Journal of Pineal Research最新文献

{"title":"Functional Characterization of GNA1 as a Serotonin N-Acetyltransferase Reveals a Key Role in the Serotonin to Melatonin Pathway in Saccharomyces cerevisiae","authors":"Qingjian Zhang,&nbsp;Dongfeng Cheng,&nbsp;Xianghua Tang,&nbsp;Yibo Li,&nbsp;Nanyu Han,&nbsp;Wei Xu,&nbsp;Junmei Ding","doi":"10.1111/jpi.70065","DOIUrl":"https://doi.org/10.1111/jpi.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin (<i>N</i>-acetyl-5-methoxytryptamine) is an evolutionarily conserved molecule with diverse physiological functions across prokaryotes, plants, and animals, including circadian rhythms regulation in animals and developmental modulation in plants. Although the biosynthetic pathways of melatonin have been well elucidated in mammals and plants, the enzymatic mechanisms underlying microbial melatonin synthesis remain largely unexplored. <i>Saccharomyces cerevisiae</i>, a genetically tractable eukaryotic model, provides a valuable system for elucidating fungal melatonin biosynthesis. In this study, we identified the <i>GNA1</i> gene as a potential serotonin <i>N</i>-acetyltransferase candidate in <i>S. cerevisiae</i> through genome-wide comparative analysis. The GNA1 protein was heterologously expressed in <i>Escherichia coli</i> BL21(DE3), purified, and subjected to detailed enzymatic characterization. In vitro assays revealed that GNA1 exhibits acetyltransferase activity toward both serotonin and 5-methoxytryptamine (5-MT), with maximal catalytic efficiency observed at 30°C and pH 8.5. Substrate specificity and kinetic analyses demonstrated a pronounced preference for 5-MT, supporting a biosynthetic route in which serotonin undergoes <i>O</i>-methylation before acetylation by GNA1 to yield melatonin. This study provides the first biochemical evidence linking GNA1 to melatonin biosynthetic pathway in yeast and offers new insights into microbial melatonin biosynthesis, highlighting its potential evolutionary and metabolic significance.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367283","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 Prevents Tumor Growth: The Role of Genes Controlling the Circadian Clock, the Cell Cycle, and Angiogenesis","authors":"Skarleth Cardenas-Romero,&nbsp;Nadia Saderi,&nbsp;Oscar Daniel Ramirez-Plascencia,&nbsp;Adrián Baez-Ruiz,&nbsp;Omar Flores-Sandoval,&nbsp;Carolina Escobar Briones,&nbsp;Roberto C. Salgado-Delgado","doi":"10.1111/jpi.70064","DOIUrl":"https://doi.org/10.1111/jpi.70064","url":null,"abstract":"<p>Recent evidence highlights the protective role of melatonin in a variety of pathological conditions, including multiple types of cancer. Epidemiological studies increasingly suggest that exposure to light at night suppresses melatonin synthesis in night-shift and rotating-shift workers, potentially elevating their risk of cancer development. Experimental data further indicate that melatonin can inhibit the proliferation of tumor cells, including glioblastoma-like stem cells. In the present study, we investigated the effect of melatonin on the expression of genes involved in regulating the circadian rhythm, cell cycle progression, and angiogenesis in rats exposed to constant light, a model of circadian disruption. Our findings demonstrate that melatonin administration significantly inhibited tumor growth and reduced the vascularization associated with circadian rhythm disturbance. Molecular analysis revealed that melatonin altered the circadian expression of several genes affecting tumor biology, including <i>p53, TNF-α</i>, <i>Per2</i>, <i>VEGF-A</i>, <i>PDGF-C</i>, and <i>Ang</i>, which are involved in circadian rhythms, cell cycle, and angiogenesis regulation. These results strengthen the existing hypothesis that circadian disruption contributes to tumor progression and suggest that melatonin exerts anticancer effects by modulating circadian gene expression and angiogenesis. Our findings provide further insight into the mechanism by which melatonin may exert oncostatic effects and highlight its potential as a therapeutic agent in cancers associated with circadian rhythm disruption.