Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers.

AIMS: We explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years. METHODS: We retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC). RESULTS: At baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (ß: 0.045, p < 0.001; ß: -0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9-2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers. CONCLUSIONS: The TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers.

Exosome Release by Glucose Deprivation Is Important for the Viability of TSC-Null Cells.

The control of exosome release is associated with numerous physiological and pathological activities, and that release is often indicative of health, disease, and environmental nutrient stress. Tuberous sclerosis complex (TSC) regulates the cell viability via the negative regulation of the mammalian target of rapamycin complex (mTORC1) during glucose deprivation. However, the mechanism by which viability of TSC-null cells is regulated by mTORC1 inhibition under glucose deprivation remains unclear. Here, we demonstrated that exosome release regulates cell death induced by glucose deprivation in TSC-null cells. The mTORC1 inhibition by rapamycin significantly increased the exosome biogenesis, exosome secretion, and cell viability in TSC-null cells. In addition, the increase in cell viability by mTORC1 inhibition was attenuated by two different types of inhibitors of exosome release under glucose deprivation. Taken together, we suggest that exosome release inhibition might be a novel way for regression of cell growth in TSC-null cells showing lack of cell death by mTORC1 inhibition.

Correlations Between Psychological Status and Perception of Facial Expression.

OBJECTIVE: Facial affect recognition is associated with neuropsychological status and psychiatric diseases. We hypothesized that facial affect recognition is associated with psychological status and perception of other affects. METHODS: A total of 80 images depicting facial affect, including 20 Neutral, 20 Angry, 20 Fear, and 20 Sad, were screened for use in our research. A total of 100 healthy individuals were asked to rate these images using a 10-point Likert scale and complete psychological scales assessing the emotional statuses and cognitive functions. RESULTS: The participants' emotional state of aggression, attention, and impulsivity may have been associated with their interpretation of the Angry facial expressions. The participants often rated the Angry facial expressions as Fear. The participants rated Fear images as Angry or Sad. In response to a Sad facial expression, the participants reported psychological statuses of attention and impulsivity which were associated with the facial expression rating. The participants rated the Sad expression as Angry or Fear. CONCLUSION: The psychological statuses of the participants were significantly correlated with their interpretation of facial affects. In particular, a psychological state of attention was often correlated with incorrect affect ratings. Attention and impulsivity could affect the rating of the sad facial expressions.

Supplemental or dietary intake of omega-3 fatty acids for the treatment of periodontitis: A meta-analysis.

AIM: To evaluate the intervention effect of omega-3 fatty acids on changes in periodontal parameters. MATERIALS AND METHODS: This meta-analysis included studies published in English language between 2010 and 2020, which were extracted from the Cochrane Library, EMBASE, and PubMed databases. The effects of omega-3 fatty acid intervention were investigated using the amount of omega-3 intake, periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP). The random-effects model was generated for data analysis. To obtain robustness of the model, sensitivity analysis was implemented. Subgroup analyses were performed based on the intervention period for each parameter. RESULTS: All 13 studies included in the meta-analysis were interventional, randomized controlled trials. Two studies implemented omega-3 fatty acid-rich diets, while 11 studies used supplements. Risk of bias was low, and publication bias was not shown. Meta-analysis showed a statistically significant PPD reduction (standardized mean difference [SMD] = -0.81, absolute mean difference [MD] = -0.44 mm), CAL gain (SMD = -0.77, MD = -0.51 mm), and BOP reduction (SMD = -0.65, MD = -9.45%) for the omega-3 fatty acid intervention overall. CONCLUSION: This study suggests that supplemental or dietary intake of omega-3 fatty acids for the treatment of periodontitis may have a positive impact on the disease.

Effect of dietary calcium on the gender-specific association between polymorphisms in the PTPRD locus and osteoporosis.

