Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Parkinson’s disease (PD) is a movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have shown that necroptosis is involved in the development of inflammatory and neurodegenerative diseases. Receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) play key roles in necroptosis, with MLKL being the final executor of necroptosis. Necrosulfonamide (NSA) is a specific inhibitor of MLKL, and its therapeutic effects in various inflammatory and neurological disorders have been previously reported. However, its role in PD has not yet been clearly demonstrated. In this study, we examined the effects of NSA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. NSA reduced dopaminergic cell death and restored the expression of neurotrophic factors, such as BDNF, GDNF, and PGC-1α, in the SN region of MPTP mice. In addition, NSA inhibited microglial/ astrocyte activation and the expression of proinflammatory markers, such as iNOS, TNF-α, IL-1β, and IL-6. NSA also reduced oxidative stress markers, such as 8-OHdG and 4-HNE, while enhancing Nrf2-driven antioxidant enzymes, including HO-1, catalase, MnSOD, GCLC, and GCLM. We found that NSA inhibited MLKL phosphorylation in dopaminergic neurons and microglia, which may have reduced neuronal cell death and inflammation. Therefore, NSA-mediated suppression of dopaminergic neuronal cell death, inflammation, and oxidative stress may have therapeutic potential in PD.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Objective: Multiple cohort studies have investigated the potential link between anesthesia and dementia. However, mixed findings necessitate closer examination. This study aimed to investigate the association between anesthesia exposure and the incidence of dementia, considering different anesthesia types and anesthetic agents. Methods: This nationwide cohort study utilized data from the South Korean Health Insurance Review and Assessment Service database, covering 62,541 participants, to investigate the correlation between anesthesia exposure and dementia incidence. Results: Results revealed an increased risk of dementia in individuals who underwent general (hazard ratio [HR], 1.318;95% confidence interval [CI], 1.061−1.637) or regional/local anesthesia (HR, 2.097; 95% CI, 1.887−2.329) compared to those who did not. However, combined general and regional/local anesthesia did not significantly increase dementia risk (HR, 1.097; 95% CI, 0.937−1.284). Notably, individual anesthetic agents exhibited varying risks; desflurane and midazolam showed increased risks, whereas propofol showed no significant difference. Conclusion This study provides unique insights into the nuanced relationship between anesthesia, individual anesthetic agents, and the incidence of dementia. While confirming a general association between anesthesia exposure and dementia risk, this study also emphasizes the importance of considering specific agents. These findings under-score the need for careful evaluation and long-term cognitive monitoring after anesthesia.

Background: This study aimed to assess the severity of postoperative delirium (PD) in elderly patients who underwent reverse total shoulder arthroplasty (rTSA) for irreparable massive rotator cuff tears (mRCTs) under general anesthesia (GA) compared to those under interscalene block (IB). Methods: Forty elderly patients aged 65 years or older diagnosed with an irreparable mRCT who underwent rTSA were included in the prospective case-controlled study. Of these, 20 patients were operated under GA and the other 20 under IB. The average age was 77.1 years (range, 65–95 years). The severity of delirious symptoms was evaluated by the Delirium Rating Scale–revised–98 (DRS) score from the patients or guardians before the surgery and at 0, 3, and 7 days and 1, 3, and 6 months after the surgery and compared between the 2 groups. Results: Immediately after surgery, the visual analog scale score difference between the groups was statistically significant, with the GA group at 6.25 (standard deviation, ± 0.85) and the IB group at 3.80 (± 0.62) (p < 0.001). On the day of operation, the mean DRS score in the GA and IB groups were 9.10 (± 5.63) and 6.60 (± 5.33), respectively (p = 0.157). On day 3 of surgery, the mean DRS score in the GA group peaked to 9.95 (± 8.73), while in the IB group, it declined to 6.40 (±5.81) (p = 0.138). After 3 days, DRS scores showed a decreasing trend in both groups. When comparing the mean change (∆) from the preoperative baseline scores to the postoperative values, the ∆DRS score was significantly higher with 4.15 (± 4.53) points in the GA group as compared to 1.30 (± 1.92) in the IB group (p = 0.014). Conclusions IB can be an attractive and efficient anesthetic choice in preventing PD for elderly patients undergoing rTSA for irreparable mRCTs. The IB group showed lower DRS scores and a peak on day 0 compared to the higher DRS scores and peak on day 3 in the GA group. Additionally, IB showed less pain than GA.

Background: Given the association between nonalcoholic fatty liver disease and metabolic risks, a new term, metabolic dysfunction- associated steatotic liver disease (MASLD) has been proposed. We aimed to explore the association between MASLD and all-cause, cause-specific mortalities. Methods: We included individuals with steatotic liver disease (SLD) from the Korean National Health Insurance Service. Moreover, SLD was defined as a fatty liver index ≥30. Furthermore, MASLD, metabolic alcohol-associated liver disease (MetALD), and alcoholic liver disease (ALD) with metabolic dysfunction (MD) were categorized based on alcohol consumption and MD. We also analyzed all-cause, liver-, cancer-, hepatocellular carcinoma (HCC)- and cardiovascular (CV)-related mortalities. Results: This retrospective nationwide cohort study included 1,298,993 individuals aged 40 to 79 years for a mean follow-up duration of 9.04 years. The prevalence of MASLD, MetALD, and ALD with MD was 33.11%, 3.93%, and 1.00%, respectively. Relative to the “no SLD” group, multivariable analysis identified that MASLD (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.26 to 1.31), MetALD (aHR, 1.38; 95% CI, 1.32 to 1.44), and ALD with MD group (aHR, 1.80; 95% CI, 1.68 to 1.93) have a significantly higher risk of all-cause mortality. Furthermore, MASLD, MetALD, ALD with MD groups showed higher liver-, cancer- and HCC-related mortality than “no SLD” group. While all-cause specific mortalities increase from MASLD to MetALD to ALD with MD, the MetALD group shows a lower risk of CV-related mortality compared to MASLD. However, ALD with MD group still have a higher risk of CV-related mortality compared to MASLD. Conclusion SLD is associated with an increased risk of all-cause, liver-, cancer-, HCC-, and CV-related mortalities.