Journal of Pineal Research最新文献

{"title":"Light-Dependent Circadian Rhythm Governs O-GlcNAc Cycling to Influence Cognitive Function in Adult Zebrafish","authors":"Jiwon Park,&nbsp;Dong Yeol Kim,&nbsp;Eok-Soo Oh,&nbsp;Inn-Oc Han","doi":"10.1111/jpi.13001","DOIUrl":"10.1111/jpi.13001","url":null,"abstract":"<p>This study explores the 24-h rhythmic cycle of protein <i>O</i>-GlcNAcylation within the brain and highlights its crucial role in regulating the circadian cycle and neuronal function based on zebrafish as an animal model. In our experiments, disruption of the circadian rhythm, achieved through inversion of the light-dark cycle or daytime melatonin treatment, not only impaired the rhythmic changes of <i>O</i>-GlcNAcylation along with altering expression patterns of <i>O</i>-GlcNAc transferase (OGT) and <i>O</i>-GlcNAcase (OGA) in zebrafish brain but also significantly impeded learning and memory function. In particular, circadian disruption affected rhythmic expression of protein <i>O</i>-GlcNAcylation and OGT in the nuclear fraction. Notably, the circadian cycle induces rhythmic alterations in <i>O</i>-GlcNAcylation of H2B histone protein that correspond to changes in H3 trimethylation. Disruption of the cycle interfered with these periodic histone code alterations. Pharmacological inhibition of OGT with OSMI-1 disrupted the wake-sleep patterns of zebrafish without affecting expression of circadian rhythm-regulating genes. OSMI-1 inhibited the expression of <i>c-fos</i>, <i>bdnf</i>, and <i>calm1</i>, key genes associated with brain function and synaptic plasticity, and decreased the binding of <i>O</i>-GlcNAcylated H2B and OGT to promoter regions of these genes. The collective findings support the potential involvement of circadian cycling of the <i>O</i>-GlcNAc histone code in regulating synaptic plasticity and brain function. Overall, data from this study provide evidence that protein <i>O</i>-GlcNAcylation serves as a pivotal posttranslational mechanism integrating circadian signals and neuronal function to regulate rhythmic physiology.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.13001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KARS Mutations Impair Brain Myelination by Inducing Oligodendrocyte Deficiency: One Potential Mechanism and Improvement by Melatonin","authors":"Lijia Yu,&nbsp;Zhilin Chen,&nbsp;Xiaolong Zhou,&nbsp;Fei Teng,&nbsp;Qing-Ran Bai,&nbsp;Lixi Li,&nbsp;Yunhong Li,&nbsp;Ying Liu,&nbsp;Qiyu Zeng,&nbsp;Yong Wang,&nbsp;Meihua Wang,&nbsp;Yaling Xu,&nbsp;Xiaohui Tang,&nbsp;Xijin Wang","doi":"10.1111/jpi.12998","DOIUrl":"10.1111/jpi.12998","url":null,"abstract":"<p>It is very crucial to investigate key molecules that are involved in myelination to gain an understanding of brain development and injury. We have reported for the first time that pathogenic variants p.R477H and p.P505S in <i>KARS</i>, which encodes lysyl-tRNA synthetase (LysRS), cause leukoencephalopathy with progressive cognitive impairment in humans. The role and action mechanisms of <i>KARS</i> in brain myelination during development are unknown. Here, we first generated <i>Kars</i> knock-in mouse models through the CRISPR-Cas9 system. <i>Kars</i> knock-in mice displayed significant cognitive deficits. These mice also showed significantly reduced myelin density and content, as well as significantly decreased myelin thickness during development. In addition, <i>Kars</i> mutations significantly induced oligodendrocyte differentiation arrest and reduction in the brain white matter of mice. Mechanically, oligodendrocytes’ significantly imbalanced expression of differentiation regulators and increased capase-3-mediated apoptosis were observed in the brain white matter of <i>Kars</i> knock-in mice. Furthermore, <i>Kars</i> mutations significantly reduced the aminoacylation and steady-state level of mitochondrial tRNA^Lys and decreased the protein expression of subunits of oxidative phosphorylation complexes in the brain white matter. <i>Kars</i> knock-in mice showed decreased activity of complex IV and significantly reduced ATP production and increased reactive oxygen species in the brain white matter. Significantly increased percentages of abnormal mitochondria and mitochondrion area were