BACKGROUND & AIMS: Osteoporosis is the most common bone disease and is characterized by low bone mineral density (BMD) and a high risk of fracture. Despite advances in our understanding of the pathogenesis of osteoporosis, complex gene-environment interactions that influence osteoporosis development remain largely unexplored. In this study, we aimed to identify genetic loci associated with low BMD and to evaluate these genetic variants under individual and environmental factors. METHODS: A genome-wide association analysis was conducted using 500,568 single-nucleotide polymorphisms (SNPs) in 8842 individuals aged 40-69 years using clinical, demographic, and dietary data (>260 traits) established by the Korean Genome and Epidemiology Study. The gPLINK program was used to detect SNPs associated with osteoporosis at a genome-wide significance level (P < 1.0 × 10-05) and conduct a haplotype analysis. Statistical differences between the osteoporosis and control groups in categorical variables (sex and dietary profiles) were assessed based on frequency distributions using the chi-squared test. RESULTS: Of the seven SNPs that were associated with osteoporosis, both rs10977574 and rs4390000 lay in the PTPRD locus encoding a protein tyrosine phosphatase-receptor type D, which has been implicated in bone metabolism. Haplotype analysis identified two minor alleles, C and G, at the rs10977574 and rs4390000 loci, respectively, forming a linkage disequilibrium block. The subsequent gender-stratified analysis using dietary calcium intake revealed an increased correlation between the CG haplotype and osteoporosis (OR = 2.069) in the low-calcium-intake-female group but not in the high-calcium-intake-female or any male group. CONCLUSIONS: This study revealed novel evidence of the sex-specific association of the CG haplotype in the PTPRD locus with osteoporosis and indicated that the association can be influenced by dietary calcium intake.

Diagnostic performance of tomosynthesis for evaluation of bone tumors and tumor-like lesions: a comparison with radiography.

BACKGROUND: Even though radiologic diagnosis of bone tumors and tumor-like lesions is usually based on radiographs, radiographically faint imaging features sometimes remain challenging due to overlapping anatomical structures. PURPOSE: To compare tomosynthesis with radiography for the evaluation of bone tumors and tumor-like lesions. MATERIAL AND METHODS: Forty-seven bone tumors and tumor-like lesions were assessed with radiographs and tomosynthesis images. Two radiologists independently analyzed imaging features of lesions, including margin, periosteal reaction, cortical thinning, matrix mineralization, cortical destruction (such as pathologic fracture), and extraosseous soft-tissue extension. Computed tomography (CT) imaging was used as a reference method. Diagnostic performances of radiography and tomosynthesis were analyzed and compared based on sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Effective radiation dose was compared among the three imaging modalities by phantom studies. RESULTS: Inter-observer variability (kappa value) for imaging features was slight to moderate on radiography (0.167-0.588), whereas it was nearly perfect on tomosynthesis (0.898-1.000) except for extraosseous soft-tissue extension (0.647 vs. 0.647). Tomosynthesis showed significantly higher sensitivity than radiography in evaluating the margin for bone tumors or tumor-like lesions (1.00 vs. 0.85; P = 0.016), and significantly higher accuracy than radiography in evaluating the margin and matrix mineralization for those (1.00 vs. 0.85; P = 0.016 and 0.91 vs.0.77; P = 0.023, respectively). In phantom studies, mean effective radiation doses were highest in order of CT, tomography, and radiography. CONCLUSION: Tomosynthesis increases sensitivity and accuracy of the margin as well as accuracy of the matrix mineralization of bone tumors and tumor-like lesions compared to radiography.

Aberrant Mitochondrial Dynamics and Exacerbated Response to Neuroinflammation in a Novel Mouse Model of CMT2A.

Charcot-Marie-Tooth disease type 2A (CMT2A) is the most common hereditary axonal neuropathy caused by mutations in MFN2 encoding Mitofusin-2, a multifunctional protein located in the outer mitochondrial membrane. In order to study the effects of a novel MFN2K357T mutation associated with early onset, autosomal dominant severe CMT2A, we generated a knock-in mouse model. While Mfn2K357T/K357T mouse pups were postnatally lethal, Mfn2+/K357T heterozygous mice were asymptomatic and had no histopathological changes in their sciatic nerves up to 10 months of age. However, immunofluorescence analysis of Mfn2+/K357T mice revealed aberrant mitochondrial clustering in the sciatic nerves from 6 months of age, in optic nerves from 8 months, and in lumbar spinal cord white matter at 10 months, along with microglia activation. Ultrastructural analyses confirmed dysmorphic mitochondrial aggregates in sciatic and optic nerves. After exposure of 6-month-old mice to lipopolysaccharide, Mfn2+/K357T mice displayed a higher immune response, a more severe motor impairment, and increased CNS inflammation, microglia activation, and macrophage infiltrates. Overall, ubiquitous Mfn2K357T expression renders the CNS and peripheral nerves of Mfn2+/K357T mice more susceptible to mitochondrial clustering, and augments their response to inflammation, modeling some cellular mechanisms that may be relevant for the development of neuropathy in patients with CMT2A.