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292517","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 Enhances Aquaporin 4 and Alpha-Syntrophin Interaction by Inhibiting Cyclin-Dependent Kinase 5 Activity to Preserve Glymphatic Function in Neonatal Hypoxic-Ischemic Encephalopathy","authors":"Yuan Li,&nbsp;Qingqing Ye,&nbsp;Weitian Lu,&nbsp;Tingsong Li,&nbsp;Shilong Tang,&nbsp;Ting Wei,&nbsp;Pengyu Xiao,&nbsp;Xingfeng Chen,&nbsp;Xiaojuan Wang,&nbsp;Xiaoran Jiang,&nbsp;Mosaab Mohamed Elmahdi,&nbsp;Juan Huang","doi":"10.1111/jpi.70063","DOIUrl":"https://doi.org/10.1111/jpi.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>The glymphatic system is a critical waste clearance system in the brain, playing an essential role in maintaining homeostasis within the central nervous system. Aquaporin 4 (AQP4), an indispensable component of the glymphatic system, is vital for ensuring the proper function of this system. Melatonin has been proven to be protective in treating hypoxic-ischemic encephalopathy (HIE). The aim of this study was to examine if alterations occur in the glymphatic system function in the brain of HIE model rats, and to determine whether melatonin can enhance the function of the glymphatic system by regulating AQP4, along with elucidating the mechanisms underlying melatonin's effects on AQP4. 10-day-old rat pups were subjected to hypoxic-ischemic (HI) injury; melatonin and roscovitine (an inhibitor of cyclin-dependent kinase 5) were injected intraperitoneally at 10 min following HI induction. At 24 h post-HI, intracisternal tracer infusion, neurobehavioral tests, immunofluorescence staining, western blot analysis, Evans blue (EB) permeability assay, brain water content test, ELISA detection, and co-immunoprecipitation tests were performed. At 28 days post-HI, neurobehavioral tests, intracisternal EB infusion, Nissl staining, and cerebral blood flow (CBF) evaluations were performed. The results showed that melatonin improved neurological function, restored glymphatic function, maintained blood–brain barrier integrity, alleviated brain edema, increased CBF, and reduced brain atrophy; both melatonin and roscovitine inhibited cyclin-dependent kinase 5 (CDK5) activity, enhanced the interaction between AQP4 and alpha-syntrophin (α-Syn), and maintained AQP4 polarity. In conclusion, the current study suggests that melatonin may enhance the interaction between AQP4 and α-Syn by inhibiting CDK5 activity after HI to maintain glymphatic function.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273177","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":"Standardized and Calibrated Light Stimuli via Head-Mounted Displays for Investigating the Nonvisual Effects of Light","authors":"Maydel Fernandez-Alonso,&nbsp;Manuel Spitschan","doi":"10.1111/jpi.70051","DOIUrl":"https://doi.org/10.1111/jpi.70051","url":null,"abstract":"<p>Light influences human physiology profoundly, affecting the circadian clock and suppressing the endogenous hormone melatonin. Experimental studies often employ either homogenous full-field stimulation, or overhead illumination, which are hard to standardize across studies and laboratories. Here, we present a novel technique to examine nonvisual responses to light using virtual-reality (VR) head-mounted displays (HMDs) for delivering standardized and calibrated light stimuli to observers in a reproducible and controlled manner. We find that VR HMDs are well-suited for delivering standardized stimuli defined in luminance and across time, with excellent properties up to 10 Hz. We examine melatonin suppression to continuous luminance-defined light stimuli in a sample of healthy participants (<i>n</i> = 32, mean ± SD age: 27.2 ± 5.6), and find robust melatonin suppression in 24 out of 32 participants (75% of the sample). Our findings demonstrate that VR HMDs are well-suited for studying the mechanisms underlying human nonvisual photoreception in a reproducible and standardized fashion.