Seasonal variation of melatonin secretion across various segments of the gastrointestinal tract in rats

Objective:To investigate whether melatonin(MT)secretion in different parts of the gastrointestinal tract(GIT)exhibits seasonal variations and its correlation with immune regulation.Methods: Sixty Sprague-Dawley rats were divided into control and model groups,and the pineal gland was removed in the model group.Stomach,jejunum,ileum,and colon tissues were obtained during the spring equinox,summer solstice,beginning of autumn,autumn equinox,and winter solstice.The levels of MT,MT receptors(MR),arylalkylamine N-acetyltransferase(AANAT),hydroxyindole-O-methyltransferase(HIOMT),interleukin-2(IL-2),and interleukin-10(IL-10)in the GIT were measured using enzyme-linked immunosorbent assay.Results: Except for the stomach,the jejunum,ileum,and the colon showed seasonal tendencies in MT secretion.In the control group,MT secretion in the jejunum and ileum was the highest in the long summer,and colonic MT secretion was the highest in winter.In the model group,MT levels in the colon were highest in the summer.The seasonal rhythms of the MR,AANAT,HIOMT,IL-2,and IL-10 in the colon were roughly similar to those of MT,and changed accordingly after pinealectomy.Conclusions: Gastrointestinal MT secretion is related to seasonal changes,and MT secretion in each intestinal segment is influenced by different seasons.The biological effects of MT in the gut are inextricably linked to the mediation of MR,and a hormone-receptor linkage exists between MT and MR.The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

Exogenous melatonin improves cotton yield under drought stress by enhancing root development and reducing root damage

The exogenous application of melatonin by the root drenching method is an effective way to improve crop drought resistance.However,the optimal concentration of melatonin by root drenching and the physiological mechanisms underlying melatonin-induced drought tolerance in cotton(Gossypium hirsutum L.)roots remain elusive.This study determined the optimal concentration of melatonin by root drenching and explored the protective effects of melatonin on cotton roots.The results showed that 50μmol L-1 melatonin was optimal and significantly mitigated the inhibitory effect of drought on cotton seedling growth.Exogenous melatonin promoted root development in drought-stressed cotton plants by remarkably increasing the root length,projected area,surface area,volume,diameter,and biomass.Melatonin also mitigated the drought-weakened photosynthetic capacity of cotton and regulated the endogenous hormone contents by regulating the relative expression levels of hormone-synthesis genes under drought stress.Melatonin-treated cotton seedlings maintained optimal enzymatic and non-enzymatic antioxidant capacities,and produced relatively lower levels of reactive oxygen species and malondialdehyde,thus reducing the drought stress damage to cotton roots(such as mitochondrial damage).Moreover,melatonin alleviated the yield and fiber length declines caused by drought stress.Taken together,these findings show that root drenching with exogenous melatonin increases the cotton yield by enhancing root development and reducing the root damage induced by drought stress.In summary,these results provide a foundation for the application of melatonin in the field by the root drenching method.

Exercise-with-melatonin therapy improves sleep disorder and motor dysfunction in a rat model of ischemic stroke

Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer's disease,but its effect on stroke is still poorly understood.In this study,we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes.We treated the rats with exercise and melatonin therapy for 7 consecutive days.Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats,increased delta power values,and regularized delta power rhythm.Additionally,exercise-with-melatonin therapy improved coordination,endurance,and grip strength,as well as learning and memory abilities.At the same time,it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone.These findings suggest that exercise-withmelatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.

