scholarly journals Exploring the Biological Activity and Mechanism of Xenoestrogens and Phytoestrogens in Cancers: Emerging Methods and Concepts

2021 ◽  
Vol 22 (16) ◽  
pp. 8798
Author(s):  
Xiaoqiang Wang ◽  
Desiree Ha ◽  
Ryohei Yoshitake ◽  
Yin S. Chan ◽  
David Sadava ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Extensive Literature ◽  
Industrial Chemicals ◽  
Therapeutic Approaches ◽  
Human Cancers ◽  
Systemic Level ◽  
Critical Timing ◽  
New Applications ◽  
Female Lifespan

Xenoestrogens and phytoestrogens are referred to as “foreign estrogens” that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.

Epigenetics

2019 ◽  
pp. 56-70
Author(s):  
Edward Hookway ◽  
Nicholas Athanasou ◽  
Udo Oppermann
Keyword(s):  
Gene Expression ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tumour Suppressor Genes ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Control Of Gene Expression ◽  
Non Coding Rnas ◽  
Epigenetic Processes

Epigenetics is a term that refers to a collection of diverse mechanisms that are important in both the control of gene expression and the transmission of this information during cell division. Epigenetic processes are deranged in many cancers, leading to a combination of inappropriate silencing of tumour suppressor genes and overexpression of oncogenes. In this chapter, the molecular mechanisms that underpin the major epigenetic processes of DNA methylation, histone modification, and non-coding RNAs will be described in both their normal physiological roles and in the context of cancer. The challenge of understanding the complexity of the interactions between different epigenetic mechanisms and the limitations of our current knowledge will be highlighted. Therapeutic approaches towards targeting deranged epigenetic processes will also be described, such as the use of small molecule inhibitors of histone deacetylases.

scholarly journals Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Gierlikowska ◽  
Albert Stachura ◽  
Wojciech Gierlikowski ◽  
Urszula Demkow
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Innate Immune ◽  
Therapeutic Approaches ◽  
Effector Functions ◽  
Pharmacological Modulation ◽  
Synthetic Drugs ◽  
Extracellular Traps

Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.

scholarly journals Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge

2021 ◽  
Vol 22 (3) ◽  
pp. 1425
Author(s):  
Hiroteru Kamimura ◽  
Takeki Sato ◽  
Kazuki Natsui ◽  
Takamasa Kobayashi ◽  
Tomoaki Yoshida ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Molecular Mechanisms ◽  
Hospital Admissions ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Negative Prognostic Factor ◽  
Increased Risk ◽  
Catabolic State ◽  
Relationship Of

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength that occurs with aging or in association with various diseases. The condition is prevalent worldwide and occurs more frequently in patients with chronic diseases owing to the intrinsic relationship of muscles with glucose, lipid, and protein metabolism. Liver cirrhosis is characterized by the progression of necro-inflammatory liver diseases, which leads to fibrosis, portal hypertension, and a catabolic state, which causes loss of muscle tissue. Sarcopenia is of significant concern in the state of liver cirrhosis because sarcopenia has been associated with higher mortality, increased hospital admissions, worse post-liver transplant outcomes, decreased quality of life, and increased risk for other complications associated with cirrhosis. Therefore, sarcopenia is also an important feature of liver cirrhosis, representing a negative prognostic factor and influencing mortality. An increased understanding of sarcopenia could lead to the development of novel therapeutic approaches that could help improve the cognitive impairment of cirrhotic patients; therefore, we present a review of the mechanisms and diagnosis of sarcopenia in liver disease and existing therapeutic approaches.

scholarly journals Induced Neurons From Germ Cells in Caenorhabditis elegans

2021 ◽  
Vol 15 ◽  
Author(s):  
Iris Marchal ◽  
Baris Tursun
Keyword(s):  
Caenorhabditis Elegans ◽  
Regenerative Medicine ◽  
Cell Fate ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
C Elegans ◽  
Cell Fate Conversion ◽  
Induced Neurons

