Platelet-rich fibrin as an apical barrier for MTA placement in the treatment of teeth with open apices: a pilot study.

OBJECTIVE: The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and open apices. METHODS: A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance. RESULTS: All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment. CONCLUSIONS: PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results. TRIAL REGISTRATION: TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .

Clinical and preclinical insights into high-dose ambroxol therapy for Gaucher disease type 2 and 3: A comprehensive systematic review.

RATIONALE: Gaucher disease (GD), an autosomal recessive lysosomal storage disease, results from GBA1 variants causing glucocerebrosidase (GCase) deficiency. While enzyme replacement therapy (ERT) helps with systemic symptoms, neurological complications in GD2 and GD3 persist due to the blood-brain-barrier (BBB) limiting ERT efficacy. Ambroxol, a BBB-permeable chaperone, enhances GCase activity. Our review explores high-dose ambroxol's therapeutic potential, both preclinical and clinical, in GD2 and GD3. METHODS: PubMed was searched for studies published before March 2023, including clinical, animal, and in vitro studies focusing on the effect of high-dose ambroxol in GD2 and GD3. A narrative synthesis was performed. RESULTS: Nine in vitro, three animal, and eight clinical studies were included, demonstrating varied responses to ambroxol across diverse outcome measures. In vitro and animal studies demonstrated reduced endoplasmatic reticulum stress due to the relocation of GCase from the ER to the lysosomes. In vitro cell lines exhibited varying degrees of increased GCase activity. Clinical trials observed reduced lyso-GL1 levels in plasma (41-89%) and cerebrospinal fluid (CSF) (26-97%), alongside increased GCase activity in GD3 patients. Ambroxol exhibited varying effects on neurological outcomes and development. No severe adverse events were reported. CONCLUSION: High-dose ambroxol shows promise in managing neurological manifestations in GD3, albeit with uncertainties resulting from genetic heterogeneity and variable response. Further clinical trials, are essential for elucidating dosage-response relationships and refining treatment outcomes and strategies for neuronopathic GD.

Financial toxicity in patients with cancer: a cross-sectional study at an oncology hospital in central Vietnam.

PURPOSE: Cancer imposes a substantial financial burden on patients because of the high out-of-pocket expenses and the significant hardships. Financial toxicity describes the impact of cancer care costs at the patient level. Although the financial impact of cancer has been recognized, understanding the extent and determinants of financial toxicity in specific contexts is crucial. This study investigated the level of financial toxicity and its associated factors among patients with cancer at an oncology hospital in central Vietnam. METHODS: This cross-sectional study included 334 patients with cancer. Direct interviews and medical record reviews were used for data collection. Financial toxicity was assessed using the 11-item Comprehensive Score for financial Toxicity (COST). A logistic regression model was used to determine factors associated with financial toxicity. RESULTS: A notable 87.7% of patients experienced financial toxicity due to cancer cost, with 37.7% experiencing mild financial toxicity and 49.7% suffering from moderate financial toxicity, 0.3% reporting severe financial toxicity. Individuals with low household income exhibited a higher proportion of financial toxicity compared to that of those with higher income (odds ratio (OR) = 5.78, 95% confidence interval (CI): 1.29-25.68). Compared with that of participants in the early stages, a higher burden was found in patients with advanced-stage cancer (OR = 3.88, 95% CI: 1.36-11.11). CONCLUSION: Our study indicates that patients with cancer in Vietnam facefinancial toxicity. It is thus necessary for interventions to mitigate the financial burden on patients with cancer, focusing on vulnerable individuals and patients in the advanced stages.

Real-time control of urban drainage systems using neuro-evolution.