Morc2a p.S87L mutant mice develop peripheral and central neuropathies associated with neuronal DNA damage and apoptosis.

The microrchidia (MORC)-family CW-type zinc finger 2 (MORC2) gene is related to DNA repair, adipogenesis and epigenetic silencing via the human silencing hub (HUSH) complex. MORC2 missense mutation is known to cause peripheral neuropathy of Charcot-Marie-Tooth disease type 2 Z (CMT2Z). However, there have been reports of peripheral and central neuropathy in patients, and the disease has been co-categorized with developmental delay, impaired growth, dysmorphic facies and axonal neuropathy (DIGFAN). The etiology of MORC2 mutation-mediated neuropathy remains uncertain. Here, we established and analyzed Morc2a p.S87L mutant mice. Morc2a p.S87L mice displayed the clinical symptoms expected in human CMT2Z patients, such as axonal neuropathy and skeletal muscle weakness. Notably, we observed severe central neuropathy with cerebella ataxia, cognition disorder and motor neuron degeneration in the spinal cord, and this seemed to be evidence of DIGFAN. Morc2a p.S87L mice exhibited an accumulation of DNA damage in neuronal cells, followed by p53/cytochrome c/caspase 9/caspase 3-mediated apoptosis. This study presents a new mouse model of CMT2Z and DIGFAN with a Morc2a p.S87L mutation. We suggest that neuronal apoptosis is a possible target for therapeutic approach in MORC2 missense mutation. This article has an associated First Person interview with the first author of the paper.

Leucyl-tRNA synthetase 1 is required for proliferation of TSC-null cells.

Uncontrolled cell proliferation associated with cancer depends on the functional abrogation of at least one of tumor suppressor. In response to nutrient cue, tuberous sclerosis complex (TSC) works as a tumor suppressor which inhibits cell growth via negative regulation of the mammalian target of rapamycin complex (mTORC1). However, the regulation mechanism of nutrient-dependent cell proliferation in TSC-null cells remains unclear. Here, we demonstrate that leucine is required for cell proliferation through the activation of leucyl-tRNA synthetase (LARS1)-mTORC1 pathway in TSC-null cells. Cell proliferation and survival were attenuated by LARS1 knock-down or inhibitors in TSC-null cells. In addition, either rapamycin or LARS1 inhibitors significantly decreased colony formation ability while their combined treatment drastically attenuated it. Taken together, we suggest that LARS1 inhibitors might considered as novel tools for the regression of tumor growth and proliferation in TSC-null tumor cells which regrow upon discontinuation of the mTORC1 inhibition.

Gender disparities in childhood obesity and household food insecurity.

OBJECTIVES: Childhood obesity is a critical health issue. The etiology of childhood obesity is multifactorial, with age, gender, race/ethnicity, and socioeconomic status interacting to affect risk. Food insecurity is known to be associated with risk of childhood obesity, but the body of evidence regarding Koreans is lacking. This study investigated the association between childhood obesity and household food insecurity in Koreans. Other lifestyle and nutritional factors associated with obesity were also examined. METHODS: Using data from the Korean National Health and Nutrition Examination Survey, a cross-sectional study was conducted with 1527 boys and 1366 girls. A comparison of general characteristics and nutritional intake between the groups was made using Student's t tests, χ2 tests, and general linear models. The association between childhood obesity and food insecurity was estimated with logistic regression models, and presented with odds ratios and 95% confidence intervals either with or without covariates. RESULTS: Boys who were obese dined out less frequently and engaged less in regular exercise, but no differences in nutrition intake were observed between children who were and were not obese. Girls who were obese were less likely to have a caregiver and consumed a higher percentage of energy from protein. Boys experiencing household food insecurity were less likely to be obese (adjusted odds ratio, 0.25; 95% confidence interval, 0.06-0.99), but girls with food insecurity were at three times higher risk of obesity (adjusted odds ratio, 3.00; 95% confidence interval, 1.23-7.31). CONCLUSIONS: Differential lifestyle factors are associated with obesity phenotypes in boys and girls. Food insecurity also showed a contrasting association with obesity risk by gender in young Koreans.

