Change in employment status and its causal effect on suicidal ideation and depressive symptoms: A marginal structural model with machine learning algorithms.

OBJECTIVE: This study aimed to assess the causal effect of a change in employment status on suicidal ideation and depressive symptoms by applying marginal structural models (MSM) with machine-learning (ML) algorithms. METHODS: We analyzed data from the 8-15th waves (2013-2020) of the Korean Welfare Panel Study, a nationally representative longitudinal dataset. Our analysis included 13 294 observations from 3621 participants who had standard employment at baseline (2013-2019). Based on employment status at follow-up year (2014-2020), respondents were classified into two groups: (i) maintained standard employment (reference group), (ii) changed to non-standard employment. Suicidal ideation during the past year and depressive symptoms during the past week were assessed through self-report questionnaire. To apply the ML algorithms to the MSM, we conducted eight ML algorithms to build the propensity score indicating a change in employment status. Then, we applied the MSM to examine the causal effect by using inverse probability weights calculated based on the propensity score from ML algorithms. RESULTS: The random forest algorithm performed best among all algorithms, showing the highest area under the curve 0.702, 95% confidence interval (CI) 0.686-0.718. In the MSM with the random forest algorithm, workers who changed from standard to non-standard employment were 2.07 times more likely to report suicidal ideation compared to those who maintained standard employment (95% CI 1.16-3.70). A similar trend was observed in the analysis of depressive symptoms. CONCLUSIONS: This study found that a change in employment status could lead to a higher risk of suicidal ideation and depressive symptoms.

Secular Trends of Incidence, Prevalence, and Healthcare Economic Burden in ANCA-Associated Vasculitis: An Analysis of the 2002-2018 South Korea National Health Insurance Database.

Objectives: The incidence and prevalence of AAV in Asia remain poorly understood, especially in a nationwide setting. This study investigated the incidence, prevalence, and healthcare burden of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in South Korea by analyzing a national database. Methods: This study included patients with AAV identified from the National Health Insurance Service Database of South Korea from 2002 to 2018. Patients were diagnosed with AAV in a general or tertiary hospital and were registered in the individual payment beneficiaries program or were prescribed glucocorticoids. A calendar-based meteorological definitions were adopted to assess the differences in the incidence of AAV according to season. The average healthcare expenditure and patient outcomes of mortality and end-stage renal disease (ESRD) in patients with AAV were compared to 1:10 age, sex and residential area matched controls. Results: A total of 2,113 patients [708, 638, and 767 with microscopic polyangiitis (MPA), granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, respectively] were identified. The annual incidence and prevalence of AAV increased continuously, and MPA being the most common disease subtype after 2015. The highest incidence and prevalence of AAV was 0.48/100,000 person-years (PY) and 2.40/100,000 PY in 2017 and 2018, respectively. There were no significant differences in monthly and seasonal incidence of AAV. The average expense of medical care, overall mortality, and ESRD rates of patients with AAV were higher in patients with AAV than in controls, especially in the case of MPA. Conclusion: An increasing trend of AAV diagnosis observed is consistent with the evidence that AAV is more common in recent years; however, a relatively lower incidence and prevalence was observed compared to that in Western countries. The higher medical cost and rates of mortality and ESRD in AAV emphasize the early recognition and implementation of optimal treatment for these patients.

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. Here, we first found that IF for 3 months caused modulation of H3K9 trimethylation (H3K9me3) in the cerebellum, which in turn orchestrated a plethora of transcriptomic changes involved in robust metabolic switching processes commonly observed during IF. Second, a portion of both the epigenomic and transcriptomic modulations induced by IF was remarkably preserved for at least 3 months post-IF refeeding, indicating that memory of IF-induced epigenetic changes was maintained. Notably, though, we found that termination of IF resulted in a loss of H3K9me3 regulation of the transcriptome. Collectively, our study characterizes the novel effects of IF on the epigenetic-transcriptomic axis, which controls myriad metabolic processes. The comprehensive analyses undertaken in this study reveal a molecular framework for understanding how IF impacts the metabolo-epigenetic axis of the brain and will serve as a valuable resource for future research.

