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Journal of Nanobiotechnology May 2024Nanoplastics, are emerging pollutants, present a potential hazard to food security and human health. Titanium dioxide nanoparticles (Nano-TiO), serving as...
Titanium dioxide nanoparticles alleviates polystyrene nanoplastics induced growth inhibition by modulating carbon and nitrogen metabolism via melatonin signaling in maize.
BACKGROUND
Nanoplastics, are emerging pollutants, present a potential hazard to food security and human health. Titanium dioxide nanoparticles (Nano-TiO), serving as nano-fertilizer in agriculture, may be important in alleviating polystyrene nanoplastics (PSNPs) toxicity.
RESULTS
Here, we performed transcriptomic, metabolomic and physiological analyzes to identify the role of Nano-TiO in regulating the metabolic processes in PSNPs-stressed maize seedlings (Zea mays L.). The growth inhibition by PSNPs stress was partially relieved by Nano-TiO. Furthermore, when considering the outcomes obtained from RNA-seq, enzyme activity, and metabolite content analyses, it becomes evident that Nano-TiO significantly enhance carbon and nitrogen metabolism levels in plants. In comparison to plants that were not subjected to Nano-TiO, plants exposed to Nano-TiO exhibited enhanced capabilities in maintaining higher rates of photosynthesis, sucrose synthesis, nitrogen assimilation, and protein synthesis under stressful conditions. Meanwhile, Nano-TiO alleviated the oxidative damage by modulating the antioxidant systems. Interestingly, we also found that Nano-TiO significantly enhanced the endogenous melatonin levels in maize seedlings. P-chlorophenylalanine (p-CPA, a melatonin synthesis inhibitor) declined Nano-TiO-induced PSNPs tolerance.
CONCLUSIONS
Taken together, our data show that melatonin is involved in Nano-TiO-induced growth promotion in maize through the regulation of carbon and nitrogen metabolism.
Topics: Zea mays; Titanium; Nitrogen; Carbon; Melatonin; Polystyrenes; Seedlings; Nanoparticles; Signal Transduction; Photosynthesis; Oxidative Stress
PubMed: 38760823
DOI: 10.1186/s12951-024-02537-x -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2024One of the most common and significant symptoms for skin disorders is pruritus. Additionally, it serves as a significant catalyst for the exacerbation or reoccurrence of... (Review)
Review
One of the most common and significant symptoms for skin disorders is pruritus. Additionally, it serves as a significant catalyst for the exacerbation or reoccurrence of skin diseases. Pruritus seriously affects patients' physical and mental health, and even the quality of life. It brings a heavy burden to the patients, the families, even the whole society. The pathogenesis and regulation mechanisms for pruritus are complicated and have not yet been elucidated. Previous clinical studies have shown that itch worsens at night in scabies, chronic pruritus, atopic dermatitis, and psoriasis, suggesting that skin pruritus may change with circadian rhythm. Cortisol, melatonin, core temperature, cytokines, and prostaglandins are the main regulatory factors of the circadian rhythm of pruritus. Recent studies have shown that some CLOCK genes, such as , , , and , play an important role in the regulation of the circadian rhythm of pruritus by regulating the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor kappa-B (NF-κB) signaling pathways. However, the mechanisms for circadian clock genes in regulation of circadian rhythm of pruritus have not been fully elucidated. Further studies on the mechanism of circadian clock genes in the regulation of circadian rhythm of pruritus will lay a foundation for elucidating the regulatory mechanisms for pruritus, and also provide new ideas for the control of pruritus and the alleviation of skin diseases.
Topics: Pruritus; Humans; Circadian Rhythm; CLOCK Proteins; Signal Transduction; Melatonin; ARNTL Transcription Factors; NF-kappa B; Circadian Clocks
PubMed: 38755715
DOI: 10.11817/j.issn.1672-7347.2024.230397 -
BMC Psychiatry May 2024This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with...
OBJECTIVE
This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database.
METHODS
This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs.
RESULTS
The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound).
CONCLUSION
Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.
Topics: Humans; Vilazodone Hydrochloride; Male; Female; Adverse Drug Reaction Reporting Systems; Middle Aged; United States; Adult; Aged; Databases, Factual; United States Food and Drug Administration; Young Adult; Adolescent; Bayes Theorem
PubMed: 38755677
DOI: 10.1186/s12888-024-05813-0 -
Nature Communications May 2024Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide...
Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear. Here we measured brain-wide responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7 T scanner and a cryoprobe. Transient activation of DRN serotonin neurons caused brain-wide activation, including the medial prefrontal cortex, the striatum, and the ventral tegmental area. The same stimulation under anesthesia with isoflurane decreased brain-wide activation, including the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 receptors. Together, these results provide insight into the DR serotonergic system, which is consistent with recent discoveries of its functions in adaptive behaviors.
