Musculoskeletal complications associated with pathological iron toxicity and its molecular mechanisms

2021 ◽  
Vol 49 (2) ◽  
pp. 747-759
Author(s):  
Márcio Simão ◽  
M. Leonor Cancela
Keyword(s):  
Tissue Regeneration ◽  
Molecular Mechanisms ◽  
Negative Impact ◽  
Life Quality ◽  
Cell Communication ◽  
Iron Toxicity ◽  
Hereditary Diseases ◽  
Biological Functions ◽  
Intracellular Iron ◽  
Susceptibility Factors

Iron is fundamental for several biological functions, but when in excess can lead to the development of toxic events. Some tissues and cells are more susceptible than others, but systemic iron levels can be controlled by treating patients with iron-chelating molecules and phlebotomy. An early diagnostic can be decisive to limit the progression of musculoskeletal complications like osteoarthritis and osteoporosis because of iron toxicity. In iron-related osteoarthritis, aggravation can be associated to a few events that can contribute to joints articular cartilage exposure to high iron concentrations, which can promote articular degeneration with very little chance of tissue regeneration. In contrast, bone metabolism is much more dynamic than cartilage, but progressive iron accumulation and ageing can be decisive factors for bone health. The iron overload associated with hereditary diseases like hemochromatosis, hemophilias, thalassemias and other hereditary anaemias increase the negative impact of iron toxicity in joints and bone, as well as in life quality, even when iron levels can be controlled. The molecular mechanisms by which iron can compromise cartilage and bone have been illusive and only in the last 20 years studies have started to shed some light into the molecular mechanisms associated with iron toxicity. Ferroptosis and the regulation of intracellular iron levels is instrumental in the balance between detoxification and induced cell death. In addition, these complications are accompanied with multiple susceptibility factors that can aggravate iron toxicity and should be identified. Therefore, understanding tissues microenvironment and cell communication is fundamental to contextualize iron toxicity.

scholarly journals Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 307 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Muniyandi Jeyaraj ◽  
Muhammad Qasim ◽  
Jin-Hoi Kim
Keyword(s):  
Molecular Mechanisms ◽  
Cell Communication ◽  
Biological Functions ◽  
Research Attention ◽  
Diagnosis And Prognosis ◽  
Imaging Probes ◽  
Health And Disease ◽  
The Stability ◽  
And Function ◽  
Invasive Diagnostics

Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.

Urtica dioica in the Management of Benign Prostate Hyperplasia (BPH)

2020 ◽  
Vol 10 (5) ◽  
pp. 535-542
Author(s):  
Mohaddese Mahboubi
Keyword(s):  
Molecular Mechanisms ◽  
Life Quality ◽  
Urtica Dioica ◽  
Urinary Flow ◽  
Prostate Hyperplasia ◽  
Long Time ◽  
Tract Infections ◽  
Preclinical And Clinical Studies ◽  
Benign Prostate ◽  
Maximum Urinary Flow

Background:: Benign Prostatic hyperplasia (BPH) is known as a disease prevalent in men after the age of 50 years old. Ninety percent of men with the age of 80 years and over have BPH. BPH is associated with functional problems like dysuria, nocturia, polyuria, urinary incontinence and recurrent urinary tract infections. Urtica dioica or nettle is a popular medicinal plant for management of BPH in men. Objective:: This article evaluates the efficacy and safety of nettle and its related possible mechanisms in the management of BPH. Methods:: For the preparation of this manuscript, all the information was gathered from accessible and inaccessible resources (Web, Books, Thesis, etc.). Results:: The results of preclinical and clinical studies confirmed the efficacy of nettle roots extracts (methanol, ethanol, and petroleum ether) in the improvement of BPH in term of IPSS score, and patient's life quality. An increase in mean and maximum urinary flow rates and a reduction in prostate volume and residual urine level were observed after treatment with nettle extract. Nettle roots should be used for 6-12 months as its use is possible for a long time without any serious adverse effects. Conclusion:: Designing the clinical trials to compare the efficacy of different extracts from roots or leaves and investigation of molecular mechanisms of action could be the approaches for future.

scholarly journals Insights into how environment shapes post-mortem RNA transcription in mouse brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raphael Severino Bonadio ◽  
Larissa Barbosa Nunes ◽  
Patricia Natália S. Moretti ◽  
Juliana Forte Mazzeu ◽  
Stefano Cagnin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Rna Degradation ◽  
The Body ◽  
Biological Processes ◽  
Post Mortem ◽  
Gene Expression Alterations ◽  
Upregulated Genes