With climate change and urbanization, existing urban drainage systems are being stressed beyond their design capacity in many parts of the world. Real-time control (RTC) can improve the performance of these systems and reduce the need for system upgrades. However, developing optimal control policies for RTC is a challenging research area due to computational demands, high uncertainties and system dynamics. This study presents a new RTC method using neuro-evolution for controlling combined sewer overflow (CSO) in urban drainage systems. Neuro-evolution is an approach to neural network research by evolutionary algorithms. Neuro-evolution realizes RTC by training the control policy in advance, thus avoiding the online optimization process in the application period. The simulation results of the benchmark Astlingen network indicate that the trained control policy outperforms the equal filling degree strategy in terms of CSO volume reduction and robustness in the face of tank level uncertainty. The performance analysis of the typical CSO events shows that the control policy mainly makes positive contributions during 'small' CSO events rather than 'large' ones. In particular, the effectiveness of the control policy in 'small' CSO events is more prominent in the initial phase of the events compared with the final phase. This work stands to support a foundation for future studies in the control of urban water systems based on neuro-evolution.

Platelet rich fibrin and MTA in the treatment of teeth with open apices.

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.

Molecular characterization of anopheline mosquitoes from the goat malaria-endemic areas of Thailand.

Despite the fact that over a 100 anopheline mosquito species have been identified as human malaria vectors, little is known about ungulate malaria vectors. Consequently, we focused on investigating the bionomics and genetic characterizations of anopheline mosquitoes in goat malaria-endemic regions. We also attempted to screen for ungulate malaria potential vectors. A total of 1019 female anopheline mosquitoes were collected from six goat farms in four provinces of Thailand from 2020 to 2021. Mosquitoes were morphologically identified and subsequently confirmed using the mitochondrial DNA barcoding region-cytochrome oxidase c subunit I (MtDNA-COI), mitochondrial DNA-cytochrome c oxidase subunit II (MtDNA-COII), and ribosomal DNA internal transcribed spacer 2 (rDNA-ITS2) sequences. The current study reveals the genetic characteristics and distribution of nine mosquito species within the Anopheles and Cellia subgenera. Four dominant species, including Anopheles peditaeniatus, Anopheles subpictus, Anopheles vagus, and Anopheles aconitus exhibited significant intraspecific gene flow within their corresponding species. Although malaria parasites were not found in 126 mosquito pools, meaning more investigation is necessary, the current study adds to the existing DNA barcoding data collection and improves the current understanding of the genetic structure and distribution of anopheline mosquito species, which could be useful for effective control of mosquito-borne diseases.

Prevalence of internet addiction and anxiety, and factors associated with the high level of anxiety among adolescents in Hanoi, Vietnam during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic and the resulting isolation measures created an increase in the usage of smart devices and internet among adolescents. This study aims to estimate the prevalence of internet addiction, the prevalence of high level of anxiety as well as to examine factors associated with the high level of anxiety among adolescents in Hanoi, Vietnam during the COVID-19 pandemic. METHOD: Data was collected using respondent-driven sampling and Google online survey forms from a sample of 5,325 school students aged 11-17 in Hanoi between October and December 2021. A short scale consisting of 5 items was used to measure internet addiction and the GAD-7 was used to measure adolescent anxiety level. RESULTS: The findings revealed that 22.8% and 7.32% of adolescents experienced moderate and severe anxiety. About 32.7% of the study sample exhibited at least three internet addiction indicators. Logistic regression analysis identified significant predictors for high levels of adolescent anxiety. Being female, family experiencing economic difficulties, and exposure to domestic violence were associated with higher risk of anxiety disorder (OR 1.78, 1.45, and 2.89, respectively). Both average daily online time and internet addiction demonstrated gradient association with high level of anxiety. CONCLUSION: The prevalence of internet addiction and high level of anxiety were high among adolescents in Hanoi, Vietnam during the COVID-19 pandemic. The study highlights the importance of implementing measures at the family and school levels to promote a balanced and healthy approach to smart device use among adolescents.

Comorbidities of diabetes and hypertension in Vietnam: current burden, trends over time, and correlated factors.