Cell fate conversion by the forced overexpression of transcription factors (TFs) is a process known as reprogramming. It leads to de-differentiation or trans-differentiation of mature cells, which could then be used for regenerative medicine applications to replenish patients suffering from, e.g., neurodegenerative diseases, with healthy neurons. However, TF-induced reprogramming is often restricted due to cell fate safeguarding mechanisms, which require a better understanding to increase reprogramming efficiency and achieve higher fidelity. The germline of the nematode Caenorhabditis elegans has been a powerful model to investigate the impediments of generating neurons from germ cells by reprogramming. A number of conserved factors have been identified that act as a barrier for TF-induced direct reprogramming of germ cells to neurons. In this review, we will first summarize our current knowledge regarding cell fate safeguarding mechanisms in the germline. Then, we will focus on the molecular mechanisms underlying neuronal induction from germ cells upon TF-mediated reprogramming. We will shortly discuss the specific characteristics that might make germ cells especially fit to change cellular fate and become neurons. For future perspectives, we will look at the potential of C. elegans research in advancing our knowledge of the mechanisms that regulate cellular identity, and what implications this has for therapeutic approaches such as regenerative medicine.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Alcohol Consumption and Risk of Uterine Fibroids

2020 ◽  
Vol 20 (4) ◽  
pp. 247-258 ◽  
Author(s):  
Hajra Takala ◽  
Qiwei Yang ◽  
Ahmed M. Abd El Razek ◽  
Mohamed Ali ◽  
Ayman Al-Hendy
Keyword(s):  
Alcohol Consumption ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Legal Status ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
Future Directions ◽  
Working Adults ◽  
The Us ◽  
Alcohol Related Problems

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

2021 ◽  
Vol 22 (3) ◽  
pp. 1201
Author(s):  
Hsuan Peng ◽  
Kazuhiro Shindo ◽  
Renée R. Donahue ◽  
Ahmed Abdel-Latif
Keyword(s):  
Stem Cell ◽  
Immune Responses ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Current Knowledge ◽  
Cell Delivery ◽  
Cardiac Cell Therapy ◽  
Stem Cell Treatment

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

scholarly journals The Effect of Gut Bacteria on the Physiology of Red Palm Weevil, Rhynchophorus ferrugineus Olivier and Their Potential for the Control of This Pest

Insects ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 594
Author(s):  
Qian-Xia Liu ◽  
Zhi-Ping Su ◽  
Hui-Hui Liu ◽  
Sheng-Ping Lu ◽  
Bing Ma ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Management Strategies ◽  
Gut Bacteria ◽  
Economic Losses ◽  
Rhynchophorus Ferrugineus ◽  
Intestinal Immunity ◽  
Red Palm Weevil ◽  
Nutrient Metabolism ◽  
Palm Weevil

Red Palm Weevil (RPW), Rhynchophorus ferrugineus Olivier, is a notorious pest, which infests palm trees and has caused great economic losses worldwide. At present, insecticide applications are still the main way to control this pest. However, pesticide resistance has been detected in the field populations of RPW. Thus, future management strategies based on the novel association biological control need be developed. Recent studies have shown that the intestinal tract of RPW is often colonized by multiple microbial species as mammals and model insects, and gut bacteria have been found to promote the growth, development and immune activity of RPW larvae by modulating nutrient metabolism. Furthermore, two peptidoglycan recognition proteins (PGRPs), PGRP-LB and PGRP-S1, can act as the negative regulators to modulate the intestinal immunity to maintain the homeostasis of gut bacteria in RPW larvae. Here, we summarized the current knowledge on the gut bacterial composition of RPW and their impact on the physiological traits of RPW larvae. In contrast with metazoans, it is much easier to make genetic engineered microbes to produce some active molecules against pests. From this perspective, because of the profound effects of gut bacteria on host phenotypes, it is promising to dissect the molecular mechanisms behind their effect on host physiology and facilitate the development of microbial resource-based management methods for pest control.

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