Serum TNFα and IL-17A levels may predict increased depressive symptoms: findings from the Shika Study cohort project in Japan.

BACKGROUND: Low-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms. METHODS: The participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p < 0.05. RESULTS: After controlling for age, BMI, smoking and alcohol consumption, in 2015 the serum concentrations of IL-17A and TNFα in 2015 were significantly positively associated with the CES-D scores of women (standardised ß (B) = .027, p < 0.01 and B = 0.26, p < 0.01, respectively). The serum concentrations of IL-17A and TNFα of men were significantly positively associated with the CES-D scores of 2019 (B = 0.62, p = 0.02 and B = 0.59, p = 0.02, respectively). CONCLUSIONS: In this cross-sectional study, we found a significant positive correlation between the depressive symptoms and serum TNFα and IL-17A levels of women. In addition, our longitudinal findings suggest the possibility that TNFα and IL-17A could elevate the depressive symptoms of men.

Relationship between coronary artery disease with dyslipidaemia and trace mineral intake: a cross-sectional analysis of the Shika study.

Although the relationship between dyslipidaemia (DL) and coronary artery disease (CAD) or between trace minerals intake and CAD is well known separately, the exact nature of this relationship remains unknown. We hypothesize that the relationship between trace mineral intake and CAD may differ depending on whether or not the individual has DL. The present study analysed the relationships among trace mineral intake, DL, and CAD in middle-aged and older adults living in Shika town, Ishikawa prefecture, Japan. This study included 895 residents following the exclusion of those with genetic risk carriers for familial hypercholesterolemia. Trace mineral intake was evaluated using the brief-type self-administered diet history questionnaire. Interactions were observed between DL and CAD with zinc (p = 0.004), copper (p = 0.010), and manganese intake (p < 0.001) in a two-way analysis of covariance adjusted for covariates such as sex, age, body mass index, and current smokers and drinkers. Multiple logistic regression analysis showed that zinc (odds ratio (OR): 0.752; 95% confidence interval (CI): 0.606, 0.934; p = 0.010), copper (OR: 0.175; 95% CI: 0.042, 0.726; p = 0.016), and manganese (OR: 0.494; 95% CI: 0.291, 0.839; p = 0.009) were significant independent variables for CAD in the dyslipidaemic group. The present results suggest that DL with a low trace mineral intake is associated with CAD. Further longitudinal studies are required to confirm this relationship.

KANPHOS: Kinase-associated neural phospho-signaling database for data-driven research.

Protein phosphorylation, a key regulator of cellular processes, plays a central role in brain function and is implicated in neurological disorders. Information on protein phosphorylation is expected to be a clue for understanding various neuropsychiatric disorders and developing therapeutic strategies. Nonetheless, existing databases lack a specific focus on phosphorylation events in the brain, which are crucial for investigating the downstream pathway regulated by neurotransmitters. To overcome the gap, we have developed a web-based database named "Kinase-Associated Neural PHOspho-Signaling (KANPHOS)." This paper presents the design concept, detailed features, and a series of improvements for KANPHOS. KANPHOS is designed to support data-driven research by fulfilling three key objectives: (1) enabling the search for protein kinases and their substrates related to extracellular signals or diseases; (2) facilitating a consolidated search for information encompassing phosphorylated substrate genes, proteins, mutant mice, diseases, and more; and (3) offering integrated functionalities to support pathway and network analysis. KANPHOS is also equipped with API functionality to interact with external databases and analysis tools, enhancing its utility in data-driven investigations. Those key features represent a critical step toward unraveling the complex landscape of protein phosphorylation in the brain, with implications for elucidating the molecular mechanisms underlying neurological disorders. KANPHOS is freely accessible to all researchers at https://kanphos.jp.

Association between animal protein intake, oral frailty and calf circumference in middle-aged and older adults: a cross-sectional analysis from the Shika study.