BACKGROUND: Vietnam conducted the national Noncommunicable Disease Risk-Factor Surveillance (STEPs) surveys in the years 2010, 2015, and 2021. This study aims to use STEPs data to assess the burden of comorbidity between diabetes and hypertension, analyze trends over time, and identify factors associated with this comorbidity. METHODS: The study extracted data for the population aged 25-64 years old from three STEPs surveys. Survey weight was used for all estimations of prevalence and 95% CI. Correlated factors with comorbidity were examined by a multivariate logistics model. RESULTS: The prevalence of comorbidity in 2021 was about 3.92% among Vietnamese people aged 25-64. In the last 10 years, this prevalence has increased more than 8 times (from 0.44% to 3.92%). Sub-populations demonstrating the most significant changes included the male population, people living in urban areas, and older people. Significant factors correlated with comorbidity included demographic factors, body mass index (BMI), and clustering of 4 noncommunicable diseases (NCDs) behavioral risk factors (OR = 3.48, p < 0.05). CONCLUSION: The high comorbidity between hypertension and diabetes underscores the imperative for integrated treatment and management approaches in Vietnam. Coordinated care is essential for addressing the complex interplay between these two prevalent conditions.

Overseas Treatment of Latent Tuberculosis Infection in US-Bound Immigrants.

Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts.

Selectively Halogenated Flavonolignans-Preparation and Antibacterial Activity.

A library of previously unknown halogenated derivatives of flavonolignans (silybins A and B, 2,3-dehydrosilybin, silychristin A, and 2,3-dehydrosilychristin A) was prepared. The effect of halogenation on the biological activity of flavonolignans was investigated. Halogenated derivatives had a significant effect on bacteria. All prepared derivatives inhibited the AI-2 type of bacterial communication (quorum sensing) at concentrations below 10 µM. All prepared compounds also inhibited the adhesion of bacteria (Staphyloccocus aureus and Pseudomonas aeruginosa) to the surface, preventing biofilm formation. These two effects indicate that the halogenated derivatives are promising antibacterial agents. Moreover, these derivatives acted synergistically with antibiotics and reduced the viability of antibiotic-resistant S. aureus. Some flavonolignans were able to reverse the resistant phenotype to a sensitive one, implying that they modulate antibiotic resistance.

Analysis of input set characteristics and variances on k-fold cross validation for a Recurrent Neural Network model on waste disposal rate estimation.

The use of machine learning techniques in waste management studies is increasingly popular. Recent literature suggests k-fold cross validation may reduce input dataset partition uncertainties and minimize overfitting issues. The objectives are to quantify the benefits of k-fold cross validation for municipal waste disposal prediction and to identify the relationship of testing dataset variance on predictive neural network model performance. It is hypothesized that the dataset characteristics and variances may dictate the necessity of k-fold cross validation on neural network waste model construction. Seven RNN-LSTM predictive models were developed using historical landfill waste records and climatic and socio-economic data. The performance of all trials was acceptable in the training and validation stages, with MAPE all less than 10%. In this study, the 7-fold cross validation reduced the bias in selection of testing sets as it helps to reduce MAPE by up to 44.57%, MSE by up to 54.15%, and increased R value by up to 8.33%. Correlation analysis suggests that fewer outliers and less variance of the testing dataset correlated well with lower modeling error. The length of the continuous high waste season and length of total high waste period appear not important to the model performance. The result suggests that k-fold cross validation should be applied to testing datasets with higher variances. The use of MSE as an evaluation index is recommended.

Identification of behaviour patterns in waste collection and disposal during the first wave of COVID-19 in Regina, Saskatchewan, Canada.

