An economically valuable woody plant species tree bean (Cajanus cajan (L.) Millsp.) is predominantly cultivated in tropical and subtropical areas and is regarded as an important food legume (or pulse) crop that is facing serious sodium ion stress. <em>N</em>AM (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) has been implicated in abiotic and biotic stress tolerance in plants. However, the role of <em>N</em>AM in sodium ion stress tolerance has not been determined. In this study, the effect of <em>N</em>AM was investigated in the economically valuable woody plant species, challenged with stress at 40 mM sodium ion for 3 days. <em>N</em>AM-treated plants (200 μM) had significantly higher fresh weight, average root length, significantly reduced cell size, increased cell number, and increased cytoskeleton filaments in single cells. The expression pattern of one of 10 Tree bean Dynamic Balance Movement Related Protein (TbDMP), TbDMP was consistent with the sodium ion-stress alleviation by <em>N</em>AM. Using TbDMP as bait, Dynamic Balance Movement Related Kinase Protein (TbDBK) was determined to interact with TbDMP by screening the tree bean root cD<em>N</em>A library in yeast. Biochemical experiments showed that <em>N</em>AM enhanced the interaction between the two proteins which promoted resist sodium ion stress resistance. This study provides evidence of a pathway through which the skeleton participates in <em>N</em>AM signaling.

<em>N</em>-Bromo<em>acetyl</em>-2-iodo-<em>5</em>-<em>methoxytryptamine</em> (BIM), a novel derivative of the biologically active melatonin analog, 2-iodomelatonin, was prepared and used to identify melatonin binding proteins in rat brain synaptosomes. Incubation of the synaptosomes with BIM resulted in a time and concentration dependent, irreversible inhibition of 2-[12<em>5</em>I]iodomelatonin binding. In parallel, the radioactive form of BIM, <em>N</em>-bromo<em>acetyl</em>-2-[12<em>5</em>I]iodo-<em>5</em>-<em>methoxytryptamine</em> ([12<em>5</em>I]BIM) became incorporated into the synaptosomes. The incorporation of [12<em>5</em>I]BIM was inhibited by BIM, 2-iodomelatonin and melatonin but not by <em>5</em>-<em>methoxytryptamine</em> or <em>N</em>-<em>acetyl</em> serotonin. [12<em>5</em>I]BIM became covalently attached to three polypeptides with apparent molecular weight values of 92, <em>5</em><em>5</em> and 4<em>5</em> kDa; the labeling of all three proteins was markedly inhibited by melatonin. These results indicate that the 92, <em>5</em><em>5</em> and 4<em>5</em> kDa polypeptides are melatonin binding proteins.

It was found that melatonin and its derivatives, such as <em>N</em>-<em>acetyl</em>- <em>5</em>-<em>methoxytryptamine</em> (MT), <em>N</em>-<em>acetyl</em>-<em>5</em>-hydroxytryptamine (<em>N</em>AS), <em>5</em>-Methoxytrypt- amine (<em>5</em>-MT), <em>5</em>-Methoxyindolyl acetic acid (<em>5</em>-MIAA) and <em>N</em>-<em>acetyl</em>-<em>5</em>-methoxy- 6-hydroxytryptamine (6-HMT) would give chemiluminescence in the acidic potassium permanganate solution, and formaldehyde would enhance this chemiluminescent reaction greatly. The optimum conditions for this chemiluminescent reaction were studied in detail by a flow injection system. A new simple rapid method has been developed under the optimum conditions for determination of melatonin. This method has the advantages of high sensitivity, wide range of linear response and low detection limit. On the basis of investigation of chemiluminescent, fluorescent and UV spectra of melatonin in acidic solution containing potassium permanganate and formaldehyde, a possible mechanism of this reaction was proposed.

Melatonin (MLT), <em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and 1H-<em>N</em>MR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracene (positive control) and sodium lauryl sulfate (SLS, negative control) were performed. The methods employed include both in vitro tests such as MTS assay using the human fibroblast cell and yeast growth inhibition assay using Candida albicans and in vivo method using the skin of guinea pig. UV absorption spectra and 1H-<em>N</em>MR spectra of MLT were changed by UVA (36<em>5</em> nm, 1<em>5</em> J/cm2), but IR spectra of MLT were not changed. The fifty percent inhibitor concentration (IC<em>5</em>0) ratio (UV-/UV+) of MLT was 10. The inhibition zone of irradiated-paper disks treated with MLT was not observed. According to the results of histopathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, hemorrhage and vasodilation in dermis were observed in the irradiated group. These results indicate that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted.

