Phytochemical investigation of the water extract and alkaloid fraction of Areca catechu L. led to theisolation of one new methoxyflavonoid rutinoside (1), together with eleven known compounds (2−12), five of which (8−12) belong to the pyridine alkaloid class. The structure of the new compound was elucidated through extensive spectroscopic analyses, including 1D and 2D NMR experiments and high-resolution mass spectrometry.Notably, rhamnazin-3-O-rutinoside (2) is reported here for the first time from this species. The isolated compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) using a p-nitrophenyl phosphate assay. Flavonoids (3 and 4) and stilbene (5) exhibited notable inhibitory activity, with IC50 values of 13.30 ± 0.71, 13.44 ± 0.84, and 8.68 ± 0.12 μM, respectively. In contrast, methoxyflavonoid rutinosides (1 and 2) and pyridine alkaloids (8−12) did not show significant inhibitory activity against PTP1B.These findings provide additional chemical insights into A. catechu and its constituents in relation to PTP1B inhibition.

Caffeic acid (CA) is a naturally occurring phenolic compound known for its strong antioxidant and cytoprotective properties.Particulate matter (PM) with an aerodynamic diameter of 2.5 μm (PM2.5) or less is a major atmospheric pollutant that induces excessive oxidative stress and apoptosis in human skin cells, contributing to various adverse effects on the skin. In this study, we investigated the protective role of CA against PM2.5-induced cellular injury in human HaCaT keratinocytes. CA reduced PM2.5-induced reactive oxygen species (ROS) accumulation and mitigated oxidative damage, including lipid peroxidation, protein carbonyl formation, mitochondrial membrane depolarization, and intracellular calcium overload. In addition, CA attenuated PM2.5-induced apoptosis by upregulating B-cell lymphoma 2 (Bcl-2) and suppressing Bcl-2-associated X protein (Bax), caspase-3, caspase-9, and phosphorylated c-Jun N-terminal kinase (phospho-JNK). Collectively, these findings demonstrate that CA protects HaCaT keratinocytes from PM2.5-induced oxidative stress and apoptosis by regulating the Bcl-2/Bax axis and inhibiting JNK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for preventing pollutant-induced skin damage.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

Purpose: This study compared healthy lifestyle (HLS) practices and awareness regarding the use of chatbots (A-uC) for health management between childhood and adolescent cancer survivors (CACSs) and their parents, with the aim of assessing the feasibility of tailored artificial intelligence (AI) chatbot-based interventions for holistic survivorship care. Methods: A descriptive comparative design was employed involving 80 CACSs and 80 parents (N=160) recruited through the Korean Pediatric Cancer Foundation. HLS practices were assessed using a validated seven-domain instrument encompassing physical activity, nutrition, interpersonal relations, stress management, positive life perspective, health responsibility, and spiritual health. A-uC was evaluated using an extended technology acceptance model-based tool. Responses to the open-ended question addressing unmet HLS practices were analyzed using latent Dirichlet allocation topic modeling. Results: No significant differences were observed between CACSs and parents in overall HLS (CACSs: 3.16±0.80; parents: 3.18±0.36, p=.74). While perceptions across most A-uC domains did not differ significantly, parents demonstrated a significantly higher “intention to use” chatbots for health management than CACSs (p=.03). The mean A-uC scores exceeded 4 (out of 5) in both groups, reflecting positive perceptions of chatbot-based HLS support. Topic modeling identified “exercise,” “healthy diet,” and “regular lifestyle” as common unmet areas. Conclusion CACSs and their parents share largely concordant views on HLS and A-uC, with a strong interest in chatbot interventions. These findings underscore the potential of tailored AI chatbot programs to address unmet lifestyle needs and promote holistic survivorship care.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

