Yukari Miki, A. Seki, H. Mishima, Yusuke Maruyama, Kazuki Watanabe, Jingjing Kobayashi-Sun, Isao Kobayashi, Kohei Kuroda, Shion Oshima, Takeru Okamoto, H. Matsubara, A. Srivastav, Y. Tabuchi, J. Hirayama, A. Hattori, Nobuo Suzuki
Melatonin has diverse effects, and has been reported to promote bone formation in addition to regulating the sleep–wake cycle. In the present study, we investigated the effects of melatonin on bone metabolism using ovariectomized (OVX) rats; a model of postmenopausal osteoporosis. Here, we focused on the differences in bone formation when melatonin was subcutaneous injected at day or early night. The OVX rats were injected with melatonin once daily (0.8 or 8 mg/head) between 11:00 to 14:00 or 18:00 to 19:30 for the day or early night, respectively, for six weeks. After completion of the injection, the femur and tibia in the OVX rats were dissected under general anesthesia and examined by quantitative computed tomography (pQCT) and histological analysis, respectively. Interestingly, the trabecular bone mineral density in the femur metaphysis of the OVX rats receiving 8 mg/head melatonin at early night was higher than those receiving melatonin during the day and they recovered to a similar level as the rats with sham treatment. In the diaphysis, the pQCT analysis results indicated that there was no significant difference in bone mineral density between the day and early night melatonin-injected OVX rats. Histological analysis of the secondary trabecular bone in the tibia of the OVX rats, revealed that the bone matrix area of the group receiving 8 mg/head melatonin at early night was higher compared with that of the day group and had a significant difference compared with OVX treatment rats. Taken together, the subcutaneous melatonin injection in OVX rats at early night was found to promote trabecular bone formation better than melatonin injection during the day. The timing of melatonin injection is a crucial factor when examining the influence of bone metabolism.
{"title":"Melatonin is more effective on bone metabolism when given at early night than during the day in ovariectomized rats","authors":"Yukari Miki, A. Seki, H. Mishima, Yusuke Maruyama, Kazuki Watanabe, Jingjing Kobayashi-Sun, Isao Kobayashi, Kohei Kuroda, Shion Oshima, Takeru Okamoto, H. Matsubara, A. Srivastav, Y. Tabuchi, J. Hirayama, A. Hattori, Nobuo Suzuki","doi":"10.32794/mr112500147","DOIUrl":"https://doi.org/10.32794/mr112500147","url":null,"abstract":"Melatonin has diverse effects, and has been reported to promote bone formation in addition to regulating the sleep–wake cycle. In the present study, we investigated the effects of melatonin on bone metabolism using ovariectomized (OVX) rats; a model of postmenopausal osteoporosis. Here, we focused on the differences in bone formation when melatonin was subcutaneous injected at day or early night. The OVX rats were injected with melatonin once daily (0.8 or 8 mg/head) between 11:00 to 14:00 or 18:00 to 19:30 for the day or early night, respectively, for six weeks. After completion of the injection, the femur and tibia in the OVX rats were dissected under general anesthesia and examined by quantitative computed tomography (pQCT) and histological analysis, respectively. Interestingly, the trabecular bone mineral density in the femur metaphysis of the OVX rats receiving 8 mg/head melatonin at early night was higher than those receiving melatonin during the day and they recovered to a similar level as the rats with sham treatment. In the diaphysis, the pQCT analysis results indicated that there was no significant difference in bone mineral density between the day and early night melatonin-injected OVX rats. Histological analysis of the secondary trabecular bone in the tibia of the OVX rats, revealed that the bone matrix area of the group receiving 8 mg/head melatonin at early night was higher compared with that of the day group and had a significant difference compared with OVX treatment rats. Taken together, the subcutaneous melatonin injection in OVX rats at early night was found to promote trabecular bone formation better than melatonin injection during the day. The timing of melatonin injection is a crucial factor when examining the influence of bone metabolism.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78611132","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}
