Kidney, ureter, and urinary bladder segmentation based on non-contrast enhanced computed tomography images using modified U-Net.

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning.

Therapeutic effects of a novel synthetic α-secretase.

Excessive accumulation of amyloid-ß (Aß) has been associated with the pathogenesis of Alzheimer's disease (AD). Clinical studies have further proven that elimination of Aß can be a viable therapeutic option. In the current study, we conceptualized a fusion membrane protein, referred to as synthetic α-secretase (SAS), that can cleave amyloid precursor protein (APP) and Aß specifically at the α-site. In mammalian cells, SAS indeed cleaved APP and Aß at the α-site. Overexpression of SAS in the hippocampus was achieved by direct injection of recombinant adeno-associated virus serotype 9 (AAV9) that expresses SAS (AAV9-SAS) into the bilateral ventricles of mouse brains. SAS enhanced the non-amyloidogenic processing of APP, thus reducing the levels of soluble Aß and plaques in the 5xFAD mice. In addition, SAS significantly attenuated the cognitive deficits in 5xFAD mice, as demonstrated by novel object recognition and Morris water maze tests. Unlike other Aß-cleaving proteases, SAS has highly strict substrate specificity. We propose that SAS can be an efficient modality to eliminate excessive Aß from diseased brains.

Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.

Executive Summary of 2023 International Conference of the Korean Dementia Association (IC-KDA 2023): A Report From the Academic Committee of the Korean Dementia Association.

The Korean Dementia Association (KDA) has been organizing biennial international academic conferences since 2019, with the International Conference of the KDA (IC-KDA) 2023 held in Busan under the theme 'Beyond Boundaries: Advancing Global Dementia Solutions.' The conference comprised 6 scientific sessions, 3 plenary lectures, and 4 luncheon symposiums, drawing 804 participants from 35 countries. Notably, a Korea-Taiwan Joint Symposium addressed insights into Alzheimer's disease (AD). Plenary lectures by renowned scholars explored topics such as microbiome-related AD pathogenesis, social cognition in neurodegenerative diseases, and genetic frontotemporal dementia (FTD). On the first day, specific presentations covered subjects like the gut-brain axis and neuroinflammation in dementia, blood-based biomarkers in AD, and updates in AD therapeutics. The second day's presentations addressed recent issues in clinical neuropsychology, FTD cohort studies, and the pathogenesis of non-AD dementia. The Academic Committee of the KDA compiles lecture summaries to provide comprehensive understanding of the advanced dementia knowledge presented at IC-KDA 2023.

An exploratory study on spatiotemporal clustering of suicide in Korean adolescents.

BACKGROUND: Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space-time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space-time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods. METHODS: From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9-18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides. RESULTS: We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7-59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups. CONCLUSION: This study has defined the space-time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.

Hypothalamic neuronal activation in non-human primates drives naturalistic goal-directed eating behavior.

Maladaptive feeding behavior is the primary cause of modern obesity. While the causal influence of the lateral hypothalamic area (LHA) on eating behavior has been established in rodents, there is currently no primate-based evidence available on naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating using chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, predominantly for palatable food. Positron emission tomography and magnetic resonance spectroscopy validated chemogenetic activation. Resting-state functional magnetic resonance imaging revealed that the functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

Defining "High Recurrence" of Depressive Episodes for Predicting Diagnostic Conversion from Major Depressive Disorder to Bipolar Disorder: A 5-year Retrospective Study.

Objective: This study determined the threshold for recurrent depressive episodes that predicted conversion from major depressive disorder (MDD) to bipolar disorder (BD). Methods: We retrospectively reviewed the medical records of 296 patients diagnosed with MDD for a minimum of 5 years in two university hospitals. We examined their the Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses and detailed clinical information at the initial admission and yearly assessments after discharge to establish the threshold for recurrent depressive episodes indicating a risk of diagnostic conversion from MDD to BD. Optimal cut-offs were derived using receiver operating characteristic (ROC) curves. Results: ROC curve analysis revealed that more than four recurrent depressive episodes was indicative of potential diagnostic conversion from MDD to BD (area under the curve, 0.604; sensitivity, 0.353; specificity, 0.855; positive predictive value, 0.421; negative predictive value, 0.816). Conclusion: These findings suggest that the best predictor of conversion from MDD to BD is more than four recurrent depressive episodes. Our findings have the potential to enhance diagnostic accuracy and treatment efficiency. To validate our results, longitudinal prospective studies are necessary.

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

Oral Administration of Probiotic Bacteria Alleviates Tau Phosphorylation, Aß Accumulation, Microglia Activation, and Memory Loss in 5xFAD Mice.

