Carbon Monoxide Protects against Hepatic Ischemia/Reperfusion Injury via ROS-Dependent Akt Signaling and Inhibition of Glycogen Synthase Kinase 3β

Carbon monoxide (CO) may exert important roles in physiological and pathophysiological states through the regulation of cellular signaling pathways. CO can protect organ tissues from ischemia/reperfusion (I/R) injury by modulating intracellular redox status and by inhibiting inflammatory, apoptotic, and proliferative responses. However, the cellular mechanisms underlying the protective effects of CO in organ I/R injury remain incompletely understood. In this study, a murine model of hepatic warm I/R injury was employed to assess the role of glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways in the protective effects of CO against inflammation and injury. Inhibition of GSK3 through the PI3K/Akt pathway played a crucial role in CO-mediated protection. CO treatment increased the phosphorylation of Akt and GSK3-beta (GSK3β) in the liver after I/R injury. Furthermore, administration of LY294002, an inhibitor of PI3K, compromised the protective effect of CO and decreased the level of phospho-GSK3β after I/R injury. These results suggest that CO protects against liver damage by maintaining GSK3β phosphorylation, which may be mediated by the PI3K/Akt signaling pathway. Our study provides additional support for the therapeutic potential of CO in organ injury and identifies GSK3β as a therapeutic target for CO in the amelioration of hepatic injury

Type and Severity of Migraine Determines Risk of Atrial Fibrillation in Women

OBJECTIVE: To evaluate sex differences in the risk of atrial fibrillation (AF) according to the type and severity of migraine. METHODS: We analyzed the nationwide health screening recipients in 2009 without previous AF diagnosis from the Korean National Health Insurance Service data. The diagnosis, type, and severity of migraine were determined using claims data. Newly developed AF was identified during a 10-year follow-up. Sex-difference in the effect of migraine on AF was evaluated. RESULTS: A total of 4,020,488 subjects were enrolled from January 1, to December 31, 2009 and followed-up through December 31, 2018; 4,986 subjects had migraine with aura (age 50.6 ± 14.0 years, men 29.3%); and 105,029 had migraine without aura (age 51.6 ± 14.3 years, men 30.9%). Risk of AF in a mild degree of migraine was similar to that in the control group, regardless of sex or the presence of aura. Severe migraine without aura modestly but significantly increased the risk of AF in both men and women compared to controls, with increase in AF risk being most prominent in women who had severe migraine with aura [incidence rate (IR) = 3.39, hazard ratio (HR)(adjust) = 1.48, 95% confidence intervals (CI) = 1.18–1.85]. No significant association according to aura was observed in men with severe migraines (p for interaction 0.011). CONCLUSION: Severe migraine with aura significantly increased the risk of incident AF in women, but not in men. Surveillance for incident AF and prompt lifestyle modification may be beneficial, particularly for young women suffering from severe migraine with aura

Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities

Cumulative burden of metabolic syndrome and its components on the risk of atrial fibrillation:a nationwide population-based study

BackgroundThe metabolic syndrome (MetS) and its components are associated with the development of atrial fibrillation (AF). However, the impact of time-burden of MetS on the risk of AF is unknown. We investigated the effect of the cumulative longitudinal burden of MetS on the development of AF.MethodsWe included 2 885 189 individuals without AF who underwent four annual health examinations during 2009-2013 from the database of the Korean national health insurance service. Metabolic burdens were evaluated in the following three ways: (1) cumulative number of MetS diagnosed at each health examination (0-4 times); (2) cumulative number of each MetS component diagnosed at each health examination (0-4 times per MetS component); and (3) cumulative number of total MetS components diagnosed at each health examination (0 to a maximum of 20). The risk of AF according to the metabolic burden was estimated using Cox proportional-hazards models.ResultsOf all individuals, 62.4%, 14.8%, 8.7%, 6.5%, and 7.6% met the MetS diagnostic criteria 0, 1, 2, 3, and 4 times, respectively. During a mean follow-up of 5.3 years, the risk of AF showed a positive association with the cumulative number of MetS diagnosed over four health examinations: adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of 1, 2, 3, and 4 times compared to 0 times were 1.18 (1.13-1.24), 1.31 (1.25-1.39), 1.46 (1.38-1.55), and 1.72 (1.63-1.82), respectively; P for trend ConclusionsGiven the positive correlations between the cumulative metabolic burdens and the risk of incident AF, maximal effort to detect and correct metabolic derangements even before MetS development might be important to prevent AF and related cardiovascular diseases

Associations between obesity parameters and the risk of incident atrial fibrillation and ischaemic stroke in the different age groups