The hormone melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) has been implicated in the regulation of several neural and endocrine processes that are cued by the daily change in photoperiod. The conformational properties of melatonin and two conformationally restricted agonists, 8-methoxy-2-acetamidotetralin and cis-1-methyl-8-methoxy-2-acetamidotetralin, were examined as a starting point for SAR studies. The conformational analysis was carried out by means of molecular mechanics calculations (MM2-8<em>5</em> force field) using a step-wise build-up procedure and the molecular modelling program MacroModel (which has a modified version of the MM2 force field) for Monte Carlo and systematic tree searches. <em>N</em>MR spectroscopy was used to evaluate the conformational behaviour in solution. The three search methods were complementary and produced a good description of the conformational characteristics. The two force fields produced different geometries of some low energy conformations and also different relative steric energies. When using the MM2-8<em>5</em> force field, an intra-molecular interaction between the amide-H and the aromatic system lowers the relative energies of several conformations of both melatonin and the 2-amidotetralins. However, <em>N</em>MR experiments indicated that these interactions, which may be quite important in vacuo, are not important in solution.

The effects of ondansetron on the neuromuscular function of the guinea-pig ileum were investigated in vitro. Ondansetron, but not tropisetron or MDL 72222 (1alpha-H-3alpha-<em>5</em>alpha-H-tropan-3-yl-3,<em>5</em>-dichlo robenzoate), enhanced submaximal electrically induced contractions (EC<em>5</em>0) = 1.3 x 10(-<em>5</em>) M). Desensitization with <em>5</em>-hydroxytryptamine (1 x 10(-<em>5</em>) M) or 2-methyl-<em>5</em>-HT (1 x 10(-<em>5</em>) M) abolished this facilitatory response, which remained unaltered after desensitization with <em>5</em>-<em>methoxytryptamine</em> (1 x 10(-<em>5</em>) M) or addition of tropisetron, MDL 72222, <em>N</em>-<em>acetyl</em>-<em>5</em>-hydroxytryptophyl-<em>5</em>-hydroxytryptophan, SB203186 (1-piperidinylethyl-1H-indole-3 carboxylate hydrochloride), pirenzepine or hexamethonium. At higher concentrations, ondansetron decreased the electrically induced contractions (EC<em>5</em>0 = 1 x 10(-4) M); the inhibitory response was unaffected by (-)-naloxone (1 x 10(-6) M) or idazoxan (1 x 10(-6) M). We conclude that, in the guinea-pig ileum, ondansetron elicits a biphasic response: facilitation of neuromuscular transmission mediated by a serotonergic receptor distinct from the <em>5</em>-HT3, <em>5</em>-HT4 or putative <em>5</em>-HT1P receptors, and an inhibitory response that does not involve opiate or alpha2-adrenoceptors.

We review our work towards the design and synthesis of high-affinity melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) agonist and antagonist compounds. High affinity melatonergic agonists were obtained by shifting the melatonin side chain from C3 to <em>N</em>1 of the indole ring system. Conversely, by moving the side chain from C3 to C2 it was possible to obtain melatonin antagonist compounds, albeit of moderate affinity.

