Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology.

Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in the year 2000 in yeast. Two homologs of Atg9, ATG9A and ATG9B, have been found in mammals. While ATG9B shows a tissue-specific expression pattern, such as in the placenta and pituitary gland, ATG9A is ubiquitously expressed. Additionally, ATG9A deficiency leads to severe defects not only at the molecular and cellular levels but also at the organismal level, suggesting key and fundamental roles for ATG9A. The subcellular localization of ATG9A on small vesicles and its functional relevance to autophagy have suggested a potential role for ATG9A in the lipid supply during autophagosome biogenesis. Nevertheless, the precise role of ATG9A in the autophagic process has remained a long-standing mystery, especially in neurons. Recent findings, however, including structural, proteomic, and biochemical analyses, have provided new insights into its function in the expansion of the phagophore membrane. In this review, we aim to understand various aspects of ATG9 (in invertebrates and plants)/ATG9A (in mammals), including its localization, trafficking, and other functions, in nonneuronal cells and neurons by comparing recent discoveries related to ATG9/ATG9A and proposing directions for future research.Abbreviation: AP-4: adaptor protein complex 4; ATG: autophagy related; cKO: conditional knockout; CLA-1: CLArinet (functional homolog of cytomatrix at the active zone proteins piccolo and fife); cryo-EM: cryogenic electron microscopy; ER: endoplasmic reticulum; KO: knockout; PAS: phagophore assembly site; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SV: synaptic vesicle; TGN: trans-Golgi network; ULK: unc-51 like autophagy activating kinase; WIPI2: WD repeat domain, phosphoinositide interacting 2.

Transport Mechanism for Nuclear Localization of Irradiation-Activated EGFR Measured by Single-Molecule Pull-Down Assay.

Nuclear transport of epidermal growth factor receptor (EGFR) is considered to be a key cause of radiation resistance in cancer therapy. Here, we showed that irradiation-activated EGFR binds to the nuclear transport protein karyopherin alpha (KPNA) rather than karyopherin subunit beta 1 (KPNB1), through a single-molecule pull-down assay, which allows measurement of the binding affinity by single proteins in cell lysate without an additional purification step. We also obtained kinetic parameters for the binding between the phosphorylated nuclear localization signal (NLS) peptide of EGFR (645RRRHIVRKRpTLRR657) and KPNA. This observation may help developing small molecules to modulate nuclear transport, which potentially reduces the radiation resistance during irradiation therapy.

Evaluation of Salivary Biomarkers of Periodontal Disease Based on Smoking Status: A Systematic Review.

Saliva is a useful biomarker for diagnosing oral health conditions, including periodontal disease (PD). Smoking is a risk factor for PD. The aim of this systematic review was to summarize the salivary biomarkers associated with PD based on smoking status. A comprehensive search of the MEDLINE (via PubMed), EMBASE, Cochrane, SCOPUS, and Web of Sciences databases was conducted up to 1 January 2021 using key terms relevant to the topic of our research and Cochrane methodology and improved with searching a gray literature resource. The methodological quality of all included studies was assessed with the revised Quality Assessment of Diagnostic Accuracy Studies-2. Seven studies were included. Smokers had increased levels of malondialdehyde, sialic acid, salivary cortisol, salivary interleukin 1ß, albumin, tissue inhibitor of matrix metalloproteinase (TIMP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), as well as decreased levels of superoxide dismutase, activity of lactate dehydrogenase, activity of enzyme activity of ß-glucuronidase, uric acid, matrix metalloproteinase-8 (MMP-8)/TIMP-1 ratio, and combinations of MMP-8 and ICTP. However, mixed results were observed some studies in detecting glutathione peroxidase, MMP-8, and MMP-14. The results were interpreted with caution because of limitations in the number of included studies and the study design. Some salivary biomarkers are potentially useful in combination or alone for diagnosing PD. Methodological and systematic studies are needed to develop more effective biomarkers.

Non-Communicable Diseases and Transitioning Health System in the Democratic People's Republic of Korea during COVID-19 Lockdown.

While there are increasing concerns on COVID-19 situation in Democratic People's Republic of Korea (DPRK, or North Korea), little is known about North Korea's health system function for Non-Communicable Diseases. Given the scarcity of available evidence, a scoping review was conducted in peer review articles from MEDLINE, SCOPUS, and Web of Science, and policy literatures from Rodongshinmun, state-run media in North Korea to analyze the North Korea health system and COVID-19 pandemic. The transition to a market economy is expected to deepen the gap between the rich and the poor over access to health care, causing a new type of health inequality in North Korea. COVID-19 lockdown intensified the DPRK's economic predicament exacerbating shortage of health financing on non-communicable diseases. The case study of mixed evidence from scoping review indicates that NCDs prevention and management are not functional in the transitioning health system under chronic economic crisis and isolation. This study indicates that NCDs prevention and management are not functional in the transitioning health system under chronic economic crisis and isolation. The destabilized markets under COVID-19 lockdown intensified the DPRK's economic predicament and exacerbated the chronic shortage of health financing especially to NCDs.

Adherence to Dietary Guidelines among Diabetes Patients: Comparison between Elderly and Non-Elderly Groups.