The novel coronavirus (2019-nCov) has had significant impacts on almost every aspect of daily life. From 'stay-at-home' orders to the progressive lifting of restrictions, the COVID-19 pandemic has had unprecedented effects on consumer behaviours and waste disposal habits. The purpose of this short communication is to examine time series waste collection and disposal data in a mid-sized Canadian city to understand how behavioural changes have affected municipal waste management. The results suggest that private waste disposal increased during the pandemic. This may be due to people doing home renovations in order to accommodate working from home. Furthermore, it appears that changes in consumer habits destabilized the consistency of waste disposal tonnage when compared to the same time period in 2019. When considering curbside residential waste collection, there was also an increase in tonnage. This may be the result of more waste being generated at home due to changes in eating and cooking habits, and cleaning routine. Finally, the ratio of residential waste collection to total disposal is examined. More residential waste is being generated, which may have environmental and operational effects, especially related to collection and transportation. The results from this study are important from an operational perspective, and will help planners and policy makers to better prepare for changes in the waste stream due to pandemics or other emergencies.

Usage of Tacrolimus and Mycophenolic Acid During Conception, Pregnancy, and Lactation, and Its Implications for Therapeutic Drug Monitoring: A Systematic Critical Review.

BACKGROUND: Conception, pregnancy, and lactation following solid organ transplantation require appropriate management. The most frequently used immunosuppressive drug combination after solid organ transplantation consists of tacrolimus (Tac) plus mycophenolic acid (MPA). Here, the effects of Tac and MPA on fertility, pregnancy, and lactation are systematically reviewed, and their implications for therapeutic drug monitoring (TDM) are discussed. METHODS: A systematic literature search was performed (August 19, 2019) using Ovid MEDLINE, EMBASE, the Cochrane Central Register of controlled trials, Google Scholar, and Web of Science, and 102 studies were included. Another 60 were included from the reference list of the published articles. RESULTS: As MPA is teratogenic, women who are trying to conceive are strongly recommended to switch from MPA to azathioprine. MPA treatment in men during conception seems to have no adverse effect on pregnancy outcomes. Nevertheless, in 2015, the drug label was updated with additional risk minimization measures in a pregnancy prevention program. Data on MPA pharmacokinetics during pregnancy and lactation are limited. Tac treatment during conception, pregnancy, and lactation seems to be safe in terms of the health of the mother, (unborn) child, and allograft. However, Tac may increase the risk of hypertension, preeclampsia, preterm birth, and low birth weight. Infants will ingest very small amounts of Tac via breast milk from mothers treated with Tac. However, no adverse outcomes have been reported in children exposed to Tac during lactation. During pregnancy, changes in Tac pharmacokinetics result in increased unbound to whole-blood Tac concentration ratio. To maintain Tac concentrations within the target range, increased Tac dose and intensified TDM may be required. However, it is unclear if dose adjustments during pregnancy are necessary, considering the higher concentration of (active) unbound Tac. CONCLUSIONS: Tac treatment during conception, pregnancy and lactation seems to be relatively safe. Due to pharmacokinetic changes during pregnancy, a higher Tac dose might be indicated to maintain target concentrations. However, more evidence is needed to make recommendations on both Tac dose adjustments and alternative matrices than whole-blood for TDM of Tac during pregnancy. MPA treatment in men during conception seems to have no adverse effect on pregnancy outcomes, whereas MPA use in women during conception and pregnancy is strongly discouraged.

Adverse influence of multilevel socioeconomic status on physical activity: results from a national survey in Vietnam.

BACKGROUND: This study aims to explore associations of individual- and provincial-level socioeconomic status (SES) and the combined interaction among these SES with individual physical activity (PA). METHOD: This analyze used data of 3068 Vietnamese people aged 18-65 years from the national representative STEPS survey in 2015 (STEPS2015). The survey collected PA-related data using the Global PA Questionnaire Version 2 and those on provicial-level characteristics from two surveys in 2014, namely the Intercensal Population and Housing Survey (IPHS) and The Vietnam Household Living Standard Survey (VLSS2014). Multilevel linear analyze was performed with individual and provincial characteristics as independent variables and the metabolic equivalent (MET) score - the indicator of individual PA - as the dependent variable. RESULTS: Male and female participants with insufficient PA accounted for 20.2 and 35.7%, respectively. Both individual- and provicial-level SES were inversely associated with the individual PA level. As the provincial-level monthly income increased by 1 million Vietnam Dongs, the total PA score of individuals residing in that province reduced by 1900 METS. A buffering effect was reported between provincial and individual SES, as the provincial average income increased, the differences in PA scores between different SES groups decreased. CONCLUSION: Our data suggest that Vietnamese individuals in low SES groups tended to be more physically active than those in high SES groups because their PA was largely related to work.

