Serum Melatonin Research Articles

Circadian rhythm disturbance and delirium in ICU patients: a prospective cohort study

BackgroundPatients treated in the intensive care unit (ICU) may experience a reversal of day and night. The circadian rhythm in ICU patients can be disturbed.MethodsTo explore the relationship between ICU delirium and the circadian rhythms of melatonin, cortisol and sleep. A prospective cohort study was carried out in a surgical ICU of a tertiary teaching hospital. Patients who were conscious during the ICU stay after surgery and were scheduled to stay in the ICU for more than 24 h were enrolled. Serum melatonin and plasma cortisol levels were measured three times a day by drawing arterial blood on the first three days after ICU admission. Daily sleep quality was assessed by the Richard-Campbell Sleep Questionnaire (RCSQ). The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was performed twice a day to screen for ICU delirium.ResultsA total of 76 patients were included in this study, and 17 patients developed delirium during their ICU stay. Melatonin levels were different at 8:00 (p = 0.048) on day 1, at 3:00 (p = 0.002) and at 8:00 (p = 0.009) on day 2, and at all three time points on day 3 (p = 0.032, 0.014, 0.047) between delirium and non-delirium patients. The plasma cortisol level in the delirium patients was significantly lower than that in the non-delirium patients at 16:00 on day 1 (p = 0.025). The changes in melatonin and cortisol secretion levels exhibited obvious biological rhythmicity in non-delirium patients (p < 0.001 for melatonin, p = 0.026 for cortisol), while no rhythmicity was found in melatonin and cortisol secretion levels in the delirium group (p = 0.064 for melatonin, p = 0.454 for cortisol). There was no significant difference in RCSQ scores in the first three days between the two groups.ConclusionsThe disturbance of the circadian rhythm of melatonin and cortisol secretion was associated with the development of delirium in ICU patients. Clinical staff should pay more attention to the importance of maintaining patients’ normal circadian rhythms in the ICU.Trial registrationThe study was registered with the US National Institutes of Health ClinicalTrials.gov(NCT05342987) (25/04/2022).

Rhythmicity in testicular melatonin and its correlation with the dynamics of spermatogenic cells in an annual reproductive cycle of Clarias batrachus under natural photo-thermal conditions

Melatonin, the pineal hormone, is synthesized and secreted rhythmically in accordance with various environmental cues especially photo-thermal conditions. The reproductive physiology of seasonal breeders is synchronized with the surroundings by melatonin as a neuroendocrine mediator to acts as an important factor in fish reproduction. However, the data on the participation of melatonin in male reproduction and the putative interaction with the process of spermatogenesis in fish is scarce till date. So, major objectives of the current study are to determine for the first time, the relationship, if any, between seasonal levels of melatonin and testicular development and maturation of the germ cells, and also the involvements of specific meteorological parameters in spermatogenesis under natural photo-thermal conditions. We measured the concentration of circulatory and testicular melatonin; value of gonadosomatic index (GSI), relative percentages of different developing spermatogenic cells, area and perimeter (size and shape) of seminiferous lobules along with the level/duration of rainfall, water temperature and day length in six reproductive phases throughout an annual cycle in adult male catfish (Clarias batrachus). Intra-testicular and serum melatonin concentration showed a similar seasonal pattern with a peak during “functional maturity” phase and trough during “slow spermatogenesis” phase. Correlation as well as regression analyses also supported this positive relationship. Interestingly, intra-testicular melatonin also showed a significant positive correlation with GSI and relative percentage as well as lobular size of mature stages (spermatid and spermatozoa) of germ cells in an annual cycle. Furthermore, meteorological factors exhibited as critical cues to regulate the dynamics (in %) of spermatogenic cells and the level of testicular melatonin throughout the annual gonadal cycle. Our results corroborated by principal component (PC) analysis and showed very clearly that active “functional maturity” state is characterized by GSI, testicular melatonin, relative abundance and lobular size of mature spermatogenic stages as key internal oscillators; and studied environmental variables as the external clues for the regulation of spawning process. Collectively, the present data revealed that there is a relationship between melatonin levels and testicular growth and development of germ cells in Clarias batrachus under natural photo-thermal conditions.