Helicobacter pylori (H. pylori) infection is associated with several disorders of the gastrointestinal tract, including gastric cancer. Studies of ours and others suggest that H. pylori infection may affect melatonin synthesis in the gastric epithelial cells. On the other hand, melatonin ameliorates gastric disorders as shown in clinical trials and experimental studies. Moreover, melatonin not only suppresses the DNA-damaging reaction of diet-related mutagens that can initiate carcinogenesis in gastric mucosa, but also the oxidative DNA damage evoked by reactive oxygen and nitrogen species produced during H. pylori-related gastric inflammation. H. pylori infection is associated with several functional and organic gastric disorders, including gastritis, peptic ulcer disease and gastric cancer, but the precise mechanism behind this association is not known and many pathways can be involved. Some of beneficial effects of melatonin in the gastrointestinal tract are underlined by mechanisms that likely play a role in detrimental effects of H. pylori in the stomach. Therefore, melatonin may modulate these mechanisms resulting in ameliorating H. pylori-related symptoms. In this narrative review the role of inflammation, oxidative stress, DNA damage response and epigenetic modifications in H. pylori-associated gastric disorders will be discussed with an emphasis on gastric cancer. We also suggest that melatonin may have potential to inhibit H. pylori-mediated pathologies through its interaction with essential pathways as described herein. Overlapping mechanisms of H. pylori-associated pathogenesis and beneficial effects of melatonin justify further studies on the action of melatonin on gastric disorders associated with H. pylori infection, including clinical trials.
{"title":"Inflammation, oxidative stress, DNA damage response and epigenetic modifications interact behind the beneficial actions of melatonin on H. pylori-mediated gastric disorders","authors":"J. Błasiak, J. Chojnacki, C. Chojnacki","doi":"10.32794/mr112500145","DOIUrl":"https://doi.org/10.32794/mr112500145","url":null,"abstract":"Helicobacter pylori (H. pylori) infection is associated with several disorders of the gastrointestinal tract, including gastric cancer. Studies of ours and others suggest that H. pylori infection may affect melatonin synthesis in the gastric epithelial cells. On the other hand, melatonin ameliorates gastric disorders as shown in clinical trials and experimental studies. Moreover, melatonin not only suppresses the DNA-damaging reaction of diet-related mutagens that can initiate carcinogenesis in gastric mucosa, but also the oxidative DNA damage evoked by reactive oxygen and nitrogen species produced during H. pylori-related gastric inflammation. H. pylori infection is associated with several functional and organic gastric disorders, including gastritis, peptic ulcer disease and gastric cancer, but the precise mechanism behind this association is not known and many pathways can be involved. Some of beneficial effects of melatonin in the gastrointestinal tract are underlined by mechanisms that likely play a role in detrimental effects of H. pylori in the stomach. Therefore, melatonin may modulate these mechanisms resulting in ameliorating H. pylori-related symptoms. In this narrative review the role of inflammation, oxidative stress, DNA damage response and epigenetic modifications in H. pylori-associated gastric disorders will be discussed with an emphasis on gastric cancer. We also suggest that melatonin may have potential to inhibit H. pylori-mediated pathologies through its interaction with essential pathways as described herein. Overlapping mechanisms of H. pylori-associated pathogenesis and beneficial effects of melatonin justify further studies on the action of melatonin on gastric disorders associated with H. pylori infection, including clinical trials. ","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82104355","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}
C. Cervino, Joaquín Xavier Cogo Pagella, M. Hernando
Increasing evidence suggests that the presence of constant light or darkness have diverse effects on circadian physiology. The aim of this study is to explore serum levels of melatonin upon return to a normal light-dark cycle (LDC) in rats exposed to constant light (LL) or darkness (DD). Results showed the different profiles of melatonin levels after exposure to LL or DD. Similarly, the restoration of the LDC (12L:12D) modified the endogenous melatonin levels. In the LL group, serum melatonin remained at levels similar to control values, and when normal LDC was restored, melatonin levels of the rats decreased but without significant difference compared to control. In the DD group, serum melatonin increased significantly (22%), and upon switching to normal LDC, serum melatonin level was significantly decreased compared to constant dark condition. Even 15 days later, a significant 76% drop in serum melatonin level was still observed in LDC condition. The results suggested that prolonged exposure to LL or DD, especially to DD, had profound effects on the serum melatonin. LL has little influence and this result can be explained by the potential compensation of extrapineal melatonin generated by other tissues and organs.