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206920","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":"A Newly Characterized Phytomelatonin Transporter Promotes Tolerance Against Multiple Inorganic Pollutants in Nicotiana benthamiana","authors":"Aditya Banerjee,&nbsp;Aryadeep Roychoudhury","doi":"10.1111/jpi.70061","DOIUrl":"https://doi.org/10.1111/jpi.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin is a known pleiotropic antioxidant and signaling molecule, found in both plants and animals. Although melatonin was found to translocate via the human glucose transporter 1 (GLUT1), any mechanism of transporter-mediated uptake of melatonin has remained unknown in plants. In the present manuscript, we found an orthologue of GLUT1 in tobacco and established its role as a functional phytomelatonin transporter (MelT) using fluorescence tracking, via melatonin-conjugated quantum dot nanoparticles. Overexpression of <i>NtMelT</i> in the model plant <i>Nicotiana benthamiana</i> showed increased uptake of the conjugated nanofluorophores to a maximum of 5.4-fold in roots and 2.1-fold in leaves, while application of <i>N</i>-ethylmaleimide (inhibitor of glucose transporter) suppressed their translocation. This ensured the specificity of NtMelT for transporting melatonin. Due to increased uptake and distribution, the transgenic lines maintained a maximum of 4.6-fold more endogenous melatonin. The transgenics were tolerant against arsenic, copper, lead, nickel, and fluoride toxicity. Increased activity of the enzymatic antioxidants detoxified excess reactive oxygen species and alleviated the associated physiological injuries. Translocation of melatonin significantly reduced bioaccumulation of the toxic pollutants and ensured normal flowering and seed setting in the transgenic plants. Overall, the present research provides a solution for safe rice cultivation under polluted environment.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190850","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: A Potential Therapy for Osteoporosis With Insights Into Molecular Mechanisms","authors":"Ko-Hsiu Lu,&nbsp;Yi-Hsien Hsieh,&nbsp;Renn-Chia Lin,&nbsp;Meng-Ying Tsai,&nbsp;Shun-Fa Yang","doi":"10.1111/jpi.70062","DOIUrl":"https://doi.org/10.1111/jpi.70062","url":null,"abstract":"<p>Melatonin is a versatile neurohormone with diverse molecular functions, including sleep regulation, inflammation reduction, antioxidant activity, immune modulation, and anticancer properties. In bone metabolism, it promotes osteoblast formation, inhibits osteoclast activity, and synchronizes skeletal tissue rhythms to support bone health. As melatonin is not yet clinically used for osteoporosis and concerns about the current treatments' side effects remain, this review highlights its role in modulating osteoblast and osteoclast interactions, particularly through regulation of the receptor activator of nuclear factor-κB ligand and osteoprotegerin, to achieve bone-forming and antiresorptive effects. These effects have been demonstrated across various concentrations in diverse cell types and In Vivo models. Furthermore, melatonin safeguards the bone microenvironment by mitigating oxidative stress and inflammation, protecting osteoblasts, preventing bone loss, and maintaining the gut microbiota and brain–gut–bone axis. These attributes underscore melatonin's potential as an effective alternative or complementary therapy for promoting bone health and managing osteoporosis. Future research is needed to determine optimal dosing and timing for maximum efficacy.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 4","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190849","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":"Analyzing the Interactions of Light and Melatonin Forcing in a Mathematical Model of the Human Circadian Oscillator","authors":"Shelby R. Stowe,&nbsp;Armelle Duston,&nbsp;Will Robinson,&nbsp;Cecilia Diniz Behn","doi":"10.1111/jpi.70056","DOIUrl":"https://doi.org/10.1111/jpi.