Seasonal variation of serum and intrafollicular concentrations of melatonin and estradiol in relation to follicular development

The main objective of this study was to compare the effect of season on serum and intrafollicular concentrations of melatonin (MT). The relationship between follicular size, MT and estradiol (E2) concentrations was also explored. Twelve mares were used. Aspiration of fluid from all follicles larger than 5 mm was carried out in each mare during the breeding season and during the anovulatory season. All aspirations were carried out between 7AM and 8AM, and a serum sample was obtained at the same time. Follicles were classified into small (≤ 15 mm); medium (16-30 mm); and large (> 30 mm). MT and E2 concentrations were measured by enzymatic immunoassay (Melatonin ELISA Mybiosource, MBS1603596; Estradiol ELISA DRG, EIA-2693). Analysis of Variance was used to evaluate the effects of season, fluid type (follicular vs serum) and follicle size. Intrafollicular concentrations of MT were higher than serum concentrations both in the reproductive season (127±1.41 vs 69.59±1.73 ng/L) and in the anovulatory season (118.5±2.93vs 115.45±3.06 ng/L). MT concentrations in serum were higher during the anovulatory season than during the reproductive season (p<0.05), but the opposite was the case for intrafollicular MT. During the ovulatory season MT was higher (p<0.05) in large follicles (141.39±2.13ng/L) than in medium (130.25±2.55 ng/L) and small follicles (109.36±2.57 ng/L). The difference between medium and small follicles was also significant(p<0.05). In contrast during the anovulatory season MT concentration was not different between small and medium follicles (123.43±3.79 vs 109.92±5.55 ng/mL). Intrafollicular levels of E2 were higher during the ovulatory season than during the anovulatory season in medium (211.89±20.4 vs 126.18±0.07) and small follicles (67.42±2.4 vs 14.78±1.06 ng/mL). E2 concentrations in large follicles during the ovulatory season was 4,312.83±65.8 ng/mL. The results of this study indicate that while serum MT concentrations were different between seasons due to the known negative correlation between pineal MT secretion and day length, this seasonal effect was not found in the case of intrafollicular MT concentrations. Also, in this study there was no correlation between serum and intrafollicular MT concentrations. Together, these findings suggest photoperiod-independent intrinsic follicular MT synthesis. E2 concentrations were correlated with follicle size in both ovulatory and anovulatory seasons but were always higher during the ovulatory season for a given size. During this season there was a positive correlation between intrafollicular MT and estradiol concentrations, thus suggesting that intrafollicular estradiol may stimulate intrafollicular melatonin synthesis. It is concluded that intrafollicular MT concentrations in the mare are at least in part of intrinsic origin and may be stimulated by estradiol.

Immunological aspects of the use of melatonin in experimental thermal trauma

The prevalence of thermal trauma, the high risk of infectious and non-infectious short- and long- term complications, and the limited effectiveness of the therapeutic approaches used are prerequisites for the search and pathogenetic justification of new therapies, among which the endogenous homeostasis regulator with pleiotropic properties melatonin attracts attention.The aim of the work is to investigate the immunological aspects of intraperitoneal use of melatonin (MT) in experimental thermal trauma (TT).The work was performed on 158 rats of the Wistar line, grade III TT and a relative area of 3.5% were simulated by skin immersion in water at 98-99 °C for 12 s. MT was administered intraperitoneally daily at a dose of 10 mg/kg for 5 days. The quantitative composition of blood cells was evaluated on a hematological analyzer. Plasma concentrations of IL-4, TNFa, IFNg, and CRP were determined on an automatic enzyme immunoassay using rat-specific test systems, and MT by capillary electrophoresis.With experimental TT, against the background of a progressive increase in the number of leukocytes in the blood from 5 to 20 days due to neutrophils, monocytes, basophils, the number of lymphocytes decreases. With TT, the concentration of CRP increases in serum on days 5 and 10. The content of TNFa, IL-4 increases on days 5, 10 and 20 in the absence of significant changes in the concentration of IFNg. The concentration of serum MT does not change significantly. Intraperitoneal use of MT in TT leads to a partial restoration of the number of lymphocytes in the blood on day 5. Evaluation of the cytokine profile in serum revealed a decrease in the concentration of TNFa on days 10 and 20, no significant changes in the concentration of IL-4 and IFNg were recorded, the concentration of CRP decreased on day 5. The concentration of serum MT increases by 5 days.With TT on the 5th, 10th, 20th day of the experiment, the number of neutrophils, monocytes, basophils in the blood increases, decreases – lymphocytes, the serum content of CRP, TNFa, IL-4 increases, the content of IFNg and melatonin does not change. Intraperitoneal use of MT in TT partially restores the number of lymphocytes in the blood, the concentration of CRP, TNFa. A decrease in serum concentrations of TNFa and CRP in TT under the conditions of MT use suggests a limitation of the acute phase response as a consequence of the antioxidant, anti-inflammatory effect of MT, which can accelerate healing and reduce the area of the lesion of TT.