Melato<em>n</em>i<em>n</em> (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>), the mai<em>n</em> secretory product of the pi<em>n</em>eal gla<em>n</em>d, is a free radical scave<em>n</em>ger that has bee<em>n</em> fou<em>n</em>d to protect agai<em>n</em>st lipid peroxidatio<em>n</em> i<em>n</em> ma<em>n</em>y experime<em>n</em>tal models. I<em>n</em> the prese<em>n</em>t study the effect of melato<em>n</em>i<em>n</em> o<em>n</em> lipid peroxidatio<em>n</em> of lo<em>n</em>g chai<em>n</em> polyu<em>n</em>saturated fatty acids located i<em>n</em> rat liver, kid<em>n</em>ey a<em>n</em>d brai<em>n</em> microsomes was determi<em>n</em>ed usi<em>n</em>g gas chromatography a<em>n</em>d a chemilumi<em>n</em>esce<em>n</em>ce assay. I<em>n</em> vitro assays showed that after i<em>n</em>cubatio<em>n</em> of rat liver, kid<em>n</em>ey or brai<em>n</em> microsomes i<em>n</em> a<em>n</em> ascorbate-Fe++ system, at 37 degrees C for 180 mi<em>n</em>, the total cpm origi<em>n</em>ated from light emissio<em>n</em> (chemilumi<em>n</em>esce<em>n</em>ce) was fou<em>n</em>d to be lower i<em>n</em> those membra<em>n</em>es i<em>n</em>cubated i<em>n</em> the prese<em>n</em>ce of melato<em>n</em>i<em>n</em>. The i<em>n</em>cubatio<em>n</em> of rat liver, kid<em>n</em>ey or brai<em>n</em> microsomes i<em>n</em> the prese<em>n</em>ce of ascorbate-Fe2+ resulted i<em>n</em> lipid-peroxidatio<em>n</em> of membra<em>n</em>es as evide<em>n</em>ced by light emissio<em>n</em> a<em>n</em>d decrease of docosahexae<em>n</em>oic acid 22:6 <em>n</em>-3 a<em>n</em>d arachido<em>n</em>ic acid 20:4 <em>n</em>-6. I<em>n</em> the prese<em>n</em>ce of melato<em>n</em>i<em>n</em> (0.<em>5</em>, 1.0, 1.<em>5</em> mm), light emissio<em>n</em> perce<em>n</em>t i<em>n</em>hibitio<em>n</em> of microsomes was: (liver - 3.33, 9.98, 39.40) (kid<em>n</em>ey - 46.79, 61.88, 68.36) a<em>n</em>d (brai<em>n</em> - 33.36, 28.89, 43.32). <em>N</em>ot all fatty acids were equally protected after the additio<em>n</em> of melato<em>n</em>i<em>n</em> to the i<em>n</em>cubatio<em>n</em> medium. Our results i<em>n</em>dicate a selective protectio<em>n</em> of C20:4 <em>n</em>6 a<em>n</em>d C22:6 <em>n</em>3 by melato<em>n</em>i<em>n</em> duri<em>n</em>g <em>n</em>o<em>n</em>-e<em>n</em>zymatic lipid peroxidatio<em>n</em> of rat liver, kid<em>n</em>ey a<em>n</em>d brai<em>n</em> microsomes.

Melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) is a pleiotropic signaling molecule that plays important roles in plant growth, development and stress responses. Alfalfa (<i>Medicago sativa</i> L.) is an important and widely cultivated leguminous forage crop with high biomass yield and rich nutritional value. The effects of exogenous melatonin content regulation on alfalfa stress tolerance have been investigated in recent years. Here, we isolated and introduced the <i>MsASMT1</i> (<em>N</em>-<em>acetyl</em>serotonin methyltransferase) gene into alfalfa, which significantly improved the endogenous melatonin content. Compared with wild-type (WT) plants, <i>MsASMT1</i> overexpression (<i>OE-MsASMT1</i>) plants exhibited a series of phenotypic changes, including vigorous growth, increased plant height, enlarged leaves and robust stems with increased cell sizes, cell numbers and vascular bundles, as well as more branches. We also found that the flavonoid content and lignin composition of syringyl to guaiacyl ratio (S/G) were decreased and the cellulose content was increased in <i>OE-MsASMT1</i> transgenic alfalfa. Further transcriptomic and metabolomic exploration revealed that a large group of genes in phenylalanine pathway related to flavonoids and lignin biosynthesis were significantly altered, accompanied by significantly reduced concentrations of the glycosides of quercetin, kaempferol, formononetin and biochanin in <i>OE-MsASMT1</i> transgenic alfalfa. Our study first uncovers the effects of endogenous melatonin on alfalfa growth and metabolism. This report provides insights into the regulation effects of melatonin on plant growth and phenylalanine metabolism, especially flavonoids and lignin biosynthesis.

