Adrita Banerjee, A. Chattopadhyay, D. Bandyopadhyay
Biological membrane, the most fluidic structure of a cell or an organelle, refrains the cells to progress toward apoptosis by sustaining their optimum environment. This bilayer-membrane equips all machineries required for cellular communication, limits the entry of foreign bodies, selectively transports molecules or ions depending on the need of the system but, it also acts as a first line defense against environmental insults. Due to the presence of a vast number of poly unsaturated fatty acids (PUFA), the biological membrane is highly prone to oxidative stress and as a consequence, acceleration in lipid peroxidation by free radicals, becomes a threat to cellular viability. Alterations in the biophysical state of bilayer caused by oxidative stress frequently occur in the in vivo as well as in vitro conditions. It has been well documented that the molecule, melatonin, exhibits profound coherence in neutralizing oxidative stress and thus, to normalize fluidity status of biological membranes. Aging associated decline in melatonin level with subsequent ascended lipid peroxidation and membrane viscosity found in almost all organisms further suggest the importance of melatonin in this context. Since disruption of membrane structure or even some modifications will cause a spectrum of diseases, keeping membrane intactness would be an adequate strategy to prevent these diseases. Considering the high permeability, safe and potent antioxidant capacity of melatonin, this molecule can be a superlative choice to alleviate membrane bilayer rigidity and its related ailments.
{"title":"Melatonin and biological membrane bilayers: a never ending amity","authors":"Adrita Banerjee, A. Chattopadhyay, D. Bandyopadhyay","doi":"10.32794/mr11250093","DOIUrl":"https://doi.org/10.32794/mr11250093","url":null,"abstract":"Biological membrane, the most fluidic structure of a cell or an organelle, refrains the cells to progress toward apoptosis by sustaining their optimum environment. This bilayer-membrane equips all machineries required for cellular communication, limits the entry of foreign bodies, selectively transports molecules or ions depending on the need of the system but, it also acts as a first line defense against environmental insults. Due to the presence of a vast number of poly unsaturated fatty acids (PUFA), the biological membrane is highly prone to oxidative stress and as a consequence, acceleration in lipid peroxidation by free radicals, becomes a threat to cellular viability. Alterations in the biophysical state of bilayer caused by oxidative stress frequently occur in the in vivo as well as in vitro conditions. It has been well documented that the molecule, melatonin, exhibits profound coherence in neutralizing oxidative stress and thus, to normalize fluidity status of biological membranes. Aging associated decline in melatonin level with subsequent ascended lipid peroxidation and membrane viscosity found in almost all organisms further suggest the importance of melatonin in this context. Since disruption of membrane structure or even some modifications will cause a spectrum of diseases, keeping membrane intactness would be an adequate strategy to prevent these diseases. Considering the high permeability, safe and potent antioxidant capacity of melatonin, this molecule can be a superlative choice to alleviate membrane bilayer rigidity and its related ailments.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"235 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82862290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. López-Muñoz, F. J. Povedano-Montero, A. Romero, J. Egea, C. Álamo
Melatonin is a molecule that has attracted a great deal of attention from the scientific community in the last 50 years. The aim of this study is to analyze the scientific production on related to melatonin using bibliometric tools. We performed a search in Web of Science, involving documents published between 1958 and 2019. We used bibliometric indicators to explore documents production, dispersion, distribution, time of duplication and annual growth, as Price's law of scientific literature growth, Lotka's law, the transient index and the Bradford model. We also calculated the participation index of the different countries and institutions. Finally, through bibliometric mapping, we explored the co-occurrence networks for the most frequently used terms in melatonin research. A total of 20,768 documents were retrieved. Scientific production was better adjusted to linear growth (r = 0.9535) than exponential (r = 0.9313). The duplication time of the documents obtained was 14.2 years. The transience index was 62%, which indicates that most of the scientific production is due to very few authors. The signature rate per document was 1.95. Thirty-four journals made up the Bradford core, highlighting Journal of Pineal Research. USA and University of Texas present the highest production. Map network visualization shows the generated term map detailing on clusters of closely related terms. The growth of the scientific literature on melatonin was linear, with a very high rate of transience, which indicates the presence of numerous authors who sporadically publish on this topic. No evidence of a saturation point was observed. In the last 10 years, there has been a relevant increase in documents on melatonin.