A novel p.A191D matrilin-3 variant in a Vietnamese family with multiple epiphyseal dysplasia: a case report.

BACKGROUND: Multiple epiphyseal dysplasia (MED) is a common skeletal dysplasia that is characterized by variable degrees of epiphyseal abnormality primarily involving the hip and knee joints. Mutations in a gene encoding matrilin-3 (MATN3) have been reported as disease causing of autosomal dominant MED. The current study identified a novel c.572 C > A variant (p.A191D) in exon 2 of MATN3 in a Vietnamese family with MED. CASE PRESENTATION: A standard clinical tests and radiological examination were performed in an 8-year-old Vietnamese girl patient. The clinical examination showed that patient height was under average, with bent lower limbs, limited mobility and dislocation of the joints at both knees. Radiological documentation revealed abnormal cartilage development at the epiphysis of the femur and patella. The patient has a varus deformity of the lower limbs. The patient was diagnosed with autosomal dominant MED using molecular testing in the order of the coding sequences and flanking sequences of five genes: COMP (exons 8-19), MATN3 (exon 2), COL9A2 (exon 3), COL9A3 (exon 3), COL9A1 (exon 8) by Sanger sequencing. A novel heterozygous missense variant (c.572 C > A, p.A191D) in MATN3 was identified in this family, which were not inherited from parents. The p.A191D was predicted and classified as a pathogenic variant. When the two predicted structures of the wild type and mutant matrilin-3 were compared, the p.A191D substitution caused conformational changes near the substitution site, resulting in deformity of the ß-sheet of the single A domain of matrilin- 3. CONCLUSIONS: This is the first Vietnamese MED family attributed to p.A191D matrilin-3 variant, and our clinical, radiological and molecular data suggest that the novel de novo missense variant in MATN3 contributed to MED.

Different fermentation strategies by Schizochytrium mangrovei strain pq6 to produce feedstock for exploitation of squalene and omega-3 fatty acids.

Schizochytrium mangrovei strain PQ6 was investigated for coproduction of docosahexaenoic acid (C22: 6ω-3, DHA) and squalene using a 30-L bioreactor with a working volume of 15 L under various batch and fed-batch fermentation process regimes. The fed-batch process was a more efficient cultivation strategy for achieving higher biomass production rich in DHA and squalene. The final biomass, total lipid, unsaponifiable lipid content, and DHA productivity were 105.25 g · L-1 , 43.40% of dry cell weight, 8.58% total lipid, and 61.66 mg · g-1  · L-1 , respectively, after a 96 h fed-batch fermentation. The squalene content was highest at 48 h after feeding glucose (98.07 mg · g-1 of lipid). Differences in lipid accumulation during fermentation were correlated with changes in ultrastructure using transmission electron microscopy and Nile Red staining of cells. The results may be of relevance to industrial-scale coproduction of DHA and squalene in heterotrophic marine microalgae such as Schizochytrium.

Use of seasonal parameters and their effects on FOD landfill gas modeling.