Mitochondrial dysfunction has been shown to be associated with normal ageing and may account for age-related vulnerability to disease. The increasing number of old people worldwide has created the need to find effective therapeutic agents to reduce the incidence of age-related disease. In the current report, we carried out an assessment of mitochondrial function in established young, middle-aged and old synaptosomal mitochondria bearing cybrids without or with melatonin treatment. The cybrids were generated by transferring isolated mitochondria from synaptosomes of brain cortical cells in mice to rho-zero mtD<em>N</em>A-less cells. In galactose media, a selective media that tests a cells ability to produce ATP through the electron transport chain and oxidative phosphorylation, <em>5</em>00µM melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) raised cell viability in young and middle-aged cybrids (P<0.0<em>5</em>) and a concentration of 1mM raised cell viability in the old cybrids (P<0.0<em>5</em>). The mitochondrial membrane potential (MMP) was lowered in the young cybrids (P<0.0<em>5</em>) treated with melatonin, but it was raised in the middle-aged and old cybrids (P<0.0<em>5</em>) with melatonin treatment. The levels of reactive oxygen species were significantly lower in the melatonin treated middle-aged and old cybrids compared with controls (P<0.0<em>5</em>). Furthermore, ATP measurements showed no significant increase in the young cybrids (P>0.0<em>5</em>), but increased significantly in the middle-aged and old cybrids (P<0.0<em>5</em>) with melatonin treatment. Light and fluorescence microscopy showed observable structural damage and cell death in the middle-aged and old cybrids without melatonin treatment. The results suggest that melatonin may be a potent therapeutic intervention during age-related neuronal mitochondrial dysfunction.

L-Tryptophan is an essential amino acid for humans, and a precursor of the neurohormones serotonin (<em>5</em>-hydroxytryptamine) and melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>), and the B vitamin nicotinic acid. It is found in small concentrations in casein, and in many foods. A bioassay of the amino acid L-tryptophan for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 3<em>5</em> rats and 3<em>5</em> mice of each sex were administered L-tryptophan at one of two doses, either 2<em>5</em>,000 or <em>5</em>0,000 ppm, <em>5</em> days per week for 78 weeks, and then observed for 26 or 27 weeks. Matched controls consisted of groups of 1<em>5</em> rats or 1<em>5</em> mice of each sex. All surviving rats and mice were killed at 104 or 10<em>5</em> weeks. L-Tryptophan had little toxic effect on the rats; mean body weight loss was minimal and survival of dosed groups of both sexes was high. In the mice, mean body weights of dosed animals were lower than those of controls throughout most of the bioassay, particularly in the females. Sufficient numbers of rats were at risk to termination of the study for development of late-appearing tumors, and sufficient numbers of mice were at risk beyond <em>5</em>2 weeks of the study for development of tumors. <em>N</em>o neoplasms occurred in a statistically significant incidence among dosed rats when compared with controls. In both male and female mice, neoplasms of the hematopoietic system occurred at higher incidences in the low-dose groups than in the matched-control groups (males: controls 0/12, low-dose 9/34, high-dose 2/33; females: controls 2/13, low-dose 6/33, high-dose 1/3<em>5</em>). These incidences, however, are not statistically significant, using the Bonferroni correction, and therefore, no tumors are considered to be related to the administration of the test chemical. It is concluded that under the conditions of this bioassay, L-tryptophan was not carcinogenic for Fischer 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: <em>N</em>egative Female Rats: <em>N</em>egative Male Mice: <em>N</em>egative Female Mice: <em>N</em>egative Synonym: L-a</SPA<em>N</em>-AMI<em>N</em>O-b-indolepropionic acid

<em>5</em>-<em>Methoxytryptamine</em> was acylated with <em>N</em>-<em>acetyl</em>-L-amino acids to give rise the corresponding <em>N</em>-(<em>N</em>-<em>acetyl</em>-L-amino acyl)-<em>5</em>-<em>methoxytryptamines</em>. The analgesic activity was evaluated by the tail flick test. Among the 6 compounds, the analgesic potency of <em>N</em>-(<em>N</em>-<em>acetyl</em>-tryptophanyl)-<em>5</em>-<em>methoxytryptamine</em> (<em>5</em>e) and <em>N</em>-(<em>N</em>-<em>acetyl</em>-glycyl)-<em>5</em>-<em>methoxytryptamine</em> (<em>5</em>a) are much more potent than that of melatonin.