{"title":"Effects of long-term exposure to light or darkness and return to normal light-dark cycle on serum melatonin levels in rats","authors":"C. Cervino, Joaquín Xavier Cogo Pagella, M. Hernando","doi":"10.32794/mr112500150","DOIUrl":"https://doi.org/10.32794/mr112500150","url":null,"abstract":"Increasing evidence suggests that the presence of \u0000constant light or darkness have diverse effects on circadian physiology. The \u0000aim of this study is to explore serum levels of melatonin upon return to a \u0000normal light-dark cycle (LDC) in rats exposed to constant light (LL) or \u0000darkness (DD). Results showed the different profiles of melatonin levels after \u0000exposure to LL or DD. Similarly, the restoration of the LDC (12L:12D) modified \u0000the endogenous melatonin levels. In the LL group, serum melatonin remained at \u0000levels similar to control values, and when normal LDC was restored, melatonin \u0000levels of the rats decreased but without significant difference compared to \u0000control. In the DD group, serum melatonin increased significantly (22%), and \u0000upon switching to normal LDC, serum melatonin level was significantly decreased \u0000compared to constant dark condition. Even 15 days later, a significant 76% drop \u0000in serum melatonin level was still observed in LDC condition. The results \u0000suggested that prolonged exposure to LL or DD, especially to DD, had profound \u0000effects on the serum melatonin. LL has little influence and this result can be \u0000explained by the potential compensation of extrapineal melatonin generated by \u0000other tissues and organs. ","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81831609","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}
Francisco Artime-Naveda, Lucas Alves-Pérez, D. Hevia, Sergio Alcón-Rodríguez, Sheila Fernández-Vega, Alejandro Álvarez-Artime, I. Quiros-Gonzalez, R. Cernuda, R. Sainz, J. Mayo
Melatonin is now considered a major physiological regulator of many different functions including synchronization of circadian rhythms, antioxidant defense at different levels, immunomodulation, cell growth control, neuroprotector and anti-tumor agent. In addition to its membrane receptor-dependent actions, it has been classically assumed that its diffusion through lipid bilayers contribute to its intracellular actions, including direct and indirect free radical scavenging activities. While pineal gland is the major site of nocturnal production of the indolamine, skin is considered an important source of melatonin synthesis. Here, using a 3-D culture model of HaCaT cells in an artificial scaffold (epidermal equivalents), we have quantified diffusion of melatonin in these cells and compared it to 2-D or spheroid cultures. Diffusion in 3-D scaffold cultures was similar to that found in 2-D culture and proportion of intracellular melatonin was low. AFMK, a major oxidative metabolite of melatonin, was also found and quantified. Redox parameters including total ROS, superoxide or mitochondrial mass were also assayed. We also report the effect of melatonin on the cytoskeleton of normal human keratinocyte HaCaT cells. We propose HaCaT epidermal equivalents as an affordable, easy-to-use, 3-D cell culture tool to test diffusion rates of melatonin but also other similar small molecules. This 3-D models can also be studied at cellular and molecular level, including redox parameters, and can provide important information regarding molecules that can be topically added to skin. Similarly, mechanisms of transportation can also be approached with this methodology.
