-
Communications Biology Jun 2024Red blood cell (RBC) transfusions facilitate many life-saving acute and chronic interventions. Transfusions are enabled through the gold-standard hypothermic storage of...
Red blood cell (RBC) transfusions facilitate many life-saving acute and chronic interventions. Transfusions are enabled through the gold-standard hypothermic storage of RBCs. Today, the demand for RBC units is unfulfilled, partially due to the limited storage time, 6 weeks, in hypothermic storage. This time limit stems from high metabolism-driven storage lesions at +1-6 °C. A recent and promising alternative to hypothermic storage is the supercooled storage of RBCs at subzero temperatures, pioneered by our group. Here, we report on long-term supercooled storage of human RBCs at physiological hematocrit levels for up to 23 weeks. Specifically, we assess hypothermic RBC additive solutions for their ability to sustain supercooled storage. We find that a commercially formulated next-generation solution (Erythro-Sol 5) enables the best storage performance and can form the basis for further improvements to supercooled storage. Our analyses indicate that oxidative stress is a prominent time- and temperature-dependent injury during supercooled storage. Thus, we report on improved supercooled storage of RBCs at -5 °C by supplementing Erythro-Sol 5 with the exogenous antioxidants, resveratrol, serotonin, melatonin, and Trolox. Overall, this study shows the long-term preservation potential of supercooled storage of RBCs and establishes a foundation for further improvement toward clinical translation.
Topics: Erythrocytes; Humans; Blood Preservation; Cold Temperature; Antioxidants; Oxidative Stress; Cryopreservation; Time Factors
PubMed: 38914723
DOI: 10.1038/s42003-024-06463-4 -
Drug Design, Development and Therapy 2024Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major... (Review)
Review
Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients' visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.
Topics: Melatonin; Humans; Diabetic Retinopathy; Macular Degeneration; Animals; Fundus Oculi; Antioxidants
PubMed: 38911030
DOI: 10.2147/DDDT.S471525 -
BMJ Open Jun 2024Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current...
INTRODUCTION
Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia.
METHODS AND ANALYSIS
This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels).
ETHICS AND DISSEMINATION
This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings.
TRIAL REGISTRATION NUMBER
This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.
Topics: Humans; Fibromyalgia; Melatonin; Pregabalin; Double-Blind Method; Cross-Over Studies; Drug Therapy, Combination; Adult; Analgesics; Female; Middle Aged; Pain Management; Randomized Controlled Trials as Topic; Male; Pain Measurement; Chronic Pain; Treatment Outcome
PubMed: 38910006
DOI: 10.1136/bmjopen-2024-087180 -
International Journal of Food... Jun 2024During alcoholic fermentation, Saccharomyces cerevisiae synthesizes different compounds, which are crucial for product quality: volatile compounds with sensory impact,...
Commercial wine yeast nitrogen requirement influences the production of secondary metabolites (aroma, hydroxytyrosol, melatonin and other bioactives) during alcoholic fermentation.
During alcoholic fermentation, Saccharomyces cerevisiae synthesizes different compounds, which are crucial for product quality: volatile compounds with sensory impact, and bioactive compounds such as melatonin (MEL) and hydroxytyrosol (HT), linked to health benefits. As many of these compounds are related with yeast's nitrogen metabolism, their production have been studied in four different commercial strains with different nitrogen requirement (Red Fruit, Uvaferm VRB, Lalvin Rhone 2323 and Lalvin QA23) being, Uvaferm UVR the higher nitrogen demander strain. All strains produced the secondary metabolites, notably Uvaferm UVR produced the highest HT concentration, despite its low growth. Uvaferm UVR emerged also as a significant producer of MEL, indicating a potential role in fermentation related stress. Moreover, Uvaferm UVR shows the highest total concentrations of volatile compounds. Multivariate analysis revealed distinct clustering based on nitrogen requirements of the strains, highlighting the strain-dependent metabolic responses.