OBJECTIVE: To investigate the relationship between oral frailty (OF), nutrient intake and calf circumference (CC) in middle-aged and older adults. DESIGN: Cross-sectional study. SETTING: Residents of four model districts of Shika town, Ishikawa Prefecture, Japan, using data from November 2017 to February 2018. PARTICIPANTS: One hundred and ninety-four residents aged ≥50 years in four model districts of Shika town. The OF total score ≥3 was defined as OF. Participants were divided into OF and non-OF groups and divided into the low-CC/kg and the high-CC/kg groups. OUTCOME MEASURES: The primary outcome is to use a two-way analysis of covariance to analyse the interaction between the two CC/kg groups and the two OF groups on nutrition intake. The secondary outcome is to use multiple regression analysis to investigate the nutrients significantly related to CC/kg when stratified by OF, with age, sex, body mass index, drinking status, smoking status and regular exercise as input covariates. RESULTS: A two-way analysis of covariance revealed a significant interaction between the two CC/kg groups and the two OF groups on animal protein intake (p=0.039). Multiple comparisons using the Bonferroni analysis revealed a significantly lower animal protein intake in the OF group than in the non-OF group with a low CC/kg (p=0.033) but not in the group with a high CC/kg. The multiple regression analysis stratified by OF revealed a positive correlation between animal protein intake and CC/kg (p=0.002). CONCLUSIONS: The present results revealed a significantly lower animal protein intake in the OF group than in the non-OF group in the low-CC/kg group, but no such difference was observed in the high-CC/kg group. Further longitudinal studies are needed to elucidate this relationship.

Identification of potential disease-associated variants in idiopathic generalized epilepsy using targeted sequencing.

Many questions remain regarding the genetics of idiopathic generalized epilepsy (IGE), a subset of genetic generalized epilepsy (GGE). We aimed to identify the candidate coding variants of epilepsy panel genes in a cohort of affected individuals, using variant frequency information from a control cohort of the same region. We performed whole-exome sequencing analysis of 121 individuals and 10 affected relatives, focusing on variants of 950 candidate genes associated with epilepsy according to the Genes4Epilepsy curated panel. We identified 168 candidate variants (CVs) in 137 of 950 candidate genes in 88 of 121 affected individuals with IGE, of which 61 were novel variants. Notably, we identified five CVs in known GGE-associated genes (CHD2, GABRA1, RORB, SCN1A, and SCN1B) in five individuals and CVs shared by affected individuals in each of four family cases for other epilepsy candidate genes. The results of this study demonstrate that IGE is a disease with high heterogeneity and provide IGE-associated CVs whose pathogenicity should be proven by future studies, including advanced functional analysis. The low detection rate of CVs in the GGE-associated genes (4.1%) in this study suggests the current incompleteness of the Genes4Epilepsy panel for the diagnosis of IGE in clinical practice.

Distinct associations between dietary omega-3 and omega-6 fatty acids intake with chronic kidney disease in adults with and without diabetes: A cross-sectional study.

OBJECTIVE: We explored the relationship of dietary intake of fatty acids with chronic kidney disease (CKD) according to glycemic status in Japanese people. METHODS: A total of 1031 participants aged ≥40 y were included in this population-based, cross-sectional study. A validated self-administered diet history questionnaire was used to measure the dietary intakes of fat and fatty acids, including omega-3 and omega-6 polyunsaturated fatty acids. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and diabetes as the use of antidiabetic medication, fasting plasma glucose ≥ 126 mg/dL, or hemoglobin A1c of ≥6.5%. Urine biomarkers of kidney injury (liver-type fatty acid-binding protein, ß2-microglobulin, and albumin) were also examined. RESULTS: The mean age of the participants was 62.5 ± 11.2 y, and 482 (46.8%) of them were men. Overall, 177 (17.2%) participants had CKD. In the multivariable model, low omega-3 intake (odds ratio = 0.109; 95% CI, 0.019-0.645) and high omega-6-to-omega-3 ratio (odds ratio = 2.112; 95% CI, 1.167-3.822) were associated with CKD in participants with diabetes but not in those without. In selected participants with diabetes, a substantial trend of urinary liver-type fatty acid-binding protein and ß2-microglobulin level elevation along with an increase in the dietary ratio of omega-6 to omega-3 was observed. CONCLUSIONS: Low dietary omega-3 intake and high omega-6-to-omega-3 ratio were associated with CKD in middle-aged and older Japanese people with diabetes but not in those without diabetes. These results may provide insight into the more tailored approaches for dietary polyunsaturated fatty acids to prevent CKD.

Nutrigenetic Interaction Between Apolipoprotein C3 Polymorphism and Fat Intake in People with Nonalcoholic Fatty Liver Disease.