Изменение концентрации мелатонина при прогрессировании катаракты

Purpose. To establish the relationship between melatonin level in the blood serum and the lens in patients with different degrees of cataract progression. Material and methods During the study, the following groups of patients were formed: group 1 – initial cataract, group 2 – immature cataract, group 3 – mature cataract and group 4 – complicated initial cataract with type 2 diabetes mellitus. All patients were surveyed. Considering the fact that melatonin secretion depends on a daily rhythm, the sampling of biomaterial for analysis was carried out at the same time during a planned surgical intervention. Melatonin content was determined by enzyme immunoassay using the commercial Human MT (Melatonin) ELISA Kit. Results. The study did not reveal statistically significant changes in the level of melatonin in the blood serum of patients with different levels of cataract progression. However, there was a trend towards lower melatonin values in the group of patients with immature and mature cataract, relative to patients with initial cataract. When comparing the group of patients with mature cataract relative to patients with initial cataract, there was a decrease in melatonin levels by 45 % (p ≤ 0.05). The level of melatonin in the lens of patients with cataract complicated by diabetes mellitus was lower by 63 % (p ≤ 0.01) compared to patients with uncomplicated initial cataract. Conclusion. It was found that the level of melatonin in the lens significantly depends on the degree of cataract progression. Cataracts complicated by diabetes mellitus were characterized by minimal values of melatonin in the lens. The obtained data show the relevance of further research to assess the role of melatonin in various ophthalmic pathologies. Keywords: melatonin, cataract, eye lens

Assessment of serum level of melatonin in migraine: a case control study

BackgroundMigraine attacks are reported to be severe enough to affect daily living events and can affect different age groups including early childhood. Chronic migraine is usually associated with several comorbidities such as anxiety, depression, sleep disorders, fibromyalgia, and fatigue. The existence of a bidirectional relationship between sleep and migraine is documented. This study aims at assessing the relationship between serum melatonin, sleep quality, and both migraine and migraine severity. This case–control study was executed on 70 patients and 70 healthy controls. Serum melatonin was assessed in morning and evening blood samples. Patients underwent a thorough clinical examination, assessing migraine severity using the Migraine Disability Assessment Scale and the sleep quality of both groups was evaluated using the sleep quality scale.ResultsSerum melatonin levels were significantly reduced among migraine patients in both morning and evening samples. Sleep quality was significantly impaired in migraine patients. There is a statistically significant negative correlation between melatonin in both samples and both of frequency of attack and migraine disability. Positive family history, presence of aura and chronic migraine had significantly lower melatonin in both samples compared to those without aura was associated with significantly lower melatonin. Sleep quality was negatively correlated with serum melatonin, and positively correlated with migraine severity and frequency.ConclusionSerum melatonin is significantly reduced among migraineurs, and linked to migraine severity; they also had impaired sleep quality so melatonin administration may represent a chance for improving headache characteristics.