<em>5</em>-<em>Methoxytryptamine</em> (<em>5</em>-MT) is a potent antioxidant and has radioprotective action. <em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em> (melatonin, <em>N</em>A-<em>5</em>-MT) is a free radical scavenger and antioxidant, which protects against oxidative damage due to a variety of toxicants. The infrared spectra of <em>5</em>-MT, <em>N</em>A-<em>5</em>-MT and new synthesized <em>N</em>-phenylsulfonamide-<em>5</em>-<em>methoxytryptamine</em> (PS-<em>5</em>-MT) were investigated in the region between 4000 and 400 cm(-1). Vibrational assignments of the molecules have been made for fundamental modes on the basis of the group vibrational concept, infrared intensity and comparison with the assignments for related molecules. X-ray powder diffraction patterns of molecules were also recorded. In order to optimize the geometries of the molecules, molecular mechanic calculations (MM3) were performed. Conformational analysis of <em>5</em>-MT, <em>N</em>A-<em>5</em>-MT and PS-<em>5</em>-MT was also established by the using PM3 method.

OBJECTIVE

Changes in the activity of beta-glucuronidase, <em>N</em>-<em>acetyl</em>-beta-glucosaminidase, cathepsin D and L, alanine aminopeptidase and lysosomal acid lipase in lysosomal fractions of the liver and kidneys of mice, which were administered 20 mg/kg b.w. of exogenous melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) for 7 and 14 days were investigated.

METHODS

The slices of the liver and kidney were homogenized in 0.1M phosphate buffer, pH 7.0. Homogenates were subjected to differentiated centrifuging and determination of studied enzymes.

RESULTS

Melatonin caused lowering of the activity of all the investigated lysosomal enzymes in the liver and kidney.

CONCLUSIONS

Administration of melatonin was caused the lowering of the activity of the investigated lysosomal enzymes in comparison with values in control groups.

A sensitive method for the measurement of endogenous <em>5</em>-<em>methoxytryptamine</em> in brain tissue has been developed using capillary column gas chromatography-electron-capture negative-ion chemical ionization mass spectrometry. <em>5</em>-<em>Methoxytryptamine</em> was first converted to <em>N</em>-[2H3]<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em> by reaction with hexa-deuterated acetic anhydride, followed by reaction with pentafluoropropionic anhydride to yield the highly electron-capturing 3,3'-spirocyclic pentafluoro-propionyl indolenine derivative. Quantitative analysis was carried out by selected-ion monitoring of the [M-HF].- and [M-HF-DF].- ion intensity of the 3.3'-spirocyclic pentafluoropropionyl indolenine derivative, using <em>5</em>-methoxy-[alpha, alpha, beta, beta-2H4]tryptamine as the internal standard. The presence of <em>5</em>-<em>methoxytryptamine</em> in the brain tissue was demonstrated. In the absence of a monoamine oxidase inhibitor, the mean +/- S.D. levels of <em>5</em>-<em>methoxytryptamine</em> in the rat and quail whole brain were found to be 30 +/- 6 and 347 +/- <em>5</em>2 pg/g, respectively. The possible physiological functions of <em>5</em>-<em>methoxytryptamine</em> as a neuromodulator and/or neurotransmitter have to be considered.

Melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) is a naturally occurring hormone with a structural resemblance to tryptophan. Its fluorescence is solvent dependent and strongly quenched in the presence of oxygen. Fluorescence quenching in aqueous and organic solutions have been studied in the presence of different quenchers. A 1: 1 inclusion complex formation between melatonin and different cyclodextrins in aqueous solution has been observed. The effects of microheterogeneous media provided by cyclodextrins, micelles and reverse micelles on the fluorescence characteristics of melatonin have been investigated. The water-soluble inorganic quenchers like KBr and KI were unable to quench the fluorescence of melatonin dissolved in a microemulsion consisting of surfactant + cyclohexane + 1-propanol + water, whereas the organic quenchers like CCl4 and CHCl3 were able to quench the fluorescence with a rate constant (on the order of 10(8) dm3 mol-1 s-1) quite similar to that in neat organic solvents.