褪黑素是近50年来备受科学界关注的一种分子。本研究的目的是利用文献计量学工具分析与褪黑素相关的科学成果。我们在Web of Science中进行了搜索，涉及1958年至2019年之间发表的文件。我们采用文献计量指标Price’s定律、Lotka定律、瞬态指数和Bradford模型来探讨文献产量、分散、分布、重复时间和年增长率。我们还计算了不同国家和机构的参与指数。最后，通过文献计量图，我们探索了褪黑素研究中最常用术语的共现网络。共检索了20 768份文件。科研产出更适合线性增长(r = 0.9535)而非指数增长(r = 0.9313)。所得文件的复制时间为14.2年。瞬时指数为62%，这表明大部分科学成果是由极少数作者完成的。每份文件的签名率为1.95。34种期刊组成了布拉德福德核心，突出的是《松果体研究杂志》。美国和德克萨斯大学的产量最高。地图网络可视化显示生成的术语地图，详细说明密切相关的术语集群。关于褪黑激素的科学文献的增长是线性的，具有非常高的瞬变率，这表明有许多作者零星地发表了这一主题。没有观察到饱和点的证据。在过去的10年里，关于褪黑素的相关文献有所增加。
{"title":"The crossroads of melatonin: Bibliometric analysis and mapping of global scientific research","authors":"F. López-Muñoz, F. J. Povedano-Montero, A. Romero, J. Egea, C. Álamo","doi":"10.32794/mr1250088","DOIUrl":"https://doi.org/10.32794/mr1250088","url":null,"abstract":"Melatonin is a molecule that has attracted a great deal of attention from the scientific community in the last 50 years. The aim of this study is to analyze the scientific production on related to melatonin using bibliometric tools. We performed a search in Web of Science, involving documents published between 1958 and 2019. We used bibliometric indicators to explore documents production, dispersion, distribution, time of duplication and annual growth, as Price's law of scientific literature growth, Lotka's law, the transient index and the Bradford model. We also calculated the participation index of the different countries and institutions. Finally, through bibliometric mapping, we explored the co-occurrence networks for the most frequently used terms in melatonin research. A total of 20,768 documents were retrieved. Scientific production was better adjusted to linear growth (r = 0.9535) than exponential (r = 0.9313). The duplication time of the documents obtained was 14.2 years. The transience index was 62%, which indicates that most of the scientific production is due to very few authors. The signature rate per document was 1.95. Thirty-four journals made up the Bradford core, highlighting Journal of Pineal Research. USA and University of Texas present the highest production. Map network visualization shows the generated term map detailing on clusters of closely related terms. The growth of the scientific literature on melatonin was linear, with a very high rate of transience, which indicates the presence of numerous authors who sporadically publish on this topic. No evidence of a saturation point was observed. In the last 10 years, there has been a relevant increase in documents on melatonin.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78351165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thodur Madapusi Balaji, Saranya Varadarajan, D. Bandyopadhyay, Raghunathan Jagannathan, S. Patil, Thirumal A. Raj
Oral submucous fibrosisis (OSMF) is a clinical condition of the oral cavity which is caused predominantly by areca nut consumption. This fibrotic condition affects almost all parts of the oral cavity and can cause significant reduction in mouth opening, thereby, resulting in functional impairment. The other potential risk of OSMF is its malignant transformation into oral squamous cell carcinoma, which occurs in a significant number of afflicted patients. Extensive researches have been conducted to understand the pathogenesis of OSMF for identification of tangible therapeutic modalities. To date, there is no effective therapeutic modality for this disorder. It is well known that melatonin has a potent anti-fibrotic, anti-oxidant, and pro-angiogenic effects. The therapeutic potential of melatonin on OSM cannot be ignored. In this article we have explored the potential mechanisms of melatonin as an adjuvant in the prevention and treatment of OSMF.