AbstractMost biological features that occur on the body after death were already deciphered by traditional medicine. However, the molecular mechanisms triggered in the cellular microenvironment are not fully comprehended yet. Previous studies reported gene expression alterations in the post-mortem condition, but little is known about how the environment could influence RNA degradation and transcriptional regulation. In this work, we analysed the transcriptome of mouse brain after death under three concealment simulations (air exposed, buried, and submerged). Our analyses identified 2,103 genes differentially expressed in all tested groups 48 h after death. Moreover, we identified 111 commonly upregulated and 497 commonly downregulated genes in mice from the concealment simulations. The gene functions shared by the individuals from the tested environments were associated with RNA homeostasis, inflammation, developmental processes, cell communication, cell proliferation, and lipid metabolism. Regarding the altered biological processes, we identified that the macroautophagy process was enriched in the upregulated genes and lipid metabolism was enriched in the downregulated genes. On the other hand, we also described a list of biomarkers associated with the submerged and buried groups, indicating that these environments can influence the post-mortem RNA abundance in its particular way.

scholarly journals Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hamed Nosrati ◽  
Reza Aramideh Khouy ◽  
Ali Nosrati ◽  
Mohammad Khodaei ◽  
Mehdi Banitalebi-Dehkordi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Tissue Regeneration ◽  
Molecular Mechanisms ◽  
Healing Process ◽  
The Body ◽  
Key Factors ◽  
Potential Applications ◽  
Nanocomposite Scaffolds

AbstractSkin is the body’s first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.

scholarly journals Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers

2021 ◽  
Vol 22 (16) ◽  
pp. 8461
Author(s):  
Emanuela Chiarella ◽  
Annamaria Aloisio ◽  
Stefania Scicchitano ◽  
Heather Mandy Bond ◽  
Maria Mesuraca
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Transitional Cell ◽  
Biological Functions ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Novel Mirna ◽  
Mirna Expression Profiling ◽  
Mirna Deregulation

Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

scholarly journals Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Orit Malka ◽  
Dorin Kalson ◽  
Karin Yaniv ◽  
Reut Shafir ◽  
Manikandan Rajendran ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gut Microbiome ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Human Microbiome ◽  
Cell Communication ◽  
Probiotic Yeast ◽  
Gut Pathogen ◽  
Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

scholarly journals Enhancement of iron toxicity in L929 cells by d-glucose: accelerated(re-)reduction

2002 ◽  
Vol 368 (2) ◽  
pp. 517-526 ◽  
Author(s):  
Ilka LEHNEN-BEYEL ◽  
Herbert de GROOT ◽  
Ursula RAUEN
Keyword(s):  
Ethyl Ester ◽  
Iron Reduction ◽  
Cell Damage ◽  
Reduction Rate ◽  
Fold Increase ◽  
Iron Complex ◽  
Iron Toxicity ◽  
Intracellular Iron ◽  
Iron Valence ◽  
Iron Pool

It has recently been shown that an increase in the cellular chelatable iron pool is sufficient to cause cell damage. To further characterize this kind of injury, we artificially enhanced the chelatable iron pool in L929 mouse fibroblasts using the highly membrane-permeable complex Fe(III)/8-hydroxyquinoline. This iron complex induced a significant oxygen-dependent loss of viability during an incubation period of 5h. Surprisingly, the addition of d-glucose strongly enhanced this toxicity whereas no such effect was exerted by l-glucose and 2-deoxyglucose. The assumption that this increase in toxicity might be due to an enhanced availability of reducing equivalents formed during the metabolism of d-glucose was supported by NAD(P)H measurements which showed a 1.5—2-fold increase in the cellular NAD(P)H content upon addition of d-glucose. To assess the influence of this enhanced cellular reducing capacity on iron valence we established a new method to measure the reduction rate of iron based on the fluorescent iron(II) indicator PhenGreen SK. We could show that the rate of intracellular iron reduction was more than doubled in the presence of d-glucose. A similar acceleration was achieved by adding the reducing agents ascorbate and glutathione (the latter as membrane-permeable ethyl ester). Glutathione ethyl ester, as well as the thiol reagent N-acetylcysteine, also caused a toxicity increase comparable with d-glucose. These results suggest an enhancement of iron toxicity by d-glucose via an accelerated (re-)reduction of iron with NAD(P)H serving as central electron provider and ascorbate, glutathione or possibly NAD(P)H itself as final reducing agent.

Automatic diagnosis of primary headaches by machine learning methods

Open Medicine ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Bartosz Krawczyk ◽  
Dragan Simić ◽  
Svetlana Simić ◽  
Michał Woźniak
Keyword(s):  
Machine Learning ◽  
Negative Impact ◽  
Life Quality ◽  
Primary Headache ◽  
Machine Learning Techniques ◽  
Future Research ◽  
Common Disease ◽  
Primary Headaches ◽  
Starting Point ◽  
Headache Diagnosis

AbstractPrimary headaches are common disease of the modern society and it has high negative impact on the productivity and the life quality of the affected person. Unfortunately, the precise diagnosis of the headache type is hard and usually imprecise, thus methods of headache diagnosis are still the focus of intense research. The paper introduces the problem of the primary headache diagnosis and presents its current taxonomy. The considered problem is simplified into the three class classification task which is solved using advanced machine learning techniques. Experiments, carried out on the large dataset collected by authors, confirmed that computer decision support systems can achieve high recognition accuracy and therefore be a useful tool in an everyday physician practice. This is the starting point for the future research on automation of the primary headache diagnosis.

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