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20 pages, 3693 KB  
Article
Cannabidiol-Loaded Mucoadhesive PLGA Nanosphere-Chitosan Hydrogel Patch for Oral Therapeutic Applications
by Badmaarag-Altai Chuluunbaatar, Jisu Park, Junyoung Song, Subin Mun, Ji-Hyun Kang and Kyung Hyun Min
Int. J. Mol. Sci. 2026, 27(2), 1127; https://doi.org/10.3390/ijms27021127 - 22 Jan 2026
Viewed by 43
Abstract
Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood. To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN [...] Read more.
Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood. To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN hydrogel) was characterized by FT-IR, SEM, particle size, rheological, swelling, and diffusion analyses, followed by biological evaluations, including wound-healing and RT-qPCR-based anti-inflammatory assays. The improved CPN hydrogel had a homogeneous shape, better viscoelastic behavior, and sustained drug release. Over 90% of CBD was released within 96 h, and Franz cell experiments showed improved permeability (124.1 μg/cm2 after 72 h). The gellan gum-based mucosal substrate significantly increased adhesion (1137.33 ± 142.25 s) compared to the control groups. Antioxidant studies indicated 73.65% DPPH radical scavenging, whereas antibacterial tests showed more than 99% suppression of Staphylococcus aureus. Furthermore, in vitro studies validated its wound healing and the downregulation of the inflammatory cytokines IL-6 and TNF-α. The results indicate that the CPN-loaded chitosan hydrogel has extended mucosal retention, strong antibacterial activity, and steady release of CBD. This underscores its significant potential as a targeted treatment for inflammatory oral diseases such as gingivitis and periodontitis. Full article
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20 pages, 908 KB  
Article
Wearable ECG-PPG Deep Learning Model for Cardiac Index-Based Noninvasive Cardiac Output Estimation in Cardiac Surgery Patients
by Minwoo Kim, Min Dong Sung, Jimyeoung Jung, Sung Pil Cho, Junghwan Park, Sarah Soh, Hyun Chel Joo and Kyung Soo Chung
Sensors 2026, 26(2), 735; https://doi.org/10.3390/s26020735 - 22 Jan 2026
Viewed by 43
Abstract
Accurate cardiac output (CO) measurement is vital for hemodynamic management; however, it usually requires invasive monitoring, which limits its continuous and out-of-hospital use. Wearable sensors integrated with deep learning offer a noninvasive alternative. This study developed and validated a lightweight deep learning model [...] Read more.
Accurate cardiac output (CO) measurement is vital for hemodynamic management; however, it usually requires invasive monitoring, which limits its continuous and out-of-hospital use. Wearable sensors integrated with deep learning offer a noninvasive alternative. This study developed and validated a lightweight deep learning model using wearable electrocardiography (ECG) and photoplethysmography (PPG) signals to predict CO and examined whether cardiac index-based normalization (Cardiac Index (CI) = CO/body surface area) improves performance. Twenty-seven patients who underwent cardiac surgery and had pulmonary artery catheters were prospectively enrolled. Single-lead ECG (HiCardi+ chest patch) and finger PPG (WristOx2 3150) were recorded simultaneously and processed through an ECG–PPG fusion network with cross-modal interaction. Three models were trained as follows: (1) CI prediction, (2) direct CO prediction, and (3) indirect CO prediction. The total number of CO = predicted CI × body surface area. Reference values were derived from thermodilution. The CI model achieved the best performance, and the indirect CO model showed significant reductions in error/agreement metrics (MAE/RMSE/bias; p < 0.0001), while correlation-based metrics are reported descriptively without implying statistical significance. The Pearson correlation coefficient (PCC) and percentage error (PE) for the indirect CO estimates (PCC = 0.904; PE = 23.75%). The indirect CO estimates met the predefined PE < 30% agreement benchmark for method-comparison; this is not a universal clinical standard. These results demonstrate that wearable ECG–PPG fusion deep learning can achieve accurate, noninvasive CO estimation and that CI-based normalization enhances model agreement with pulmonary artery catheter measurements, supporting continuous catheter-free hemodynamic monitoring. Full article
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12 pages, 611 KB  
Article
Prognostic Performance of the Korean Triage and Acuity Scale Combined with the National Early Warning Score for Predicting Mortality and ICU Admission at Emergency Department Triage: A Retrospective Observational Study
by Jungtaek Park, Sang Hoon Oh, Ae Kyung Gong, Jee Yong Lim, Sun Hee Woo, Won Jung Jeong, Ji Hoon Kim, In Soo Kim and Soo Hyun Kim
Diagnostics 2026, 16(2), 345; https://doi.org/10.3390/diagnostics16020345 - 21 Jan 2026
Viewed by 105
Abstract
Objectives: This study aimed to compare the predictive performance of the Korean Triage and Acuity Scale (KTAS) and the National Early Warning Score (NEWS) for serious adverse events (SAEs), including mortality and intensive care unit (ICU) admission, during emergency department (ED) stay. [...] Read more.