Topics: Animals; Optogenetics; Dorsal Raphe Nucleus; Male; Serotonergic Neurons; Mice; Serotonin; Magnetic Resonance Imaging; Prefrontal Cortex; Mice, Inbred C57BL; Brain; Ventral Tegmental Area; Hippocampus; Receptors, Serotonin
PubMed: 38755120
DOI: 10.1038/s41467-024-48489-6 -
Iranian Journal of Medical Sciences May 2024There is no definite recommendation for melatonin supplementation in episodic migraine. This study aimed to evaluate the effect of melatonin on reducing the frequency... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There is no definite recommendation for melatonin supplementation in episodic migraine. This study aimed to evaluate the effect of melatonin on reducing the frequency and severity of migraine attacks.
METHODS
This randomized, double-blind clinical trial was conducted at Golestan Hospital of Ahvaz, Iran, in 2021. A total of 60 patients with episodic migraine were randomly assigned into 2 groups of receiving 3 mg melatonin (intervention group; n=30) or the same dose of placebo (control group; n=30) along with baseline therapy (propranolol 20 mg, BID) for two months. The attack frequency, attack duration, attack severity (based on VAS), the number of analgesic intakes, drug complications, Migraine Disability Assessment score (MIDAS), and Pittsburgh sleep quality index (PSQI) were evaluated at baseline and in the first, second, third, and fourth months of follow-up. The independent test, chi-square, and analysis of variance (ANOVA) with repeated measures were used to compare variables between the two groups.
RESULTS
In both groups, the frequency, duration, and severity of attacks, taking analgesics, MIDAS, and PSQI scores during follow-up decreased significantly (P<0.001). After treatment, the mean frequency (P=0.032) and duration of attacks (P=0.001), taking analgesic (P<0.001), and MIDAS (P<0.001) and PSQI scores (P<0.001) in the melatonin group were lower than placebo. Only the attack severity was not significantly different between the two groups (P=0.126). Side effects were observed in two patients (6.7%) in the melatonin group and one patient (3.3%) in the placebo group (P>0.999).
CONCLUSION
Our study shows that melatonin was more efficacious than the placebo in the reduction of frequency and duration of migraine attacks. It was equally safe as the placebo and might be effective in the preventive treatment of episodic migraine in adults. IRCT20190107042264N5.
Topics: Humans; Melatonin; Migraine Disorders; Double-Blind Method; Male; Female; Adult; Middle Aged; Iran; Severity of Illness Index; Treatment Outcome; Analgesics
PubMed: 38751874
DOI: 10.30476/ijms.2023.97782.2965 -
Scientific Reports May 2024Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has...
Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has abnormalities in the neurotransmitter, serotonin (5-hydroxytryptamine [5-HT]) and the adaptor molecule, 14-3-3 pathways in regions of the brain involved in gasping, response to hypoxia, and arousal. To evaluate our hypothesis that SIDS is, at least in part, a multi-organ dysregulation of 5-HT, we examined whether blood platelets, which have 5-HT and 14-3-3 signaling pathways similar to brain neurons, are abnormal in SIDS. We also studied platelet surface glycoprotein IX (GPIX), a cell adhesion receptor which is physically linked to 14-3-3. In infants dying of SIDS compared to infants dying of known causes, we found significantly higher intra-platelet 5-HT and 14-3-3 and lower platelet surface GPIX. Serum and plasma 5-HT were also elevated in SIDS compared to controls. The presence in SIDS of both platelet and brainstem 5-HT and 14-3-3 abnormalities suggests a global dysregulation of these pathways and the potential for platelets to be used as a model system to study 5-HT and 14-3-3 interactions in SIDS. Platelet and serum biomarkers may aid in the forensic determination of SIDS and have the potential to be predictive of SIDS risk in living infants.
Topics: Humans; Serotonin; Sudden Infant Death; Blood Platelets; 14-3-3 Proteins; Female; Male; Infant; Infant, Newborn
PubMed: 38750089
DOI: 10.1038/s41598-024-61949-9 -
Cell Communication and Signaling : CCS May 2024Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and...
Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and abnormal serotonin metabolism. Previous studies have investigated the tumor suppressor function of aldolase C (ALDOC), a glycolytic enzyme in GBM. However, it is unclear how ALDOC regulates production of serotonin and its associated receptors, HTRs. In this study, we analyzed ALDOC mRNA levels and methylation status using sequencing data and in silico datasets. Furthermore, we investigated pathways, phenotypes, and drug effects using cell and mouse models. Our results suggest that loss of ALDOC function in GBM promotes tumor cell invasion and migration. We observed that hypermethylation, which results in loss of ALDOC expression, is associated with serotonin hypersecretion and the inhibition of PPAR-γ signaling. Using several omics datasets, we present evidence that ALDOC regulates serotonin levels and safeguards PPAR-γ against serotonin metabolism mediated by 5-HT, which leads to a reduction in PPAR-γ expression. PPAR-γ activation inhibits serotonin release by HTR and diminishes GBM tumor growth in our cellular and animal models. Importantly, research has demonstrated that PPAR-γ agonists prolong animal survival rates and increase the efficacy of temozolomide in an orthotopic brain model of GBM. The relationship and function of the ALDOC-PPAR-γ axis could serve as a potential prognostic indicator. Furthermore, PPAR-γ agonists offer a new treatment alternative for glioblastoma multiforme (GBM).