{"title":"A novel study of melatonin diffusion in a 3D cell culture model","authors":"Francisco Artime-Naveda, Lucas Alves-Pérez, D. Hevia, Sergio Alcón-Rodríguez, Sheila Fernández-Vega, Alejandro Álvarez-Artime, I. Quiros-Gonzalez, R. Cernuda, R. Sainz, J. Mayo","doi":"10.32794/mr112500148","DOIUrl":"https://doi.org/10.32794/mr112500148","url":null,"abstract":"Melatonin is now considered a major physiological regulator of many different functions including synchronization of circadian rhythms, antioxidant defense at different levels, immunomodulation, cell growth control, neuroprotector and anti-tumor agent. In addition to its membrane receptor-dependent actions, it has been classically assumed that its diffusion through lipid bilayers contribute to its intracellular actions, including direct and indirect free radical scavenging activities. While pineal gland is the major site of nocturnal production of the indolamine, skin is considered an important source of melatonin synthesis. Here, using a 3-D culture model of HaCaT cells in an artificial scaffold (epidermal equivalents), we have quantified diffusion of melatonin in these cells and compared it to 2-D or spheroid cultures. Diffusion in 3-D scaffold cultures was similar to that found in 2-D culture and proportion of intracellular melatonin was low. AFMK, a major oxidative metabolite of melatonin, was also found and quantified. Redox parameters including total ROS, superoxide or mitochondrial mass were also assayed. We also report the effect of melatonin on the cytoskeleton of normal human keratinocyte HaCaT cells. We propose HaCaT epidermal equivalents as an affordable, easy-to-use, 3-D cell culture tool to test diffusion rates of melatonin but also other similar small molecules. This 3-D models can also be studied at cellular and molecular level, including redox parameters, and can provide important information regarding molecules that can be topically added to skin. Similarly, mechanisms of transportation can also be approached with this methodology.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82067837","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. Hosseinzadeh, S. Changizi-Ashtiyani, Fereshteh Koosha, Shiva Amiri, Arman Karimi-Behnagh, S. Mehrzadi
Neurodegenerative diseases are a serious health issue globally. High morbidity and mortality of these disorders lead to researchers further exploring more effective preventive and therapeutic remedies to combat these devastating diseases. An important strategy is to delay the progression of these debilitating diseases. The prevalence of neurodegenerative disease increases with aging which not only results in neuronal deterioration, but also causes the brain ischemia leading to stroke, and death. Melatonin, a potent endogenous antioxidant mainly secreted by the pineal gland, has often used in the treatment of neuropathologies with great success. Herein, we review the current evidence documenting melatonin’s therapeutic effects on neurodegenerative and brain ischemic diseases; we also summarize the known molecular mechanisms of its protective actions.
{"title":"Melatonin: therapeutic potential for stroke and other neurodegenerative diseases","authors":"A. Hosseinzadeh, S. Changizi-Ashtiyani, Fereshteh Koosha, Shiva Amiri, Arman Karimi-Behnagh, S. Mehrzadi","doi":"10.32794/mr112500144","DOIUrl":"https://doi.org/10.32794/mr112500144","url":null,"abstract":"Neurodegenerative diseases are a serious health issue globally. High morbidity and mortality of these disorders lead to researchers further exploring more effective preventive and therapeutic remedies to combat these devastating diseases. An important strategy is to delay the progression of these debilitating diseases. The prevalence of neurodegenerative disease increases with aging which not only results in neuronal deterioration, but also causes the brain ischemia leading to stroke, and death. Melatonin, a potent endogenous antioxidant mainly secreted by the pineal gland, has often used in the treatment of neuropathologies with great success. Herein, we review the current evidence documenting melatonin’s therapeutic effects on neurodegenerative and brain ischemic diseases; we also summarize the known molecular mechanisms of its protective actions.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83403475","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}
N. Heydari, M. Y. Memar, R. Reiter, Setareh Rezatabar, Zahra i Arab-Bafran, Amirreza A Jaz, Seyed Mostafa Mir
Several factors impact the mortality rate of patients with gastrointestinal cancers including late diagnosis, metastases to distance sites, and lack of efficacy of the conventional therapies. To reduce mortality rate, the novel effective remedies should be explored. Melatonin is an anti-inflammatory, antioxidant and oncostatic molecule and has been showed potential in controlling various malignancies. In the gastrointestinal tract, melatonin plays an important role via its membrane receptors of MT1 and MT2. It can diminish esophageal lesions resulting from acid–pepsin–bile contact and also inhibits expression of myosin light chain kinase as well as reduces its activity by regulating extracellular signal-transduction of protein kinase. The aim of the present study was to review the critical functions of melatonin in the prevention and treatment of esophageal squamous cell carcinoma including its influence on gastrointestinal pathology, oncostatic role and potential mechanisms. Particularly, the inhibitory function of melatonin on esophageal squamous cell carcinoma and its therapeutic effects are summarized. We suggest that melatonin co-treatment will enhance the efficacy of conventional treatments and survival times in patients with esophageal squamous cell carcinoma.
