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.

Background: Human muscle satellite (stem) cells (MuSCs) are essential for investigating muscle physiology, regeneration, and disease mechanisms. Primary cultures derived directly from human tissues offer a more physiologically relevant model than immortalized cell lines. However, the isolation and characterization of MuSCs from human upper limb tissues are limited. Therefore, this study aimed to establish and characterize a primary culture system for MuSCs obtained from human upper limb muscle tissue. Methods: Human muscle tissues were obtained from upper limb surgical specimens. Muscle samples were mechanically and enzymatically dissociated to isolate muscle-derived cells, which were cultured under standard growth conditions. Cell morphology and proliferation were monitored during the culture period. Myogenic characteristics were assessed by examining the expression of muscle-specific markers including myogenic regulatory factors and structural proteins. Additionally, myogenic differentiation capacity was evaluated by inducing differentiation and analyzing the formation of multinucleated myotubes. Results: Primary MuSCs were isolated from human upper limb tissues and expanded in vitro. The cultured cells exhibited a typical spindle-shaped morphology and demonstrated significant proliferative capacity. Characterization confirmed the expression of myogenic markers, indicating the presence of muscle-derived precursor cells. Following induction of differentiation, the cells formed multinucleated myotube-like structures and expressed muscle proteins associated with differentiation, highlighting their potential for myogenic differentiation. Conclusion This study established a reliable protocol for isolating and culturing MuSCs from human upper limb tissues. Cultured cells displayed typical myogenic characteristics and differentiation capacity, indicating that this model could be a valuable platform for studying human muscle biology and potential therapeutic applications.

Purpose: The purpose of this study was to explore and assess the experiences of cancer patients and their caregivers who had been admitted to comprehensive nursing care service wards. Methods: Data were collected from 10 patients and 10 caregivers by in-depth interviews. The data were analyzed using content analysis of Downe-Wamboldt. Results: Three categories and seven subcategories were extracted. 1) Realizing institutional limitations of comprehensive nursing care service: ‘Wishing for precise operating systems based on patient severity,’ ‘Anticipating active caregiver participation in treatment process,’ ‘Requiring a countermeasure for safety accidents,’ 2) Professional nursing service which provides relief: ‘Patient-centered professional nursing service,’ ‘Inpatient service that provides relief for patients and caregivers,’ 3) Anticipating continuous use of the service: ‘Inpatient service which users are willing to reuse,’ ‘Wishing for expansion and reinforcement of the service.’ Conclusion Cancer patients and their caregivers experienced institutional limitations while satisfied with professional nursing service and willing to reuse the service. To improve this situation, institutional support such as separate wards for severe patients, measures for active caregiver participation and prevention of safety accidents, and adequate staffing would be helpful for relatively severe level cancer patients and their caregivers.

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H 2O 2). The results showed that mangiferin attenuated H 2O 2-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H 2O 2-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H 2O 2-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.

Purpose: The purpose of this study was to explore and assess the experiences of cancer patients and their caregivers who had been admitted to comprehensive nursing care service wards. Methods: Data were collected from 10 patients and 10 caregivers by in-depth interviews. The data were analyzed using content analysis of Downe-Wamboldt. Results: Three categories and seven subcategories were extracted. 1) Realizing institutional limitations of comprehensive nursing care service: ‘Wishing for precise operating systems based on patient severity,’ ‘Anticipating active caregiver participation in treatment process,’ ‘Requiring a countermeasure for safety accidents,’ 2) Professional nursing service which provides relief: ‘Patient-centered professional nursing service,’ ‘Inpatient service that provides relief for patients and caregivers,’ 3) Anticipating continuous use of the service: ‘Inpatient service which users are willing to reuse,’ ‘Wishing for expansion and reinforcement of the service.’ Conclusion Cancer patients and their caregivers experienced institutional limitations while satisfied with professional nursing service and willing to reuse the service. To improve this situation, institutional support such as separate wards for severe patients, measures for active caregiver participation and prevention of safety accidents, and adequate staffing would be helpful for relatively severe level cancer patients and their caregivers.