{"title":"A potential protection of melatonin on pathogenesis of oral sub-mucous fibrosis (OSMF) : a current update","authors":"Thodur Madapusi Balaji, Saranya Varadarajan, D. Bandyopadhyay, Raghunathan Jagannathan, S. Patil, Thirumal A. Raj","doi":"10.32794/mr11250083","DOIUrl":"https://doi.org/10.32794/mr11250083","url":null,"abstract":"Oral submucous fibrosisis (OSMF) is a clinical condition of the oral cavity which is caused predominantly by areca nut consumption. This fibrotic condition affects almost all parts of the oral cavity and can cause significant reduction in mouth opening, thereby, resulting in functional impairment. The other potential risk of OSMF is its malignant transformation into oral squamous cell carcinoma, which occurs in a significant number of afflicted patients. Extensive researches have been conducted to understand the pathogenesis of OSMF for identification of tangible therapeutic modalities. To date, there is no effective therapeutic modality for this disorder. It is well known that melatonin has a potent anti-fibrotic, anti-oxidant, and pro-angiogenic effects. The therapeutic potential of melatonin on OSM cannot be ignored. In this article we have explored the potential mechanisms of melatonin as an adjuvant in the prevention and treatment of OSMF.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"302 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75815719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Shukla, V. Bajwa, José A. Freixas-Coutin, P. Saxena
Salinity is a major environmental stress in agriculture with significantly detrimental effects on crop productivity. The development of strategies to enhance salinity stress tolerance in plants is essential to ensure crop production in saline environments. Melatonin (Mel) and serotonin (Ser) accumulate in response to environmental stresses and are presumed to play protective roles and improve growth of tissues during recovery. In this study, the effects of Mel and Ser were investigated in Arabidopsis under NaCl stress. Exogenous Mel (10 µM) and Ser (10 µM) treatment significantly increased fresh weight, lateral root number, and shoot height in A. thaliana seedlings exposed to NaCl stress (25 mM and 50 mM) compared to the non-treated control seedlings. In order to understand the role of these indoleamines in alleviating salt stress, we investigated the effects of Mel and Ser treatments on the expression of salt stress responsive genes including, transcription factors involved in abscisic acid (ABA) signaling pathway, ABA-INSENSITIVE 3 (ABI3)and ABA-INSENSITIVE 5 (ABI5); ABA responsive gene, RESPONSIVE TO DESSICATION 29B (RD29B), ABA-independent gene, RESPONSIVE TO DESSICATION 29A (RD29A) and Arabidopsis trithorax-like gene (ATX1) which function in stress responses via ABA-dependent and ABA-independent manner. Other genes included, ROS-signaling transcription factor ZAT10 and ZAT12, and the genes encoding ion transporters crucial for maintaining ion homeostasis, HIGH AFFINITY K+ TRANSPORTER 5 (HAK5) and SALT OVERLY SENSITIVE 1 (SOS1). Mel (10 µM) pre-treatment for 24 hrs followed by 50 mM salt treatment up-regulated ABI3, RD29B, ZAT12 and HAK5. The Ser (10 µM) pre-treatment significantly up-regulated ZAT12.These results indicate that indoleamine pre-treatment improved plant growth under salt stress with Mel facilitating salt tolerance via upregulation of ABA responsive genes, mediation of antioxidant defense systems to counteract the salt-induced ROS overproduction as well as controlling ion homeostasis. Although Ser displayed no significant effects on ABA signaling, it was found to increase the expression of antioxidant defense gene, ZAT12. This study demonstrates the importance of indoleamine pathway in mediation of salt stress response and provides the first indication of the involvement of Ser in salt stress tolerance.
