Mechanisms for Radioprotection by Melatonin; Can it be Used as a Radiation Countermeasure?

2019 ◽  
Vol 12 (1) ◽  
pp. 2-11 ◽  
Author(s):  
Peyman Amini ◽  
Hanifeh Mirtavoos-Mahyari ◽  
Elahe Motevaseli ◽  
Dheyauldeen Shabeeb ◽  
Ahmed Eleojo Musa ◽  
...  
Keyword(s):  
Animal Studies ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Experimental Studies ◽  
Antioxidant Property ◽  
Interesting Property ◽  
Ir Studies ◽  
Radiation Induced ◽  
Radiosensitive Organs ◽  
Clinical Radiotherapy

Background:Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) have been proved. However, in the recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products.Discussion:Moreover, melatonin affects several signaling pathways, such as inflammatory responses, antioxidant defense, DNA repair response enzymes, pro-oxidant enzymes etc. Animal studies have confirmed that melatonin is able to alleviate radiation-induced cell death via inhibiting pro-apoptosis and upregulation of anti-apoptosis genes. These properties are very interesting for clinical radiotherapy applications, as well as mitigation of radiation injury in a possible radiation disaster. An interesting property of melatonin is mitochondrial ROS targeting that has been proposed as a strategy for mitigating effects in radiosensitive organs, such as bone marrow, gastrointestinal system and lungs. However, there is a need to prove the mitigatory effects of melatonin in experimental studies.Conclusion:In this review, we aim to clarify the molecular mechanisms of radioprotective effects of melatonin, as well as possible applications as a radiation countermeasure in accidental exposure or nuclear/radiological disasters.

scholarly journals An endothelial link between the benefits of physical exercise in dementia

2017 ◽  
Vol 37 (8) ◽  
pp. 2649-2664 ◽  
Author(s):  
Lianne J Trigiani ◽  
Edith Hamel
Keyword(s):  
Physical Exercise ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Vascular Cognitive Impairment ◽  
Endothelial Cell Function ◽  
Positive Effects ◽  
Disease Modifying ◽  
Disease Modifying Treatment

The current absence of a disease-modifying treatment for Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) highlights the necessity for investigating the benefits of non-pharmacological approaches such as physical exercise (PE). Although evidence exists to support an association between regular PE and higher scores on cognitive function tests, and a slower rate of cognitive decline, there is no clear consensus on the underlying molecular mechanisms of the advantages of PE. This review seeks to summarize the positive effects of PE in human and animal studies while highlighting the vascular link between these benefits. Lifestyle factors such as cardiovascular diseases, metabolic syndrome, and sleep apnea will be addressed in relation to the risk they pose in developing AD and VCID, as will molecular factors known to have an impact on either the initiation or the progression of AD and/or VCID. This will include amyloid-beta clearance, oxidative stress, inflammatory responses, neurogenesis, angiogenesis, glucose metabolism, and white matter integrity. Particularly, this review will address how engaging in PE can counter factors that contribute to disease pathogenesis, and how these alterations are linked to endothelial cell function.

scholarly journals Specialized pro-resolving mediator network: an update on production and actions

2020 ◽  
Vol 64 (3) ◽  
pp. 443-462 ◽  
Author(s):  
Nan Chiang ◽  
Charles N. Serhan
Keyword(s):  
Tissue Regeneration ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Docosapentaenoic Acid ◽  
Health Concern ◽  
Public Health Concern ◽  
Protective Actions ◽  
Chemical Mediators ◽  
The Ideal