急性呼吸窘迫综合征患儿血清Melatonin、MIP-1α与NLRP3炎症小体和预后的关系分析

目的探讨急性呼吸窘迫综合征(ARDS)患儿血清褪黑素(Melatonin)、巨噬细胞炎性蛋白-1α(MIP-1α)与核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体和预后的关系。方法选取2021年1月至2023年1月该院收治的ARDS患儿140例纳入ARDS组,另选取同期100例体检健康儿童纳入对照组。根据入院28 d临床结局将ARDS患儿分为死亡组29例和存活组111例。采用酶联免疫吸附试验检测血清Melatonin、MIP-1α、白细胞介素(IL)-1β、IL-18水平,实时荧光定量PCR检测NLRP3 mRNA、半胱氨酸蛋白酶-1(Caspase-1)mRNA水平。采用Pearson相关分析ARDS患儿血清Melatonin、MIP-1α水平与NLRP3炎症小体相关指标(NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18)的相关性。采用多因素Cox回归分析影响ARDS患儿预后的因素。根据ARDS患儿血清Melatonin、MIP-1α水平均值分为高/低血清Melatonin、MIP-1α组,Kaplan-Meier法绘制高/低血清Melatonin、MIP-1α水平ARDS患儿生存曲线。采用受试者工作特征(ROC)曲线分析血清Melatonin、MIP-1α对ARDS患儿死亡的预测价值。结果与对照组比较,ARDS组血清Melatonin水平降低,血清MIP-1α、IL-1β、IL-18和外周血单核细胞NLRP3 mRNA、Caspase-1 mRNA水平升高(P<0.05)。Pearson相关分析显示,ARDS患儿血清Melatonin水平与NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18均呈负相关(P<0.05),MIP-1α水平与NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18均呈正相关(P<0.05)。多因素Cox回归分析显示,急性生理学和慢性健康状况评价Ⅱ评分、NLRP3 mRNA、Caspase-1 mRNA、IL-1β、IL-18、MIP-1α为影响ARDS患儿预后的独立危险因素,Melatonin为独立保护因素(P<0.05)。Kaplan-Meier生存曲线分析显示,高血清Melatonin组28 d生存率高于低血清Melatonin组(P<0.05),高血清MIP-1α组28 d生存率低于低血清MIP-1α组(P<0.05)。ROC曲线分析显示,血清Melatonin、MIP-1α联合预测ARDS患儿死亡的曲线下面积为0.881(95%CI 0.816~0.930),大于血清Melatonin、MIP-1α单独预测的0.785(95%CI 0.708~0.850)、0.778(95%CI 0.700~0.844)。结论ARDS患儿血清Melatonin水平降低、MIP-1α水平升高,与NLRP3炎症小体和预后密切相关,联合检测血清Melatonin、MIP-1α水平对ARDS患儿预后具有较高的预测价值。

Melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience

Melatonin and dopamine can potentially prevent waterlogging stress in apples.The current study investigated the mechanism by which melatonin and dopamine alleviate apple waterlogging stress.This study demonstrated that melatonin and dopamine alleviated waterlogging by removing reactive oxygen species(ROS),and that the nitric oxide(NO)content and nitrate reductase(NR)activity were significantly correlated.Melatonin and dopamine were also found to recruit different candidate beneficial endophytes(melatonin:Novosphingobium,Propionivibrio,and Cellvibrio;dopamine:Hydrogenophaga,Simplicispira,Methyloversatilis,Candidatus_Kaiserbacteria,and Humicola),and these endophytes were significantly and positively correlated with plant growth.Network analyses showed that melatonin and dopamine significantly affected the endophytic bacterial and fungal communities under waterlogging stress.The metabolomic results showed that melatonin and dopamine led to waterlogging resistance by upregulating the abundance of beneficial substances such as amino acids,flavonoids,coumarins,and organic acids.In addition,melatonin and dopamine regulated the physicochemical properties of the soil,which altered the endophyte community and affected plant growth.The co-occurrence network demonstrated close and complex relationships among endophytes,metabolites,soil,and the plants.Our results demonstrate that melatonin and dopamine alleviate waterlogging stress in apples by recruiting beneficial endophytes to enhance physiological resilience.This study provides new insights into how melatonin and dopamine alleviate stress and a theoretical basis for synergistic beneficial microbial resistance to waterlogging stress.

UV-B irradiation enhances the accumulation of beneficial glucosinolates induced by melatonin in Chinese kale sprout