{"title":"Salt stress in Arabidopsis thaliana seedlings: Role of indoleamines in stress alleviation","authors":"M. Shukla, V. Bajwa, José A. Freixas-Coutin, P. Saxena","doi":"10.32794/mr11250082","DOIUrl":"https://doi.org/10.32794/mr11250082","url":null,"abstract":"Salinity is a major environmental stress in agriculture with significantly detrimental effects on crop productivity. The development of strategies to enhance salinity stress tolerance in plants is essential to ensure crop production in saline environments. Melatonin (Mel) and serotonin (Ser) accumulate in response to environmental stresses and are presumed to play protective roles and improve growth of tissues during recovery. In this study, the effects of Mel and Ser were investigated in Arabidopsis under NaCl stress. Exogenous Mel (10 µM) and Ser (10 µM) treatment significantly increased fresh weight, lateral root number, and shoot height in A. thaliana seedlings exposed to NaCl stress (25 mM and 50 mM) compared to the non-treated control seedlings. In order to understand the role of these indoleamines in alleviating salt stress, we investigated the effects of Mel and Ser treatments on the expression of salt stress responsive genes including, transcription factors involved in abscisic acid (ABA) signaling pathway, ABA-INSENSITIVE 3 (ABI3)and ABA-INSENSITIVE 5 (ABI5); ABA responsive gene, RESPONSIVE TO DESSICATION 29B (RD29B), ABA-independent gene, RESPONSIVE TO DESSICATION 29A (RD29A) and Arabidopsis trithorax-like gene (ATX1) which function in stress responses via ABA-dependent and ABA-independent manner. Other genes included, ROS-signaling transcription factor ZAT10 and ZAT12, and the genes encoding ion transporters crucial for maintaining ion homeostasis, HIGH AFFINITY K+ TRANSPORTER 5 (HAK5) and SALT OVERLY SENSITIVE 1 (SOS1). Mel (10 µM) pre-treatment for 24 hrs followed by 50 mM salt treatment up-regulated ABI3, RD29B, ZAT12 and HAK5. The Ser (10 µM) pre-treatment significantly up-regulated ZAT12.These results indicate that indoleamine pre-treatment improved plant growth under salt stress with Mel facilitating salt tolerance via upregulation of ABA responsive genes, mediation of antioxidant defense systems to counteract the salt-induced ROS overproduction as well as controlling ion homeostasis. Although Ser displayed no significant effects on ABA signaling, it was found to increase the expression of antioxidant defense gene, ZAT12. This study demonstrates the importance of indoleamine pathway in mediation of salt stress response and provides the first indication of the involvement of Ser in salt stress tolerance. ","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79723744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Swaimanti Sarkar, A. Chattopadhyay, D. Bandyopadhyay
The onset and progression of baneful chronic diseases are often accompanied by a torrent of uncontrolled inflammatory reactions. Although inflammation is a natural response to detect, eliminate, and counterpoise the harmful insults to physiological integrity, a persistent inflammation causes tissue damage or more serious disorders, for example, the atherosclerosis and myocardial infarction. Inflammation often occurs in the cardiovascular system, but are also caused by other disorders including metabolic syndrome, autoimmune diseases, AIDS, and cancer that can affect the cardiac health. To effectively treat heart diseases a potent remedy is necessary which not only suppresses the inflammation but also prevents inflammation-associated cardio-pathogenesis. The ubiquitous antioxidant molecule melatonin has both anti-inflammatory and cardioprotective activities. Melatonin executes its anti-inflammatory activity by its antioxidant function or by targeting multiple intracellular signalling cascades such as modulating cytokine profile, blocking inflammasome activation and apoptosis. Lipid dysregulation and endothelial dysfunction that play a crucial role in the pathogenesis of atherosclerosis, insulin resistance, and diabetes are prevented by melatonin. Attenuation of mitochondrial and ER stress by melatonin is also pertinent to its cardioprotective action. Additionally, melatonin by its immuno-stimulatory activity can suppress inflammaging and immuno-senescence in HIV patients and thereby averts chronic inflammation-induced cardiovascular abnormality in these subjects. Modulation of cytokine profile and decrease in MMP-9 secretion by melatonin is beneficial in autoimmune conditions. In addition to its anti-tumour potency, melatonin can reduce chemotherapy-induced cardio-toxicity in cancer patients. This review, therefore, provides a concise summary of the currently available information appertaining to the roles of melatonin in mitigation of chronic inflammation and its effect on cardiovascular integrity.
