scholarly journals Hypothyroidism Affects Uterine Function via the Modulation of Prostaglandin Signaling

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2636
Author(s):  
Ilona Kowalczyk-Zieba ◽  
Joanna Staszkiewicz-Chodor ◽  
Dorota Boruszewska ◽  
Krzysztof Lukaszuk ◽  
Joanna Jaworska ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Sexual Development ◽  
Thyroid Disorders ◽  
Uterine Tissue ◽  
Uterine Receptivity ◽  
Female Reproduction ◽  
Subsequent Reduction ◽  
Implantation Window ◽  
Pathological Conditions ◽  
Almost All

Thyroid hormones control the functions of almost all body systems. Reproductive dysfunctions, such as abnormal sexual development, infertility, or irregularities in the reproductive cycle, might be associated with thyroid disorders. Uterine receptivity is the period when the uterus is receptive to the implantation of an embryo. During the receptivity period (implantation window), a newly formed blastocyst is incorporated into the uterine epithelium. Prostaglandins are well-known primary mediators of pathological conditions such as inflammation and cancer but are also essential for the physiology of female reproduction. The aim of this study was to evaluate the possible relationship between hypothyroidism and changes in the prostaglandin signaling pathways in the uterus and in the process of uterine receptivity in a rat model. The results show that hypothyroidism impaired uterine receptivity by decreasing the level of E2 as well as decreasing the expression of the uterine-receptivity factors homeobox A10 and osteopontin. Moreover, hypothyroidism caused changes in the expression of elements of the prostaglandin E2, F2α, and I2 signaling pathways and changed the levels of those prostaglandins in the uterine tissue. The results suggest that the mechanisms by which hypothyroidism affects female reproductive abnormalities might involve the prostaglandin signaling pathway, resulting in a subsequent reduction in uterine receptivity.

A Brief Review on Dual Target of PARP1 and STAT3 for Cancer Therapy: A Novel Perception

2020 ◽  
Vol 16 (2) ◽  
pp. 115-134
Author(s):  
Kaviarasan Lakshmanan ◽  
Gowramma Byran ◽  
Manal Mohammed
Keyword(s):  
Signaling Pathways ◽  
Single Molecule ◽  
Treatment Options ◽  
Poor Response ◽  
Cytotoxic Agents ◽  
Acquired Drug Resistance ◽  
Single Target ◽  
New Strategy ◽  
Cancer Multiple ◽  
Almost All

Background: Cancer is a disease characterized by the uncontrolled growth and spread of abnormal cells. Around the world, over 10 million cancer cases occur annually. Half of all men and one-third of all women will develop some form of cancer during their lifetime. It is one of the most feared diseases, primarily because half of those diagnosed with cancer die from it. There are several treatments available for cancer. Almost all traditional cytotoxic agents suffer from severe toxicities and other undesirable side effects. Objective: In recent years, the development of targeted medicines has made significant achievements. Unfortunately, though these agents can block key regulators of signaling pathways in cancer, multiple compensatory pathways always attenuate pharmacological effect of single-target drugs. In addition, poor response rates and acquired drug resistance also represent a significant barrier to widespread use of targeted medicines. More recently, a number of combinatorial therapies have expanded treatment options, which can directly block several key signaling pathways and create a synergistic effect. Conclusion: Therefore, in order to overcome these barriers, the present investigation aims to develop a new strategy for designing a single molecule with inhibition of two receptors (PARP1 and STAT3) simultaneously and producing enhanced anti-cancer activity with less and/or null toxicity.

scholarly journals Heparan Sulfate Proteoglycan Sulfation Regulates Uterine Differentiation and Signaling During Embryo Implantation

Endocrinology ◽  
2018 ◽  
Vol 159 (6) ◽  
pp. 2459-2472 ◽  
Author(s):  
Yan Yin ◽  
Adam Wang ◽  
Li Feng ◽  
Yu Wang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Heparan Sulfate ◽  
Signaling Pathways ◽  
Reproductive Tract ◽  
Ovarian Function ◽  
Embryo Implantation ◽  
Uterine Epithelium ◽  
Female Reproductive Tract ◽  
Uterine Receptivity ◽  
Mouse Uterus

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.

scholarly journals Circadian Deregulation as Possible New Player in Pollution-Induced Tissue Damage

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 116
Author(s):  
Mascia Benedusi ◽  
Elena Frigato ◽  
Cristiano Bertolucci ◽  
Giuseppe Valacchi
Keyword(s):  
Cardiovascular Diseases ◽  
Air Pollutants ◽  
Environmental Stressors ◽  
Common Mechanism ◽  
Particulate Matters ◽  
Circadian Misalignment ◽  
Pathological Conditions ◽  
Peripheral Clocks ◽  
Living Organisms ◽  
Almost All

Circadian rhythms are 24-h oscillations driven by a hypothalamic master oscillator that entrains peripheral clocks in almost all cells, tissues and organs. Circadian misalignment, triggered by industrialization and modern lifestyles, has been linked to several pathological conditions, with possible impairment of the quality or even the very existence of life. Living organisms are continuously exposed to air pollutants, and among them, ozone or particulate matters (PMs) are considered to be among the most toxic to human health. In particular, exposure to environmental stressors may result not only in pulmonary and cardiovascular diseases, but, as it has been demonstrated in the last two decades, the skin can also be affected by pollution. In this context, we hypothesize that chronodistruption can exacerbate cell vulnerability to exogenous damaging agents, and we suggest a possible common mechanism of action in deregulation of the homeostasis of the pulmonary, cardiovascular and cutaneous tissues and in its involvement in the development of pathological conditions.