Topics: Temozolomide; Glioblastoma; Humans; Animals; PPAR gamma; Mice; Cell Line, Tumor; Brain Neoplasms; Disease Progression; Serotonin; Signal Transduction; Antineoplastic Agents, Alkylating; Gene Expression Regulation, Neoplastic; PPAR-gamma Agonists
PubMed: 38741139
DOI: 10.1186/s12964-024-01645-3 -
Scientific Reports May 2024Melatonin receptors MT and MT are G protein-coupled receptors that mediate the effects of melatonin, a hormone involved in circadian rhythms and other physiological...
Melatonin receptors MT and MT are G protein-coupled receptors that mediate the effects of melatonin, a hormone involved in circadian rhythms and other physiological functions. Understanding the molecular interactions between these receptors and their ligands is crucial for developing novel therapeutic agents. In this study, we used molecular docking, molecular dynamics simulations, and quantum mechanics calculation to investigate the binding modes and affinities of three ligands: melatonin (MLT), ramelteon (RMT), and 2-phenylmelatonin (2-PMT) with both receptors. Based on the results, we identified key amino acids that contributed to the receptor-ligand interactions, such as Gln181/194, Phe179/192, and Asn162/175, which are conserved in both receptors. Additionally, we described new meaningful interactions with Gly108/Gly121, Val111/Val124, and Val191/Val204. Our results provide insights into receptor-ligand recognition's structural and energetic determinants and suggest potential strategies for designing more optimized molecules. This study enhances our understanding of receptor-ligand interactions and offers implications for future drug development.
Topics: Melatonin; Receptor, Melatonin, MT2; Receptor, Melatonin, MT1; Molecular Dynamics Simulation; Protein Binding; Humans; Molecular Docking Simulation; Ligands; Quantum Theory; Binding Sites; Indenes
PubMed: 38740789
DOI: 10.1038/s41598-024-59786-x -
The Journal of International Medical... May 2024To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD).
METHODS
We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery.
RESULTS
In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54).
CONCLUSION
Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.
Topics: Melatonin; Humans; Postoperative Complications; Delirium; Perioperative Care; Indenes; Randomized Controlled Trials as Topic; Length of Stay; Treatment Outcome; Hospital Mortality
PubMed: 38735057
DOI: 10.1177/03000605241239854 -
International Journal of Molecular... May 2024Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the...
Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the underlying effect of melatonin priming on root hydraulic conductivity of seedlings under drought-salinity combined remains greatly unclear. In the current report, we investigated the influence of seeds of three wheat lines' 12 h priming with 100 μM of melatonin on root hydraulic conductivity (Lpr) and relevant physiological indicators of seedlings under PEG, NaCl, and PEG + NaCl combined stress. A previous study found that the combined PEG and NaCl stress remarkably reduced the Lpr of three wheat varieties, and its value could not be detected. Melatonin priming mitigated the adverse effects of combined PEG + NaCl stress on Lpr of H4399, Y1212, and X19 to 0.0071 mL·h·MPa, 0.2477 mL·h·MPa, and 0.4444 mL·h·MPa, respectively, by modulating translation levels of aquaporin genes and contributed root elongation and seedlings growth. The root length of H4399, Y1212, and X19 was increased by 129.07%, 141.64%, and 497.58%, respectively, after seeds pre-treatment with melatonin under PEG + NaCl combined stress. Melatonin -priming appreciably regulated antioxidant enzyme activities, reduced accumulation of osmotic regulators, decreased levels of malondialdehyde (MDA), and increased K content in stems and root of H4399, Y1212, and X19 under PEG + NaCl stress. The path investigation displayed that seeds primed with melatonin altered the modification of the path relationship between Lpr and leaf area under stress. The present study suggested that melatonin priming was a strategy as regards the enhancement of root hydraulic conductivity under PEG, NaCl, and PEG + NaCl stress, which efficiently enhanced wheat resistant to drought-salinity stress.
Topics: Melatonin; Triticum; Plant Roots; Seeds; Droughts; Salinity; Seedlings; Stress, Physiological; Gene Expression Regulation, Plant; Salt Stress; Sodium Chloride; Antioxidants; Water
PubMed: 38732273
DOI: 10.3390/ijms25095055