Risk of Pregnancy Complications and Low Birth Weight Offsprings in Korean Women With Rheumatic Diseases: A Nationwide Population-Based Study.

BACKGROUND: To determine the risk of pregnancy complications and adverse offspring outcomes in Korean women with rheumatic diseases (RDs). METHODS: Women aged 20-44 years with pregnancies ending in delivery were identified from the National Health Insurance Service-National Health Information Database (2009-2016). Women with RD including systemic lupus erythematosus (SLE), seropositive rheumatoid arthritis (SPRA), and ankylosing spondylitis (AS) (n = 4,284) were age-matched with controls (n = 26,023). Outcome variables included threatened abortion (TA), preterm birth (PB), preeclampsia/eclampsia (PE/E), intrauterine growth retardation (IGR), urinary tract infection, low birth weight (LBW) offsprings, and offspring death within 1 year of birth. RESULTS: Women with RDs had increased risks for cesarean section delivery (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), TA (OR, 1.4; 95% CI, 1.2-1.5), PB (OR, 2.4; 95% CI, 1.9-3.2), PE/E (OR, 4.4; 95% CI, 3.3-5.9), and IGR (OR, 2.4; 95% CI, 2.0-3.1) than the controls. The risk of pregnancy complications was increased in SLE and SPRA pregnancies but not in AS pregnancies. Offsprings of women with RDs had an increased risk of LBW (OR, 4.0; 95% CI, 3.2-4.9). The offspring mortality rate within 1 year of birth was higher in women with RDs (6.2/10,000 persons) than in the controls (4.9/10,000 persons). CONCLUSION: Women with RDs are at a risk of developing pregnancy complications, and the risk of LBW offsprings and offspring death within 1 year of birth is increased in these women. Therefore, this population requires special attention during their childbearing years.

Engineered small extracellular vesicles displaying ACE2 variants on the surface protect against SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry is mediated by the interaction of the viral spike (S) protein with angiotensin-converting enzyme 2 (ACE2) on the host cell surface. Although a clinical trial testing soluble ACE2 (sACE2) for COVID-19 is currently ongoing, our understanding of the delivery of sACE2 via small extracellular vesicles (sEVs) is still rudimentary. With excellent biocompatibility allowing for the effective delivery of molecular cargos, sEVs are broadly studied as nanoscale protein carriers. In order to exploit the potential of sEVs, we design truncated CD9 scaffolds to display sACE2 on the sEV surface as a decoy receptor for the S protein of SARS-CoV-2. Moreover, to enhance the sACE2-S binding interaction, we employ sACE2 variants. sACE2-loaded sEVs exhibit typical sEVs characteristics and bind to the S protein. Furthermore, engineered sEVs inhibit the entry of wild-type (WT), the globally dominant D614G variant, Beta (K417N-E484K-N501Y) variant, and Delta (L452R-T478K-D614G) variant SARS-CoV-2 pseudovirus, and protect against authentic SARS-CoV-2 and Delta variant infection. Of note, sACE2 variants harbouring sEVs show superior antiviral efficacy than WT sACE2 loaded sEVs. Therapeutic efficacy of the engineered sEVs against SARS-CoV-2 challenge was confirmed using K18-hACE2 mice. The current findings provide opportunities for the development of new sEVs-based antiviral therapeutics.

Frontal polymerization-triggered simultaneous ring-opening metathesis polymerization and cross metathesis affords anisotropic macroporous dicyclopentadiene cellulose nanocrystal foam.

