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.

Patients with ectodermal dysplasia often have atrophied alveolar bone and an inadequate maxillomandibular relationship owing to congenital edentulism.Accurate implant placement that can overcomes anatomical limitations and orthognathic surgery to improve the maxillomandibular relationship is necessary for creating implant-supported prosthesis for these patients. Implant placement and provisional prosthesis fabrication before orthognathic surgery can provide critical fixed reference points and ensure accuracy during orthognathic surgery.In our patient, a digital system was used to design a surgical guide that considered the predictable position of the definitive prosthesis, allowing the placement of implants to overcome anatomical limitations and the creation of fixed reference points via the delivery of a provisional prosthesis for effective orthognathic surgery. The lack of compensation during orthognathic surgery was considered in the definitive prosthesis. As a result, a prosthesis with a minimal anterior cantilever was fabricated. This study aimed to determine the appropriate sequence of multidisciplinary collaborations that would, result in the best functional and aesthetic outcomes.

Objective: This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance. Methods: We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations. Results: A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes. Conclusion Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.

Purpose: To evaluate the feasibility of robot-assisted ureteral reconstruction as a minimally invasive alternative to open surgery for managing ureteric complications in transplanted kidneys. Materials and Methods: From January 2020 to December 2023, robot-assisted ureteral reconstruction was performed on fifteen kidney transplant patients with vesicoureteral reflux (VUR) or ureteral stricture who had previously failed endoscopic treatments. Results: Twelve females and three males, with a mean age of 48.6±6.6 years, were included in the study. Nine patients (60.0%) underwent surgery due to VUR (grade III or higher) of the transplanted kidney, and six patients (40.0%) had transplanted ureteral strictures. Postoperative voiding cystourethrogram (VCUG) was performed at 3.2±1.6 months. Seven patients (77.8%) became VUR-free, while two patients (22.2%) had VUR regression from grade IV to I. All six patients who underwent reconstruction due to anastomosis site stricture became stenosis-free without the need for an indwelling ureteral catheter. In cases where the ureter was too short for reimplantation, a Boari flap or end-to-end anastomosis with the native ureter was performed. The mean hospital stay was 5.9±4.5 days. The urethral catheter was removed after 15.1±5.4 days, and the ureteral catheter was removed after 4.9±1.5 weeks. The mean follow-up period was 23.9±6.8 months, with no additional interventions required after surgery. No complications above Clavien-Dindo grade I were recorded. Conclusions Robotic ureteral reconstruction is technically feasible and offers an effective, minimally invasive treatment for ureteric complications in kidney transplant patients, serving as an alternative to open surgery.

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.