Abstract Today, persistent and uncontrolled inflammation is appreciated to play a pivotal role in many diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic syndrome and many other diseases of public health concern (e.g. Coronavirus Disease 2019 (COVID-19) and periodontal disease). The ideal response to initial challenge in humans is a self-limited inflammatory response leading to complete resolution. The resolution phase is now widely recognized as a biosynthetically active process, governed by a superfamily of endogenous chemical mediators that stimulate resolution of inflammatory responses, namely specialized proresolving mediators (SPMs). Because resolution is the natural ideal response, the SPMs have gained attention. SPMs are mediators that include ω-6 arachidonic acid-derived lipoxins, ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-derived resolvins, protectins and maresins, cysteinyl-SPMs, as well as n-3 docosapentaenoic acid (DPA)-derived SPMs. These novel immunoresolvents, their biosynthetic pathways and receptors have proven to promote resolution of inflammation, clearance of microbes, reduce pain and promote tissue regeneration via specific cellular and molecular mechanisms. As of 17 August, 2020, PubMed.gov reported >1170 publications for resolvins, confirming their potent protective actions from many laboratories worldwide. Since this field is rapidly expanding, we provide a short update of advances within 2–3 years from human and preclinical animal studies, together with the structural–functional elucidation of SPMs and identification of novel SPM receptors. These new discoveries indicate that SPMs, their pathways and receptors could provide a basis for new approaches for treating inflammation-associated diseases and for stimulating tissue regeneration via resolution pharmacology and precision nutrition.

Radiation cataract

2012 ◽  
Vol 41 (3-4) ◽  
pp. 80-97 ◽  
Author(s):  
N.J. Kleiman
Keyword(s):  
Animal Studies ◽  
Molecular Mechanisms ◽  
Atomic Bomb ◽  
Atomic Bomb Survivors ◽  
Lens Opacification ◽  
Exposure Limit ◽  
Radiation Induced ◽  
New Guidelines ◽  
Ocular Exposure ◽  
Radiation Cataract

Until very recently, ocular exposure guidelines were based on the assumption that radiation cataract is a deterministic event requiring threshold doses generally greater than 2 Gy. This view was, in part, based on older studies which generally had short follow-up periods, failed to take into account increasing latency as dose decreased, had relatively few subjects with doses below a few Gy, and were not designed to detect early lens changes. Newer findings, including those in populations exposed to much lower radiation doses and in subjects as diverse as astronauts, medical workers, atomic bomb survivors, accidentally exposed individuals, and those undergoing diagnostic or radiotherapeutic procedures, strongly suggest dose-related lens opacification at significantly lower doses. These observations resulted in a recent re-evaluation of current lens occupational exposure guidelines, and a proposed lowering of the presumptive radiation cataract threshold to 0.5 Gy/year and the occupational lens exposure limit to 20 mSv/year, regardless of whether received as an acute, protracted, or chronic exposure. Experimental animal studies support these conclusions and suggest a role for genotoxicity in the development of radiation cataract. Recent findings of a low or even zero threshold for radiation-induced lens opacification are likely to influence current research efforts and directions concerning the cellular and molecular mechanisms underlying this pathology. Furthermore, new guidelines are likely to have significant implications for occupational and/or accidental exposure, and the need for occupational eye protection (e.g. in fields such as interventional medicine).

Diosmin attenuates radiation-induced hepatic fibrosis by boosting PPAR-γ expression and hampering miR-17-5p-activated canonical Wnt–β-catenin signaling

2017 ◽  
Vol 95 (3) ◽  
pp. 400-414 ◽  
Author(s):  
Hesham Farouk Hasan ◽  
Mohamed Khairy Abdel-Rafei ◽  
Shereen Mohamed Galal
Keyword(s):  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Stellate Cell ◽  
Antioxidant Defenses ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Radiation Induced ◽  
Canonical Wnt