The effect of diet, exercise, and lifestyle intervention on childhood obesity: A network meta-analysis.

BACKGROUND & AIMS: Trials investigating the efficacy of different interventions for overweight children are limited and controversial. Therefore, the aim of this study is to perform a network meta-analysis on the efficacy of various interventions for children with obesity (an average age of 6-12 years old). METHODS: We obtained the data of trials reporting pre-post obesity relevant outcomes (e.g. BMI, BMI z-score, percent body fat, or percent overweight) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), PubMed, and Web of Science databases (completed before February 25, 2019) and included at least one pair of direct comparison groups. The mean difference of outcomes and their associated 95% CI were used to determine the efficacy. The P-score was calculated to illustrate the rank probability of various treatments for different outcomes using a network meta-analysis. Our meta-analysis included 24 studies that evaluated the interventions for childhood obesity. RESULTS: All 24 trials had no high risk of bias. Interventions such as exercise without parents (E w/o P); diet with parents (D w/P); and diet, exercise, and lifestyle with parents (D+E+L w/P) were significantly effective for children with obesity when compared with no intervention. CONCLUSIONS: E w/o P exhibited the highest P-score, with the D w/P and D+E+L w/P ranks having P-scores of 0.7486 and 0.5464, respectively. Moreover, the results indicate that E w/o P, D w/P, and D+E+L w/P were significantly effective treatments for children with obesity when compared with no intervention.

Agrimonia pilosa Ledeb. Ameliorates Hyperglycemia and Hepatic Steatosis in Ovariectomized Rats Fed a High-Fat Diet.

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. An efficient therapeutic agent prevents or improves postmenopausal conditions induced by estrogen deficiency. Here, we investigated the effects of aqueous Agrimonia pilosa Ledeb. extract on glucose and lipid metabolism in ovariectomized rats fed a high-fat diet (HFD). Female Sprague-Dawley rats were sham-operated or ovariectomized, and 3 weeks later were assigned to the following groups: sham-operated + HFD (S); ovariectomized + HFD (OVX); and ovariectomized + HFD with 0.5% A. pilosa aqueous extract (OVX + 0.5A) groups. Ovariectomy significantly increased body weight and dietary intake relative to the S group. However, A. pilosa treatment did not significantly affect weight gain or dietary intake. Blood triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol levels tended to decrease in the A. pilosa-supplemented group. Blood glucose levels were significantly lower in the OVX + 0.5A group than those in the OVX group. Blood adiponectin and insulin concentrations increased significantly after A. pilosa treatment in the ovariectomized group. A. pilosa supplementation tended to decrease liver weights and prevented lipid accumulation. These effects correlated with reduced hepatic expression of lipogenesis-related genes (fatty acid synthase, acetyl-coenzyme A carboxylase alpha, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase). Therefore, A. pilosa may improve metabolic disorders in ovariectomized rats.

Efficient and specific generation of knockout mice using Campylobacter jejuni CRISPR/Cas9 system.

The Streptococcus pyogenes CRISPR/Cas9 (SpCas9) system is now widely utilized to generate genome engineered mice; however, some studies raised issues related to off-target mutations with this system. Herein, we utilized the Campylobacter jejuni Cas9 (CjCas9) system to generate knockout mice. We designed sgRNAs targeting mouse Tyr or Foxn1 and microinjected into zygotes along with CjCas9 mRNA. We obtained newborn mice from the microinjected embryos and confirmed that 50% (Tyr) and 38.5% (Foxn1) of the newborn mice have biallelic mutation on the intended target sequences, indicating efficient genome targeting by CjCas9. In addition, we analyzed off-target mutations in founder mutant mice by targeted deep sequencing and whole genome sequencing. Both analyses revealed no off-target mutations at potential off-target sites predicted in silico and no unexpected random mutations in analyzed founder animals. In conclusion, the CjCas9 system can be utilized to generate genome edited mice in a precise manner.

Effect of Paper-Based Cognitive Training in Early Stage of Alzheimer's Dementia.