{"title":"Multiple strategies of melatonin protecting against cardiovascular injury related to inflammation: A comprehensive overview","authors":"Swaimanti Sarkar, A. Chattopadhyay, D. Bandyopadhyay","doi":"10.32794/mr11250080","DOIUrl":"https://doi.org/10.32794/mr11250080","url":null,"abstract":"The onset and progression of baneful chronic diseases are often accompanied by a torrent of uncontrolled inflammatory reactions. Although inflammation is a natural response to detect, eliminate, and counterpoise the harmful insults to physiological integrity, a persistent inflammation causes tissue damage or more serious disorders, for example, the atherosclerosis and myocardial infarction. Inflammation often occurs in the cardiovascular system, but are also caused by other disorders including metabolic syndrome, autoimmune diseases, AIDS, and cancer that can affect the cardiac health. To effectively treat heart diseases a potent remedy is necessary which not only suppresses the inflammation but also prevents inflammation-associated cardio-pathogenesis. The ubiquitous antioxidant molecule melatonin has both anti-inflammatory and cardioprotective activities. Melatonin executes its anti-inflammatory activity by its antioxidant function or by targeting multiple intracellular signalling cascades such as modulating cytokine profile, blocking inflammasome activation and apoptosis. Lipid dysregulation and endothelial dysfunction that play a crucial role in the pathogenesis of atherosclerosis, insulin resistance, and diabetes are prevented by melatonin. Attenuation of mitochondrial and ER stress by melatonin is also pertinent to its cardioprotective action. Additionally, melatonin by its immuno-stimulatory activity can suppress inflammaging and immuno-senescence in HIV patients and thereby averts chronic inflammation-induced cardiovascular abnormality in these subjects. Modulation of cytokine profile and decrease in MMP-9 secretion by melatonin is beneficial in autoimmune conditions. In addition to its anti-tumour potency, melatonin can reduce chemotherapy-induced cardio-toxicity in cancer patients. This review, therefore, provides a concise summary of the currently available information appertaining to the roles of melatonin in mitigation of chronic inflammation and its effect on cardiovascular integrity.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82669542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prevalence of bile duct and gastrointestinal (GI) tract associated diseases is increasing globally. Commonly, the bile duct epithelial cell (cholangiocytes) malfunction and its uncontrolled proliferation often cause liver fibrosis and tumorigenesis, particularly the cholangiocarcinoma. Specifically, GI tract is constantly under diverse endogenous and exogenous stressors which interrupt GI physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD) and gastritis. On the other hand, melatonin exhibits important functions in both cholangiocyte and GI tract. The abundance of melatonin generated in the GI tract and its widely distributed receptors facilitate its protective effects in GI tissues. In the most of the cases, the disease progression in GI tract, particularly in bile duct, is associated with endogenous melatonergic system suppression. Therefore, to increase the endogenous melatonin production appears a suitable strategy to retard the disease development in these tissues. Melatonin administration or, exposure to prolonged darkness not only reverse the detrimental biochemical alterations, but also inhibit cholangiocyte proliferation as well as ulceration in the GI tract. Thus, use of melatonin as a natural therapeutic agent is beneficial and exhibits advantages over other contemporary drugs in prevention and treatment of bile duct and gastrointestinal tract associated diseases.