Objectives: This study aimed to compare the predictive performance of the Korean Triage and Acuity Scale (KTAS) and the National Early Warning Score (NEWS) for serious adverse events (SAEs), including mortality and intensive care unit (ICU) admission, during emergency department (ED) stay. We also evaluated whether combining the two systems improves prediction accuracy. Methods: This retrospective study included adult patients (≥19 years) who presented to a university-affiliated ED between October and December 2024. KTAS and NEWS were assessed simultaneously at triage. NEWS2 was calculated retrospectively based on routinely documented vital signs and medical history without performing routine arterial blood gas analysis. The primary outcome was the occurrence of SAE during the ED stay. Predictive performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and logistic regression models were used to identify independent associations. Results: A total of 4216 patients were analyzed, of whom 255 (6.0%) experienced SAEs. All three scores—KTAS, NEWS and NEWS2—were independently associated with the occurrence of SAEs. The AUCs for KTAS, NEWS and NEWS2 were 0.75 (95% CI, 0.74–0.76), 0.73 (95% CI, 0.71–0.74) and 0.73 (95% CI, 0.71–0.74), respectively. Combining KTAS with NEWS or NEWS2 significantly improved predictive accuracy (AUC 0.81, 95% CI 0.79–0.82; p < 0.001). Conclusions: Both KTAS and NEWS/NEWS2 reliably predicted in-ED adverse outcomes, and their combination further enhanced prognostic performance. Integrating physiology-based early warning scores with structured triage systems may help identify high-risk ED patients earlier and optimize resource allocation. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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13 pages, 302 KB  
Article
Gastrointestinal Diagnostic Coding After Spinal Cord Injury: Health Behavior Correlates and Implications for Neurogenic Bowel Management in a Nationwide Claim-Based Cohort
by Young-Hwan Lim, Jae-Hyeong Yoo, Jeong-Won Park, Jong-Moon Hwang, Dongwoo Kang, Jungkuk Lee, Hyun Wook Han, Kyung-Tae Kim, Myung-Gwan Kim and Tae-Du Jung
J. Clin. Med. 2026, 15(2), 760; https://doi.org/10.3390/jcm15020760 - 16 Jan 2026
Viewed by 196
Abstract
Background: Neurogenic bowel dysfunction (NBD) is a major chronic sequela of spinal cord injury (SCI) with substantial implications for rehabilitation and long-term management. However, population-level evidence describing how gastrointestinal (GI) diagnostic codes are used following SCI, particularly within administrative healthcare systems, remains [...] Read more.