{"title":"Melatonin: An anticancer molecule in esophageal squamous cell carcinoma: A mechanistic review","authors":"N. Heydari, M. Y. Memar, R. Reiter, Setareh Rezatabar, Zahra i Arab-Bafran, Amirreza A Jaz, Seyed Mostafa Mir","doi":"10.32794/mr112500141","DOIUrl":"https://doi.org/10.32794/mr112500141","url":null,"abstract":"Several factors impact the mortality rate of patients with gastrointestinal cancers including late diagnosis, metastases to distance sites, and lack of efficacy of the conventional therapies. To reduce mortality rate, the novel effective remedies should be explored. Melatonin is an anti-inflammatory, antioxidant and oncostatic molecule and has been showed potential in controlling various malignancies. In the gastrointestinal tract, melatonin plays an important role via its membrane receptors of MT1 and MT2. It can diminish esophageal lesions resulting from acid–pepsin–bile contact and also inhibits expression of myosin light chain kinase as well as reduces its activity by regulating extracellular signal-transduction of protein kinase. The aim of the present study was to review the critical functions of melatonin in the prevention and treatment of esophageal squamous cell carcinoma including its influence on gastrointestinal pathology, oncostatic role and potential mechanisms. Particularly, the inhibitory function of melatonin on esophageal squamous cell carcinoma and its therapeutic effects are summarized. We suggest that melatonin co-treatment will enhance the efficacy of conventional treatments and survival times in patients with esophageal squamous cell carcinoma.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84829536","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}
Songita Ghosh, R. Khatoon, Swaimanti Sarkar, D. Bandyopadhyay
Non-alcoholic fatty liver disease (NAFLD) is caused by hepatic fat accumulation with a high prevalence globally, especially in Western countries in which individuals have excessive fat consumption. Prolonged intake of high dietary fat causes various diseases due to the imbalance of energy metabolism, which leads to obesity and other pathological conditions. Currently, the exact pathogenesis of NAFLD is still obscure. In this review, the potential etiologies for NAFLD will be discussed, including adipose tissue dysfunction, intrahepatic de novo lipogenesis, hepatic fat accumulation, insulin resistance, hepatic inflammation, inflammasome activation, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress. Melatonin is a potent antioxidant and anti-inflammatory molecule. It is also a regulator of lipid and glucose metabolism which is indicated by melatonin’s effects on weight loss, reduction of liver weight, blood levels of lipids, glucose and insulin, activities of hepatic enzymes, steatohepatitis, and fibrosis. Melatonin considerably reduces mitochondrial dysfunction and proinflammatory cytokines. Moreover, it downregulates NLRP3 and its associated downstream effectors of caspase-1, IL-1β, and IL-18 proteins. This review will update the molecular mechanisms behind high-fat diet induced hepatic dysfunction and the protective role of melatonin in NAFLD.