Multifunctionality and effectiveness of macroporous solid foams in extreme environments have captivated the attention of both academia and industries. The most recent rapid, energy-efficient strategy to manufacture solid foams with directionality is the frontal polymerization (FP) of dicyclopentadiene (DCPD). However, there still remains the need for a time efficient one-pot approach to induce anisotropic macroporosity in DCPD foams. Here we show a rapid production of cellular solids by frontally polymerizing a mixture of DCPD monomer and allyl-functionalized cellulose nanocrystals (ACs). Our results demonstrate a clear correlation between increasing % allylation and AC wt%, and the formed pore architectures. Especially, we show enhanced front velocity (vf) and reduced reaction initiation time (tinit) by introducing an optimal amount of 2 wt% AC. Conclusively, the small- and wide-angle X-ray scattering (SAXS, WAXS) analyses reveal that the incorporation of 2 wt% AC affects the crystal structure of FP-mediated DCPD/AC foams and enhances their oxidation resistance.

Gender differences in under-reporting hiring discrimination in Korea: a machine learning approach.

OBJECTIVES: This study was conducted to examine gender differences in under-reporting hiring discrimination by building a prediction model for workers who responded "not applicable (NA)" to a question about hiring discrimination despite being eligible to answer. METHODS: Using data from 3,576 wage workers in the seventh wave (2004) of the Korea Labor and Income Panel Study, we trained and tested 9 machine learning algorithms using "yes" or "no" responses regarding the lifetime experience of hiring discrimination. We then applied the best-performing model to estimate the prevalence of experiencing hiring discrimination among those who answered "NA." Under-reporting of hiring discrimination was calculated by comparing the prevalence of hiring discrimination between the "yes" or "no" group and the "NA" group. RESULTS: Based on the predictions from the random forest model, we found that 58.8% of the "NA" group were predicted to have experienced hiring discrimination, while 19.7% of the "yes" or "no" group reported hiring discrimination. Among the "NA" group, the predicted prevalence of hiring discrimination for men and women was 45.3% and 84.8%, respectively. CONCLUSIONS: This study introduces a methodological strategy for epidemiologic studies to address the under-reporting of discrimination by applying machine learning algorithms.

Loss of zinc-finger protein 212 leads to Purkinje cell death and locomotive abnormalities with phospholipase D3 downregulation.

Although Krüppel-associated box domain-containing zinc-finger proteins (K-ZNFs) may be associated with sophisticated gene regulation in higher organisms, the physiological functions of most K-ZNFs remain unknown. The Zfp212 protein was highly conserved in mammals and abundant in the brain; it was mainly expressed in the cerebellum (Cb). Zfp212 (mouse homolog of human ZNF212) knockout (Zfp212-KO) mice showed a reduction in survival rate compared to wild-type mice after 20 months of age. GABAergic Purkinje cell degeneration in the Cb and aberrant locomotion were observed in adult Zfp212-KO mice. To identify genes related to the ataxia-like phenotype of Zfp212-KO mice, 39 ataxia-associated genes in the Cb were monitored. Substantial alterations in the expression of ataxin 10, protein phosphatase 2 regulatory subunit beta, protein kinase C gamma, and phospholipase D3 (Pld3) were observed. Among them, Pld3 alone was tightly regulated by Flag-tagged ZNF212 overexpression or Zfp212 knockdown in the HT22 cell line. The Cyclic Amplification and Selection of Targets assay identified the TATTTC sequence as a recognition motif of ZNF212, and these motifs occurred in both human and mouse PLD3 gene promoters. Adeno-associated virus-mediated introduction of human ZNF212 into the Cb of 3-week-old Zfp212-KO mice prevented Purkinje cell death and motor behavioral deficits. We confirmed the reduction of Zfp212 and Pld3 in the Cb of an alcohol-induced cerebellar degeneration mouse model, suggesting that the ZNF212-PLD3 relationship is important for Purkinje cell survival.

Early Chronic Memantine Treatment-Induced Transcriptomic Changes in Wild-Type and Shank2-Mutant Mice.