observed in the oligodendrocytes of <i>Kars</i> knock-in mouse brain. Finally, melatonin (a mitochondrion protectant) significantly attenuated mitochondrion and oligodendrocyte deficiency in the brain white matter of <i>Kars</i>^{<i>R504H/P532S</i>} mice. The mice treated with melatonin also showed significantly restored myelination and cognitive function. Our study first establishes <i>Kars</i> knock-in mammal models of leukoencephalopathy and cognitive impairment and indicates important roles of KARS in the regulation of mitochondria, oligodendrocyte differentiation and survival, and myelination during brain development and application prospects of melatonin in KARS (or even aaRS)<i>-</i>related diseases.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12998","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro and In Vivo Effects of Melatonin-Containing Combinations in Human Pancreatic Ductal Adenocarcinoma","authors":"Laura Zeppa,&nbsp;Cristina Aguzzi,&nbsp;Maria Beatrice Morelli,&nbsp;Oliviero Marinelli,&nbsp;Consuelo Amantini,&nbsp;Martina Giangrossi,&nbsp;Giorgio Santoni,&nbsp;Alessandro Fanelli,&nbsp;Margherita Luongo,&nbsp;Massimo Nabissi","doi":"10.1111/jpi.12997","DOIUrl":"10.1111/jpi.12997","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen–ozone (O₂/O₃) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O₂/O₃ was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O₂/O₃ could serve as a potential adjuvant therapeutic strategy for PDAC.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12997","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Increases Root Cell Wall Phosphorus Reutilization via an NO Dependent Pathway in Rice (Oryza sativa)","authors":"Yong Qiang Gao,&nbsp;Rui Guo,&nbsp;Hao Yu Wang,&nbsp;Jie Ya Sun,&nbsp;Chang Zhao Chen,&nbsp;Die Hu,&nbsp;Chong Wei Zhong,&nbsp;Meng Meng Jiang,&nbsp;Ren Fang Shen,&nbsp;Xiao Fang Zhu,&nbsp;Jiu Huang","doi":"10.1111/jpi.12995","DOIUrl":"10.1111/jpi.12995","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of <i>OsPT8</i>, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of the Suprachiasmatic Nucleus Disturbs the Circadian Rhythm and Aggravates Epileptic Seizures by Inducing Hippocampal GABAergic Dysfunction in C57BL/6 Mice","authors":"Xiaoshan Liang,&nbsp;Xiaotao Liang,&nbsp;Yunyan Zhao,&nbsp;Yuewen Ding,&nbsp;Xiaoyu Zhu,&nbsp;Jieli Zhou,&nbsp;Jing Qiu,&nbsp;Xiaoqin Shen,&nbsp;Wei Xie","doi":"10.1111/jpi.12993","DOIUrl":"10.1111/jpi.12993","url":null,"abstract":"<div>\u0000 \u0000 <p>The interplay between circadian rhythms and epilepsy has gained increasing attention. The suprachiasmatic nucleus (SCN), which acts as the master circadian pacemaker, regulates physiological and behavioral rhythms through its complex neural networks. However, the exact role of the SCN and its <i>Bmal1</i> gene in the development of epilepsy remains unclear. In this study, we utilized a lithium–pilocarpine model to induce epilepsy in mice and simulated circadian disturbances by creating lesions in the SCN and specifically knocking out the <i>Bmal1</i> gene in the SCN neurons. We observed that the pilocarpine-induced epileptic mice experienced increased daytime seizure frequency, irregular oscillations in core body temperature, and circadian gene alterations in both the SCN and the hippocampus. Additionally, there was enhanced activation of GABAergic projections from the SCN to the hippocampus. Notably, SCN lesions intensified seizure activity, concomitant with hippocampal neuronal damage and GABAergic signaling impairment. Further analyses using the Gene Expression Omnibus database and gene set enrichment analysis indicated reduced <i>Bmal1</i> expression in patients with medial temporal lobe epilepsy, potentially affecting GABA receptor pathways. Targeted deletion of <i>Bmal1</i> in SCN neurons exacerbated seizures and pathology in epilepsy, as well as diminished hippocampal GABAergic efficacy. These results underscore the crucial role of the SCN in modulating circadian rhythms and GABAergic function in the hippocampus, aggravating the severity of seizures. This study provides significant insights into how circadian rhythm disturbances can influence neuronal dysfunction and epilepsy, highlighting the therapeutic potential of targeting SCN and the Bmal1 gene within it in epilepsy management.