Angiotensin converting enzyme 2 gene expression and markers of oxidative stress are correlated with disease severity in patients with COVID-19

BackgroundOxidative stress is thought to play a significant role in the pathogenesis and severity of COVID-19. Additionally, angiotensin converting enzyme 2 (ACE2) expression may predict the severity and clinical course of COVID-19. Accordingly, the aim of the present study was to evaluate the association of oxidative stress and ACE2 expression with the clinical severity in patients with COVID-19.Methods and resultsThe present study comprised 40 patients with COVID-19 and 40 matched healthy controls, recruited between September 2021 and March 2022. ACE 2 expression levels were measured using Hera plus SYBR Green qPCR kits with GAPDH used as an internal control. Serum melatonin (MLT) levels, serum malondialdehyde (MDA) levels, and total antioxidant capacity (TAC) were estimated using ELISA. The correlations between the levels of the studied markers and clinical indicators of disease severity were evaluated. Significantly, lower expression of ACE2 was observed in COVID-19 patients compared to controls. Patients with COVID-19 had lower serum levels of TAC and MLT but higher serum levels of MDA compared to normal controls. Serum MDA levels were correlated with diastolic blood pressure (DBP), Glasgow coma scale (GCS) scores, and serum potassium levels. Serum MLT levels were positively correlated with DBP, mean arterial pressure (MAP), respiratory rate, and serum potassium levels. TAC was correlated with GCS, mean platelet volume, and serum creatinine levels. Serum MLT levels were significantly lower in patients treated with remdesivir and inotropes. Receiver operating characteristic curve analysis demonstrates that all markers had utility in discriminating COVID-19 patients from healthy controls.ConclusionsIncreased oxidative stress and increased ACE2 expression were correlated with disease severity and poor outcomes in hospitalized patients with COVID-19 in the present study. Melatonin supplementation may provide a utility as an adjuvant therapy in decreasing disease severity and death in COVID-19 patients.

Melatonin alleviates lung injury in H1N1-infected mice by mast cell inactivation and cytokine storm suppression.

Influenza A virus (IAV) H1N1 infection is a constant threat to human health and it remains so due to the lack of an effective treatment. Since melatonin is a potent antioxidant and anti-inflammatory molecule with anti-viral action, in the present study we used melatonin to protect against H1N1 infection under in vitro and in vivo conditions. The death rate of the H1N1-infected mice was negatively associated with the nose and lung tissue local melatonin levels but not with serum melatonin concentrations. The H1N1-infected AANAT-/- melatonin-deficient mice had a significantly higher death rate than that of the WT mice and melatonin administration significantly reduced the death rate. All evidence confirmed the protective effects of melatonin against H1N1 infection. Further study identified that the mast cells were the primary targets of melatonin action, i.e., melatonin suppresses the mast cell activation caused by H1N1 infection. The molecular mechanisms involved melatonin down-regulation of gene expression for the HIF-1 pathway and inhibition of proinflammatory cytokine release from mast cells; this resulted in a reduction in the migration and activation of the macrophages and neutrophils in the lung tissue. This pathway was mediated by melatonin receptor 2 (MT2) since the MT2 specific antagonist 4P-PDOT significantly blocked the effects of melatonin on mast cell activation. Via targeting mast cells, melatonin suppressed apoptosis of alveolar epithelial cells and the lung injury caused by H1N1 infection. The findings provide a novel mechanism to protect against the H1N1-induced pulmonary injury, which may better facilitate the progress of new strategies to fight H1N1 infection or other IAV viral infections.

Clinical changes of serum melatonin and ICAM-1 levels in patients with basal ganglia hypertensive intracerebral hemorrhage.

To investigate the clinical changes of serum melatonin and intercellular adhesion molecule-1 (ICAM-1) levels in patients with basal ganglia hypertensive intracerebral hemorrhage (HICH). In this retrospective observational study, patients with HICH in Suzhou Hospital of Traditional Chinese and Western Medicine from January 2020 to January 2021 were included as the observation group (n=120), and 120 healthy volunteers who underwent physical examination were included as the control group. According to the Glasgow Coma Scale (GCS), the observation group was divided into four subgroups: normal group (n=27), mild group (n=51), moderate group (n=24), and severe group (n=18). Differences in serum melatonin and ICAM-1 were compared between the observation group and the control group, and between the subgroups. Logistic regression was used to analyze the risk factors of poor prognosis, and the ROC curve was used to analyze the influence of melatonin and ICAM-1 levels on patient prognosis. Serum melatonin levels were lower in the observation group compared to the control group, while ICAM-1 levels were higher (P<0.05). With the aggravation of brain injury, serum melatonin decreased and ICAM increased (P<0.05). Decreased serum melatonin and increased ICAM-1 were independent risk factors for poor prognosis in patients with HICH. The combined AUC of serum melatonin and ICAM-1 for the detection of poor prognosis in patients with HICH was 0.860, which was higher than that of the two alone (P<0.05). Low serum melatonin levels and high ICAM-1 levels are associated with poor prognosis in patients with HICH and can be used as predictors of patients' prognosis.