Background: We aimed to investigate the characteristics of pediatric ulcerative colitis (UC) at diagnosis in Korea. Methods: This was a multicenter, registry-based, inception cohort study conducted in Korea between 2021 and 2023. Children and adolescents newly diagnosed with UC < 18 years were included. Baseline clinicodemographics, results from laboratory, endoscopic exams, and Paris classification factors were collected, and associations between factors at diagnosis were investigated. Results: A total 205 patients with UC were included. Male-to-female ratio was 1.59:1, and the median age at diagnosis was 14.7 years (interquartile range 11.9–16.2). Disease extent of E1 comprised 12.2% (25/205), E2 24.9% (51/205), E3 11.2% (23/205), and E4 51.7% (106/205) of the patients. S1 comprised 13.7% (28/205) of the patients. The proportion of patients with a disease severity of S1 was significantly higher in patients with E4 compared to the other groups (E1: 0% vs. E2: 2% vs. E3: 0% vs. E4: 24.5%, P < 0.001). Significant differences between disease extent groups were also observed in Pediatric Ulcerative Colitis Activity Index (median 25 vs. 35 vs. 40 vs. 45, respectively, P < 0.001), hemoglobin (median 13.5 vs.13.2 vs. 11.6 vs. 11.4 g/dL, respectively, P < 0.001), platelet count (median 301 vs. 324 vs. 372 vs. 377 × 103 /μL, respectively, P = 0.001), C-reactive protein (median 0.05 vs. 0.10 vs. 0.17 vs. 0.38 mg/dL, respectively, P < 0.001), and Ulcerative Colitis Endoscopic Index of Severity (median 4 vs. 4 vs. 4 vs. 5, respectively, P = 0.006). No significant differences were observed in factors between groups divided according to sex and diagnosis age. Conclusion This study represents the largest multicenter pediatric inflammatory bowel disease cohort in Korea. Disease severity was associated with disease extent in pediatric patients with UC at diagnosis.

The Controlling Nutritional Status (CONUT) score and the prognostic nutritional index (PNI) have emerged as important nutritional indices because they provide an objective assessment based on data. We aimed to investigate how these nutritional indices relate to outcomes in patients with sepsis. Methods: Data were collected retrospectively at five hospitals for patients aged ≥18 years receiving treatment for sepsis between January 1, 2017, and December 31, 2021. Serum albumin and total cholesterol concentrations, and peripheral lymphocytes were used to calculate the CONUT score and PNI. To identify predictors correlated with 30-day mortality, analyses were conducted using univariate and multivariate Cox proportional hazards models. Results: The 30-day mortality rate among 9,763 patients was 15.8% (n=1,546). The median CONUT score was 5 (interquartile range [IQR], 3–7) and the median PNI score was 39.6 (IQR, 33.846.4). Higher 30-day mortality rates were associated with individuals with moderate (CONUT score: 5–8; PNI: 35–38) or severe (CONUT: 9–12; PNI: <35) malnutrition compared with those with no malnutrition (CONUT: 0–1; PNI: >38). With CONUT scores, the hazard ratio (HR) associated with moderate malnutrition was 1.52 (95% confidence interval [CI], 1.24–1.87; P<0.001); for severe, HR=2.42 (95% CI, 1.95–3.02; P<0.001). With PNI scores, the HR for moderate malnutrition was 1.29 (95% CI, 1.09–1.53; P=0.003); for severe, HR=1.88 (95% CI, 1.67–2.12; P<0.001). Conclusions: The nutritional indices CONUT score and PNI showed significant associations with mortality of sepsis patients within 30 days.