Melatonin (<em>N</em>-<em>Acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) is a hormone secreted mainly by the pineal gland or epiphyse and in smaller amounts by the retina. It is biosynthesized from tryptophan, the two critical enzymatic steps depend upon <em>N</em>-<em>Acetyl</em>-transferase (<em>N</em>AT) and <em>5</em>-hydroxyindole-O-methyltransferase (<em>5</em>-HIOMT). The circadian rhythm of melatonin is the same in man and all the laboratory animals studied until now with noctural plasma concentrations 3-10 times greater than during daytime. The secretion and release of melatonin depend upon a large number of exogenous and endogenous factors as e.g. sex, age, pubertal stage, menstrual cycle, drugs, season... Light is the major regulating factor which acts through the retino-hypothalamic tract. Melatonin is considered as a transducer of the light signal forwarding to the organism the information about day length (relative length of day and night). It is a time-clue provider used by the organism to adapt itself to its environment.

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p<em>5</em>3. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

Keywords: Warburg effect; anti-depressant; anti-inflammatory; anti-tumor; antioxidant; cancer; melatonin; metabolism; mitochondrial dysfunction; predictive preventive personalized medicine (PPPM/3PM).

<strong class="sub-title"> Purpose: </strong> Intestinal damage induced by radiation exposure is a major clinic concern of radiotherapy for patients with abdominal or pelvic tumor. Melatonin (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) is likely be an ideal radioprotector to protect individuals from radiation exposure. The study aimed to define the role of melatonin in small intestinal damage caused by abdominal irradiation (ABI).

Materials and methods: 30-day survival rate and pathological histology of the intestines from melatonin-treated mice after 13Gy ABI exposure was firstly detected. Next, quantitative proteomics analysis of the small intestines tissue was examined and GO term and KEGG pathways analysis were performed.

<strong class="sub-title"> Results: </strong> Melatonin treatment before ABI exposure significantly increased 30-day survival rate to 83% and ameliorated damage to the intestinal epithelial cells. Melatonin significantly altered the proteins profile of the small intestines following irradiation. For the irradiated mice treated with melatonin in comparision with the irradiated mice, the enriched GO terms were mainly involved in denfense response to other organism (BP, GO: 0098<em>5</em>42), response to other organism (BP, GO: 00<em>5</em>1707), anion transmembrane transporter activity (MF, GO: 0008<em>5</em>09) and secondary active transmembrane transporter activity (MF, GO: 001<em>5</em>291). In the process of antioxidant activity (MF, GO: 0016209), melatonin treatment prior to radiation exhibited high protein levels of Sod3 and Gpx3. The markedly KEGG pathways for melatonin treatment prior to radiation mainly included protein digestion and absorption (ko 04974) and mineral absorption (ko 04978). p<em>5</em>3 signaling pathway and D<em>N</em>A repair pathways were enriched in melatonin treated mice. The amount of radiation-induced D<em>N</em>A damage and the cell apoptosis of the small intestines was decreased in the melatonin-treated mice.

Conclusions: Melatonin may protect small intestines from radiation damage through increasing DNA repair and decreasing cell apoptosis of the small intestines. Our data provided perspective for the study of melatonin in mitigating ABI-caused intestinal damage.

Keywords: abdominal irradiation; intestinal damage; melatonin; radioprotection.

Cadmium (Cd) is one of the most injurious heavy metals, affecting plant growth and development. Melatonin (<i><em>N</em></i>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>) was discovered in plants in 199<em>5</em>, and it is since known to act as a multifunctional molecule to alleviate abiotic and biotic stresses, especially Cd stress. Endogenously triggered or exogenously applied melatonin re-establishes the redox homeostasis by the improvement of the antioxidant defense system. It can also affect the Cd transportation and sequestration by regulating the transcripts of genes related to the major metal transport system, as well as the increase in glutathione (GSH) and phytochelatins (PCs). Melatonin activates several downstream signals, such as nitric oxide (<em>N</em>O), hydrogen peroxide (H₂O₂), and salicylic acid (SA), which are required for plant Cd tolerance. Similar to the physiological functions of <em>N</em>O, hydrogen sulfide (H₂S) is also involved in the abiotic stress-related processes in plants. Moreover, exogenous melatonin induces H₂S generation in plants under salinity or heat stress. However, the involvement of H₂S action in melatonin-induced Cd tolerance is still largely unknown. In this review, we summarize the progresses in various physiological and molecular mechanisms regulated by melatonin in plants under Cd stress. The complex interactions between melatonin and H₂S in acquisition of Cd stress tolerance are also discussed.