A Pilot Study to Evaluate the Potential of Melatonin Implants to Control Cyclicity in the Bitch.

In short-day breeders such as the sheep, melatonin stimulates oestrus activity; in contrast, a high serum concentration of melatonin inhibits oestrus in long-day breeders such as the cat. Therefore, implants with melatonin have been used to suppress or induce oestrus depending on the species. The aim of this pilot study was to evaluate if melatonin could be an alternative to control the reproductive cycle in the bitch. Nine beagle bitches were observed for three oestrus cycles. Five beagle bitches were treated with 18 mg melatonin implants on average 27 days before the next expected oestrus based on the previous interoestrus interval. Four bitches served as untreated controls. Blood samples for evaluation of serum melatonin were collected at the time of assignment to treatment or control group and 1-4 weeks thereafter. Clinical signs and vaginal smears were used to follow the cycle. Melatonin varied significantly with bitch (p < 0.05) but not with treatment. Treatment did not affect the interoestrus interval (p > 0.05). In conclusion, treatment with 18 mg melatonin implants approximately one month before expected oestrus is not likely to be a useful method to control cyclicity in the bitch. It is still not known if melatonin is involved in regulation of the oestrus cycle in the domestic dog.

Examination of correlations between vitamin D and melatonin levels with sleep among women aged 18-49 years.

Although clinical research is still going on to determine any relationship between vitamin D and sleep regulation, only few studies have identified the role of vitamin D metabolism in sleep disorders. The current study aims to examine the incidence of vitamin D deficiency/insufficiency in the sample group and its effects on sleep quality and melatonin level. A cross-sectional study was designed. A total of 79 women aged 18-49 years who applied to the research and training hospital between 1 October and 30 November 2021 participated in the study. Data were collected using a socio-demographic questionnaire prepared by the authors and the Pittsburgh Sleep Quality Index (PSQI). Blood samples were taken from the participants, also, 25-OH-vitamin D3 and melatonin levels in serum samples were measured by ELISA. The participants (n = 79) were aged 29.61 ± 11.14 years. The mean total PSQI scores of the participants were calculated as 5.77 ± 2.70. We determined that 64.6% of the participants had vitamin D deficiency, 21.5% had vitamin D insufficiency, and 13.9% of the participants were vitamin D sufficient. The mean melatonin level was found to be 24.77 ± 27.77 ng/L. We determined that an increase in the melatonin levels decreases the risk of vitamin D deficiency. Besides, our findings showed a good positive correlation between serum melatonin and 25 OH vitamin D3 levels (r = 0.544, p < 0.001). Our results indicate that the correction of vitamin D insufficiency can positively affect melatonin levels, therefore, it may positively contribute to the treatment of sleep disorders related to melatonin deficiency.

Electroacupuncture alleviates cerebral ischemia injury in rats by regulating melatonin-NLRP3 and inhibiting pyroptosis