Shank2 is an excitatory postsynaptic scaffolding protein strongly implicated in autism spectrum disorders (ASDs). Shank2-mutant mice with a homozygous deletion of exons 6 and 7 (Shank2-KO mice) show decreased NMDA receptor (NMDAR) function and autistic-like behaviors at juvenile [∼postnatal day (P21)] and adult (>P56) stages that are rescued by NMDAR activation. However, at ∼P14, these mice show the opposite change - increased NMDAR function; moreover, suppression of NMDAR activity with early, chronic memantine treatment during P7-21 prevents NMDAR hypofunction and autistic-like behaviors at later (∼P21 and >P56) stages. To better understand the mechanisms underlying this rescue, we performed RNA-Seq gene-set enrichment analysis of forebrain transcriptomes from wild-type (WT) and Shank2-KO juvenile (P25) mice treated early and chronically (P7-21) with vehicle or memantine. Vehicle-treated Shank2-KO mice showed upregulation of synapse-related genes and downregulation of ribosome- and mitochondria-related genes compared with vehicle-treated WT mice. They also showed a transcriptomic pattern largely opposite that observed in ASD (reverse-ASD pattern), based on ASD-related/risk genes and cell-type-specific genes. In memantine-treated Shank2-KO mice, chromatin-related genes were upregulated; mitochondria, extracellular matrix (ECM), and actin-related genes were downregulated; and the reverse-ASD pattern was weakened compared with that in vehicle-treated Shank2-KO mice. In WT mice, memantine treatment, which does not alter NMDAR function, upregulated synaptic genes and downregulated ECM genes; memantine-treated WT mice also exhibited a reverse-ASD pattern. Therefore, early chronic treatment of Shank2-KO mice with memantine alters expression of chromatin, mitochondria, ECM, actin, and ASD-related genes.

Alzheimer's disease-causing presenilin-1 mutations have deleterious effects on mitochondrial function.

Mitochondrial dysfunction and oxidative stress are frequently observed in the early stages of Alzheimer's disease (AD). Studies have shown that presenilin-1 (PS1), the catalytic subunit of γ-secretase whose mutation is linked to familial AD (FAD), localizes to the mitochondrial membrane and regulates its homeostasis. Thus, we investigated how five PS1 mutations (A431E, E280A, H163R, M146V, and Δexon9) observed in FAD affect mitochondrial functions. Methods: We used H4 glioblastoma cell lines genetically engineered to inducibly express either the wild-type PS1 or one of the five PS1 mutants in order to examine mitochondrial morphology, dynamics, membrane potential, ATP production, mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), oxidative stress, and bioenergetics. Furthermore, we used brains of PS1M146V knock-in mice, 3xTg-AD mice, and human AD patients in order to investigate the role of PS1 in regulating MAMs formation. Results: Each PS1 mutant exhibited slightly different mitochondrial dysfunction. Δexon9 mutant induced mitochondrial fragmentation while A431E, E280A, H163R, and M146V mutants increased MAMs formation. A431E, E280A, M146V, and Δexon9 mutants also induced mitochondrial ROS production. A431E mutant impaired both complex I and peroxidase activity while M146V mutant only impaired peroxidase activity. All PS1 mutants compromised mitochondrial membrane potential and cellular ATP levels were reduced by A431E, M146V, and Δexon9 mutants. Through comparative profiling of hippocampal gene expression in PS1M146V knock-in mice, we found that PS1M146V upregulates Atlastin 2 (ATL2) expression level, which increases ER-mitochondria contacts. Down-regulation of ATL2 after PS1 mutant induction rescued abnormally elevated ER-mitochondria interactions back to the normal level. Moreover, ATL2 expression levels were significantly elevated in the brains of 3xTg-AD mice and AD patients. Conclusions: Overall, our findings suggest that each of the five FAD-linked PS1 mutations has a deleterious effect on mitochondrial functions in a variety of ways. The adverse effects of PS1 mutations on mitochondria may contribute to MAMs formation and oxidative stress resulting in an accelerated age of disease onset in people harboring mutant PS1.

Immunostimulatory Activity of Polysaccharides Extracted from Celosia cristata Flowers.