Background: Recent genome-wide association studies have revealed that nonalcoholic fatty liver disease (NAFLD) is correlated with genetic polymorphisms. However, the effects of genetic variation on nutritional metabolism and NAFLD are complex and further studies are still needed. Objectives: This study aimed to assess the nutritional characteristics interacting with the correlation between genetic predisposition and NAFLD. Methods: We assessed the 2013-2017 health examination data of 1191 adults aged ≥40 y living in Shika town, Ishikawa Prefecture, Japan. Adults with moderate or heavy alcohol consumption and hepatitis were excluded, and 464 participants who underwent genetic analyses were included in the study. Abdominal echography was performed to diagnose fatty liver condition, and dietary intake and nutritional balance were evaluated using the brief self-administered diet history questionnaire. NAFLD-related gene polymorphisms were identified using Japonica Array v2 (Toshiba). Results: Among the 31 single nucleotide polymorphisms, only the polymorphism T-455C in the apolipoprotein C3 (APOC3) gene (rs2854116) was significantly associated with fatty liver condition. The condition was more common in participants with heterozygotes of the APOC3 gene (rs2854116) than in those with the TT and CC genotypes. Significant interactions were observed between NAFLD and the intake of fat, vegetable fat, MUFAs, PUFAs, cholesterol, n-3 FAs, and n-6 FAs. Moreover, participants with NAFLD who presented with the TT genotype had a significantly higher fat intake than those without NAFLD. Conclusions: The polymorphism T-455C in the APOC3 gene (rs2854116) and fat intake are associated with the NAFLD risk in Japanese adults. Participants with a fatty liver who presented with the TT genotype of rs2854116 had a higher fat intake. Such nutrigenetic interaction can deepen our understanding of the NAFLD pathology. Moreover, in clinical settings, the correlation between genetic factors and nutrition intake should be considered in personalized nutritional interventions against NAFLD. Curr Dev Nutr 2023;xx:xx.The study was registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN 000024915.

Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory.

Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.

Relationships among Depressive Symptoms, Body Weight, and Chronic Pain: A Cross-Sectional Analysis of the Shika Study.

Although depression and body weight have individually been associated with chronic pain (CP), it currently remains unclear whether the combination of depressive symptoms (DS) and being underweight/overweight is related to CP. Therefore, we herein investigated the relationships among depression, body mass index (BMI), and CP in community-dwelling middle-aged and elderly individuals. Participants comprised 2216 inhabitants of Shika town in Ishikawa prefecture, Japan, including 1003 males (mean age of 68.72 years, standard deviation (SD) of 8.36) and 1213 females (mean age of 69.65 years, SD of 9.36). CP and DS were assessed using a CP questionnaire and Geriatric Depression Scale-15, respectively. The Breslow-Day test indicated that DS positively correlated with lumbar/knee pain in the BMI < 25 group, but not in the BMI ≥ 25 group. Furthermore, lumber/knee pain was related to a higher BMI. These results were confirmed by a logistic analysis with age, sex, BMI, solitary living, the duration of education, no exercise/hobbies, smoking history, alcohol intake, and medical treatment for diabetes, hyperlipidemia, or hypertension as confounding factors. The present study indicates the importance of considering DS and BMI in the prevention of CP. Further studies are needed to clarify the causal relationships among depression, BMI, and CP.

Higher Intake of Vegetable Protein and Lower Intake of Animal Fats Reduce the Incidence of Diabetes in Non-Drinking Males: A Prospective Epidemiological Analysis of the Shika Study.

Although nutrient intake and alcohol consumption are both closely associated with the incidence of diabetes, their interrelationships remain unclear. Therefore, we herein have investigated the interrelationships among nutrient intake, alcohol consumption, and the incidence of diabetes using longitudinal data. This study included 969 residents ≥40 years living in Japan. In 2011 and 2012, a baseline study was conducted using questionnaires on basic demographics, diabetes, nutrient intake, and lifestyle habits. In 2018 and 2019, a follow-up study was performed using questionnaires and medical records on diabetes. Two-way analysis of covariance (two-way ANCOVA) was used to test the interactions of drinking habits and diabetes incidence on nutrients intake. The prospective relationship between nutrient intake at baseline and the incidence of diabetes in the follow-up stratified by drinkers and non-drinkers was evaluated using multiple logistic regression analysis. Interactions were observed for vegetable protein intake (p = 0.023) and animal fat intake (p = 0.016) in males. Vegetable protein intake negatively correlated with the incidence of diabetes in non-drinkers (odds ratio (OR): 0.208; 95% confidence interval (95% CI): 0.046-0.935; p = 0.041). Furthermore, animal fat intake positively correlated with the incidence of diabetes in non-drinkers (OR: 1.625; 95% CI: 1.020-2.589; p = 0.041). Therefore, vegetable protein and animal fat intakes in combination with drinking habits need to be considered for the prevention of diabetes.