To investigate the mechanism of electroacupuncture in alleviating cerebral ischemia injury in cerebral ischemia-reperfusion rats by regulating melatonin - NOD-like receptor protein 3 (NLRP3) mediated pyroptosis. A total of 48 SD rats were randomly divided into sham operation group, model group, electroacupuncture (EA) group and EA +Luz group, with 12 rats in each group. The focal cerebral ischemia-reperfusion injury model was established by middle cerebral artery embolization. Rats of the EA group was treated with EA stimulation (4 Hz/20 Hz, 0.5 mA,20 min) at "Baihui" (GV20) and "Shenting" (GV24) once a day for 7 consecutive days; rats of EA+Luz group were given the same EA treatment and intraperitoneally administered melatonin receptor antagonist (luzindole, 30 mg/kg), once a day for 7 consecutive days. The neurological impairment was evaluated by Zea Longa score. The level of serum melatonin content at 12:00 and 24:00 was detected by ELISA. The percentage of cerebral infarction volume was evaluated by MRI of small animals. The apoptosis rate of nerve cells in cerebral cortex of infarct side was detected by TUNEL staining. The activation of microglia cells was detected by immunofluorescence staining. The expression levels of pyroptosis-related proteins NLRP3, Caspase-1 and interleukin (IL) -1β were detected by Western blot. Compared with the sham operation group, the neural function score was significantly increased (P<0.01); the melatonin content was significantly decreased at 24:00 (P<0.01); the percentage of cerebral infarction volume, apoptosis rate of nerve cells in cerebral cortex area of infarction side, the expressions of NLRP3, Caspase-1 and IL-1β proteins were significantly increased (P<0.01); and microglia cells were significantly activated in the model group.Compared with the model and EA +Luz groups, the nerve function score was significantly decreased (P<0.05); the percentage of cerebral infarction volume, the nerve cell apoptosis rate, the activation level of microglia cells, the expression levels of NLRP3, Caspase-1 and IL-1β were significantly decreased (P<0.01, P<0.05) in the EA group. Compared with the model and EA+Luz groups, the melatonin content at 24:00 was significantly increased (P<0.01, P<0.05) in the EA group. EA at GV20 and GV24 can reduce the neurolo-gical injury in cerebral ischemia reperfusion model rats, which may be related to regulating the expression of endogenous melatonin, inhibiting cell scorchification and reducing cerebral ischemia injury.

Вплив модуляторів факторів транскрипції NF-κB і Nrf2 на показники оксидативно–нітрозативного стресу в скелетних м’язах щурів за умов хронічної гіпомелатонінемії та вуглеводно-ліпідної дієти

This article describes the effect of NF-κB inhibitor ammonium pyrrolidine dithiocarbamate and Nrf2 inducer dimethylfumarate on indicators of oxidative-nitrosative stress in skeletal muscles of rats with chronic hypomelatoninemia, induced by roundthe-clock illumination with an intensity of 1500 lux for 30 days, against the background of a carbohydrate-lipid diet (20% fructose solution and appropriate food) for 60 days. The study demonstrated that the administration of ammonium pyrrolidine dithiocarbamate and dimethylfumarate under the experimental conditions impedes the development of hypomelatoninemia, this was accompanied by a two-fold increase in the blood serum melatonin concentration compared to the control group. Moreover, the administration of ammonium pyrrolidine dithiocarbamate and dimethylfumarate significantly reduces the production of superoxide anion radical by electron transport chains of mitochondria (by 47.9 and 51.3%) and sarcoplasmic reticulum (by 48.6 and 52.0%) in the homogenate of femoral muscles, the total activity of NO synthase (by 37.2 and 36.2%) and its inducible isoform (by 41.1 and 40.0%), the concentration of peroxynitrites of alkaline and alkaline earth metals (by 37.2 and 41.0 %), while the activity of constitutive NO-synthases (by 2.9 and 2.8 times) and their conjugation index (by 5.2 and 5.4 times) increases compared to the respective control values. We suggest that modulators of redox-sensitive transcription factors NF-κB and Nrf2 under conditions of chronic hypomelatoninemia and the exposure to the carbohydrate-lipid diet are effective means to restrain the development of oxidative-nitrosative stress in skeletal muscles.

Melatonin attenuates cholestatic liver injury via inhibition of the inflammatory response.

Melatonin, an indole neurohormone secreted mainly by the pineal gland, has been found to be involved in a variety of liver diseases. However, the underlying mechanism by which melatonin ameliorates cholestatic liver injury is not fully understood. In this study, we investigated the mechanism by which melatonin attenuates cholestatic liver injury via inhibition of the inflammatory response. We measured the levels of serum melatonin in patients with obstructive cholestasis (n = 9), patients with primary biliary cholangitis (PBC) (n = 11), and control patients (n = 7). We performed experiments with C57BL/6J mice treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and melatonin to verify the role of melatonin in the mouse model of cholestasis. Primary mouse hepatocytes were used for in vitro studies to study the mechanisms of action of melatonin in cholestasis. The levels of serum melatonin were markedly increased and negatively correlated with serum markers of liver injury in cholestatic patients. As expected, oral administration of melatonin significantly attenuated cholestasis-induced liver inflammation and fibrosis in 0.1% DDC diet-fed mice. Further mechanistic studies in cholestatic mice and primary hepatocytes revealed that melatonin reduced the conjugate BA-stimulated expression of cytokines (e.g. Ccl2, Tnfα, and Il6) through the ERK/Egr1 signalling pathway in these models. The levels of serum melatonin are significantly elevated in cholestatic patients. Melatonin treatment ameliorates cholestatic liver injury by suppressing the inflammatory response in vivo and in vitro. Therefore, melatonin is a promising novel therapeutic strategy for cholestasis.