Keywords: Cd stress; antioxidant defense systems; hydrogen sulfide; melatonin; oxidative stress; transportation and sequestration.

Heavy metal toxicity is one of the most devastating abiotic stresses. Heavy metals cause serious damage to plant growth and productivity, which is a major problem for sustainable agriculture. It adversely affects plant molecular physiology and biochemistry by generating osmotic stress, ionic imbalance, oxidative stress, membrane disorganization, cellular toxicity, and metabolic homeostasis. To improve and stimulate plant tolerance to heavy metal stress, the application of biostimulants can be an effective approach without threatening the ecosystem. Melatonin (<i><em>N</em></i>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>), a biostimulator, plant growth regulator, and antioxidant, promotes plant tolerance to heavy metal stress by improving redox and nutrient homeostasis, osmotic balance, and primary and secondary metabolism. It is important to perceive the complete and detailed regulatory mechanisms of exogenous and endogenous melatonin-mediated heavy metal-toxicity mitigation in plants to identify potential research gaps that should be addressed in the future. This review provides a novel insight to understand the multifunctional role of melatonin in reducing heavy metal stress and the underlying molecular mechanisms.

Keywords: abiotic stress; heavy metal; oxidative stress; phytomelatonin; plant growth.

Serotonin <em>N</em> -<em>acetyl</em>transferase (S<em>N</em>AT) is the key rate-limiting enzyme in melatonin biosynthesis. S<em>N</em>AT mediates dual pathways of melatonin biosynthesis in plants by using serotonin and <em>5</em>-<em>methoxytryptamine</em> (<em>5</em>-MT) as substrates, and a high reaction pH and temperature are essential to its activity. However, little is known of its underlying mechanisms. Herein, we present a detailed reaction mechanism of a S<em>N</em>AT from Oryza sativa through combined structural and molecular dynamics (MD) analysis. We report for the first time the crystal structures of plant S<em>N</em>AT in the apo and binary/ternary complex forms with <em>acetyl</em>-CoA (AcCoA), serotonin, and <em>5</em>-MT. These structures reveal that Os S<em>N</em>AT exhibits a unique enzymatically active dimeric fold that is not found in all the known structures of arylalkylamine <em>N</em>-<em>acetyl</em>transferase (AA<em>N</em>AT) family. The key residues W188, D189, D226, <em>N</em>220, and Y233 located around the active pocket have important role in catalysis which is subsequently confirmed by site-directed mutagenesis. Combined with MD simulations, we hypothesize a novel plausible catalytic mechanism in which D226 and Y233 function as catalytic base and acid during the <em>acetyl</em>-transfer reaction. This work provides a molecular framework for understanding the catalytic mechanisms of plant S<em>N</em>AT and has implications for future protein engineering and biocatalytic applications.

Keywords: melatonin * serotonin N-acetyltransferase * crystal structure * molecular dynamics * density functional theory.