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Rescues Influenza A Virus–Induced Cellular Energy Exhaustion via OMA1-OPA1-S in Acute Exacerbation of COPD","authors":"Yuan-Yuan Wei,&nbsp;Jing-Jing Ye,&nbsp;Da-Wei Zhang,&nbsp;Lei Hu,&nbsp;Hui-Mei Wu,&nbsp;Guang-He Fei","doi":"10.1111/jpi.12991","DOIUrl":"10.1111/jpi.12991","url":null,"abstract":"<div>\u0000 \u0000 <p>Although rapid progression and a poor prognosis in influenza A virus (IAV) infection–induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV-induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV-infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV-inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1-dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV-infected pDHBE cells; however, these changes were rescued by <i>OMA1</i>-siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV–induced cellular energy exhaustion via OMA1-OPA1-S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytomelatonin: From Intracellular Signaling to Global Horticulture Market","authors":"Morteza Soleimani Aghdam,&nbsp;Marino B. Arnao","doi":"10.1111/jpi.12990","DOIUrl":"https://doi.org/10.1111/jpi.12990","url":null,"abstract":"<p>Melatonin (<i>N</i>-acetyl-5-methoxytryptamine), a well-known mammalian hormone, has been having a great relevance in the Plant World in recent years. Many of its physiological actions in plants are leading to possible features of agronomic interest, especially those related to improvements in tolerance to stressors and in the postharvest life of fruits and vegetables. Thus, through the exogenous application of melatonin or by modifying the endogenous biosynthesis of phytomelatonin, some change can be made in the functional levels of melatonin in tissues and their responses. Also, acting in the respective phytomelatonin biosynthesis enzymes, regulating the expression of tryptophan decarboxylase (<i>TDC</i>), tryptamine 5-hydroxylase (<i>T5H</i>), serotonin <i>N</i>-acetyltransferase (<i>SNAT</i>), <i>N</i>-acetylserotonin <i>O</i>-methyltransferase (<i>ASMT</i>), and caffeic acid <i>O</i>-methyltransferase (<i>COMT</i>), and recently the possible action of deacetylases on some intermediates offers promising opportunities for improving fruits and vegetables in postharvest and its marketability. Other regulators/effectors such as different transcription factors, protein kinases, phosphatases, miRNAs, protein–protein interactions, and some gasotransmitters such as nitric oxide or hydrogen sulfide were also considered in an exhaustive vision. Other interesting aspects such as the role of phytomelatonin in autophagic responses, the posttranslational reprogramming by protein-phosphorylation, ubiquitylation, SUMOylation, PARylation, persulfidation, and nitrosylation described in the phytomelatonin-mediated responses were also discussed, including the relationship of phytomelatonin and several plant hormones, for chilling injury and fungal decay alleviating. The current data about the phytomelatonin receptor in plants (CAND2/PMTR1), the effect of UV-B light and cold storage on the postharvest damage are presented and discussed. All this on the focus of a possible new action in the preservation of the quality of fruits and vegetables.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12990","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Ameliorates Atherosclerotic Plaque Vulnerability by Regulating PPARδ-Associated Smooth Muscle Cell Phenotypic Switching","authors":"Sy-Jou Chen,&nbsp;Hung-Che Chien,&nbsp;Shih-Hung Tsai,&nbsp;Yu-Sin Jheng,&nbsp;Yi Chen,&nbsp;Po-Shiuan Hsieh,&nbsp;Pi-Fen Tsui,&nbsp;Shu Chien,&nbsp;Min-Chien Tsai","doi":"10.1111/jpi.12988","DOIUrl":"10.1111/jpi.12988","url":null,"abstract":"<div>\u0000 \u0000 <p>Vulnerable atherosclerotic plaque rupture, the leading cause of fatal atherothrombotic events, is associated with an increased risk of mortality worldwide. Peroxisome proliferator–activated receptor delta (PPARδ) has been shown to modulate vascular smooth muscle cell (SMC) phenotypic switching, and, hence, atherosclerotic plaque stability. Melatonin reportedly plays a beneficial role in cardiovascular