The gut-brain axis (GBA) plays a significant role in various neurodegenerative disorders, such as Alzheimer's disease (AD), and the gut microbiome (GM) can bidirectionally communicate with the brain through the GBA. Thus, recent evidence indicates that the GM may affect the pathological features and the progression of AD in humans. The aim of our study was to elucidate the impact of probiotics on the pathological features of AD in a 5xFAD model. Probiotics (Bifidobacterium lactis, Levilactobacillus brevis, and Limosilactobacillus fermentum) were orally administered in 5xFAD mice to modify the GM composition. Additionally, freeze-dried food containing phosphatidylserine was used as the positive control. Behavioral pathogenesis was assessed through the cross maze and Morris water maze tests. Our findings revealed that probiotic administration resulted in significant improvements in spatial and recognition memories. Furthermore, the neuroprotective effects of probiotics were substantiated by a reduction in amyloid-ß accumulation in critical brain regions. Microglial activation in 5xFAD mice was also attenuated by probiotics in the hippocampus and cerebral cortex. Moreover, elevated tau phosphorylation in 5xFAD mice was ameliorated in the probiotics-treated group. The results highlight the potential use of probiotics as a neuroprotective intervention in AD.

The Oligomeric Form of Amyloid Beta Triggers Astrocyte Activation, Independent of Neurons.

The most common aging-related neurodegenerative disorder is Alzheimer's disease (AD), of which the main symptom is memory disturbance. Though the mechanism of AD pathogenesis is not fully defined, abnormal aggregation of amyloid beta (Aß) plaques and tau have been considered as key factors and main histological hallmarks of the disease. Astrocyte is responsible for the control of cells and the environment around brain and spinal cord cells. Astrocytes have been implicated with AD. However, the exact function of astrocytes in AD has not been established. In this study, we investigated the regulation of astrocytes in the AD model using primary cultures. We have demonstrated that oligomerized Aß is toxic to neurons and can induce cell death in primary cultures. In the primary cultures containing neurons and astrocytes, amyloid beta uptake was observed in both neurons and astrocytes. To verify if the uptake of amyloid beta in astrocytes is dependent on neurons, we separated and cultured primary astrocytes with no neurons. Amyloid uptake was still observed in this pure astrocyte culture, suggesting that the uptake of amyloid beta is a neuron-independent function of astrocytes. Astrocyte activation was observed in both pure and mixed cultures. Taken together, our data suggest that astrocyte is activated by oligomerized Aß and uptakes it, which is independent of neurons.

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization.

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

Antiinflammatory effect of the ethanolic extract of Korean native herb Potentilla rugulosa Nakai in Bisphenol-a-stimulated A549 cells.

Potentilla rugulosa Nakai (P. rugulosa) is a perennial herb in the Rosaceae family and found in the Korean mountains. Previously, our findings demonstrated that P. rugulosa contains numerous polyphenols and flavonoids exhibiting important antioxidant and anti-obesity bioactivities. Bisphenol A (BPA) is a xenoestrogen that was shown to produce pulmonary inflammation in humans. However, the mechanisms underlying BPA-induced inflammation remain to be determined. The aim of this study was to examine whether ethanolic extract of P. rugulosa exerted an inhibitory effect on BPA-induced inflammation utilizing an adenocarcinoma human alveolar basal epithelial cell line A549. The P. rugulosa extract inhibited BPA-mediated cytotoxicity by reducing levels of reactive oxygen species (ROS). Further, P. rugulosa extract suppressed the upregulation of various pro-inflammatory mediators induced by activation of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, inhibition of the NF-κB and MAPK signaling pathways by P. rugulosa extract was found to occur via decrease in the transcriptional activity of NF-κB. Further, blockade of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) was noted. Thus, our findings suggest that the ethanolic extract of P. rugulosa may act as a natural anti-inflammatory therapeutic agent.

The Impact of COVID-19 on Psychiatric Health in the Korean Population.

Coronavirus disease 2019 (COVID-19) has multiple negative impacts on the psychiatric health of both those previously infected and not infected with severe acute respiratory syndrome coronavirus 2. Moreover, the negative impacts of COVID-19 are closely associated with geographical region, culture, medical system, and ethnic background. We summarized the evidence of the impact of COVID-19 on the psychiatric health of the Korean population. This narrative review included thirteen research articles, which investigated the impact of COVID-19 on the psychiatric health of Koreans. COVID-19 survivors were reported to have a 2.4 times greater risk of developing psychiatric disorders compared to members of a control group, and anxiety and stress-related disorders were the most common newly diagnosed psychiatric illnesses. Studies also reported that COVID-19 survivors had a 3.33-fold higher prevalence of insomnia, a 2.72-fold higher prevalence of mild cognitive impairment, and a 3.09-fold higher prevalence of dementia compared to the control group. In addition, more than four studies have highlighted that the medical staff members, including nurses and medical students, exhibit a greater negative psychiatric impact of COVID-19. However, none of the articles investigated the biological pathophysiology or mechanism linking COVID-19 and the risk of diverse psychiatric disorders. Moreover, none of the studies were actual prospective studies. Thus, longitudinal studies are needed to more clearly elucidate the effect of COVID-19 on the psychiatric health of the Korean population. Lastly, studies focusing on preventing and treating COVID-19-associated psychiatric problems are needed to provide a benefit in real clinical settings.