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>The pineal secretion of the hormone melatonin demonstrates a circadian (~24 h) rhythm with the onset of melatonin production at night and offset each morning under tight circadian control for entrained individuals. Melatonin exerts both acute sleep-promoting effects and phase-shifting effects on the circadian clock. Due to its hypnotic and chronobiotic (phase shifting) effects, exogenous melatonin supplements are increasingly being used as a treatment for a variety of sleep and circadian diseases and disorders. Phase shifting of the circadian clock can also be accomplished through ocular exposure to light. However, the interacting effects of light and melatonin on the circadian clock are not well understood. To analyze the dynamic behavior of both endogenous and exogenous melatonin's influence on the circadian clock, we extend a previously published mathematical model of the circadian clock to account for forcing due to both endogenous melatonin produced by the pineal gland and exogenous melatonin entering the system through ingested oral supplements. We fit model parameters using published melatonin pharmacokinetics, a melatonin suppression illuminance-response curve, and a 3-pulse 3 mg melatonin phase response curve (PRC). Simulated microscopic PRCs to light and melatonin are determined by the model fits and demonstrate a relative phase difference consistent with previous observations in experimental PRC data. Finally, we simulate a phase advancing experimental protocol utilizing both light exposure and exogenous melatonin to generate model predictions for the effects of interacting inputs to the clock. This modeling framework allows for the study of melatonin's dynamic properties and interaction with the circadian clock. Furthermore, it provides a framework for determining optimal light exposure and exogenous melatonin administration schedules to induce desired phase shifting of the circadian clock.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135592","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 as a Ripening Inhibitor: Enhancing Shelf Life and Quality in Red Banana","authors":"Anchana Kandasamy,&nbsp;Kavitha Chinnasamy,&nbsp;Suresh Kumar Paramasivam,&nbsp;Johnson Iruthayasamy","doi":"10.1111/jpi.70060","DOIUrl":"https://doi.org/10.1111/jpi.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>In climacteric fruits like banana (<i>Musa</i> spp.), ripening is driven by ethylene production and increased respiration, leading to rapid softening, quality loss, and disease susceptibility. This study was aimed to evaluate the effect of postharvest melatonin dip (1.0 mM and 1.5 mM for 15 min) on Red Banana stored under ambient and cold storage conditions. Melatonin significantly suppressed ethylene biosynthesis (Cohen's <i>d ƞ</i>² = 0.85), reduced respiration rate (<i>ƞ</i>² = 0.89), and delayed textural degradation by inhibiting cell wall-degrading enzymes (polygalacturonase, pectin methyl esterase, amylase, cellulase, and β-glucosidase) with 35.94% and 45.48% reduction in cumulative enzyme activity under ambient and cold storage, respectively. It also enhanced antioxidant enzyme activity resulting in 1.8- and 1.5-fold increases in enzyme activity in ambient and cold storage, respectively, mitigating oxidative stress and reducing anthracnose incidence. Consequently, melatonin extended shelf life by 2.67 days in ambient storage and 5.33 days in cold storage, without inducing chilling injury. These findings highlight melatonin as a natural, eco-friendly alternative, offering a sustainable strategy to enhance Red Banana storage and reduce postharvest losses. Its ability to modulate fruit metabolism, enhance stress responses, and membrane protection properties underscores its applied potential in postharvest management.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135528","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 Alleviates Oxidative Stress-Induced Mitochondrial Dysfunction Through Ameliorating NAD+ Homeostasis of hDPSCs for Cell-Based Therapy","authors":"Xiu Peng,&nbsp;Li Zhao,&nbsp;Jiale Wang,&nbsp;Yinmo Zhang,&nbsp;Zihan Liu,&nbsp;Kun Wang,&nbsp;Linglin Zhang","doi":"10.1111/jpi.70058","DOIUrl":"https://doi.org/10.1111/jpi.