{"title":"Ameliorating effects of melatonin on high-fat diet induced non-alcoholic fatty liver diseases and their associated pathologies: A comprehensive review","authors":"Songita Ghosh, R. Khatoon, Swaimanti Sarkar, D. Bandyopadhyay","doi":"10.32794/mr112500138","DOIUrl":"https://doi.org/10.32794/mr112500138","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is caused by hepatic fat accumulation with a high prevalence globally, especially in Western countries in which individuals have excessive fat consumption. Prolonged intake of high dietary fat causes various diseases due to the imbalance of energy metabolism, which leads to obesity and other pathological conditions. Currently, the exact pathogenesis of NAFLD is still obscure. In this review, the potential etiologies for NAFLD will be discussed, including adipose tissue dysfunction, intrahepatic de novo lipogenesis, hepatic fat accumulation, insulin resistance, hepatic inflammation, inflammasome activation, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress. Melatonin is a potent antioxidant and anti-inflammatory molecule. It is also a regulator of lipid and glucose metabolism which is indicated by melatonin’s effects on weight loss, reduction of liver weight, blood levels of lipids, glucose and insulin, activities of hepatic enzymes, steatohepatitis, and fibrosis. Melatonin considerably reduces mitochondrial dysfunction and proinflammatory cytokines. Moreover, it downregulates NLRP3 and its associated downstream effectors of caspase-1, IL-1β, and IL-18 proteins. This review will update the molecular mechanisms behind high-fat diet induced hepatic dysfunction and the protective role of melatonin in NAFLD.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87097195","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}
Currently, the majority of the melatonin manufactured is chemically synthesized replacing the previous method that extracted it from biological materials. Due to environmental concerns, biomanufacturing of chemical-related products is now gaining favor over chemical synthesis. Melatonin is synthesized from tryptophan in a four-step pathway that includes a hydroxylase and methyl transferase, both representing major challenges for metabolic engineering. Using novel technologies, including genome editing and laboratory evolution, the metabolic pathway of melatonin synthesis has been reconstructed in a microbial host which has the capacity to produce melatonin in gram-level quantities.
{"title":"Biomanufacturing of melatonin is now possible","authors":"Lei Yang, B. Palsson","doi":"10.32794/mr112500142","DOIUrl":"https://doi.org/10.32794/mr112500142","url":null,"abstract":"Currently, the majority of the melatonin manufactured is chemically synthesized replacing the previous method that extracted it from biological materials. Due to environmental concerns, biomanufacturing of chemical-related products is now gaining favor over chemical synthesis. Melatonin is synthesized from tryptophan in a four-step pathway that includes a hydroxylase and methyl transferase, both representing major challenges for metabolic engineering. Using novel technologies, including genome editing and laboratory evolution, the metabolic pathway of melatonin synthesis has been reconstructed in a microbial host which has the capacity to produce melatonin in gram-level quantities. ","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87388521","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}
Melatonin (MEL), an indoleamine hormone synthesized in almost all organisms including humans, has been the object of a considerable body of research due to its pleiotropic functions. Recently, focus has been given to its roles as a regulator of the immune and inflammatory response, in the context of numerous disorders; likewise, it has been studied as a potential therapeutic option in numerous infectious diseases. In this sense, the relationship between this molecule and parasitic infections is of particular interest; thus, the present review aims to compile knowledge acquired in the last few years, regarding the participation of MEL in the pathophysiology of parasitic infections, and its potential clinical applications. Since parasitic diseases still represent a significant burden on health systems worldwide, particularly in low and lower-middle income countries with limited access to sanitation facilities and resources for therapeutic approaches, the continuing study of MEL, as an affordable and fundamentally safe healing option, might help better control of these infections.