Cruciferous sprout is a new form of vegetable product rich in bioactive compounds,especially glucosinolates.Previous studies have focused on increasing the accumulation of glucosinolates in cruciferous sprouts by applying different chemical regulators,with a particular focus on their contribution to nutritional quality and health benefits.Nevertheless,the effects of melatonin and UV-B irradiation on glucosinolate biosynthesis remain unclear.In this study,it was found that changes in melatonin concentrations significantly affected the contents of individual as well as total aliphatic and indolic glucosinolates.The 5μmol·L^(-1)melatonin was decided as the optimum concentration that could increase the content of beneficial glucosinolates including glucoraphanin and 4-methoxy glucobrassicin in Chinese kale sprouts.Notably,the enhancement of glucosinolate accumulation by melatonin treatment could be further amplified by UV-B irradiation.Furthermore,our results showed that R2R3-MYB transcription factor BoaMYB28 and BoaMYB51,which are central regulators of aliphatic and indolic glucosinolate biosynthesis respectively,were both involved in the regulation of glucosinolate biosynthesis by melatonin and UV-B irradiation.Additionally,the expression of glucosinolate biosynthetic genes,including BoaCYP79F1,BoaCYP83A1,BoaSUR1,BoaUGT74B1,BoaCYP79B2,BoaCYP79B3,and BoaCYP83B1 participated in the formation of core structures and BoaFMOGS-OX5,BoaAOP2,BoaCYP81F2,and BoaIGMT1 involved in the sidechain modification of aliphatic and indolic glucosinolate,was regulated by melatonin or UV-B irradiation.Taken together,these findings provide a potential strategy for improving the nutritional quality and resistance of Chinese kale sprouts.

Rice melatonin deficiency causes premature leaf senescence via DNA methylation regulation

In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

Melatonin delays leaf senescence in pak choi(Brassica rapa subsp.chinensis)by regulating biosynthesis of the second messenger cGMP

Melatonin(MT)is a low molecular weight compound with multiple biological functions in plants.It is known to delay leaf senescence in various species.However,no data are available on the MT signaling pathway in postharvest vegetables.This study demonstrates that MT increases cGMP concentration and the expression of the cGMP synthesis gene BcGC1 in pak choi.The c GMP inhibitor LY83583 destroys effect of MT delaying the leaf senescence.LY83583 also prevents MT treatment from reducing the expression of chlorophyll metabolism-related genes(BcNYC1,BcNOL,BcPPH1/2,BcSGR1/2,and BcPAO)and senescence genes(BcSAG12 and BcSAG21).It also inhibits MT from reducing the activity of the key chlorophyll catabolism enzymes Mg-dechelatase,pheophytinase,and pheide a oxygenase.Thus,the ability of MT to maintain high levels of chlorophyll metabolites is also destroyed.The Arabidopsis c GMP synthetic gene mutant atgc1 was used to confirm that delayed leaf senescence caused by MT is mediated,at least in part,by the second messenger c GMP.

Melatonin mitigates cold-induced damage to pepper seedlings by promoting redox homeostasis and regulating antioxidant profiling

This study assessed the influence of exogenous ME in the mitigation of cold damage in pepper seedlings. Melatonin(ME) is a dynamic molecule that helps plants cope with stress in several ways. Cold stress(CS) is one of the most important environmental factors that restrict plant growth and yield. Pepper(Capsicum annuum L.) is a valuable commercial crop, highly sensitive to CS. Thus, identifying an efficient strategy to mitigate cold damage is critical for long-term pepper production. For this purpose, the roots of pepper seedlings were pretreated with ME(5 μmol · L^(-1)) and exposed to CS for 7 d. The results indicated that CS suppressed pepper growth, hampered photosynthetic capacity, and damaged root architecture in pepper plants. In contrast, the production of reactive oxygen species(ROS), malondialdehyde(MDA), electrolyte leakage(EL), proline, and soluble sugars were enhanced in plants under CS. ME(5 μmol · L^(-1)) pretreatment reduced the negative effects of CS by recovering plant growth, root traits, gas exchange elements, and pigment molecules compared to CS control treatment. Furthermore, ME application efficiently reduced oxidative stress markers [hydrogen peroxide(H_(2)O_(2)), superoxide ion(O_(2)^(·-)), EL, and MDA] while increasing proline and soluble sugar content in pepper leaves. ME application combined with CS further increased antioxidant enzymes and related gene expression. Collectively, our results confirmed the mitigating potential of ME supplementation for CS by maintaining pepper seedling growth,improving the photosynthesis apparatus, regulating pigments, and osmolyte content.