{"title":"Functional interplay of melatonin in the bile duct and gastrointestinal tract to mitigate disease development: An overview","authors":"P. Pal, A. Chattopadhyay, D. Bandyopadhyay","doi":"10.32794/mr11250086","DOIUrl":"https://doi.org/10.32794/mr11250086","url":null,"abstract":"Prevalence of bile duct and gastrointestinal (GI) tract associated diseases is increasing globally. Commonly, the bile duct epithelial cell (cholangiocytes) malfunction and its uncontrolled proliferation often cause liver fibrosis and tumorigenesis, particularly the cholangiocarcinoma. Specifically, GI tract is constantly under diverse endogenous and exogenous stressors which interrupt GI physiological functions and promote inflammation, tissue damage, ulceration, gastrointestinal bleeding, gastroesophageal reflux disease (GERD), irritable bowel disease (IBD) and gastritis. On the other hand, melatonin exhibits important functions in both cholangiocyte and GI tract. The abundance of melatonin generated in the GI tract and its widely distributed receptors facilitate its protective effects in GI tissues. In the most of the cases, the disease progression in GI tract, particularly in bile duct, is associated with endogenous melatonergic system suppression. Therefore, to increase the endogenous melatonin production appears a suitable strategy to retard the disease development in these tissues. Melatonin administration or, exposure to prolonged darkness not only reverse the detrimental biochemical alterations, but also inhibit cholangiocyte proliferation as well as ulceration in the GI tract. Thus, use of melatonin as a natural therapeutic agent is beneficial and exhibits advantages over other contemporary drugs in prevention and treatment of bile duct and gastrointestinal tract associated diseases.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85273760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High mortality rates in severe progression of COVID-19 are predominantly caused by pulmonary failure due to high-grade airway inflammation. As investigations on the efficacy of melatonin in this disease are still in their beginning, it may be worth-while to recall the body of evidence on protective effects in other respiratory dysfunctions, which have been studied pre-clinically and clinically. In various diseases and corresponding animal models, melatonin has been shown to be protective, mainly because of its anti-inflammatory and antioxidant properties. This was documented in pathologies as different as allergic airway inflammation, toxicologically or radiation-induced acute lung injury, respiratory disorders such as COPD, obstructive sleep apnea, neonatal respiratory distress syndrome, bronchopulmonary dysplasia and asphyxia, impaired respiration in sepsis, idiopathic pulmonary fibrosis, and pulmonary hypertension. The prevailing outcome has been protection or amelioration by melatonin, in conjunction with reduced expression and release of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-8, and TNFα, which was often explained by interference with toll-like receptors, inhibition of NLRP3 inflammasome activation and suppression of NF-κB signaling. In several studies, these beneficial effects were partially related to the upregulation of sirtuin-1 (SIRT1) by melatonin. The body of knowledge on melatonin’s efficacy in respiratory diseases is encouraging for the use of this powerful agent in COVID-19.