Background: Neurogenic bowel dysfunction (NBD) is a major chronic sequela of spinal cord injury (SCI) with substantial implications for rehabilitation and long-term management. However, population-level evidence describing how gastrointestinal (GI) diagnostic codes are used following SCI, particularly within administrative healthcare systems, remains limited. Methods: We conducted a nationwide retrospective cohort study using administrative claims data from the Korean National Health Insurance Service (NHIS). A total of 584,266 adults with trauma-related SCI encounters between 2009 and 2019 were identified. GI diagnostic codes—paralytic ileus (K56), irritable bowel syndrome (K58), and functional bowel disorders (K59)—were evaluated as administrative proxies for bowel dysfunction. Demographic characteristics, disability status, regional factors, and health behaviors were analyzed using multivariable logistic regression. Results: GI diagnostic codes were frequently recorded after SCI, most commonly irritable bowel syndrome (approximately 30%) and functional bowel disorders (approximately 37%), whereas paralytic ileus was uncommon. Greater disability severity, female sex, older age, and rural residence were consistently associated with higher odds of GI diagnostic coding. Physical activity showed robust inverse associations across all models. Inverse associations observed with smoking and alcohol consumption were interpreted as reflecting residual confounding or health-related selection, rather than biological protective effects. Conclusions: Patterns of GI diagnostic coding after SCI likely reflect the clinical burden and management needs of neurogenic bowel dysfunction within healthcare systems, rather than the development of new gastrointestinal diseases. These findings underscore the importance of individualized bowel management, incorporation of structured physical activity into rehabilitation programs, and equitable access to SCI rehabilitation services, particularly for individuals with greater disability or those living in rural areas. Full article
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18 pages, 898 KB  
Article
Dynamic K-Line Status and Surgical Outcomes in Multilevel Cervical OPLL: A Multicenter Comparative Study
by Jun Jae Shin, Sun Joon Yoo, Se Jun Park, Dong Kyu Kim, Hyun Jun Jang, Bong Ju Moon, Kyung Hyun Kim, Jeong Yoon Park, Sung Uk Kuh, Dong Kyu Chin, Keun Su Kim, Chang Kyu Lee, Keung Nyun Kim, Tae Woo Kim and Yoon Ha
J. Clin. Med. 2026, 15(2), 520; https://doi.org/10.3390/jcm15020520 - 8 Jan 2026
Viewed by 230
Abstract
Background/Objectives: To evaluate the clinical and radiological outcomes of surgical interventions stratified by dynamic K-line status and to identify predictors of neurological recovery in multilevel cervical ossification of the posterior longitudinal ligament (OPLL). Methods: This study analyzed 535 patients with multilevel [...] Read more.
Background/Objectives: To evaluate the clinical and radiological outcomes of surgical interventions stratified by dynamic K-line status and to identify predictors of neurological recovery in multilevel cervical ossification of the posterior longitudinal ligament (OPLL). Methods: This study analyzed 535 patients with multilevel cervical OPLL who underwent anterior cervical discectomy and fusion (ACDF), laminoplasty (LP), or laminectomy with fusion (LF), with a minimum 24 months of follow-up. Patients were classified based on dynamic K-line status—neutral (NK-line) and flexion (FK-line)—into three groups: Group 1 (NK-line [+]/FK-line [+]), Group 2 (NK-line [+]/FK-line [−]), and Group 3 (NK-line [−]/FK-line [−]). Radiographic parameters, JOA scores, and VAS were compared, and multivariate regression identified predictors of recovery. A multinomial inverse probability of treatment weighting (IPTW) analysis was conducted to reduce treatment selection bias. Results: Progressive dynamic K-line negativity was associated with greater cervical kyphosis, a higher canal-occupying ratio, reduced FK-line distance, and poorer neurological recovery. After IPTW analysis, ACDF showed higher adjusted recovery across subgroups. In Group 1, younger age and fewer operative levels predicted better recovery. In Groups 2 and 3, LF demonstrated significantly greater neurological recovery than LP. A larger preoperative FK-line distance and a greater postoperative FK-line distance increase were independent predictors of favorable outcomes. Conclusions: Dynamic K-line stratification has good prognostic value in multilevel cervical OPLL. ACDF remains the most effective procedure across dynamic K-line status groups, and LF is preferred over LP in patients with latent or fixed FK-line (−). Incorporating dynamic K-line metrics into surgical planning could improve procedure selection and enhance neurological recovery. Full article
(This article belongs to the Section Clinical Neurology)
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10 pages, 231 KB  
Article
Effectiveness of the Cell-Based Quadrivalent Influenza Vaccine (SKYCellflu® QIV) in Children and Adolescents: A Multicenter Test-Negative Case–Control Study in Korea
by Yoonsun Yoon, Hye Su Jeong, Kyeongmin Oh, Young June Choe, Hyun Mi Kang, Ji Young Park, Hye Young Kim and Yun-Kyung Kim
Vaccines 2026, 14(1), 70; https://doi.org/10.3390/vaccines14010070 - 8 Jan 2026
Viewed by 442
Abstract
Background: Children and adolescents are pivotal in the transmission of influenza, and vaccination remains the most effective preventive measure. Cell-based influenza vaccines offer advantages over traditional egg-based vaccines by reducing egg-adapted mutations and improving antigenic match. SKYCellflu® quadrivalent influenza vaccine (QIV; [...] Read more.