This study aimed to compare adherence to dietary guidelines between elderly and non-elderly individuals with type 2 diabetes mellitus (T2DM) in Korea. Data of 4,577 participants with T2DM were collected from the 1998-2015 Korea National Health and Nutrition Examination Surveys. The participants were classified into two groups based on age: non-elderly T2DM group comprising participants aged 30-64 years and elderly T2DM group comprising participants aged ≥ 65 years. Adherence to dietary guidelines was assessed using the Korean Diabetes Association-Korean Ministry of Health and Welfare (KDA-KMHW) index, comprising six components of dietary guidelines for T2DM patients. Multivariable generalized linear regression analysis was performed to analyze the KDA-KMHW index scores. The adherence levels to the individual components of the KDA-KMHW index were mostly lower in non-elderly group (p < 0.001) than elderly group, except for moderate carbohydrate consumption. The total KDA-KMHW index score was significantly lower in non-elderly T2DM group than in the elderly T2DM group (p < 0.001). The study results suggest the need for developing patient-specific education programs that focus on adherence to dietary guidelines, particularly for non-elderly patients, to adequately intervene with the difficulties experienced in T2DM dietary management.

Omega-3 and omega-6 polyunsaturated fatty acids and metabolic syndrome: A systematic review and meta-analysis.

BACKGROUND & AIMS: Previous studies suggest that polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but some have shown ambiguous results. The aim of this study was to systematically evaluate and summarize available evidence on the association between omega-3 and omega-6 PUFA levels and risk of metabolic syndrome (MetS). METHODS: A systematic literature search of articles published until December 2017 was conducted in PubMed, Web of Science, and Cochrane Library databases. Meta-analyses of the highest vs. lowest categories of omega-3 and omega-6 PUFAs were conducted using the random effects models. RESULTS: Thirteen studies (2 case-control, 9 cross-sectional, 1 nested case-control, and 1 prospective cohort) with 36,542 individuals were included. Higher omega-3 PUFA levels in diets or blood were associated with a 26% reduction in the risk of MetS (odds ratio (OR)/relative risk (RR) 0.74, 95% confidence interval (CI) 0.62-0.89). This inverse association was evident among studies with Asian populations (OR/RR 0.69, 95% CI 0.54-0.87), but not among those with American/European populations (OR/RR 0.84, 95% CI 0.55-1.28). Null results were found regarding the association between circulating/dietary omega-6 PUFAs and MetS. CONCLUSION: The present meta-analysis indicates that higher intakes of omega-3 PUFAs, but not omega-6 PUFAs, was associated with lower MetS risk; adding to the current body of evidence on the metabolic health effects of circulating/dietary omega-3 PUFAs.

Obesity and Vitamin D Insufficiency among Adolescent Girls and Young Adult Women from Korea.

Although there is evidence of the biological mechanisms by which obesity may induce vitamin D insufficiency or deficiency, limited epidemiological studies have been conducted, especially among Asian adolescent girls and young adult women who are at a high risk of vitamin D deficiency. This study aimed to examine the cross-sectional association between obesity and vitamin D insufficiency among adolescent girls and young adult women in Korea. We used data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2014, and 3623 girls and young adult women aged 12-29 years were included. Demographic and lifestyle data were collected using a self-administered questionnaire from the health interview survey. Serum 25-hydroxyvitamin D (25(OH)D) level, body mass index (BMI), and body fat percentage (BF%) were measured during health examinations. Multivariable logistic regression was used considering the complex, multistage probability sample design of KNHANES. In the multivariable-adjusted analyses, obese girls and women, defined by BMI, were more likely to have a higher prevalence of vitamin D insufficiency (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.17). This association was also evident for BF%. Participants with ≥30% BF% had a significantly higher prevalence of vitamin D insufficiency (OR: 1.52, 95% CI: 1.07-2.16). Obesity may worsen vitamin D insufficiency among adolescents and young women because of the fat-soluble characteristics of vitamin D and related health behaviors, such as a lack of outdoor activity. Further large-scale prospective cohort studies or randomized controlled trials are warranted to confirm this causality.

Trends in the management levels of metabolic risk factors in middle-aged and elderly patients with type 2 diabetes mellitus: The Korean National Health and Nutrition Examination Survey 1998-2014.

The present study examined the temporal trends in the management of blood pressure, glucose, and lipid levels among middle-aged and elderly patients with type 2 diabetes using data from the Korean National Health and Nutrition Examination Survey (1998-2014). A total of 3,689 patients with diabetes were included and divided into middle-aged (30-64 years old) and elderly (≥65 years old) groups. Demographic and lifestyle data were obtained using a self-reported questionnaire, and trained medical staff obtained fasting blood samples and blood pressure data. Laboratory testing was performed to determine blood glucose, cholesterol, and triglyceride levels. In the multivariable adjusted models, significant decreasing trends in the prevalences of hyperglycemia and hypertension were observed in both age groups during 1998-2014, although no trends were observed for lipid levels. Based on the most recent survey, approximately 50% of patients with diabetes had hyperglycemia, and one-third of patients with diabetes and hypertension did not appropriately manage their blood pressure. In addition, 50% of the patients in both age groups did not manage their lipid profiles, and the management of lipid profiles did not improve in recent years. These results suggest that continuous follow-up is needed to effectively manage metabolic risk factors, especially lipid profiles, among patients with diabetes.