Children face the excitement of a changing world but also encounter environmental threats to their health that were neither known nor suspected several decades ago. Children are at particular risk of exposure to pollutants that are widely dispersed in the air, water, and food. Children and adolescents are exposed to chemical, physical, and biological risks at home, in school, and elsewhere. Actions are needed to reduce these risks for children exposed to a series of environmental hazards. Exposure to a number of persistent environmental pollutants including air pollutants, endocrine disruptors, noise, electromagnetic waves (EMWs), tobacco and other noxious substances, heavy metals, and microplastics, is linked to damage to the nervous and immune systems and affects reproductive function and development. Exposure to environmental hazards is responsible for several acute and chronic diseases that have replaced infectious diseases as the principal cause of illnesses and death during childhood. Children are disproportionately exposed to environmental toxicities. Children drink more water, eat more food, and breathe more frequently than adults. As a result, children have a substantially heavier exposure to toxins present in water, food, or air than adults. In addition, their hand-to-mouth behaviors and the fact that they live and play close to the ground make them more vulnerable than adults. Children undergo rapid growth and development processes that are easily disrupted. These systems are very delicate and cannot adequately repair thetional development in children’s environmental health was the Declaration of the Environment Leaders of the Eight on Children’s Environmental Health by the Group of Eight. In 2002, the World Health Organization launched an initiative to improve children’s environmental protection effort. Here, we review major environmental pollutants and related hazards among children and adolescents.

The Controlling Nutritional Status (CONUT) score and the prognostic nutritional index (PNI) have emerged as important nutritional indices because they provide an objective assessment based on data. We aimed to investigate how these nutritional indices relate to outcomes in patients with sepsis. Methods: Data were collected retrospectively at five hospitals for patients aged ≥18 years receiving treatment for sepsis between January 1, 2017, and December 31, 2021. Serum albumin and total cholesterol concentrations, and peripheral lymphocytes were used to calculate the CONUT score and PNI. To identify predictors correlated with 30-day mortality, analyses were conducted using univariate and multivariate Cox proportional hazards models. Results: The 30-day mortality rate among 9,763 patients was 15.8% (n=1,546). The median CONUT score was 5 (interquartile range [IQR], 3–7) and the median PNI score was 39.6 (IQR, 33.846.4). Higher 30-day mortality rates were associated with individuals with moderate (CONUT score: 5–8; PNI: 35–38) or severe (CONUT: 9–12; PNI: <35) malnutrition compared with those with no malnutrition (CONUT: 0–1; PNI: >38). With CONUT scores, the hazard ratio (HR) associated with moderate malnutrition was 1.52 (95% confidence interval [CI], 1.24–1.87; P<0.001); for severe, HR=2.42 (95% CI, 1.95–3.02; P<0.001). With PNI scores, the HR for moderate malnutrition was 1.29 (95% CI, 1.09–1.53; P=0.003); for severe, HR=1.88 (95% CI, 1.67–2.12; P<0.001). Conclusions: The nutritional indices CONUT score and PNI showed significant associations with mortality of sepsis patients within 30 days.

Children face the excitement of a changing world but also encounter environmental threats to their health that were neither known nor suspected several decades ago. Children are at particular risk of exposure to pollutants that are widely dispersed in the air, water, and food. Children and adolescents are exposed to chemical, physical, and biological risks at home, in school, and elsewhere. Actions are needed to reduce these risks for children exposed to a series of environmental hazards. Exposure to a number of persistent environmental pollutants including air pollutants, endocrine disruptors, noise, electromagnetic waves (EMWs), tobacco and other noxious substances, heavy metals, and microplastics, is linked to damage to the nervous and immune systems and affects reproductive function and development. Exposure to environmental hazards is responsible for several acute and chronic diseases that have replaced infectious diseases as the principal cause of illnesses and death during childhood. Children are disproportionately exposed to environmental toxicities. Children drink more water, eat more food, and breathe more frequently than adults. As a result, children have a substantially heavier exposure to toxins present in water, food, or air than adults. In addition, their hand-to-mouth behaviors and the fact that they live and play close to the ground make them more vulnerable than adults. Children undergo rapid growth and development processes that are easily disrupted. These systems are very delicate and cannot adequately repair thetional development in children’s environmental health was the Declaration of the Environment Leaders of the Eight on Children’s Environmental Health by the Group of Eight. In 2002, the World Health Organization launched an initiative to improve children’s environmental protection effort. Here, we review major environmental pollutants and related hazards among children and adolescents.