Abnormal Development of Neural Stem Cell Niche in the Dentate Gyrus of Menkes Disease

Copyright © 2022 by the Korean Society for Stem Cell ResearchBackground and Objectives: Menkes disease (MNK) is a rare X-linked recessive disease, caused by mutations in the copper transporting ATP7A gene that is required for copper homeostasis. MNK patients experience various clinical symptoms including neurological defects that are closely related to the prognosis of MNK patients. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) produce new neurons throughout life, and defects in DG neurogenesis are often correlated with cognitive and behavioral problems. However, neurodevelopmental defects in the DG during postnatal period in MNK have not been understood yet. Methods and Results: Mottled-brindled (MoBr/y) mice (MNK mice) and littermate controls were used in this study. In vivo microCT imaging and immunohistochemistry results demonstrate that blood vasculatures in hippocampus are abnormally decreased in MNK mice. Furthermore, postnatal establishment of NSC population and their neurogenesis are severely compromised in the DG of MNK mice. In addition, in vitro analyses using hippocampal neurosphere culture followed by immunocytochemistry and immunoblotting suggest that neurogenesis from MNK NSCs is also significantly compromised, corresponding to defective neurogenic gene expression in MNK derived neurons. Conclusions: Our study is the first reports demonstrating that improper expansion of the postnatal NSC population followed by significant reduction of neurogenesis may contribute to neurodevelopmental symptoms in MNK. In conclusion, our results provide new insight into early neurodevelopmental defects in MNK and emphasize the needs for early diagnosis and new therapeutic strategies in the postnatal central nerve system damage of MNK patients.N

Antimicrobial effects of silver nanoparticles

The antimicrobial effects of silver (Ag) ion or salts are well known, but the effects of Ag nanoparticles on microorganisms and antimicrobial mechanism have not been revealed clearly. Stable Ag nanoparticles were prepared and their shape and size distribution characterized by particle characterizer and transmission electron microscopic study. The antimicrobial activity of Ag nanoparticles was investigated against yeast, Escherichia coli, and Staphylococcus aureus. In these tests, Muller Hinton agar plates were used and Ag nanoparticles of various concentrations were supplemented in liquid systems. As results, yeast and E. coli were inhibited at the low concentration of Ag nanoparticles, whereas the growth-inhibitory effects on S. aureus were mild. The free-radical generation effect of Ag nanoparticles on microbial growth inhibition was investigated by electron spin resonance spectroscopy. These results suggest that Ag nanoparticles can be used as effective growth inhibitors in various microorganisms, making them applicable to diverse medical devices and antimicrobial control systems.This work was supported by the NSI-NCRC program of KOSEF. D.H.J. was supported by BK21 program. H.J.L. was supported by the the Korean Research Foundation Grant funded by the Korea Government (MOEHRD) (R05-2004-10627-0)

Comparison of 2-year mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background After acute myocardial infarction (AMI), the replicated phenomenon of obesity paradox, i.e., obesity appearing to be associated with increased survival, has not been evaluated in stabilized (i.e., without clinical events within 1 month post AMI) Asian patients with diabetes mellitus (DM). Methods Among 1192 patients in the DIabetic Acute Myocardial InfarctiON Disease (DIAMOND) Korean multicenter registry between April 2010 and June 2012, 2-year cardiac and all-cause death were compared according to obesity (body mass index ≥25 kg/m2) in 1125 stabilized DM patients. Results Compared with non-obese DM patients (62 % of AMI patients), obese DM patients had: higher incidence of dyslipidemia (31 vs. 24 %, P < 0.01); lower incidence of chronic kidney disease (26 vs. 33 %) (P < 0.01); higher left ventricular ejection fraction after AMI (53 ± 11 vs. 50 ± 12 %, P < 0.001); and lower 2-year cardiac and all-cause death occurrence (0.7 vs. 3.6 % and 1.9 vs. 5.2 %, both P < 0.01) and cumulative incidence in Kaplan–Meier analysis (P < 0.005, respectively). Likewise, both univariate and multivariate Cox hazard regression analyses adjusted for the respective confounders showed that obesity was associated with decreased risk of both cardiac [HR, 0.18 (95 % CI 0.06–0.60), P = 0.005; and 0.24 (0.07–0.78), P = 0.018, respectively] and all-cause death [0.34 (0.16–0.73), P = 0.005; and 0.44 (0.20–0.95), P = 0.038]. Conclusions In a Korean population of stabilized DM patients after AMI, non-obese patients appear to have higher cardiac and all-cause mortality compared with obese patients after adjusting for confounding factors

Comparison of 2-year mortality according to obesity in stabilized patients with type 2 diabetes mellitus after acute myocardial infarction: results from the DIAMOND prospective cohort registry

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background After acute myocardial infarction (AMI), the replicated phenomenon of obesity paradox, i.e., obesity appearing to be associated with increased survival, has not been evaluated in stabilized (i.e., without clinical events within 1 month post AMI) Asian patients with diabetes mellitus (DM). Methods Among 1192 patients in the DIabetic Acute Myocardial InfarctiON Disease (DIAMOND) Korean multicenter registry between April 2010 and June 2012, 2-year cardiac and all-cause death were compared according to obesity (body mass index ≥25 kg/m2) in 1125 stabilized DM patients. Results Compared with non-obese DM patients (62 % of AMI patients), obese DM patients had: higher incidence of dyslipidemia (31 vs. 24 %, P < 0.01); lower incidence of chronic kidney disease (26 vs. 33 %) (P < 0.01); higher left ventricular ejection fraction after AMI (53 ± 11 vs. 50 ± 12 %, P < 0.001); and lower 2-year cardiac and all-cause death occurrence (0.7 vs. 3.6 % and 1.9 vs. 5.2 %, both P < 0.01) and cumulative incidence in Kaplan–Meier analysis (P < 0.005, respectively). Likewise, both univariate and multivariate Cox hazard regression analyses adjusted for the respective confounders showed that obesity was associated with decreased risk of both cardiac [HR, 0.18 (95 % CI 0.06–0.60), P = 0.005; and 0.24 (0.07–0.78), P = 0.018, respectively] and all-cause death [0.34 (0.16–0.73), P = 0.005; and 0.44 (0.20–0.95), P = 0.038]. Conclusions In a Korean population of stabilized DM patients after AMI, non-obese patients appear to have higher cardiac and all-cause mortality compared with obese patients after adjusting for confounding factors

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA &amp; EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA &amp; EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA &amp; EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843