PubMed: 38905810
DOI: 10.1016/j.ijfoodmicro.2024.110788 -
Journal of Oral Microbiology 2024Erythrosine+potassium iodide-mediated photodynamic therapy has shown an anticandidal effect. Single session, however, has inadequate fungal inhibition.
BACKGROUND
Erythrosine+potassium iodide-mediated photodynamic therapy has shown an anticandidal effect. Single session, however, has inadequate fungal inhibition.
OBJECTIVES
We aimed to examine the effects of multiple aPDT sessions on inhibition and singlet oxygen formation.
METHODS
220 μM erythrosine +/-100 mM potassium iodide was applied to biofilms for 1 min prior to irradiation at 530±10 nm using a 250 mW/cm light-emitting diode. Negative and positive controls were phosphate buffer saline and nystatin, respectively. Single, double and triple irradiation sessions with a 5 min resting time between sessions were performed. Post-treatment candidal counts were done at 0, 1 6 and 24 hr while log colony forming unit/ml was calculated and compared using a Kruskal-Wallis with Dunn's post hoc test at a <0.05 - Singlet oxygen amount was compared using one-way ANOVA with a post hoc test at a < 0.05.
RESULTS
Two and three irradiation sessions to erythrosine+potassium iodide could inhibit at 7.92 logCFU/ml ( < 0.001) . Singlet oxygen from a combination groups was significantly higher than for erythrosine (positive control). Moreover, the correlation coefficient (r) between singlet oxygen production and decreased counts was equal to 1.
CONCLUSION
Multiple sessions PDT of 220 μM erythrosine+100 mM potassium iodide effectively inhibited a biofilm.
PubMed: 38903483
DOI: 10.1080/20002297.2024.2369357 -
Frontiers in Plant Science 2024Oxidative damage leading to loss of nutritional quality and pericarp discoloration of harvested litchi fruits drastically limits consumer acceptance and marketability....
Oxidative damage leading to loss of nutritional quality and pericarp discoloration of harvested litchi fruits drastically limits consumer acceptance and marketability. In the present investigation, the impact of postharvest melatonin application at different concentrations, i.e., 0.1 mM, 0.25 mM, and 0.5 mM, on fruit quality and shelf life of litchi fruits under cold storage conditions was studied. The results revealed the positive effect of melatonin application at all concentrations on fruit quality and shelf life. However, treatment with 0.5 mM concentration of melatonin resulted in minimum weight loss, decay loss, pericarp discoloration, and also retained higher levels of TSS, acidity, total sugar, ascorbic acid, anthocyanin, antioxidant, and phenolics content during cold storage. Melatonin administration also restricted the enzymatic activity of the polyphenol oxidase (PPO) and peroxidase (POD) enzymes in the fruit pericarp and maintained freshness of the fruits up to 30 days in cold storage. At the molecular level, a similar reduction in the expression of browning-associated genes, , and Laccase, was detected in preserved litchi fruits treated with melatonin. Anthocyanin biosynthetic genes, and , on the other hand showed enhanced expression in melatonin treated fruits compared to untreated fruits. Melatonin, owing to its antioxidant properties, when applied to harvested litchi fruits retained taste, nutritional quality and red color pericarp up till 30 days in cold storage.
PubMed: 38903429
DOI: 10.3389/fpls.2024.1402607 -
Seminars in Perinatology Jun 2024Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is...
Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is beneficial, it is only partially protective and adjuvant treatments that further improve outcomes are urgently needed. In high-income countries where HT is standard care, novel treatments are tested in conjunction with HT. Mesenchymal stromal cells (MSC) represent a paradigm shift in brain protection, uniquely adapting to the host cellular microenvironment. MSC have low immunogenicity and potent paracrine effects stimulating the host tissue repair and regeneration and reducing inflammation and apoptosis. Preclinical studies in perinatal brain injury suggest that MSC are beneficial after hypoxia-ischemia (HI) and most preclinical studies of MSC with HT show protection. Preclinical and early phase clinical trials have shown that allogenic administration of MSC to neonates with perinatal stroke and HIE is safe and feasible but further safety and efficacy studies of HT with MSC in these populations are needed. Combination therapies that target all stages of the evolution of injury after HI (eg HT, melatonin and MSC) show promise for improving outcomes in HIE.