Background: Liver fibrosis is one of the major complications from upper right quadrant radiotherapy. MicroRNA-17-5p (miR-17-5p) is hypothesized to act as a regulator of hepatic stellate cell (HSCs) activation by activation of the canonical Wnt–β-catenin pathway. Diosmin (Dios), a citrus bioflavonoid, is known to possess potent antioxidant, anti-inflammatory, and anti-apoptotic properties. Purpose: To explore the molecular mechanisms that underlie radiation-induced liver fibrosis, and to evaluate the possible influence of Dios on the miR-17-5p–Wnt–β-catenin signaling axis during fibrogenesis provoked by irradiation (IRR) in rats. Also, the effect of Dios on hepatic peroxisome proliferator activated receptor-γ (PPAR-γ) expression as a regulator for HSC activation was considered. Methods: We administered 100 mg·(kg body mass)–1·day–1(per oral) of Dios were administered to IRR-exposed rats (overall dose of 12 Gy on 6 fractions of 2 Gy each) for 6 successive weeks. Results: Data analysis revealed that Dios treatment mitigated oxidative stress, enhanced antioxidant defenses, alleviated hepatic inflammatory responses, abrogated pro-fibrogenic cytokines, and stimulated PPAR-γ expression. Dios treatment repressed the miR-17-5p activated Wnt–β-catenin signaling induced by IRR. Moreover, Dios treatment restored the normal hepatic architecture and reversed pathological alterations induced by IRR. Conclusion: We hypothesize that the stimulation of PPAR-γ expression and interference with miR-17-5p activated Wnt–β-catenin signaling mediates the antifibrotic properties of Dios.

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.

Molecular Investigations of the Newly Synthesized Azomethines as Antioxidants: Theoretical and Experimental Studies

2019 ◽  
Vol 19 (6) ◽  
pp. 419-433 ◽  
Author(s):  
Siyamak Shahab ◽  
Masoome Sheikhi ◽  
Liudmila Filippovich ◽  
Evgenij Dikusar ◽  
Anhelina Pazniak ◽  
...  
Keyword(s):  
Density Functional ◽  
Energy Gap ◽  
Experimental Studies ◽  
Antioxidant Property ◽  
Nbo Analysis ◽  
Antioxidant Potential ◽  
Functional Theory ◽  
Homo And Lumo ◽  
Intramolecular Hydrogen ◽  
Activity Mechanism

: In this study, the antioxidant property of new synthesized azomethins has been investigated as theoretical and experimental. Methods and Results: Density functional theory (DFT) was employed to investigate the Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electron Affinities (EA), HOMO and LUMO energies, Hardness (η), Softness (S), Electronegativity (µ), Electrophilic Index (ω), Electron Donating Power (ω-), Electron Accepting Power (ω+) and Energy Gap (Eg) in order to deduce scavenging action of the two new synthesized azomethines (FD-1 and FD-2). Spin density calculations and NBO analysis were also carried out to understand the antioxidant activity mechanism. Comparison of BDE of FD-1 and FD-2 indicate the weal antioxidant potential of these structures. Conclusion: FD-1 and FD-2 have very high antioxidant potential due to the planarity and formation of intramolecular hydrogen bonds.

Resolution-Associated Molecular Patterns (RAMPs) as Endogenous Regulators of Glia Functions in Neuroinflammatory Disease

2020 ◽  
Vol 19 (7) ◽  
pp. 483-494
Author(s):  
Tyler J. Wenzel ◽  
Evan Kwong ◽  
Ekta Bajwa ◽  
Andis Klegeris
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Bioactive Lipids ◽  
Prothymosin Α ◽  
Neuroinflammatory Disease ◽  
Cellular Debris ◽  
Αb Crystallin ◽  
Endogenous Regulators ◽  
The Central Nervous System ◽  
Molecular Patterns