Background: Children and adolescents are pivotal in the transmission of influenza, and vaccination remains the most effective preventive measure. Cell-based influenza vaccines offer advantages over traditional egg-based vaccines by reducing egg-adapted mutations and improving antigenic match. SKYCellflu® quadrivalent influenza vaccine (QIV; SK bioscience, Korea), the first cell-based QIV licensed in Korea for individuals aged 6 months and older, offers potential advantages; however, its real-world effectiveness in the Korean pediatric population remains limited. Objective: This study aimed to estimate the real-world effectiveness of SKYCellflu® QIV, a cell-based QIV, in preventing laboratory-confirmed influenza among children and adolescents aged 6 months to 18 years in Korea during the 2024–2025 influenza season. Methods: A multicenter, prospective, test-negative case–control study was conducted from October 2024 to May 2025 across 25 institutions in Korea. Children and adolescents aged 6 months to 18 years who presented within 7 days of the onset of influenza-like illness (fever ≥ 38 °C and at least one respiratory symptom) were enrolled. Influenza infection was confirmed using rapid antigen tests or polymerase chain reaction; participants who tested positive were classified as cases, and those who tested negative for influenza served as controls. All participants were further categorized as vaccinated or unvaccinated based on receipt of SKYCellflu® QIV. Those who received other influenza vaccines during the season were excluded. Vaccination status was verified through medical records and the national immunization registry. Results: A total of 1476 participants were included (751 cases, 725 controls). The overall adjusted vaccine effectiveness (aVE) was 45.57% (95% CI, 29.38–58.04). The vaccine demonstrated the highest effectiveness in children aged 6–35 months (aVE: 88.55%; 95% CI, 60.39–96.11). Effectiveness was higher against influenza B (aVE: 61.28%; 95% CI, 35.76–76.30) than influenza A (aVE: 41.63%; 95% CI, 22.55–56.01). The vaccine’s effectiveness in adolescents was not statistically significant due to the small sample size in this age group. Conclusions: This multicenter test-negative study provides the first real-world effectiveness of SKYCellflu® QIV in a Korean pediatric population. The results suggest substantial protection in younger children, particularly against influenza B, and support the continued use of annual influenza vaccination in this population. Further studies with larger adolescent cohorts are needed to confirm these findings in older age groups. Full article
(This article belongs to the Section Influenza Virus Vaccines)
11 pages, 632 KB  
Article
Comparative Evaluation of a Domestic Automatic Milking System and a Commercial System: Effects of Parity on Milk Performance and System Capacity
by Dong-Hyun Lim, Jun Sik Eom, Seong Min Park, Jihoo Park, Dong Hyeon Kim, Taejeong Choi, Young Kyung Choi, Jongseon Kim and Younghoon Kim
Animals 2025, 15(24), 3649; https://doi.org/10.3390/ani15243649 - 18 Dec 2025
Viewed by 364
Abstract
This study evaluated milking characteristics and milk productivity of a domestically developed automatic milking system (AMS-K) and compared its performance with a commercially imported AMS (AMS-C), under identical farm management conditions. Milking performance of AMS-K was monitored over a three-month operating period, and [...] Read more.