Korean adolescent suicide and search volume for "self-injury" on internet search engines.

Introduction: Many adolescents with suicidal ideation receive support through the Internet. However, they also find ways to attempt suicide or strengthen their suicidal ideation through this medium. This study analyzed the association between the search volume of suicide-related terms and the number of suicides among Korean adolescents. We also analyzed the correlations between the search volumes of suicide-related terms. Methods: We selected seven words (suicide, self-injury, depression, academic score, school violence, outcasts, and family trouble) related to adolescent suicide. A dataset was constructed by combining data from the most commonly used search engine in Korea (Naver Datalab) and the daily number of adolescent suicides in school settings (n = 347) from January 1, 2016 to December 31, 2018, collected from the Ministry of Education. Poisson regression and Pearson correlation analyses were performed. Results: Significant associations were found between suicide attempts and search term volumes, which differed according to sex and time interval. Among the search terms, "self-injury" was most strongly associated with suicide, and this association was significant at all time intervals (daily, weekly, and monthly) in female adolescents and in the total population. Further, the association was strongest in the daily suicide data. More search term volumes were related to suicide in the daily and weekly data than in the monthly data. There were positive correlations between "suicide," "self-injury," and "depression" search volumes. Conclusion: Further studies with larger sample sizes, more search terms, and analysis of time intervals between suicide-related term search and suicide death are required. These studies can contribute to the establishment of an online suicide prevention system to detect suicide risk in adolescents and provide interventions.

Percutaneous cholecystostomy as a definitive treatment for acute acalculous cholecystitis: clinical outcomes and risk factors for recurrent cholecystitis.

OBJECTIVE: To investigate the outcomes of percutaneous cholecystostomy (PC) as a definitive treatment for acute acalculous cholecystitis (AAC) and to identify the risk factors for cholecystitis recurrence after catheter removal. METHODS: Between January 2008 and December 2017, 124 patients who had undergone PC as definitive treatment for moderate or severe AAC. The initial clinical success, complications, and recurrent cholecystitis after PC removal were retrospectively assessed. Twenty-one relevant variables were analyzed to identify risk factors for recurrent cholecystitis. RESULTS: Clinical effectiveness was achieved in 107 patients (86.3%) at 3 days and in all patients (100%) at 5 days after PC placement. Six Grade 2 adverse events occurred, including catheter dislodgement (n = 3) and clogging (n = 3), which required catheter exchange. The PC catheter was removed in 123 patients (99.2%), with a median indwelling duration of 18 days (range 5-116 days). During the follow-up period (median, 1624 days; range, 40-4945 days), five patients experienced recurrent cholecystitis (4.1%). The cumulative recurrence rates were 3.3%, 4.1%, and 4.1% at 6 months, 1 year, and 5 years, respectively. Multivariate analysis revealed that an age-adjusted Charlson comorbidity index (aCCI)≥7 positively correlated with recurrence (OR, 1.97; 95% confidence interval, 1.07-3.64; p = 0.029). CONCLUSIONS: Definitive PC is a safe and effective treatment option for patients with AAC. The PC catheters can be safely removed in most patients. An aCCI≥7 was a risk factor for cholecystitis recurrence after catheter removal. ADVANCES IN KNOWLEDGE: 1. Percutaneous cholecystostomy (PC) is a safe and effective as a definitive treatment in patients with acute acalculous cholecystitis (AAC).2. PC can be safely removed after recover from AAC in the majority of patients (99.2%) with low rate of recurrence of cholecystitis (4.1%).3. Age-adjusted Charlson comorbidity index ≥7 was a risk factor for recurrence of cholecystitis after PC removal.

Problems and alternatives of testing significance using null hypothesis and P-value in food research.

A testing method to identify statistically significant differences by comparing the significance level and the probability value based on the Null Hypothesis Significance Test (NHST) has been used in food research. However, problems with this testing method have been discussed. Several alternatives to the NHST and the P-value test methods have been proposed including lowering the P-value threshold and using confidence interval (CI), effect size, and Bayesian statistics. The CI estimates the extent of the effect or difference and determines the presence or absence of statistical significance. The effect size index determines the degree of effect difference and allows for the comparison of various statistical results. Bayesian statistics enable predictions to be made even when only a small amount of data is available. In conclusion, CI, effect size, and Bayesian statistics can complement or replace traditional statistical tests in food research by replacing the use of NHST and P-value.