diseases; however, the mechanisms underlying improvements in atherosclerotic plaque vulnerability remain unknown. In this study, we assessed the role of melatonin in regulating SMC phenotypic switching and its consequential contribution to the amelioration of atherosclerotic plaque vulnerability and explored the mechanisms underlying this process. We analyzed features of atherosclerotic plaque vulnerability and markers of SMC phenotypic transition in high-cholesterol diet (HCD)–fed apolipoprotein E knockout (<i>ApoE</i>^−/−) mice and human aortic SMCs (HASMCs). Melatonin reduced atherosclerotic plaque size and necrotic core area while enhancing collagen content, fibrous cap thickness, and smooth muscle alpha-actin positive cell coverage on the plaque cap, which are all known phenotypic characteristics of vulnerable plaques. In atherosclerotic lesions, melatonin significantly decreased the synthetic SMC phenotype and KLF4 expression and increased the expression of PPARδ, but not PPARα and PPARγ, in HCD-fed <i>ApoE</i>^−/− mice. These results were subsequently confirmed in the melatonin-treated HASMCs. Further analysis using PPARδ silencing and immunoprecipitation assays revealed that PPARδ plays a role in the melatonin-induced SMC phenotype switching from synthetic to contractile. Collectively, we provided the first evidence that melatonin mediates its protective effect against plaque destabilization by enhancing PPARδ-mediated SMC phenotypic switching, thereby indicating the potential of melatonin in treating atherosclerosis.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Deprivation Induces Gut Damage via Ferroptosis","authors":"Zi-Jian Zheng,&nbsp;Hai-Yi Zhang,&nbsp;Ya-Lin Hu,&nbsp;Yan Li,&nbsp;Zhi-Hong Wu,&nbsp;Zhi-Peng Li,&nbsp;Dong-Rui Chen,&nbsp;Yang Luo,&nbsp;Xiao-Jing Zhang,&nbsp;Cang Li,&nbsp;Xiao-Yu Wang,&nbsp;Dan Xu,&nbsp;Wei Qiu,&nbsp;Hong-Ping Li,&nbsp;Xiao-Ping Liao,&nbsp;Hao Ren,&nbsp;Jian Sun","doi":"10.1111/jpi.12987","DOIUrl":"10.1111/jpi.12987","url":null,"abstract":"<div>\u0000 \u0000 <p>Sleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Protects Against Colistin-Induced Intestinal Inflammation and Microbiota Dysbiosis","authors":"Yuqian Jia,&nbsp;Tingting Zhang,&nbsp;Mengping He,&nbsp;Bingqing Yang,&nbsp;Zhiqiang Wang,&nbsp;Yuan Liu","doi":"10.1111/jpi.12989","DOIUrl":"10.1111/jpi.12989","url":null,"abstract":"<div>\u0000 \u0000 <p>Colistin is renowned as a last-resort antibiotic due to the emergence of multidrug-resistant pathogens. However, its potential toxicity significantly hampers its clinical utilization. Melatonin, chemically known as <i>N</i>-acetyl-5-hydroxytryptamine, is an endogenous hormone produced by the pineal gland and possesses diverse biological functions. However, the protective role of melatonin in alleviating antibiotic-induced intestinal inflammation remains unknown. Herein, we reveal that colistin stimulation markedly elevates intestinal inflammatory levels and compromises the gut barrier. In contrast, pretreatment with melatonin safeguards mice against intestinal inflammation and mucosal damage. Microbial diversity analysis indicates that melatonin supplementation prevents a reduction in the abundance of <i>Erysipelotrichales</i> and <i>Bifidobacteriales</i>, as well as an increase in <i>Desulfovibrionales</i> abundance, following colistin exposure. Remarkably, short-chain fatty acids (SCFAs) analysis shows that propanoic acid contributes to the protective effect of melatonin on colistin-induced intestinal inflammation. Furthermore, the protection effects of melatonin and propanoic acid on LPS-induced cellular inflammation in RAW 264.7 cells are confirmed. Mechanistic investigations suggest that intervention with melatonin and propanoic acid can repress the activation of the TLR4 signal and its downstream NF-κB and MAPK signaling pathways, thereby mitigating the toxic effects of colistin. Our work highlights the unappreciated role of melatonin in preventing the potential detrimental effects of colistin on intestinal health and suggests a combined therapeutic strategy to effectively manage intestinal infectious diseases.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 5","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}