Macrophages play a major role in innate immune responses by producing a variety of immune mediators and cytokines. The stimulation of macrophages by natural products may lead to an enhanced innate immune system. This study evaluated the immunostimulatory effects of a polysaccharide-rich crude fraction of Celosia cristata L. flowers (CCP) on murine macrophages. CCP treatment induced the production of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines by macrophages. Mechanistically, the activation of mitogen-activated protein kinases, NF-κB and toll-like receptor 4 were found to be associated with the stimulatory functions of CCP. CCP was found to be primarily composed of galacturonic acid and glucose in addition to small amounts of arabinose and galactose. This study demonstrated that CCP may enhance the innate immune responses and potentially improve the immune functions in the body.

Nonparametric Bayesian functional two-part random effects model for longitudinal semicontinuous data analysis.

Longitudinal semicontinuous data, characterized by repeated measures of a large portion of zeros and continuous positive values, are frequently encountered in many applications including biomedical, epidemiological, and social science studies. Two-part random effects models (TPREM) have been used to investigate the association between such longitudinal semicontinuous data and covariates accounting for the within-subject correlation. The existing TPREM is, however, limited to incorporate a functional covariate, which is often available in a longitudinal study. Moreover, the existing TPREM typically assumes the normality of subject-specific random effects, which can be easily violated when there exists a subgroup structure. In this article, we propose a nonparametric Bayesian functional TPREM to assess the relationship between the longitudinal semicontinuous outcome and various types of covariates including a functional covariate. The proposed model also relaxes the normality assumption for the random effects through a Dirichlet process mixture of normals, which allows for identifying an underlying subgroup structure. The methodology is illustrated through an application to social insurance expenditure data collected by the Korean Welfare Panel Study and a simulation study.

Alterations of functional connectivity in auditory and sensorimotor neural networks: A case report in a patient with cortical deafness after bilateral putaminal hemorrhagic stroke.

RATIONALE: Cortical deafness is a rare auditory dysfunction caused by damage to brain auditory networks. The aim was to report alterations of functional connectivity in intrinsic auditory, motor, and sensory networks in a cortical deafness patient. PATIENT CONCERNS: A 41-year-old woman suffered a right putaminal hemorrhage. Eight years earlier, she had suffered a left putaminal hemorrhage and had minimal sequelae. She had quadriparesis, imbalance, hypoesthesia, and complete hearing loss. DIAGNOSES: She was diagnosed with cortical deafness. After 6 months, resting-state functional magnetic resonance imaging (rs-fMRI) and diffuse tensor imaging (DTI) were performed. DTI revealed that the acoustic radiation was disrupted while the corticospinal tract and somatosensory track were intact using deterministic tracking methods. Furthermore, the patient showed decreased functional connectivity between auditory and sensorimotor networks. INTERVENTIONS: The patient underwent in-patient stroke rehabilitation therapy for 2 months. OUTCOMES: Gait function and ability for activities of daily living were improved. However, complete hearing impairment persisted in 6 months after bilateral putaminal hemorrhagic stroke. LESSONS: Our case report seems to suggest that functional alterations of spontaneous neuronal activity in auditory and sensorimotor networks are related to motor and sensory impairments in a patient with cortical deafness.

O-GlcNAcylation ameliorates the pathological manifestations of Alzheimer's disease by inhibiting necroptosis.

O-GlcNAcylation (O-linked ß-N-acetylglucosaminylation) is notably decreased in Alzheimer's disease (AD) brain. Necroptosis is activated in AD brain and is positively correlated with neuroinflammation and tau pathology. However, the links among altered O-GlcNAcylation, ß-amyloid (Aß) accumulation, and necroptosis are unclear. Here, we found that O-GlcNAcylation plays a protective role in AD by inhibiting necroptosis. Necroptosis was increased in AD patients and AD mouse model compared with controls; however, decreased necroptosis due to O-GlcNAcylation of RIPK3 (receptor-interacting serine/threonine protein kinase 3) was observed in 5xFAD mice with insufficient O-linked ß-N-acetylglucosaminase. O-GlcNAcylation of RIPK3 suppresses phosphorylation of RIPK3 and its interaction with RIPK1. Moreover, increased O-GlcNAcylation ameliorated AD pathology, including Aß burden, neuronal loss, neuroinflammation, and damaged mitochondria and recovered the M2 phenotype and phagocytic activity of microglia. Thus, our data establish the influence of O-GlcNAcylation on Aß accumulation and neurodegeneration, suggesting O-GlcNAcylation-based treatments as potential interventions for AD.