Effects of Age Group, Gender, and Consumption Frequency on Texture Perception and Liking of Cooked Rice or Bread.

This study aimed to determine whether and how three demographic factors-age group, gender, and consumption frequency-affect texture perception and liking of two staple foods-cooked rice and wheat bread. In total, 346 adults evaluated three cooked rice and four wheat bread samples in terms of three (hardness, stickiness, and chewiness) and four textural attributes (hardness, moistness, chewiness, and softness), respectively, on both 9-point intensity and 5-point Just-About-Right (JAR) scales. Liking of test samples was also rated on 9-point hedonic scales. Age group and gender differed in mean ratings, standard deviations, and JAR responses regarding textural attribute intensity and overall liking of test samples, while the effect of consumption frequency was minimal in this regard. Significant contributors of textural attributes to overall liking of cooked rice and wheat bread differed with age group, gender, and consumption frequency. Effects of age group, gender, and consumption frequency on texture perception and overall liking also varied with test samples. This study provides agricultural and food systems professionals with systematic evidence of how textural attribute perception and liking of foods can change based on demographics and test samples.

Association Between Internet Searches Related to Suicide/Self-harm and Adolescent Suicide Death in South Korea in 2016-2020: Secondary Data Analysis.

BACKGROUND: Previous studies have investigated the association between suicide and internet search volumes of terms related to suicide or self-harm. However, the results varied by people's age, period, and country, and no study has exclusively investigated suicide or self-harm rates among adolescents. OBJECTIVE: This study aims to determine the association between the internet search volumes of terms related to suicide/self-harm and the number of suicides among South Korean adolescents. We investigated gender differences in this association and the time lag between the internet search volumes of the terms and the connected suicide deaths. METHODS: We selected 26 search terms related to suicide and self-harm among South Korean adolescents, and the search volumes of these terms for adolescents aged 13-18 years were obtained from the leading internet search engine in South Korea (Naver Datalab). A data set was constructed by combining data from Naver Datalab and the number of suicide deaths of adolescents on a daily basis from January 1, 2016, to December 31, 2020. Spearman rank correlation and multivariate Poisson regression analyses were performed to identify the association between the search volumes of the terms and the suicide deaths during that period. The time lag between suicide death and the increasing trend in the search volumes of the related terms was estimated from the cross-correlation coefficients. RESULTS: Significant correlations were observed within the search volumes of the 26 terms related to suicide/self-harm. The internet search volumes of several terms were associated with the number of suicide deaths among South Korean adolescents, and this association differed by gender. The search volume for "dropout" showed a statistically significant correlation with the number of suicides in all adolescent population groups. The correlation between the internet search volume for "dropout" and the connected suicide deaths was the strongest for a time lag of 0 days. In females, self-harm and academic score showed significant associations with suicide deaths, but academic score showed a negative correlation, and the time lags with the strongest correlations were 0 and -11 days, respectively. In the total population, self-harm and suicide method were associated with the number of suicides, and the time lags with the strongest correlations were +7 and 0 days, respectively. CONCLUSIONS: This study identifies a correlation between suicides and internet search volumes related to suicide/self-harm among South Korean adolescents, but the relatively weak correlation (incidence rate ratio 0.990-1.068) should be interpreted with caution.

Expression of the melatonergic system during meiotic maturation of cynomolgus monkey cumulus-oocyte complexes.

BACKGROUND: Melatonin is a multifunctional hormone synthesized in the pineal gland and peripheral reproductive tissues that regulates many biological processes. There is increasing evidence for a role of melatonin in oocyte maturation and embryonic development in various mammals. However, no study has reported evidence for the existence of melatonergic system, such as melatonin synthesis enzymes, melatonin membrane receptors, or melatonin binding sites in non-human primate cumulus-oocyte complexes (COCs). METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to detect transcripts and proteins of the rate-limiting enzyme in melatonin synthesis (arylalkylamine N-acetyltransferase, AANAT), melatonin membrane receptors (MT1 and MT2), and a melatonin binding site (NRH: quinone oxidoreductase 2, NQO2) in cynomolgus monkey COCs. RESULTS: RT-PCR analyses revealed the presence of AANAT, MT1, MT2, and NQO2 transcripts in granulosa cells, germinal vesicle (GV)- and metaphase II (MII)-stage cumulus cells, and oocytes. Immunocytochemistry revealed the presence of AANAT, MT1, MT2, and NQO2 proteins in GV- and MII-stage COCs. CONCLUSIONS: Our results provide the first evidence for the existence of the rate-limiting enzyme required for melatonin synthesis, melatonin membrane receptors, and a melatonin binding site in non-human primate COCs.