{"title":"Protection by melatonin in respiratory diseases: valuable information for the treatment of COVID-19","authors":"R. Hardeland, D. Tan","doi":"10.32794/mr11250061","DOIUrl":"https://doi.org/10.32794/mr11250061","url":null,"abstract":" High mortality rates in severe progression of COVID-19 are predominantly caused by pulmonary failure due to high-grade airway inflammation. As investigations on the efficacy of melatonin in this disease are still in their beginning, it may be worth-while to recall the body of evidence on protective effects in other respiratory dysfunctions, which have been studied pre-clinically and clinically. In various diseases and corresponding animal models, melatonin has been shown to be protective, mainly because of its anti-inflammatory and antioxidant properties. This was documented in pathologies as different as allergic airway inflammation, toxicologically or radiation-induced acute lung injury, respiratory disorders such as COPD, obstructive sleep apnea, neonatal respiratory distress syndrome, bronchopulmonary dysplasia and asphyxia, impaired respiration in sepsis, idiopathic pulmonary fibrosis, and pulmonary hypertension. The prevailing outcome has been protection or amelioration by melatonin, in conjunction with reduced expression and release of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-8, and TNFα, which was often explained by interference with toll-like receptors, inhibition of NLRP3 inflammasome activation and suppression of NF-κB signaling. In several studies, these beneficial effects were partially related to the upregulation of sirtuin-1 (SIRT1) by melatonin. The body of knowledge on melatonin’s efficacy in respiratory diseases is encouraging for the use of this powerful agent in COVID-19.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84449316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coronavirus disease 19 (COVID-19) is a viral disease caused by the new coronavirus SARS-CoV-2. Like other coronaviral infections, SARS-CoV-2 causes oxidative and ER stress triggering cellular response pathways, mainly PERK and IRE1 branches of the UPR. This excessive oxidative stress and the increasing of unfolded and misfolded proteins induce autophagy. Once this process is triggered, the blockage of the fusion of autophagosomes and lysosomes induced by virus leads to an incomplete autophagy. Double-membraned vesicles, which create a membranous support for viral RNA replication complexes, are formed. Melatonin is a pleiotropic molecule, which reduces oxidative and ER stress, regulates immune system, and modulates autophagy pathway. Thus, melatonin reinforces UPR and unlocks autophagy blockage, allowing autophagosomes to bind to lysosomes, completing the process of autophagy and decreasing viral replication capacity. Based on these activities of melatonin the recommendation of melatonin for patients with COVID-19 should be seriously considered, especially in elderlies and patients with different comorbidities, which are the highest risk population for serious cases.
{"title":"ER stress and autophagy induced by SARS-CoV-2: The targets for melatonin treatment","authors":"J. Boga, A. Coto-Montes","doi":"10.32794/mr11250067","DOIUrl":"https://doi.org/10.32794/mr11250067","url":null,"abstract":"Coronavirus disease 19 (COVID-19) is a viral disease caused by the new coronavirus SARS-CoV-2. Like other coronaviral infections, SARS-CoV-2 causes oxidative and ER stress triggering cellular response pathways, mainly PERK and IRE1 branches of the UPR. This excessive oxidative stress and the increasing of unfolded and misfolded proteins induce autophagy. Once this process is triggered, the blockage of the fusion of autophagosomes and lysosomes induced by virus leads to an incomplete autophagy. Double-membraned vesicles, which create a membranous support for viral RNA replication complexes, are formed. Melatonin is a pleiotropic molecule, which reduces oxidative and ER stress, regulates immune system, and modulates autophagy pathway. Thus, melatonin reinforces UPR and unlocks autophagy blockage, allowing autophagosomes to bind to lysosomes, completing the process of autophagy and decreasing viral replication capacity. Based on these activities of melatonin the recommendation of melatonin for patients with COVID-19 should be seriously considered, especially in elderlies and patients with different comorbidities, which are the highest risk population for serious cases. ","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73839894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Domínguez-Rodríguez, P. Abreu-González, P. Marik, R. Reiter
The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. SARS-CoV-2 induced endothelial dysfunction and cardiovascular injury are probably initiated by increases in the phosphorylation levels of JAK2 and STAT3 and resultant reactive oxygen species (ROS) formation. These pathological alterations are speculated to be strikingly reversed by melatonin