miR-351-5p/Miro2 axis contributes to hippocampal neural progenitor cell death via unbalanced mitochondrial fission.

Adult hippocampal neurogenesis supports the structural and functional plasticity of the brain, while its decline is associated with neurodegeneration common in Alzheimer's disease (AD). Although the dysregulation of certain microRNAs (miRNAs) in AD have been observed, the effects of miRNAs on hippocampal neurogenesis are largely unknown. In this study, we demonstrated miR-351-5p as a causative factor in hippocampal neural progenitor cell death through modulation of the mitochondrial guanosine triphosphatase (GTPase), Miro2. Downregulation of Miro2 by siMiro2 induced cell death, similar to miR-351-5p, whereas ectopic Miro2 expression using an adenovirus abolished these effects. Excessively fragmented mitochondria and dysfunctional mitochondria were indexed by decreased mitochondrial potential, and increased reactive oxygen species were identified in miR-351-5p-induced cell death. Moreover, subsequent induction of mitophagy via Pink1 and Parkin was observed in the presence of miR-351-5p and siMiro2. The suppression of mitochondrial fission by Mdivi-1 completely inhibited cell death by miR-351-5p. miR-351-5p expression increased whereas the level of Miro2 decreased in the hippocampus of AD model mice, emulating expression in AD patients. Collectively, the data indicate the mitochondrial fission and accompanying mitophagy by miR-351-5p/Miro2 axis as critical in hippocampal neural progenitor cell death, and a potential therapeutic target in AD.

Clinical Study Using Healthcare Claims Database.

The healthcare claims database is a database created using claims data accumulated while operating the government's health insurance system. The National Health Insurance Service (NHIS) provides benefits for health promotion, prevention, diagnosis, and disease and injury treatment, as well as for rehabilitation, birth, and death. Ninety-seven percent of the total population is enrolled in the NHIS; individuals pay a monthly insurance contribution to the system, and the NHIS pays a portion of the cost of reimbursement items to the medical institution when the subscriber receives medical services. In this process, the NHIS and Health Insurance Review Agency (HIRA) decide on payment, and claims data are documented items that medical institutions claim to these government agencies. The NHIS and HIRA have established a database to support policy and academic research, and they provide this database to researchers. Health claims data are representative of the nation, reflecting the actual medical environment. They also shorten the time and cost required for research and have several advantages as research data. However, studies should be conducted with an understanding of the limitations of claims data, a sufficient understanding of the characteristics of the Korean insurance system, and criteria for providing reimbursed services. Moreover, validating the healthcare claims database will facilitate more useful and reliable research.

Neuronal Aquaporin 1 Inhibits Amyloidogenesis by Suppressing the Interaction Between Beta-Secretase and Amyloid Precursor Protein.