The agei<em>n</em>g process is a multifactorial phe<em>n</em>ome<em>n</em>o<em>n</em>, associated with decreased physiological a<em>n</em>d cellular fu<em>n</em>ctio<em>n</em>s a<em>n</em>d a<em>n</em> i<em>n</em>creased prope<em>n</em>sity for various dege<em>n</em>erative diseases. Studies o<em>n</em> melato<em>n</em>i<em>n</em> (<em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em>), a pote<em>n</em>t a<em>n</em>tioxida<em>n</em>t, are gai<em>n</em>i<em>n</em>g atte<em>n</em>tio<em>n</em> si<em>n</em>ce melato<em>n</em>i<em>n</em> productio<em>n</em> decli<em>n</em>es with adva<em>n</em>ci<em>n</em>g age. He<em>n</em>ce, the aim of this study was to evaluate the effects of chro<em>n</em>ic melato<em>n</em>i<em>n</em> co<em>n</em>sumptio<em>n</em> o<em>n</em> ge<em>n</em>otoxic a<em>n</em>d mutage<em>n</em>ic parameters of old Swiss mice. Herei<em>n</em>, 3-mo<em>n</em>th-old Swiss albi<em>n</em>o male mice (<em>n</em> = 240) were divided i<em>n</em>to eight groups a<em>n</em>d subdivided i<em>n</em>to two experime<em>n</em>ts: first (three groups): <em>n</em>atural agei<em>n</em>g experime<em>n</em>t; seco<em>n</em>d (five groups): a<em>n</em>imals that started water or melato<em>n</em>i<em>n</em> suppleme<em>n</em>tatio<em>n</em> at differe<em>n</em>t ages (3, 6, 12 a<em>n</em>d 18 mo<em>n</em>ths) u<em>n</em>til 21 mo<em>n</em>ths. After 21 mo<em>n</em>ths, the a<em>n</em>imals from the seco<em>n</em>d experime<em>n</em>t were eutha<em>n</em>ized to perform the comet assay, micro<em>n</em>ucleus test a<em>n</em>d wester<em>n</em> blot a<em>n</em>alysis. The results demo<em>n</em>strated that melato<em>n</em>i<em>n</em> prolo<em>n</em>ged the life spa<em>n</em> of the a<em>n</em>imals. Relative to ge<em>n</em>omic i<em>n</em>stability, melato<em>n</em>i<em>n</em> was effective i<em>n</em> reduci<em>n</em>g D<em>N</em>A damage caused by agei<em>n</em>g, prese<em>n</em>ti<em>n</em>g a<em>n</em>tige<em>n</em>otoxic a<em>n</em>d a<em>n</em>timutage<em>n</em>ic activities, i<em>n</em>depe<em>n</em>de<em>n</em>tly of i<em>n</em>itiatio<em>n</em> age. The group receivi<em>n</em>g melato<em>n</em>i<em>n</em> for 18 mo<em>n</em>ths had high levels of APE1 a<em>n</em>d OGG1 repair e<em>n</em>zymes. Co<em>n</em>clusively, melato<em>n</em>i<em>n</em> prese<em>n</em>ts a<em>n</em> efficie<em>n</em>t a<em>n</em>tioxida<em>n</em>t mecha<em>n</em>ism aidi<em>n</em>g modulati<em>n</em>g ge<em>n</em>etic a<em>n</em>d physiological alteratio<em>n</em>s due to agei<em>n</em>g.

Nowadays acute myocardial infarction (AMI) is a serious cardiovascular disease threatening the human life and health worldwide. The most effective treatment is to quickly restore coronary blood flow through revascularization. However, timely revascularization may lead to reperfusion injury, thereby reducing the clinical benefits of revascularization. At present, no effective treatment is available for myocardial ischemia/reperfusion injury. Emerging evidence indicates that epigenetic regulation is closely related to the pathogenesis of myocardial ischemia/reperfusion injury, indicating that epigenetics may serve as a novel therapeutic target to ameliorate or prevent ischemia/reperfusion injury. This review aimed to briefly summarize the role of histone modification, DNA methylation, noncoding RNAs, and N⁶-methyladenosine (m⁶A) methylation in myocardial ischemia/reperfusion injury, with a view to providing new methods and ideas for the research and treatment of myocardial ischemia/reperfusion injury.

<strong class="sub-title"> Keywords: </strong> 3-bromo-4,<em>5</em>-dihydroxybenzaldehyde (PubChem CID: 8768); <em>5</em>-aza-2’-deoxycytidine (PubChem CID: 4<em>5</em>1668); Alleviate; Curcumin (PubChem CID: 969<em>5</em>16); Dihydromyricetin (PubChem CID: 161<em>5</em><em>5</em>7); <em>N</em>-<em>acetyl</em>-<em>5</em>-<em>methoxytryptamine</em> (PubChem CID: 896); Suberoylanilide hydroxamic acid (PubChem CID: <em>5</em>311); Trans sodium crocetinate (PubChem CID: 10287099); Trichostatin A (PubChem CID: 444732); Tubastatin A (PubChem CID: 498<em>5</em>0262); epigenetic regulation; myocardial ischemia/reperfusion injury.