BACKGROUND AND PURPOSE: Cognitive training refers to a series of standardized tasks with inherent challenges that target specific cognitive domains. Positive outcome of cognitive training in persons with Alzheimer's disease has been reported. In this study, the objective was to design sets of cognitive training program, "Gipum-seo" which is combined cognitive training, consists of different levels of difficulty using predesigned paper-and-pencil exercises. Also, to evaluate the effects of the cognitive training on patients' with early stage of Alzheimer's disease. METHODS: The subjects for this study were forty participants who were diagnosed with early stage of Alzheimer's dementia. To test the efficacy of paper-based cognitive training programs to cognition, all patients were randomly grouped to either an intervention group (n=20) or a control group (n=20). The intervention group regularly received 24 sessions of paper-based cognitive training over a 12-week period. Neuropsychological examinations were conducted before and after this training period. RESULTS: After the 12 weeks, the intervention group showed a significant change in Korean version of the Mini-Mental State Examination (25.90±3.8), compared to the control group (23.7±2.8) (p=0.042). The training group also showed a significant improvement in language, attention and executive function, as compared with controls. CONCLUSIONS: Paper-based cognitive training might have beneficial effects on the general cognitive functions in the early stage of Alzheimer's dementia.

Treatment of non-odontogenic orofacial pain using botulinum toxin-A: a retrospective case series study.

BACKGROUND: The purpose of this study was to evaluate the clinical outcomes of treatment of non-odontogenic atypical orofacial pain using botulinum toxin-A. METHODS: This study involved seven patients (seven females, mean age 65.1 years) who had non-odontogenic orofacial pain (neuropathic pain and atypical orofacial pain) and visited the Seoul National University Bundang Hospital between 2015 and 2017. All medication therapies were preceded by botulinum toxin-A injections, followed by injections in the insignificant effects of medication therapies. Five of the seven patients received intraoral injections in the gingival vestibule or mucosa, while the remaining two received extraoral injections in the masseter and temporal muscle areas. RESULTS: In five of the seven patients, pain after botulinum toxin-A injection was significantly reduced. Most of the patients who underwent surgery for dental implantation or facial nerve reconstruction recovered after injections. However, the pain did not disappear in two patients who reported experiencing persistent pain without any cause. CONCLUSIONS: The use of botulinum toxin-A for the treatment of non-odontogenic neuropathic orofacial pain is clinically useful. It is more effective to administer botulinum toxin-A in combination with other medications and physical therapy to improve pain.

Zinc transporter SLC39A11 polymorphisms are associated with chronic gastritis in the Korean population: the possible effect on spicy food intake.

Herein, we hypothesized that ZIP11 variants would be important risk factors for chronic gastritis and that there would be an interaction effect of the relationship between their variants and spicy food intake on the development of chronic gastritis. Participants in this cross-sectional study (n = 3882 + 252) were recruited from a cohort of the Korean Genome and Epidemiology Study in 2001. Age, sex, education, smoking and drinking status, exercise, stress, and income level of all participants were determined by a questionnaire. Demographic and anthropometric data were collected. Fasting blood samples were collected to determine the serum levels of glucose, insulin, total bilirubin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The presence of chronic gastritis was defined as a confirmed diagnosis by a physician. Food consumption was determined using a semiquantitative food frequency questionnaire. We found 8 different single nucleotide polymorphisms (SNPs) that are significantly different between subjects without gastritis and those with gastritis. Of these 8 SNPs, 3 SNP (rs17183225 [C/T], rs17780814 [A/C], and rs17780820 [A/G]) are closely located in the intronic region of zinc transporter SLC39A11, commonly known as ZIP11, and show linkage disequilibrium (D' = 1.0). We also found that participants with (TCA + TCG) haplotype of ZIP11 at high levels of dietary intake of spicy foods show a significantly increasing tendency in the odds of having chronic gastritis when compared with those with CAA haplotype (odds ratio, 2.620; 95% confidence interval, 1.207-5.689). The data indicate positive associations between higher meal frequency and lower spicy food preference and gastritis. In conclusion, we found that zinc transporter gene ZIP11 is associated with chronic gastritis in the Korean population and it may interact with spicy food, which suggests ZIP11 as a therapeutic target for precision nutrition.