{"title":"Melatonin: A review of its physiopathological and therapeutic relationship with parasitic diseases","authors":"R. Cardenas, L. Chacin-Bonilla, E. Bonilla","doi":"10.32794/mr112500139","DOIUrl":"https://doi.org/10.32794/mr112500139","url":null,"abstract":"Melatonin (MEL), an indoleamine hormone synthesized in almost all organisms including humans, has been the object of a considerable body of research due to its pleiotropic functions. Recently, focus has been given to its roles as a regulator of the immune and inflammatory response, in the context of numerous disorders; likewise, it has been studied as a potential therapeutic option in numerous infectious diseases. In this sense, the relationship between this molecule and parasitic infections is of particular interest; thus, the present review aims to compile knowledge acquired in the last few years, regarding the participation of MEL in the pathophysiology of parasitic infections, and its potential clinical applications. Since parasitic diseases still represent a significant burden on health systems worldwide, particularly in low and lower-middle income countries with limited access to sanitation facilities and resources for therapeutic approaches, the continuing study of MEL, as an affordable and fundamentally safe healing option, might help better control of these infections.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89658930","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}
The prevalence of mental illnesses has significantly increased globally in recent decades due to multifactorial causes. Of these, schizophrenia and bipolar disorder, due to their high incidence and high associated disability, stand out. However, the effective treatments on these disorders are lagged behind their increased incidence. Melatonin, as an essential molecule in the regulation of sleep-wake rhythm and the naturally occurring antioxidant, has only received attention for the treatment of such psychiatric disorders in relation to its circadian rhythm regulation, but its overwhelming role as a regulator of oxidative stress that facilitates the amelioration of neuronal damage has not been addressed for this respect. In this communication, the novel aspects of melatonin on mental illnesses have been discussed. We provide the necessary literature to justify the beneficial roles and the mechanisms of melatonin to treat schizophrenia and bipolar disorder. These mechanisms include that melatonin enhances reticulum stress, potentiates the unfolded protein response, and increases endoplasmic reticulum synthesis to facilitate autophagy and even suppresses apoptosis. This process involves not only the expected organelles but is a more complex cohesion that even includes the mitochondria, a well-known target of melatonin, which reinforces the robustness of our hypothesis, i.e., melatonin prevents the development of protein aggregates and abnormal structures typically observed in brain damage. Its documented capacity and the need to improve treatment efficiency in a growing population afflicted by mental illnesses are the basis of this hypothesis and support a role of melatonin, as antioxidant, in psychiatric disorders.
{"title":"Can melatonin improve the alteration of protein synthesis occurring in schizophrenia and bipolar disorder?","authors":"A. Coto-Montes, Nerea Menéndez-Coto, J. Boga","doi":"10.32794/mr112500140","DOIUrl":"https://doi.org/10.32794/mr112500140","url":null,"abstract":"The prevalence of mental illnesses has significantly increased globally in recent decades due to multifactorial causes. Of these, schizophrenia and bipolar disorder, due to their high incidence and high associated disability, stand out. However, the effective treatments on these disorders are lagged behind their increased incidence. Melatonin, as an essential molecule in the regulation of sleep-wake rhythm and the naturally occurring antioxidant, has only received attention for the treatment of such psychiatric disorders in relation to its circadian rhythm regulation, but its overwhelming role as a regulator of oxidative stress that facilitates the amelioration of neuronal damage has not been addressed for this respect. In this communication, the novel aspects of melatonin on mental illnesses have been discussed. We provide the necessary literature to justify the beneficial roles and the mechanisms of melatonin to treat schizophrenia and bipolar disorder. These mechanisms include that melatonin enhances reticulum stress, potentiates the unfolded protein response, and increases endoplasmic reticulum synthesis to facilitate autophagy and even suppresses apoptosis. This process involves not only the expected organelles but is a more complex cohesion that even includes the mitochondria, a well-known target of melatonin, which reinforces the robustness of our hypothesis, i.e., melatonin prevents the development of protein aggregates and abnormal structures typically observed in brain damage. Its documented capacity and the need to improve treatment efficiency in a growing population afflicted by mental illnesses are the basis of this hypothesis and support a role of melatonin, as antioxidant, in psychiatric disorders.","PeriodicalId":18604,"journal":{"name":"Melatonin Research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82033977","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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