{"title":"Melatonin, cardiovascular disease and COVID-19: A potential therapeutic strategy?","authors":"A. Domínguez-Rodríguez, P. Abreu-González, P. Marik, R. Reiter","doi":"10.32794/mr11250065","DOIUrl":"https://doi.org/10.32794/mr11250065","url":null,"abstract":"The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. SARS-CoV-2 induced endothelial dysfunction and cardiovascular injury are probably initiated by increases in the phosphorylation levels of JAK2 and STAT3 and resultant reactive oxygen species (ROS) formation. These pathological alterations are speculated to be strikingly reversed by melatonin","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86216611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. C. R. Moreno, R. F. Saito, Manoela Tiago, R. R. Massaro, R. Pagni, Rafael Pegoraro, Patrícia da Cruz Souza, R. Reiter, A. Campa, M. Soengas, S. Maria-Engler
Among skin cancers, melanoma has the highest mortality rate. The heterogeneous genetic melanoma background leads to a tumor-propagating capacity particularly important in maintaining therapeutic resistance, and tumor recurrence. The identification of efficient molecules able to control melanoma progress represents an important opportunity for new therapeutic strategies, particularly in combination with the current standard-of-care treatments. In this context, several studies have reported the antitumor effects of melatonin against different types of cancer, including melanoma. Here, we describe the underlying mechanisms associated with melatonin’s activity in human melanoma cell lines, focusing on cell cycle and cytoskeleton remodeling. Interestingly, while melatonin induced melanocyte DNA replication, melanoma cells exhibited cell cycle arrest in the G1-phase. This phenomenon was associated with cyclin-D1 downregulation or p21 overexpression. The efficacy of melatonin on melanoma cells survival and proliferation was detected using the clonogenic assay, with a decrease in both the number and size of colonies. Additionally, melatonin induced a dramatic cytoskeleton remodeling in all melanoma cell lines, leading to a star-like morphology or cell swelling. The role of melatonin on melanoma cytoskeleton was associated with the actin disruption, with thinning and/or broken actin fibers, and weak and/or loss of paxillin along stress fibers. These data support the observed findings that melatonin impairs melanoma invasion in skin reconstructed models. Together, our results suggest that melatonin could be used to control melanoma growth and support basic and clinical studies on melatonin as a promising immunometabolic adjuvant for melanoma therapy.
{"title":"Melatonin inhibits human melanoma cells proliferation and invasion via cell cycle arrest and cytoskeleton remodeling","authors":"A. C. R. Moreno, R. F. Saito, Manoela Tiago, R. R. Massaro, R. Pagni, Rafael Pegoraro, Patrícia da Cruz Souza, R. Reiter, A. Campa, M. Soengas, S. Maria-Engler","doi":"10.32794/mr11250057","DOIUrl":"https://doi.org/10.32794/mr11250057","url":null,"abstract":"Among skin cancers, \u0000melanoma has the highest mortality rate. The heterogeneous genetic melanoma \u0000background leads to a tumor-propagating capacity particularly important in \u0000maintaining therapeutic resistance, and tumor recurrence. The identification of \u0000efficient molecules able to control melanoma progress represents an important \u0000opportunity for new therapeutic strategies, particularly in combination with the \u0000current standard-of-care treatments. In this context, \u0000several studies have reported the antitumor effects of melatonin against \u0000different types of cancer, including melanoma. Here, \u0000we describe the underlying mechanisms associated with melatonin’s activity in \u0000human melanoma cell lines, focusing on cell cycle and cytoskeleton \u0000remodeling. Interestingly, while melatonin induced melanocyte \u0000DNA replication, melanoma cells exhibited cell cycle arrest in the G1-phase. \u0000This phenomenon was associated with cyclin-D1 downregulation or p21 \u0000overexpression. The efficacy of melatonin on melanoma cells survival and \u0000proliferation was detected using the clonogenic assay, with a decrease in both \u0000the number and size of colonies. Additionally, melatonin induced a dramatic \u0000cytoskeleton remodeling in all melanoma cell lines, leading to a star-like \u0000morphology or cell swelling. The role of melatonin on melanoma cytoskeleton was \u0000associated with the actin disruption, with thinning and/or broken actin fibers, \u0000and weak and/or loss of paxillin along stress fibers. These data support the \u0000observed findings that melatonin impairs melanoma invasion in skin \u0000reconstructed models. Together, our results suggest that melatonin could be \u0000used to control melanoma growth and support basic and \u0000clinical studies on melatonin as a promising immunometabolic \u0000adjuvant for melanoma therapy.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90699344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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