: Glial cells, including microglia and astrocytes, facilitate the survival and health of all cells within the Central Nervous System (CNS) by secreting a range of growth factors and contributing to tissue and synaptic remodeling. Microglia and astrocytes can also secrete cytotoxins in response to specific stimuli, such as exogenous Pathogen-Associated Molecular Patterns (PAMPs), or endogenous Damage-Associated Molecular Patterns (DAMPs). Excessive cytotoxic secretions can induce the death of neurons and contribute to the progression of neurodegenerative disorders, such as Alzheimer’s disease (AD). The transition between various activation states of glia, which include beneficial and detrimental modes, is regulated by endogenous molecules that include DAMPs, cytokines, neurotransmitters, and bioactive lipids, as well as a diverse group of mediators sometimes collectively referred to as Resolution-Associated Molecular Patterns (RAMPs). RAMPs are released by damaged or dying CNS cells into the extracellular space where they can induce signals in autocrine and paracrine fashions by interacting with glial cell receptors. While the complete range of their effects on glia has not been described yet, it is believed that their overall function is to inhibit adverse CNS inflammatory responses, facilitate tissue remodeling and cellular debris removal. This article summarizes the available evidence implicating the following RAMPs in CNS physiological processes and neurodegenerative diseases: cardiolipin (CL), prothymosin α (ProTα), binding immunoglobulin protein (BiP), heat shock protein (HSP) 10, HSP 27, and αB-crystallin. Studies on the molecular mechanisms engaged by RAMPs could identify novel glial targets for development of therapeutic agents that effectively slow down neuroinflammatory disorders including AD.

scholarly journals Immunomodulatory Effects of Radiotherapy

2020 ◽  
Vol 21 (21) ◽  
pp. 8151
Author(s):  
Sharda Kumari ◽  
Shibani Mukherjee ◽  
Debapriya Sinha ◽  
Salim Abdisalaam ◽  
Sunil Krishnan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Carbon Particle ◽  
Dna Lesions ◽  
X Rays ◽  
Adaptive Immune ◽  
High Let Radiation ◽  
Different Types ◽  
High Let ◽  
Radiation Induced ◽  
Tumor Death

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

scholarly journals Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marjan Talebi ◽  
Mohsen Talebi ◽  
Tahereh Farkhondeh ◽  
Jesus Simal-Gandara ◽  
Dalia M. Kopustinskiene ◽  
...  
Keyword(s):  
Blood Cells ◽  
Molecular Mechanisms ◽  
Web Of Science ◽  
Experimental Studies ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Current Review ◽  
Mesh Terms ◽  
Online Databases ◽  
Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

scholarly journals Deficiency of Lipin2 Results in Enhanced NF-κB Signaling and Osteoclast Formation in RAW-D Murine Macrophages

2021 ◽  
Vol 22 (6) ◽  
pp. 2893
Author(s):  
Asami Watahiki ◽  
Seira Hoshikawa ◽  
Mitsuki Chiba ◽  
Hiroshi Egusa ◽  
Satoshi Fukumoto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Osteoclast Formation ◽  
Fine Tuning ◽  
Nuclear Accumulation ◽  
Innate Immune Responses ◽  
Osteoclastic Resorption ◽  
Bone Disorder ◽  
Proinflammatory Responses ◽  
Potential Therapeutic Intervention

Lipin2 is a phosphatidate phosphatase that plays critical roles in fat homeostasis. Alterations in Lpin2, which encodes lipin2, cause the autoinflammatory bone disorder Majeed syndrome. Lipin2 limits lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. However, little is known about the precise molecular mechanisms underlying its anti-inflammatory function. In this study, we attempted to elucidate the molecular link between the loss of lipin2 function and autoinflammatory bone disorder. Using a Lpin2 knockout murine macrophage cell line, we showed that lipin2 deficiency enhances innate immune responses to LPS stimulation through excessive activation of the NF-κB signaling pathway, partly because of TAK1 signaling upregulation. Lipin2 depletion also enhanced RANKL-mediated osteoclastogenesis and osteoclastic resorption activity accompanied by NFATc1 dephosphorylation and increased nuclear accumulation. These results suggest that lipin2 suppresses the development of autoinflammatory bone disorder by fine-tuning proinflammatory responses and osteoclastogenesis in macrophages. Therefore, this study provides insights into the molecular pathogenesis of monogenic autoinflammatory bone disorders and presents a potential therapeutic intervention.

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