Dietary Supplementation with Resveratrol Attenuates Serum Melatonin Level, Pro-Inflammatory Response and Metabolic Disorder in Rats Fed High-Fructose High-Lipid Diet under Round-the-Clock Lighting.

This study aims to investigate the effect of resveratrol on systemic inflammatory response and metabolic disorder in rats fed a high-fructose high-lipid diet (HFHLD) and exposed to round-the-clock lighting (RCL). 21 adult male Wistar rats were randomly divided into 3 groups: control (group 1, n = 7); HFHLD for 8 weeks + round-the-clock lighting (RCL) (group 2, n = 7); HFHLD + RCL + Resveratrol (in a daily dose of 5 mg/kg intragastrically (group 3, n = 7). Results show that the combined effect of HFHLD and RCL reduces the serum melatonin (p < 0.001) and accelerates pro-inflammatory activities, oxidative stress, and metabolic disorder. There is a significant increase in the serum tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) (both p < 0.001), blood malondialdehyde-thiobarbituric acid adducts (MDA-TBA2) (p < 0.001), serum glucose (p < 0.01), insulin concentration, and the homeostatic model assessment insulin resistance (HOMA-IR) index (both p < 0.001), serum with very low-density lipoprotein (VLDL), and triacylglycerol (TAG) (both p < 0.001). At the same time, the decrease in the serum high-density lipoprotein (HDL) level (p < 0.001) is observed in the HFHLD + RCL group compared to the control. In the HFHLD + RCL + Resveratrol group, hypomelatonaemia (p < 0.001), pro-inflammatory actions, oxidative stress, and metabolic disorder were mitigated. Resveratrol can cause a significant rise in the serum melatonin and reduce serum TNF-α and CRP levels (both p < 0.001), blood MDA-TBA2 (p < 0.001), serum glucose (both p < 0.01), insulin concentration, and HOMA-IR (both p < 0.001), serum VLDL and TAG (both p < 0.001) compared to the group 2, while serum HDL level increases (p < 0.01). Resveratrol attenuates pro-inflammatory responses and prevents considerable metabolic disorder in rats fed HFHLD under RCL.

Subchronic Low-Dose Methylmercury Exposure Accelerated Cerebral Telomere Shortening in Relevant with Declined Urinary aMT6s Level in Rats

Methylmercury (MeHg) is a global pollutant with established toxic effects on the central nervous system (CNS). However, early events and early-warning biomarkers of CNS damage following exposure to low-dose MeHg are still lacking. This study aimed to investigate whether subchronic low-dose MeHg exposure had adverse effects on the cerebral telomere length, as well as serum melatonin and its urinary metabolite 6-sulfatoxymelatonin (aMT6s) in rats. Sixteen male Sprague Dawley rats were divided into two groups. Group I was the control group. In group II, rats were exposed to MeHg by gavage at a dose of 0.1 mg/kg/day for 3 months. This study revealed that MeHg exposure resulted in impairment of learning and memory ability, a slightly reduced number of neurons and an irregular arrangement of neurons in the hippocampus. It also significantly accelerated telomere shortening in the cerebral cortex, hippocampus and hypothalamus. Moreover, MeHg exposure decreased the levels of melatonin in serum and aMT6s in urine, partly by suppressing the synthesis of 5-hydroxytryptamine (5-HT) in the brain but promoted the expression of melatonin-catalyzing AANAT and ASMT. Importantly, cerebral telomere length was positively correlated with MT and aMT6s after MeHg exposure. These results suggested that the shortened telomere length in the brain may be an early event in MeHg-induced CNS toxicity, and the level of aMT6s in urine may serve as an early-warning biomarker for MeHg-induced CNS damage.

Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy

BackgroundLarge-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy.MethodsMelatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16–20 h after inducing fatal sepsis.ResultsWe observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague–Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation.ConclusionsThese findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.