Melatonin Alleviates Abscisic Acid Deficiency Inhibition on Photosynthesis and Antioxidant Systems in Rice under Salt Stress

Melatonin and abscisic acid,as major plant hormones,play important roles in the physiological and biochemical activities of crops,but the interaction between the two under salt stress is not yet clear.This study investigated the endogenous levels of melatonin and abscisic acid in rice by using exogenous melatonin,abscisic acid,and their synthetic inhibitors,and examined their interactions under salt stress.The research results indicate that melatonin and abscisic acid can improve rice salt tolerance.Melatonin alleviated the salt sensitivity caused by abscisic acid deficiency,increased antioxidant enzyme activity and antioxidant content in rice treated with abscisic acid synth-esis inhibitors,and reduced total reactive oxygen species content and thiobarbituric acid reactive substance accu-mulation.Melatonin also increased the activity of key photosynthetic enzymes and the content of photosynthetic pigments,maintaining the parameters of photosynthetic gas exchange and chlorophyllfluorescence.In summary,melatonin alleviated the effects of abscisic acid deficiency on photosynthesis and antioxidant systems in rice and improved salt tolerance.This study is beneficial for expanding the understanding of melatonin regulation of crop salt tolerance.

Starch Orodispersible Film Loaded with Melatonin for Human Supplementation

An innovative pharmaceutical form for administering melatonin,based on starch orodispersiblefilm(ODF),was designed and prepared.The composition of the ODF included starch as the polymer matrix,the active drug melatonin,and a plasticizer.Melatonin,a natural hormone produced by the pineal gland in the brain,can be absorbed by passive diffusion across the mucous membrane,resulting in improved bioavailability when compared to conventional oral administration.This study shows a simple and efficient method for preparing melatonin-loaded orodispersiblefilms with a physically stable and commercially viable matrix,suitable for use in the pharmaceutical industry.Thefilms were prepared by treating the starch with microwave irradiation,followed by plasticization with glycerol,melatonin loading and drying by solvent casting.Mechanical tests showed thefilms’robustness,with a modulus of approximately 97 MPa,indicating good handling properties.Moisture uptake analysis showed fast water absorption,reaching about 150%within 2 min,indicating its fast oral disintegration potential.Disintegration tests in artificial saliva and dissolution studies indicated the release of the drug in min-utes,indicating the potential properties of thefilm for oral drug delivery.To the best of our knowledge,there is no melatonin ODF based on starch described in the literature.

Gene expression analysis of cytokines and MMPs in melatonin and rhBMP-2 enhanced bone remodeling

BACKGROUND In the medical and dental fields,there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss.Melatonin may be an important endogenous biological factor for bone remodeling,and growth factors may enhance the repair process.AIM To evaluate the gene expression of cytokines(IL-1β,IL-6,IL-10 and TNF-α),markers of osteoclastogenesis(RANK,RANKL and OPG)and MMPs(MMP-1,MMP-2,MMP-8 and MMP-13)from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.METHODS Sixty-four rats were used and divided into 9 experimental groups and were formed according to the treatment carried out in the region of the bone lesion,which varied between the combination of 1,10 and 100μmol/L of melatonin.Gene Expression analysis was performed using real time-PCR by reading the concentration of total RNA and reverse transcription.RESULTS There were differences between groups when compared with clot or scaffold control,and improvement with a higher concentration of melatonin or rhBMP-2.The combination melatonin(1μg)with 5μg of rhBMP-2,using the guided bone regeneration technique,demonstrated some effects,albeit mild,on bone repair of critical bone defects.CONCLUSION This indicates that the approach for administering these substances needs to be reassessed,with the goal of ensuring their direct application to the affected area.Therefore,future research must be carried out,seeking to produce materials with these ideal characteristics.

2-Iodomelatonin上调NRF2表达对缺血性脑损伤神经保护作用

目的探讨褪黑激素受体1(MT1)激动剂2-Iodomelatonin通过上调核因子E2相关因子2(NRF2)对大脑中动脉栓塞小鼠的神经保护作用。方法采用大脑中动脉栓塞(MCAO)法制备小鼠缺血性脑损伤体内模型,给予2-Iodomelatonin及NRF2抑制剂(Nrf2-IN-1)干预。采用三苯基氯化四氮唑(TTC)染色法检测小鼠大脑的梗死体积,Western Blot法检测缺血损伤后大脑皮质半暗带NRF2表达水平,改良神经功能缺损程度评分(mNSS)评估2-Iodomelatonin和Nrf2-IN-1干预对小鼠缺血性脑损伤亚急性期运动功能的影响。结果TTC染色结果显示,2-Iodomelatonin干预可以显著降低缺血性脑损伤小鼠的大脑梗死体积(F=7.79,q=5.06,P<0.05)。Western Blot结果显示,2-Iodomelatonin干预可上调小鼠皮质梗死半暗带NRF2的表达水平(F=10.56,q=3.99,P<0.05)。mNSS评分结果显示,2-Iodomelatonin干预可以显著改善缺血性脑损伤第14天的运动功能损伤(F=6.12,q=4.79,P<0.05),该效应可被Nrf2-IN-1逆转(q=3.60,P<0.05)。结论2-Iodomelatonin干预可以通过上调NRF2降低缺血性脑损伤小鼠的大脑梗死体积并改善14 d时的运动功能损伤。