OBJECTIVE: Obesity and aging are important predisposing factors to atrial fibrillation (AF) and ischaemic stroke (IS). However, limited data comprehensively evaluated the relationships between obesity measurements and AF and IS in different ages. METHODS: A total of 9,432,332 adults from the Korean National Health Insurance Service Database were included. The study population was categorized into the six age subgroups by an increase every decade from the twenties. We evaluated AF and IS risk according to body mass index (BMI) and waist circumference (WC) in the different age groups. RESULTS: During a mean follow-up of 8.2 ± 1.0 years, BMI-AF presented a J-shaped association across ages. The highest hazard ratio (HR) of the BMI ≥ 30 kg/m(2) group was observed in subjects aged 30–39 years [HR 1.80, 95% CI 1.63–1.98, p 60 years. Among the BMI ≥ 30 kg/m(2) groups, subjects aged 20–29 years presented the highest risk of IS [HR 3.00, 95% CI (2.34–3.84), p < 0.001]. Overall, WC-AF and WC-IS showed positive linear correlations, but the WC-IS association was weak in subjects aged ≥ 40 years. CONCLUSION: The higher risks of AF and IS according to an increment of BMI and WC were most apparent among the young ages. The association between obesity measurements and IS was not significantly above the midlife. Weight management in the young and integrated risk factor management in the elderly are warranted

Improvement in the Oxidation Resistance of Cu Films by an Electroless Co-Alloy Capping Process

Co-alloy films with various solution compositions CoB, CoWB, and CoW B P were deposited with an electroless technique on Cu films without Pd activation, and their oxidation barrier performance was analyzed. The degrees of oxidation of all films were intensively studied. CoB showed excellent capping performance as an oxidation barrier, whereas CoWB and CoW B P exhibited even poorer oxidation resistance than the case of bare Cu at 400°C. The depth profile of the film compositions and chemical states of the CoB film before and after oxidation was investigated, the results of which suggested that the oxidation of the B component in the film had a clear role in the prevention of continuous Cu diffusion to the surface. The multilayer structure of CoB/ CoW B P/Cu for obtaining both electromigration and oxidation resistance was optimized, showing excellent oxidation resistance comparable to a single-composition CoB film.Korea Science and Engineering Foundation (KOSEF), which is funded by the Ministry of Education, Science and Technology (no. 2008-02857), and by the KOSEF through the Research Center for Energy Conversion and Storage (RCECS)

Impact of components of metabolic syndrome on the risk of adverse renal outcomes in patients with atrial fibrillation: a nationwide cohort study

Background: The renal effect of metabolic syndrome components is unclear in patients with atrial fibrillation. This study aimed to investigate the association between metabolic syndrome components and incident end-stage renal disease among patients with atrial fibrillation. Methods: A total of 202,434 atrial fibrillation patients without prevalent end-stage renal disease were identified from the National Health Insurance Service database between 2009 and 2016. We defined the metabolic score range from 0 to 5 points such that a patient received every 1 point if the patient met each component listed in the diagnostic criteria of metabolic syndrome. The population was divided into 6 groups: MS 0–MS 5 for a metabolic score of 0–5, respectively. Multivariate Cox regression analysis was used to estimate the risks of end-stage renal disease. Results: There were 12,747, 31,059, 40,361, 48,068, 46,630, and 23,569 patients for MS 0–MS 5, respectively. Compared with MS 0, MS 5 had a higher CHA 2DS 2-VASc score (3.8 vs. 1.0) (P &lt;.001). During a median follow-up of 3.5 years, compared with MS 0, MS 1–MS 5 were associated with a gradually increasing incidence of end-stage renal disease, in relation to an increase in the metabolic score, (log-rank P &lt;.001). After multivariate adjustment, a higher metabolic score was associated with a greater risk of incident end-stage renal disease: adjusted hazard ratio [95% confidence interval] = 1.60 [0.78–3.48], 2.08 [1.01–4.31], 2.94 [1.43–6.06], 3.71 [1.80–7.66], and 4.82 [2.29–10.15], for MS 1–MS 5, respectively. Conclusions: Metabolic syndrome components additively impacts the risk of incident end-stage renal disease among patients with atrial fibrillation.</p

Silver Direct Electrodeposition on Ru Thin Films

Electrodeposition of Ag was performed on Ru thin films following electrochemical reduction of native Ru oxide. Oxide reduction in a tetramethylammonium hydroxide solution was critical for the formation of continuous Ag film, and a large overpotential was important for high-density nucleation. From a kinetics viewpoint, the thermal stability of the Ag film was improved by the application of a more negative potential, which suggested that better nucleation density at the initial stage of growth induced better substrate adhesion. Suppression of growth by addition of an organic additive generated a larger and more uniformly distributed initial population of Ag particles, and as a result a smooth film was obtained.This work was supported by KOSEF through the Research Center for Energy Conversion and Storage (RCECS), the Institute of Chemical Processing (ICP) in Seoul National University, and Dongbu HiTek

Impact of mental disorders on the risk of atrial fibrillation in patients with diabetes mellitus:a nationwide population-based study

BACKGROUND: It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF. METHODS: Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed. RESULTS: Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17–1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12–1.17], 1.15 [1.13–1.18], and 1.19 [1.67–1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not. CONCLUSIONS: Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01682-7