The accumulation of amyloid-ß (Aß) is a characteristic event in the pathogenesis of Alzheimer's disease (AD). Aquaporin 1 (AQP1) is a membrane water channel protein belonging to the AQP family. AQP1 levels are elevated in the cerebral cortex during the early stages of AD, but the role of AQP1 in AD pathogenesis is unclear. We first determined the expression and distribution of AQP1 in brain tissue samples of AD patients and two AD mouse models (3xTg-AD and 5xFAD). AQP1 accumulation was observed in vulnerable neurons in the cerebral cortex of AD patients, and in neurons affected by the Aß or tau pathology in the 3xTg-AD and 5xFAD mice. AQP1 levels increased in neurons as aging progressed in the AD mouse models. Stress stimuli increased AQP1 in primary cortical neurons. In response to cellular stress, AQP1 appeared to translocate to endocytic compartments of ß- and γ-secretase activities. Ectopic expression of AQP1 in human neuroblastoma cells overexpressing amyloid precussir protein (APP) with the Swedish mutations reduced ß-secretase (BACE1)-mediated cleavage of APP and reduced Aß production without altering the nonamyloidogenic pathway. Conversely, knockdown of AQP1 enhanced BACE1 activity and Aß production. Immunoprecipitation experiments showed that AQP1 decreased the association of BACE1 with APP. Analysis of a human database showed that the amount of Aß decreases as the expression of AQP1 increases. These results suggest that the upregulation of AQP1 is an adaptive response of neurons to stress that reduces Aß production by inhibiting the binding between BACE1 and APP.

O-GlcNAcylation as a Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia and the number of elderly patients suffering from AD has been steadily increasing. Despite worldwide efforts to cope with this disease, little progress has been achieved with regard to identification of effective therapeutics. Thus, active research focusing on identification of new therapeutic targets of AD is ongoing. Among the new targets, post-translational modifications which modify the properties of mature proteins have gained attention. O-GlcNAcylation, a type of PTM that attaches O-linked ß-N-acetylglucosamine (O-GlcNAc) to a protein, is being sought as a new target to treat AD pathologies. O-GlcNAcylation has been known to modify the two important components of AD pathological hallmarks, amyloid precursor protein, and tau protein. In addition, elevating O-GlcNAcylation levels in AD animal models has been shown to be effective in alleviating AD-associated pathology. Although studies investigating the precise mechanism of reversal of AD pathologies by targeting O-GlcNAcylation are not yet complete, it is clearly important to examine O-GlcNAcylation regulation as a target of AD therapeutics. This review highlights the mechanisms of O-GlcNAcylation and its role as a potential therapeutic target under physiological and pathological AD conditions.

Antioxidant Activities of Viviparus Contectus Extract Against Tert-Butylhydroperoxide-Induced Oxidative Stress.

In this study, the antioxidant properties of Viviparus contectus (V. contectus) extract were evaluated for various radical scavenging activities, ferric reducing antioxidant power (FRAP), ABTS radical scavenging activity and oxygen radical absorbance capacity (ORAC). In addition, inhibition effect of the V. contectus extract against DNA scission induced by hydroxyl radical was measured. We also studied the protective effect of V. contectus extract against oxidative damage through measurements of intracellular reactive oxygen species (ROS) in Chang cells and zebrafish embryo. We found that V. contectus extract contains strong radical scavenging activities and antioxidant properties, which prevent tert-butylhydroperoxide (t-BHP)-induced oxidative stress, enhance cell viability, reduce ROS production, inhibit oxidative damage and improve mitochondrial function in Chang cells. Also, we determined that the V. contectus extract reduced ROS production mediated by t-BHP induced oxidative stress on zebrafish embryo.

Antioxidant and Protective Effects of Atrina Pectinata Extract.

Atrina pectinata (A. pectinata), called pen shell, is an edible shellfish that adheres to the seabed pointed downward and has a triangular shell reaching about 40 cm in length.In this study, we examined the antioxidant effect of an A. pectinata extract exhibiting various radical scavenging activities. These scavenging activities were evaluated using electron spin resonance. Anti-oxidant activities were also determined using the ferric reducing antioxidant power (FRAP) and the ABTS radical scavenging assays. Lipid peroxidation inhibitory activity was confirmed using ferric thiocyanate and thiobarbituric acid assays. Furthermore, the protective effect of the A. pectinata extract against t-BHP-induced oxidative stress on Chang cells were evaluated using MTT assay and the measurement of reactive oxygen species (ROS). These results showed that the A. pectinata extract have strong radical scavenging activities, and exerts protective effect against oxidative stress through reducing intracellular ROS content of Chang cells.