Effects of Melatonin on Spermatozoa Activity and Associated Mechanisms in Heat-Stressed Rats

In animals,heat stress(HS)disrupts spermatogenesis,reducing sperm quality and,in severe cases,potentially inducing the loss of male reproductive function.Melatonin confers significant resistance to oxidative stress and apoptosis;however,its specific effects on rat spermatocytes and the mechanism underlying its anti-HS effects remain inadequately explored.Therefore,this study aimed to analyze the effects of melatonin at different concentrations on sperm cell activity in heat-stressed rats.Modeling heat stress injury,sperm viability and density assay,sperm plasma membrane integrity analysis,and oxidative stress assay of testicular tissue were conducted.The results revealed that HS caused sperm cell injury.However,the intraperitoneal injection of melatonin effectively improved spermatozoa quality,and a dose of 1 mM significantly alleviated the HS-induced damage.Moreover,HS increased the levels of oxidative and endoplasmic reticulum(ES)stress in rat testicular tissues,inducing germ cell apoptosis and pathological changes.Similarly,melatonin treatment improved sperm cell viability and density,inhibited germ cell apoptosis,and reduced oxidative and ES stress levels.Overall,melatonin effectively reduced the adverse effects of HS on rat sperm cells,and an intraperitoneal injection of 1 mM(0.6966 mg)melatonin facilitated the normal production of spermatozoa.Notably,its mechanism may involve reduced ES and oxidative stress levels in testicular tissues,increased expression of the anti-apoptotic protein Bcl-2,and inhibition of germ cell apoptosis.

Exogenous melatonin improves the chilling tolerance and preharvest fruit shelf life in eggplant by affecting ROS-and senescence-related processes

Low temperature is the most common abiotic stress factors during the eggplant cultivation in solar greenhouses.Melatonin plays important roles in plant resistance to low temperature.However,the role of melatonin in regulating chilling tolerance and extending the preharvest shelf life of eggplant fruits is still unknown.In this study,we investigated the effects of exogenous melatonin on eggplant plants and fruits in response to low temperature.Under simulated low-temperature conditions,exogenous melatonin significantly relieved the chilling symptoms of seedlings by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and relative leakage rates.These reductions were caused by higher superoxide dismutase (SOD) and catalase (CAT) activities and increased endogenous polyamine and melatonin levels compared with those in untreated seedlings.Notably,the expression levels of SOD,CAT1/2,and polyamine synthesis genes (ADC and ODC) were also increased by 100μmol·L~(-1)melatonin,as well as those of genes involved in melatonin synthesis (TDC,T5H,SNAT,ASMT,and COMT) and cold regulation (COR1,CBFa/b,and ZAT2/6/12).To further investigate the effects of melatonin on eggplant leaves and fruits under natural low temperature conditions,100μmol·L~(-1)melatonin was sprayed on the functional leaves at three days before commodity maturation.Melatonin significantly alleviated chilling injury in the leaves and pericarp and extended the preharvest shelf life of the fruit by increasing the expression of COR1,CBF,ZAT2/6/12,and API5 and decreasing the expression of senescence-related genes (NCED1/2 and SAG12).Therefore,100μmol·L~(-1)melatonin improved chilling tolerance and fruit shelf life by upregulating ZAT2/6/12 to affect ROS-and senescence-related processes,which provides a reference for alleviating cold stress and extending the preharvest fruit shelf life in eggplant.

Melatonin:a multitasking indoleamine to modulate hippocampal neurogenesis

Neurodegeneration affects a large number of cell types including neurons,astrocytes or oligodendrocytes,and neural stem cells.Neural stem cells can generate new neuronal populations through proliferation,migration,and differentiation.This neurogenic potential may be a relevant factor to fight neurodegeneration and aging.In the last years,we can find growing evidence suggesting that melatonin may be a potential modulator of adult hippocampal neurogenesis.The lack of therapeutic strategies targeting neurogenesis led researchers to explore new molecules.Numerous preclinical studies with melatonin observed how melatonin can modulate and enhance molecular and signaling pathways involved in neurogenesis.We made a special focus on the connection between these modulation mechanisms and their implication in neurodegeneration,to summarize the current knowledge and highlight the therapeutic potential of melatonin.