PubMed: 38902120
DOI: 10.1016/j.semperi.2024.151929 -
Plant Signaling & Behavior Dec 2024In the decades since their discovery in plants in the mid-to-late 1900s, melatonin (-acetyl-5-methoxytryptamine) and serotonin (5-methoxytryptamine) have been... (Review)
Review
In the decades since their discovery in plants in the mid-to-late 1900s, melatonin (-acetyl-5-methoxytryptamine) and serotonin (5-methoxytryptamine) have been established as their own class of phytohormone and have become popular targets for examination and study as stress ameliorating compounds. The indoleamines play roles across the plant life cycle from reproduction to morphogenesis and plant environmental perception. There is growing interest in harnessing the power of these plant neurotransmitters in applied and agricultural settings, particularly as we face increasingly volatile climates for food production; however, there is still a lot to learn about the mechanisms of indoleamine action in plants. A recent explosion of interest in these compounds has led to exponential growth in the field of melatonin research in particular. This concept paper aims to summarize the current status of indoleamine research and highlight some emerging trends.
Topics: Melatonin; Serotonin; Plants; Plant Growth Regulators
PubMed: 38899558
DOI: 10.1080/15592324.2024.2366545 -
Frontiers in Nutrition 2024Phenolic acids are secondary metabolites in higher plants, with antioxidant, anticancer, and anti-aging effects on the human body. Therefore, foods rich in phenolic...
Phenolic acids are secondary metabolites in higher plants, with antioxidant, anticancer, and anti-aging effects on the human body. Therefore, foods rich in phenolic acids are popular. Methyl jasmonate (MeJA) promoted phenolic acids accumulation but also inhibited sprout growth. Melatonin (MT) was a new type of plant hormone that not only alleviated plants' abiotic stress, but also promoted the synthesis of plant-stimulating metabolism. This study aimed to elucidate the mechanism of exogenous MT on the growth and development, and phenolic acids metabolism of barley sprouts under MeJA treatment. The results showed that MT increased the phenolic acids content in sprouts by increasing the activities of phenylalanine ammonia-lyase and cinnamic acid 4-hydroxylase, and up-regulating the gene expression of , , , and . MT attenuated the growth inhibition of barley sprouts under MeJA stress by increasing the activities of regulated antioxidant enzymes and the expression of their corresponding genes. Furthermore, MT increased the NO content and induced Ca burst in barley sprouts under MeJA stress. These events were inhibited by DL-4-Chlorophenylalanine. These results suggested that MT ameliorated growth inhibition and promoted the biosynthesis of phenolic acids in barley sprouts under MeJA stress.
PubMed: 38899320
DOI: 10.3389/fnut.2024.1403293 -
Cureus May 2024Anesthesia is critical to pediatric care, ensuring the safety and comfort of children undergoing medical procedures. With a growing interest in alternative anesthetic... (Review)
Review
Anesthesia is critical to pediatric care, ensuring the safety and comfort of children undergoing medical procedures. With a growing interest in alternative anesthetic agents, melatonin has emerged as a promising candidate due to its sedative, analgesic, anti-inflammatory, and neuroprotective properties. This comprehensive review explores the potential applications of melatonin in pediatric anesthesia. We delve into the pharmacological characteristics of melatonin, its anesthetic properties, and its clinical applications in pediatric care, including preoperative sedation, adjunct to general anesthesia, postoperative pain management, and prevention of emergence delirium. Additionally, we discuss the safety profile of melatonin, potential adverse effects, and comparative analysis with traditional anesthetics. Finally, we highlight future research directions to provide insights into melatonin's role in pediatric anesthesia and its implications for clinical practice.
PubMed: 38894785
DOI: 10.7759/cureus.60575