Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Background/Aims: The clinical outcomes and optimal treatment of esophageal squamous cell carcinoma (ESCC) in elderly patients are unclear. This study aimed to assess the clinical outcomes of ESCC in patients aged ≥ 80 years. Methods: Medical records of patients diagnosed with ESCC between December 2008 and February 2024 were retrospectively reviewed. In total, 479 patients with ESCC were included and divided into the elderly (n = 52) and younger (n = 427) groups based on age. The clinical outcomes and survival rates, according to treatment, were compared between the two groups. Results: The median ages of the two groups were 82 years (range, 80–95 yr) and 66 years (41–79 yr). The overall survival was slightly lower in the elderly group; however, no statistical significance (hazard ratio [HR] 1.27, 95% confidence interval [CI] 0.85−1.91; p = 0.238) was observed. No differences were observed in the outcomes or survival between the two groups according to the treatment method (surgery, chemoradiotherapy or radiotherapy alone, and endoscopic resection). The elderly group was more likely to receive no treatment for cancer (30.8% vs. 13.6%, p = 0.002) than the younger group. However, when there was no treatment for cancer in the elderly group, survival was significantly lower than when treatment was administered (HR 0.08, 95% CI 0.03−020; p < 0.001). Conclusions In patients with ESCC aged ≥ 80 years, active cancer treatment was beneficial, and the results did not differ from those of younger patients.

Purpose: The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity. Materials and Methods: We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire. Results: We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported. Conclusion Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.