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Spinal cord injury (SCI), primarily caused by trauma, leads to permanent and lasting loss of motor, sensory, and autonomic functions. Current therapeutic strategies are focused on mitigating secondary injury, a crucial aspect of SCI pathophysiology. Among these strategies, stem cell therapy has shown considerable therapeutic potential. This study builds on our previous work, which demonstrated the functional recovery and neuronal regeneration capabilities of peripheral nerve-derived stem cell (PNSC) spheroids, which are akin to neural crest stem cells, in SCI models. However, the limited anti-inflammatory capacity of PNSC spheroids necessitates a combined therapeutic approach. As a result, we investigated the potential of co-administering resolvin D1 (RvD1), known for its anti-inflammatory and neuroprotective properties, with PNSC spheroids. In vitro analysis confirmed RvD1’s anti-inflammatory activity and its inhibitory effect on pro-inflammatory cytokines. In vivo studies involving a rat SCI model demonstrated that combined therapy of RvD1 and PNSC spheroids outperformed monotherapies, exhibiting enhanced neuronal regeneration and anti-inflammatory effects as validated through behavior tests, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry. Thus, our findings suggest that the combined application of RvD1 and PNSC spheroids may represent a novel therapeutic approach for SCI management.

Ticagrelor has been widely accepted in clinical practice for treatment of acute myocardial infarction (AMI), however its clinical safety and efficacy have not been revealed sufficiently in Asian populations.Among a total 20,270 patients (age75 years) with AMI undergoing percutaneous coronary intervention who received dual antiplatelet therapy for at least 30 days, clinical outcomes at 1 year were assessed from the database of Health Insurance Review and Assessment Service in Korea between 2013 and 2014. Ticagrelor showed a significant effect on reduction of all-cause death [stabilized inverse probability of treatment weighted (sIPTW)-adjusted odds ratio (aOR) 0.57, 95% confidence interval (CI) 0.42-0.77, p0.001]. Stroke was also reduced by using ticagrelor (sIPTW-aOR 0.58, 95% CI 0.41-0.82, p=0.002). Bleeding risk was not increased by ticagrelor use. There were nearly 30% of patients who switched from ticagrelor to different P2Y12 inhibitors. Switching P2Y12 inhibitors was associated with clinical adverse events including MI, stroke, and bleeding.Among patients aged younger than 75 years, ticagrelor was associated with lower incidence of all-cause mortality. Stroke risk was also reduced in patients with a prescription for ticagrelor without an increase in bleeding risk.

Importance In OECD countries, pharmaceutical spending reached around 800 billion USD in 2013, accounting for about 20% of total spending in the retail sector. Pharmaceutical expenditures are steadily increasing in South Korea, necessitating strategies to promote efficiency. Objective This study investigated factors associated with high-cost users (HCUs), who account for the majority of outpatient prescriptions in the total South Korean population. The top 20 frequently prescribed therapeutic subgroups were also investigated. Design This is an observational study performed using health insurance claims data in 2019. Participants In total, 44,744,632 people (including 6,806,339 aged 65 years or older) who were prescribed outpatient medications were included. Main measures HCUs were defined as those for whom prescription drug costs were in the top 5%. Multivariate logistic regression analysis was performed using factors including age, insurance type, number of prescription drugs, outpatient visit days, prescription treatment days, and chronic diseases. Results HCUs accounted for 3.6 million (5% of the total population) and 1.4 million (21.1% of those 65 years or older). Furthermore, 4.1% of HCUs in the total population had few comorbidities. Male sex, older age, insurance (Medical Aid), comorbidities, chronic diseases, number of prescription drugs, outpatient visit days, and prescription days were all associated with an increased probability of being an HCU. The highest spending was found for B01 (antithrombotic agents) with 0.4 billion USD, followed by C10 (lipid-modifying agents) and A10 (drugs used in diabetes). The proportion of spending for HCUs among the general population was highest in L01 (antineoplastic agents), at 98.2%, and L04 (immunosuppressants), at 87.8%, whereas among the elderly, the highest proportions were found for B01 (antithrombotic agents), at 44.5%, and N06 (antidepressants), at 44.3%. Conclusion Age and multiple chronic conditions were strongly associated with HCUs, and it seems necessary to reduce drug prescriptions in patients without complex comorbidities. Several measures should target those without multiple chronic conditions who are nonetheless HCUs.

BACKGROUND AND OBJECTIVES Despite the favorable efficacy of new antiplatelet agents demonstrated in randomized controlled trials, their clinical implications in Korea are unclear. The purpose of this study was to investigate trends in antiplatelet agent use for acute myocardial infarction (AMI) and their impact on 30-day clinical outcomes. METHODS AMI patients undergoing percutaneous coronary intervention between 2010 and 2015 were assessed using claim data from the Health Insurance Review and Assessment Service. RESULTS The use of new antiplatelet agents has rapidly increased since 2013 and has been preferred over clopidogrel (Plavix; Bristol-Myers Squibb/Sanofi Pharmaceuticals) since 2015. Both prasugrel (Effient; Eli Lilly and Company) (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.31-0.67; p

The cell cycle and the circadian clock communicate with each other, resulting in circadian-gated cell division cycles. Alterations in this network may lead to diseases such as cancer. Therefore, it is critical to identify molecular components that connect these two oscillators. However, molecular mechanisms between the clock and the cell cycle remain largely unknown. A model filamentous fungus, Neurospora crassa, is a multinucleate system used to elucidate molecular mechanisms of circadian rhythms, but not used to investigate the molecular coupling between these two oscillators. In this report, we show that a conserved coupling between the circadian clock and the cell cycle exists via serine/threonine protein kinase-29 (STK-29), the Neurospora homolog of mammalian WEE1 kinase. Based on this finding, we established a mathematical model that predicts circadian oscillations of cell cycle components and circadian clock-dependent synchronized nuclear divisions. We experimentally demonstrate that G1 and G2 cyclins, CLN-1 and CLB-1, respectively, oscillate in a circadian manner with bioluminescence reporters. The oscillations of clb-1 and stk-29 gene expression are abolished in a circadian arrhythmic frq(ko) mutant. Additionally, we show the light-induced phase shifts of a core circadian component, frq, as well as the gene expression of the cell cycle components clb-1 and stk-29, which may alter the timing of divisions. We then used a histone hH1-GFP reporter to observe nuclear divisions over time, and show that a large number of nuclear divisions occur in the evening. Our findings demonstrate the circadian clock-dependent molecular dynamics of cell cycle components that result in synchronized nuclear divisions in Neurospora.