scholarly journals Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1947
Author(s):  
Alice-Anaïs Varlet ◽  
Emmanuèle Helfer ◽  
Catherine Badens
Keyword(s):  
Mechanical Properties ◽  
Signaling Pathways ◽  
Metabolic Disorders ◽  
Lamin A ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Almost All ◽  
Type V

Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the LMNA gene, with at least 20 mutations that are considered pathogenic. LMNA encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis.

scholarly journals MicroRNAs in Cardiac Hypertrophy

2019 ◽  
Vol 20 (19) ◽  
pp. 4714 ◽  
Author(s):  
Nadine Wehbe ◽  
Suzanne Nasser ◽  
Gianfranco Pintus ◽  
Adnan Badran ◽  
Ali Eid ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Cardiac Hypertrophy ◽  
Signaling Pathways ◽  
Cardiac Remodeling ◽  
Pathological Conditions ◽  
Recent Advances ◽  
Short Period

Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy.

scholarly journals Exosome microRNAs in Metabolic Syndrome as Tools for the Early Monitoring of Diabetes and Possible Therapeutic Options

2021 ◽  
Vol 14 (12) ◽  
pp. 1257
Author(s):  
Erika Cione ◽  
Roberto Cannataro ◽  
Luca Gallelli ◽  
Giovambattista De Sarro ◽  
Maria Cristina Caroleo
Keyword(s):  
Essential Role ◽  
Cell Injury ◽  
Cell Types ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Pathological Conditions ◽  
Novel Approach ◽  
Almost All

Exosomes are nano-sized extracellular vesicles produced and released by almost all cell types. They play an essential role in cell–cell communications by delivering cellular bioactive compounds such as functional proteins, metabolites, and nucleic acids, including microRNA, to recipient cells. Thus, they are involved in various physio-pathological conditions. Exosome-miRNAs are associated with numerous diseases, including type 2 diabetes, a complex multifactorial metabolic disorder linked to obesity. In addition, exosome-miRNAs are emerging as essential regulators in the progression of diabetes, principally for pancreatic β-cell injury and insulin resistance. Here, we have clustered the recent findings concerning exosome-miRNAs associated with β-cell dysfunction to provide a novel approach for the early diagnosis and therapy of diabetes.

scholarly journals The long Non-coding RNA Orchestrator of Cancer Axis of Evil Insights into the Multiple Modes of Action of the H19 Gene

2021 ◽  
Vol 01 (1) ◽  
pp. 9-15
Author(s):  
Imad Matouk
Keyword(s):  
Mechanisms Of Action ◽  
Biological Processes ◽  
Rna Molecules ◽  
Pathological Conditions ◽  
Non Coding Rna ◽  
H19 Gene ◽  
Almost All ◽  
Long Non Coding Rna ◽  
Shed Light

Increasing evidence has indicated that the non-coding RNA molecules play central roles in almost all biological processes and many pathological conditions including carcinogenesis. This review focuses on the pathological tumorigenic role of the first discovered long non-coding RNA gene called H19 and its pivotal contribution to the cancer axis of evil. H19 RNA utilizes a variety of mechanisms to perform its pathological function. Some key unanswered questions are presented by the end. Understanding the H19 RNA mechanisms of action will shed light into the class of long non-coding RNA which contains thousands of members mostly with unknown function and will help in delineating the pathological role played by at least some of them.

scholarly journals Targeting MicroRNAs in Cancer Gene Therapy

2017 ◽  
Author(s):  
Weidan Ji ◽  
Bin Sun ◽  
Changqing Su
Keyword(s):  
Tumor Suppressor Genes ◽  
Cancer Gene Therapy ◽  
Clinical Applications ◽  
Biological Processes ◽  
Cancer Gene ◽  
Pathological Conditions ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Almost All ◽  
Multiple Molecules

MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer.

scholarly journals Extracellular Vesicles: Novel Roles in Neurological Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Qian Jin ◽  
Peipei Wu ◽  
Xinru Zhou ◽  
Hui Qian ◽  
Wenrong Xu
Keyword(s):  
Central Nervous System ◽  
Extracellular Vesicles ◽  
Neurological Disorders ◽  
Unique Feature ◽  
Cns Development ◽  
Diagnostic Biomarkers ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Therapeutic Tools ◽  
Almost All

Exosomes are small extracellular vesicles (EVs) secreted by almost all cells, which have been recognized as a novel platform for intercellular communication in the central nervous system (CNS). Exosomes are capable of transferring proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, contributing to CNS development and maintenance of homeostasis. Evidence shows that exosomes originating from CNS cells act as suppressors or promoters in the initiation and progression of neurological disorders. Moreover, these exosomes have been shown to transfer molecules associated with diseases through the blood-brain barrier (BBB) and thus can be detected in blood. This unique feature enables exosomes to act as potential diagnostic biomarkers for neurological disorders. In addition, a substantial number of researches have indicated that exosomes derived from mesenchymal stem cells (MSCs) have repair effects on neurological disorders. Herein, we briefly introduce the roles of exosomes under physiological and pathological conditions. In particular, novel roles of exosomes as potential diagnostic biomarkers and therapeutic tools for neurological disorders are highlighted.

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