into the cellular and molecular mechanisms of retinal diseases, using either animal models or human cell-derived 2D systems, facilitated the development of several therapeutic interventions. Recently, human stem cell-derived 3D retinal organoids have been developed. These self-organizing 3D organ systems have shown to recapitulate the in vivo human retinogenesis resulting in morphological and functionally similar retinal cell types in vitro. In less than a decade, retinal organoids have assisted in modeling several retinal diseases that were rather difficult to mimic in rodent models. Retinal organoids are also considered as a photoreceptor source for cell transplantation therapies to counteract blindness. Here, we highlight the development and field’s improvements of retinal organoids and discuss their application aspects as human disease models, pharmaceutical testbeds, and cell sources for transplantations.

scholarly journals Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm

2020 ◽  
Vol 9 (1) ◽  
pp. 264 ◽  
Author(s):  
Laura Governini ◽  
Bianca Semplici ◽  
Valentina Pavone ◽  
Laura Crifasi ◽  
Camilla Marrocco ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Receptor Activation ◽  
Taste Buds ◽  
The Body ◽  
Semen Parameters ◽  
Human Testis ◽  
Taste Receptors ◽  
Organ Systems

Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.

scholarly journals Evidence for a link between IGF-I and cancer

2004 ◽  
pp. S17-S22 ◽  
Author(s):  
PJ Jenkins ◽  
SA Bustin
Keyword(s):  
Cancer Risk ◽  
Molecular Mechanisms ◽  
Normal Function ◽  
The Body ◽  
Signalling Pathways ◽  
Biological Functions ◽  
Related Factors ◽  
Wide Range ◽  
Igf I ◽  
Inappropriate Expression

Cancer risk is determined by a combination of environmental factors and genetic predisposition. Recent evidence suggests that dietary and related factors such as physical activity and body size may influence cancer risk through their effects on the serum concentration of IGF-I and its binding proteins. The growth hormone (GH)/IGF-I axis is involved in both human development as well as the maintenance of normal function and homeostasis in most cells of the body. In addition to their classical role as endocrine hormones, its members regulate a wide range of biological functions such as cell proliferation, differentiation and apoptosis through paracrine and autocrine mechanisms. During cancer development this complex network regulating tissue homeostasis breaks down, with inappropriate expression of the GH/IGF-I axis making an important contribution. The increased understanding of the molecular mechanisms and signalling pathways regulated by the GH/IGF-I axis has started to provide significant insights into the aetiology, prevention and therapy for a number of common cancers.

scholarly journals Estrogen Receptor β, But Not Estrogen Receptor α, Is Present in the Vascular Endothelium of the Human and Nonhuman Primate Endometrium1

2001 ◽  
Vol 86 (3) ◽  
pp. 1370-1378 ◽  
Author(s):  
Hilary O. D. Critchley ◽  
Robert M. Brenner ◽  
Teresa A. Henderson ◽  
Karin Williams ◽  
Nihar R. Nayak ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Vascular Endothelium ◽  
Estrogen Receptor Β ◽  
Glandular Cell ◽  
Receptor Subtypes ◽  
Cell Nuclei ◽  
Perivascular Cells ◽  
Estrogen Action ◽  
Secretory Phase ◽  
Western Blots

Estrogen action is dependent upon the presence of specific ligand-activated receptors in target tissues. The aim of the present experiments was to compare the spatial and temporal pattern of expression of estrogen receptor β (ERβ) with that of ERα in full thickness endometrial samples (from the superficial to the basal zone) obtained from both women and rhesus macaques. Immunohistochemical localization with specific antibodies revealed that ERα and ERβ were both expressed in nuclei of the glands and stroma. Consistent with previous studies, expression of ERα declined in the glands and stroma of the functionalis during the secretory phase. The luminal epithelium also displayed positive immunoreactivity for ERβ. Expression of ERβ declined in glandular cell nuclei, but not stroma, within the functionalis during the late secretory phase. Levels of expression of ERα and ERβ in all cellular compartments remained unchanged in the basalis. Both receptor subtypes were detected on Western blots using proteins extracted from uterine samples obtained throughout the menstrual cycle. There was a striking contrast between the pattern of expression of ERα and ERβ in the vascular endothelium and the perivascular cells surrounding endometrial blood vessels; only ERβ was present in the endothelial cell population, although both forms of ER were expressed in perivascular cells. We conclude that estrogen action(s) within the vascular endothelium in the endometrium may be mediated via direct binding to the ERβ isoform and that these cells could therefore be a target for agonists or antagonists that selectively target the β form of the ER.

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