Background: To assess the mediation effect of gestational weight gain (GWG) and blood heavy metal levels in the late pregnancy affecting the association between early pregnancy metal exposure and fetal growth. Methods: We analyzed data from Korean Children’s Environmental Health Study cohort comprising 4,712 full-term births. Blood levels of lead (Pb), mercury (Hg), and cadmium (Cd) during pregnancy, and newborn birthweights were retrieved. We applied single-exposure model to assess the association between heavy metal levels and newborn anthropometric measures and conducted path analyses to examine the direct and indirect effects of heavy metal levels in early pregnancy on newborn measures. Results: Exposure to Pb (β = −15.470, P = 0.036) and Cd (β = −24.150, P = 0.004) during late pregnancy were associated with lower birthweight. Early exposure to Pb was not directly associated with lower birthweight, however, mediation of late exposure to Pb (β = −7.417, P = 0.049) resulted in lower birthweight (β = −14.787, P = 0.036). Early exposure to Hg was associated with higher birthweight, however, indirect paths via GWG (β = 3.626, P = 0.048) and late Hg levels (β = −12.929, P = 0.111) countered each other, resulting in the nullification of the total effect (β = −8.519, P = 0.301). Conclusion The effect of Pb exposure in early pregnancy on birthweight was mediated by GWG and Pb exposures during late pregnancy. When assessing the impact of heavy metal exposure on birthweight, it is important to note that GWG and late heavy metal levels act as mediators, rather than confounders.

Connecting peptide (C-peptide), a byproduct of insulin biosynthesis, has diverse cellular and biological functions. Particulate mat-ter 2.5 (PM2.5 ) adversely affects human skin, leading to skin thickening, wrinkle formation, skin aging, and inflammation. This study aimed to investigate the protective effects of C-peptide against PM2.5 -induced damage to skin cells, focusing on oxidative stressas a key mechanism. C-peptide mitigated NADPH oxidation and intracellular reactive oxygen species (ROS) production inducedby PM2.5 . It also suppressed PM2.5 -induced NADPH oxidase (NOX) activity and alleviated PM2.5 -induced NOX1 and NOX4 expression. C-peptide protected against PM2.5 -induced DNA damage, lipid peroxidation, and protein carbonylation. Additionally, C-peptide mitigated PM2.5 -induced apoptosis by inhibiting intracellular ROS production. In summary, our findings suggest that C-peptide mitigates PM2.5 -induced apoptosis in human HaCaT keratinocytes by inhibiting intracellular ROS production and NOX activity.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

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.

Background: There are few safe effective ways to relieve osteoarthritis (OA) pain; as a result, off-label psychotropic drug prescriptions have increased worldwide. This study examined the change in psychotropic drug prescriptions for patients with OA from 2011 to 2020 using the Korean National Health Insurance Service dataset. Methods: The study population consisted of patients with hip or knee OA aged ≥ 65 years.Psychotropic drugs included opioids, benzodiazepines, non-benzodiazepine hypnotics (Z-drugs), anti-epileptics, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), typical antipsychotics, atypical antipsychotics, and anxiolytics. The prevalence and long-term (> 3 months) prescription rates of psychotropic drugs in OA patients were calculated. Results: The study included 1,821,158 patients with OA (mean age 71.7 years; 65.32% female).Of the cohort, 49% had comorbidities for which psychotropics were indicated. The prevalence of psychotropic prescriptions decreased from 58.2% to 52.0% in 2018 and then leveled off.The long-term prescription rate remained constant until 2018 and then increased slightly.The most commonly prescribed psychotropics were opioids and long- and short-acting benzodiazepines. The prescription rates of opioids and long-acting benzodiazepines decreased from 2011 to 2020. For those with psychiatric co-morbidities, the prescription rates of anti-epileptics and SNRIs increased, while the prescription rates of anti-epileptics, SSRIs, other antidepressants, and atypical psychotropics increased for those without such co-morbidities. The most commonly prescribed psychotropics were diazepam and alprazolam, excluding tramadol and tramadol–acetaminophen combination. For those with psychiatric co-morbidities, the prescription rates of gabapentin and fentanyl increased, while for those without such co-morbidities, the prescription rates of lorazepam, fentanyl, escitalopram and quetiapine increased. Conclusion A significant number of older Korean patients with OA were prescribed psychotropic drugs in the absence of comorbidities requiring such drugs, including drugs that have little effect on OA and unfavorable safety profiles in older adults.