Adult Male Syrian Hamsters (Mesocricetus auratus) Exhibit Daily Oscillations in Their Serum Levels of Melatonin and Leptin As Well As in the Expression of the GnRH, GnIH, and Kisspeptin Genes

The complex neuronal and hormonal interaction between the brain and gonads controls the neuroendocrine reproductive axis. GnRH, GnIH, and kisspeptin are important neuropeptides in this relationship. Although seasonal variations of these neuropeptides have been demonstrated in photoperiodic animals, there is no clear evidence in their daily rhythms. Melatonin and leptin hormones are also two important hormones in reproductive regulation. In our study, the relationship of melatonin and leptin hormones with daily rhythm with GnIH, GnRH, and kisspeptin gene expressions and protein oscillations was examined. Adult male Syrian hamsters were exposed to the long photoperiod and at the end of the 30-day experimental period, blood and tissue samples from each group were collected at 04:00 h, 12:00 h, 20:00 h, and 00:00 h. Daily rhythms of melatonin and leptin hormones were determined by ELISA. Quantitative analysis of GnRH, GnIH, Kisspeptin, and β-actin genes was performed with the corresponding primers in Real-Time PCR. Protein expressions were determined by the Western Blot technique. Serum melatonin and leptin levels showed an inverse rhythmic relationship. Leptin level was found to be low while melatonin was high in the dark. Daily rhythms were observed in GnIH, GnRH, and kisspeptin mRNA expressions and protein oscillations. As a result, our findings could imply that all of the relationships between melatonin, leptin, GnIH, GnRH, and kisspeptin are not reproductive, but rather metabolic in nature.

Effects of short photoperiod on cashmere growth, hormone concentrations and hair follicle development-related gene expression in cashmere goats

ABSTRACT Shanbei White Cashmere goat is a typical goat species, the growth of cashmere is affected by photoperiod. To further investigate the effects of short photoperiod treatment on cashmere growth, hormone concentrations and hair follicle development-related gene expression in cashmere goats, twenty Shannbei white cashmere goats were selected and randomly divided into long-day photoperiod treatment group and short-day photoperiod treatment group. The results revealed the cashmere on short-day photoperiod treatment began to develop earlier, and its length and growth rate increased dramatically (P < 0.05). The short-day photoperiod treatment increased the concentration of serum Melatonin, reduced the concentration of serum prolactin, decreased the expression of estrogen receptor alpha and raised the expression of hair follicle development-related genes [catenin beta-1, Bone morphogenetic protein 2, Fibroblast growth factor 5 and platelet-derived growth factor subunit A] (P < 0.05), thereby accelerating the reconstruction of the secondary follicle, increasing the density of the secondary follicle (P < 0.05) and triggering the growth of cashmere goats. The present study provides new insights into the dynamic changes in cashmere growth, hormone concentrations and hair follicle development-related gene expression in cashmere goats under short photoperiod, and is expected to be useful for future studies on intensive feeding research.

SALIVARY MELATONIN VALUES SIGNIFICANTLY CORRELATE WITH REDUCED QUALITY OF LIFE IN CHRONIC SPONTANEOUS URTICARIA PATIENTS: A PILOT STUDY.

Chronic spontaneous urticaria (CSU) is a dermatological disorder accompanied by itching that greatly affects the quality of life and quality of sleep. Therefore, it is assumed that CSU patients consequently experience reduced melatonin secretion and lower values of serum or salivary melatonin. This pilot study included 20 patients with CSU (chronic urticaria of unknown etiology that lasts for more than 6 weeks) and 10 healthy controls. All subjects were examined by a dermatovenereologist-allergist, as well as an oral pathologist, to exclude oral pathological conditions. Salivary melatonin levels were determined by ELISA and all subjects completed a standardized Dermatology Life Quality Index questionnaire and Pittsburgh Sleep Quality Index on the same day they gave a saliva sample for analysis. According to our results, 86% of CSU patients had decreased values of salivary melatonin, and lower salivary melatonin values significantly correlated with a reduced quality of life in CSU patients. This study was the first to analyze melatonin in CSU patients, also suggesting a possible new therapeutic option for the treatment of CSU.