Presence of Dental Caries Is Associated with Food Insecurity and Frequency of Breakfast Consumption in Korean Children and Adolescents.

Dental caries remains one of the most common chronic diseases affecting children worldwide with a multi-factorial etiology. The objective of the study was to evaluate the association between socioeconomic status (SES), dietary intake, food insecurity (FI), and dental caries in Korean children and adolescents. The study utilized data from the 2-year Korean National Health and Nutrition Examination Survey (KNHANES) conducted with 1,559 Korean boys and 1,391 girls aged 2 to 18 years from 2012 to 2013. Fathers' education (P=0.017), mothers' education (P<0.001), and household income (P=0.049) were all significantly associated with dental caries among Korean boys. As for dietary practices, both eating breakfast (P<0.001) and frequency of eating out (P<0.001) were strongly associated with dental caries (P<0.001). Three models of FI were used and no differences were found regarding genders. In model 3, both food insecure male [odds ratio (OR)=1.682, 95% confidence interval (CI): 0.999~2.832] and female (OR=1.900, 95% CI: 1.094~3.299) subjects had higher odds of developing dental caries than food secure subjects after adjusting the confounding factors. The present study showed a strong association between FI mediated by SES and dental caries. Nutrition education programs targeting low-socioeconomic families are necessary as a tool to prevent dental caries in Korea.

Multiple sgRNAs with overlapping sequences enhance CRISPR/Cas9-mediated knock-in efficiency.

The CRISPR/Cas9 system is widely applied in genome engineering due to its simplicity and versatility. Although this has revolutionized genome-editing technology, knockin animal generation via homology directed repair (HDR) is not as efficient as nonhomologous end-joining DNA-repair-dependent knockout. Although its double-strand break activity may vary, Cas9 derived from Streptococcus pyogenens allows robust design of single-guide RNAs (sgRNAs) within the target sequence; However, prescreening for different sgRNA activities delays the process of transgenic animal generation. To overcome this limitation, multiple sets of different sgRNAs were examined for their knockin efficiency. We discovered profound advantages associated with single-stranded oligo-donor-mediated HDR processes using overlapping sgRNAs (sharing at least five base pairs of the target sites) as compared with using non-overlapping sgRNAs for knock-in mouse generation. Studies utilizing cell lines revealed shorter sequence deletions near target mutations using overlapping sgRNAs as compared with those observed using non-overlapping sgRNAs, which may favor the HDR process. Using this simple method, we successfully generated several transgenic mouse lines harboring loxP insertions or single-nucleotide substitutions with a highly efficiency of 18-38%. Our results demonstrate a simple and efficient method for generating transgenic animals harboring foreign-sequence knockins or short-nucleotide substitutions by the use of overlapping sgRNAs.

The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro.

Systematic review and meta-analysis of omega-3-fatty acids in elderly patients with depression.

One of the typical symptoms of a psychological crisis is depression, an increasing concern in the elderly population. Although omega-3-polyunsaturated fatty acids (PUFAs) are reported to be promising nutrients for treating depression, currently, there are no systematic reviews or meta-analyses of randomized control trials that provide critical evidence regarding the potential benefits of omega-3 fatty acids in elderly patients with depression. This analysis was conducted to provide evidence for the clinical application of omega-3 fatty acids in the treatment of depressive symptoms of elderly subjects older than 65 years. Seven databases were searched from their inception date until September 2016. Following this search, 6 studies were selected, which included 4605 patients (mean age, 76.97 years; male-female ratio=3752:853; mean dose of omega 3 intake, 1.3 g/d). These results were divided into 2 categories: well-being mental health group and depressive group. In the well-being mental health group, the Hedges g was 0.12 (95% confidence interval, -0.05 to 0.29), which indicated no significant effect of n-3 PUFA supplementation on depressed mood compared with placebo. In the depressive group, the pooled Hedges g was -0.94 (95% CI, -1.37 to -0.50]) for the random-effects model, which indicated a large effect of n-3 PUFA supplementation on those with depressed mood compared with placebo. Although this review shows that omega-3 fatty acids are effective in the treatment of elderly depressed patients, the benefits of omega-3 fatty acid supplementation were significant only in the elderly patients with mild to moderate depression.