Temporal and spatial variations in landfill gas generations and emissions have been observed and reported by others. Real-time gas data between 2008 and 2014 from a municipal landfill located in a cold, semi-arid climate were consolidated to fit a linear-interpolated form of LandGEM. Seasonal variations in gas collection were observed in the landfill. LandGEM's default decay rate k was not applicable for this Canadian landfill due to significant overestimation (32.2% error). Optimal seasonal k and Lo collection parameters had 8.1% error compared to field data, compared to 8.3% error using optimal annual parameters. The optimal kwinter was 0.0118 year-1 and the ksummer was 0.0141 year-1 (14.7% difference), with a corresponding Lo of 100.0 m3/Mg which changed negligibly between the sets. Three pseudo-second order iterative methods were considered, and evaluated using RSS and generation parameters in the literature. A simple application study was conducted using LFGcost-Web, and found the increased precision of seasonal k's resulted in negligible differences with annual optimized k. The default parameters overestimated the net present worth by 12-155% for three of the four common LFG energy projects.

Transcription of the immediate-early gene Arc in CA1 of the hippocampus reveals activity differences along the proximodistal axis that are attenuated by advanced age.

The CA1 region of the hippocampus receives distinct patterns of afferent input to distal (near subiculum) and proximal (near CA2) zones. Specifically, distal CA1 receives a direct projection from cells in the lateral entorhinal cortex that are sensitive to objects, whereas proximal CA1 is innervated by cells in the medial entorhinal cortex that are responsive to space. This suggests that neurons in different areas along the proximodistal axis of CA1 of the hippocampus will be functionally distinct. The current experiment investigated this possibility by monitoring behavior-induced cell activity across the CA1 axis using Arc mRNA imaging methods that compared adult and old rats in two conditions: (1) exploration of the same environment containing the same objects twice (AA) or (2) exploration of two different environments that contained identical objects (AB). The hypothesis was that CA1 place cells should show field remapping in the condition in which environments were changed, but the extent of remapping was expected to differ between proximal and distal regions and between age groups. In fact, neurons in the proximal region of CA1 in adult animals exhibited a greater degree of remapping than did distal CA1 cells when the environment changed, suggesting that cells receiving input from the medial entorhinal cortex are more sensitive to spatial context. However, in old rats, there were no differences in remapping across the proximodistal CA1 axis. Together, these data suggest that distal and proximal CA1 may be functionally distinct and differentially vulnerable to normative aging processes.

Melatonin attenuates memory impairment induced by Klotho gene deficiency via interactive signaling between MT2 receptor, ERK, and Nrf2-related antioxidant potential.

BACKGROUND: We demonstrated that oxidative stress plays a crucial role in cognitive impairment in klotho mutant mice, a genetic model of aging. Since down-regulation of melatonin due to aging is well documented, we used this genetic model to determine whether the antioxidant property of melatonin affects memory impairment. METHODS: First, we examined the effects of melatonin on hippocampal oxidative parameters and the glutathione/oxidized glutathione (GSH/GSSG) ratio and memory dysfunction of klotho mutant mice. Second, we investigated whether a specific melatonin receptor is involved in the melatonin-mediated pharmacological response by application with melatonin receptor antagonists. Third, we examined phospho-extracellular-signal-regulated kinase (ERK) expression, nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, Nrf2 DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression. Finally, we examined effects of the ERK inhibitor SL327 in response to antioxidant efficacy and memory enhancement mediated by melatonin. RESULTS: Treatment with melatonin resulted in significant attenuations of oxidative damage, a decrease in the GSH/GSSG ratio, and a significant amelioration of memory impairment in this aging model. These effects of melatonin were significantly counteracted by the selective MT2 receptor antagonist 4-P-PDOT. Importantly, 4-P-PDOT or SL327 also counteracted melatonin-mediated attenuation in response to the decreases in phospho-ERK expression, Nrf2 nuclear translocation, Nrf2 DNA-binding activity, and GCL mRNA expression in the hippocampi of klotho mutant mice. SL327 also counteracted the up-regulation of the GSH/GSSG ratio and the memory enhancement mediated by melatonin in klotho mutant mice. CONCLUSIONS: Melatonin attenuates oxidative stress and the associated memory impairment induced by klotho deficiency via signaling interaction between the MT2 receptor and ERK- and Nrf2-related antioxidant potential.