Melatonin,tunneling nanotubes,mesenchymal cells,and tissue regeneration

Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs.Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages.However,when transplanted,they lose part of their multipotency and immunomodulatory properties,and most of them die after injection into the damaged tissue.In this review,we discuss the potential utility of melatonin in preserving mesenchymal stem cells’survival and function after transplantation.Melatonin is a pleiotropic molecule regulating critical cell functions including apoptosis,endoplasmic reticulum stress,and autophagy.Melatonin is also synthesized in the mitochondria where it reduces oxidative stress,the opening of the mitochondrial permeability transition pore and the downstream caspase activation,activates uncoupling proteins,and curtails the proinflammatory response.In addition,recent findings showed that melatonin also promotes the formation of tunneling nanotubes and the transfer of mitochondria between cells through the connecting tubules.As mitochondrial dysfunction is a primary cause of mesenchymal stem cells death and senescence and a critical issue for survival after transplantation,we propose that melatonin by favoring mitochondria functionality and their transfer through tunneling nanotubes from healthy to suffering cells could improve mesenchymal stem cellbased therapy in a large number of diseases for which basic and clinical trials are underway.

Physiological and transcriptome analyses provide new insights into the mechanism mediating the enhanced tolerance of melatonin-treated rhododendron plants to heat stress

Rhododendron is a well-known genus consisting of commercially valuable ornamental woody plant species.Heat stress is a major environmental factor that affects rhododendron growth.Melatonin was recently reported to alleviate the effects of abiotic stress on plants.However,the role of melatonin in rhododendron plants is unknown.In this study,the effect of melatonin on rhododendron plants exposed to heat stress and the potential underlying mechanism were investigated.Analyses of morphological characteristics and chlorophyll a fluorescence indicated 200μmol L–1 was the optimal melatonin concentration for protecting rhododendron plants from heat stress.To elucidate how melatonin limits the adverse effects of high temperatures,melatonin contents,photosynthetic indices,Rubisco activity,and adenosine triphosphate(ATP)contents were analyzed at 25,35,and 40℃,respectively.Compared with the control,exogenous application of melatonin improved the melatonin contents,electron transport rate,photosystem II and I activities,Rubisco activity,and ATP contents under heat stress.The transcriptome analysis revealed many of the heat-induced differentially expressed genes were associated with the photosynthetic pathway;the expression of most of these genes was down-regulated by heat stress more in the melatonin-free plants than in the melatonin-treated plants.We identified Rh PGR5A,Rh ATPB,Rh LHCB3,and Rh Rbs A as key genes.Thus,we speculate that melatonin promotes photosynthetic electron transport,improves Calvin cycle enzyme activities,and increases ATP production.These changes lead to increased photosynthetic efficiency and CO_(2) assimilation under heat stress conditions via the regulated expression of specific genes,including Rh Rbs A.Therefore,the application of exogenous melatonin may increase the tolerance of rhododendron to heat stress.

Melatonin promotes the development of the secondary hair follicles by regulating circMPP5

Background The quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats.The higher the density of secondary hair follicles,the higher the quality and yield of cashmere from the fleece.Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth.Preliminary experimental results from our laboratory showed that melatonin(MT)treatment of goat kids after their birth could increase the density of secondary hair follicles and,thus,improve the subsequent yield and quality of cashmere.These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein,and from a reduction in apoptosis.The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.Results MT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere,and this dominant effect continued to the second year.Melatonin promotes the proliferation of secondary hair follicle cells at an early age.The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year.The genome-wide data results involved KEGG analysis of 1044 DEmRNAs,91 DElncRNAs,1054 DEcircRNAs,and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase(MAPK)signaling pathway is involved in the development of secondary hair follicles,with key genes(FGF2,FGF21,FGFR3,MAPK3(ERK1))being up-regulated and expressed.We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3.Conclusions We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211,regulating the expression of MAPK3,to induce the differentiation and proliferation of secondary hair follicle cells.In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells.Collectively,these events increase the numbers of secondary hair follicles,thus improving the production of cashmere from these goats.