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Human dental pulp stem cells (hDPSCs) exhibit amazing therapeutic abilities in a variety of diseases due to their remarkable self-renewal capacity and multi-differentiation potential. However, their therapeutic potential could be weakened by various factors such as oxidative stress in cell survival microenvironment In Vivo. Here, we explored the protective effect and mechanism of melatonin (Mel) on hDPSCs transplanted in a type 1 diabetes mellitus (T1DM) rat model. Nicotinamide adenine dinucleotide (NAD⁺) metabolism and mitochondrial function were remarkably impaired in T1DM rats caused by oxidative stress, while the combination of Mel and post-hDPSCs transplantation could rebalance NAD⁺ homeostasis through regulating NAMPT-NAD⁺-SIRT1 axis. Furthermore, Mel significantly reduced intracellular and mitochondrial reactive oxygen species, and alleviated cell senescence and apoptosis of hDPSCs exposed to hydrogen peroxide through ameliorating NAD⁺ depletion and mitochondrial dysfunction. The protective role of Mel could be extremely essential to stem cells in tissue engineering and regenerative medicine.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091950","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":"Microbial Melatonin Production Improves Plant Metabolic Function in Short-Term Climate-Induced Stresses","authors":"Eun-Hae Kwon,&nbsp;Arjun Adhikari,&nbsp;Abdul Latif Khan,&nbsp;Eunsu Do,&nbsp;Nusrat Jahan Methela,&nbsp;Chung-Yeol Lee,&nbsp;Sang-Mo Kang,&nbsp;Kang-Mo Ku,&nbsp;Byung-Wook Yun,&nbsp;In-Jung Lee","doi":"10.1111/jpi.70052","DOIUrl":"https://doi.org/10.1111/jpi.70052","url":null,"abstract":"<p>Climate change, specifically high temperatures, can reduce soil moisture and cause hypersaline conditions, which creates an unsustainable agro-production system. Microbial symbionts associated with plants relinquish stressful conditions by producing stress-protecting substances. Melatonin is a signaling and stress-protecting molecule for plants, but is least known for microbial symbionts and their function in stress protection. Here, our study shows that the melatonin-synthesizing <i>Bacillus velezensis</i> EH151 (27.9 ng/mL at 96 h) significantly improved host plant (<i>Glycine max</i> L.) growth, biomass, photosynthesis, and reduced oxidative stress during heat and salinity stress conditions than the non-inculcated control. The EH151 symbiosis enhanced the macronutrient (P, Ca, and K) and reduced Na uptake in shoots during stress conditions. The microbial inoculation significantly expressed the <i>high-affinity K</i>^<i>+</i> <i>transporter</i>, <i>MYB transcription factor</i>, <i>Salt Overly Sensitive 1</i>, <i>Na</i>^<i>+</i><i>/H</i>^<i>+</i> <i>antiporter 2</i>, and <i>heat shock transcription factors</i> in spatio-temporal orders during heat and salinity stress (H&amp;S 1, 3, 10, and 14 h). We observed that microbial strain significantly increased the plant's endogenous abscisic acid (49.5% in H&amp;S 10 h), jasmonic acid (71% in H&amp;S 10 h), and melatonin biosynthesis (418% in H&amp;S 14 h). Metabolome map of plant defense response showed that EH151 enhanced activation of amino acid metabolism pathways (e.g., glutamate (34%) <span>L</span>-aspartate (82%), glycine (18.5%), and serine (58%) under H&amp;S 14 h compared to non-inoculation). Conversely, the free sugars and organic acids within the central carbon metabolism were significantly activated in non-inoculated combined heat and salinity stress compared to inoculated plants—suggesting lesser defense energy activated for stress tolerance. In conclusion, the current results show promising effects of the microbial abilities of melatonin that can regulate host growth and defense responses. Utilization of beneficial strains like <i>B. velezensis</i> EH151 could be the ideal strategy to improve stress tolerance and overcome the adverse impact of climate-induced abrupt changes.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 3","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085462","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}