This study evaluated milking characteristics and milk productivity of a domestically developed automatic milking system (AMS-K) and compared its performance with a commercially imported AMS (AMS-C), under identical farm management conditions. Milking performance of AMS-K was monitored over a three-month operating period, and a comparative analysis was subsequently conducted using a total of 50 Holstein cows, with 25 cows allocated to each system based on similar parity, days in milk, and milk yield. During the three-month operation of AMS-K, milk yield per milking significantly increased in from 13.81 kg in the 1st month to 15.99 kg in the 3rd month, and daily milk yield increased by 4.01–7.52% compared with the initial operating period. Milking frequency decreased from 2.53 to 2.27 times per day, but remained higher than conventional twice-daily milking. Average milking interval increased from 9.37 to 10.34 h, which was within the optimal range (9–10 h) for AMS operation. Milking stall occupancy and teat-cup attachment times gradually increased, whereas milking time showed no significant change. Somatic cell count initially increased but stabilized after three months. Milking efficiency ranged from 2.44 to 2.56 kg/min. In the system comparison, AMS-C showed shorter milking stall occupancy time, higher milking frequency, and higher milking efficiency than AMS-K, whereas AMS-K showed higher milk yield per milking, associated with longer milking interval. Across both systems, multiparous cows exhibited longer milking intervals and higher milk yields than primiparous cows in both AMSs. Theoretical milking capacity per AMS was 54.45 cows (primiparous) and 37.77 cows (multiparous) for AMS-K, sufficient for an average Korean dairy farm. Our results demonstrate that AMS-K achieved stable milking performance, milk quality, and operational efficiency comparable to the imported AMS. AMS-K shows great potential for practical applications and commercialization in Korean dairy farms. Full article
(This article belongs to the Section Animal System and Management)
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14 pages, 2397 KB  
Article
Development of Drug-in-Adhesive Patch Formulation for Transdermal Delivery of Pelubiprofen
by Min-Sung Lee, Chang-Soo Han, Kyung Hyun Min, Dong-Wook Kim, Chun-Woong Park, Kwon-Yeon Weon and Ji-Hyun Kang
Pharmaceutics 2025, 17(12), 1580; https://doi.org/10.3390/pharmaceutics17121580 - 8 Dec 2025
Viewed by 755
Abstract
Background: Pelubiprofen (PBF) is a cyclooxygenase-2 inhibitor currently marketed as an oral tablet in South Korea. Oral dosing is limited by gastrointestinal variability, first-pass metabolism, which can reduce therapeutic efficiency and increase adverse effects. Transdermal drug-in-adhesive patches provide a noninvasive alternative that bypasses [...] Read more.
Background: Pelubiprofen (PBF) is a cyclooxygenase-2 inhibitor currently marketed as an oral tablet in South Korea. Oral dosing is limited by gastrointestinal variability, first-pass metabolism, which can reduce therapeutic efficiency and increase adverse effects. Transdermal drug-in-adhesive patches provide a noninvasive alternative that bypasses these limitations and enables controlled delivery through the skin. Methods: The solubility of PBF in ethanol was evaluated, and its adhesive compatibility was tested using acrylic- and silicone-based systems. Different drug-loaded formulations were prepared, and their miscibility was assessed. Several permeation enhancers were screened. The physicochemical properties were analyzed. In vitro permeation was studied using rat skin in Franz cells. Accelerated stability was tested at 40 °C and 75% relative humidity for three months. Results: PBF reached near saturation at 120 mg/mL in ethanol. Among the adhesives, Duro-Tak® 8076 showed the best compatibility with ethanol and PBF. Drug loading above 15% led to crystallization; 15% was selected as the optimal loading. The addition of 2% oleic acid (OA) significantly increased the permeation flux to 11.31 ± 1.50 μg/cm2/h, showing a 3.6-fold enhancement over the control and enhanced deposition in the stratum corneum and dermis. Based on the physicochemical evaluation, PBF was present in an amorphous state within the adhesive matrix. Stability studies revealed no recrystallization, with the drug content maintained at 97–100%. Permeation remained unchanged during storage. Conclusions: The PD-OA2 patch achieved stable drug incorporation, enhanced skin permeation, and robust stability. These findings support the potential of PBF as a clinically relevant alternative to oral PBF formulations for treating localized inflammation and pain. Full article
(This article belongs to the Special Issue Dermal and Transdermal Drug Delivery Systems)
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14 pages, 5930 KB  
Article
The Levonorgestrel Intrauterine System Attenuates the Expression of Angiopoietin-1, Angiopoietin-2, and Vascular Endothelial Growth Factor in Adenomyosis
by SiHyun Cho, Hyun Kyung Kim, Young Sik Choi and Joo Hyun Park
J. Clin. Med. 2025, 14(24), 8629; https://doi.org/10.3390/jcm14248629 - 5 Dec 2025
Viewed by 427
Abstract
Background/Objectives: Adenomyosis is characterized by aberrant endometrial invasion and heavy menstrual bleeding, with angiogenesis being implicated as a key mechanism of this condition. We compared vascular endothelial growth factor (VEGF), angiopoietin-1 (ANGPT-1), and angiopoietin-2 (ANGPT-2) expression in eutopic and ectopic endometria from [...] Read more.
Background/Objectives: Adenomyosis is characterized by aberrant endometrial invasion and heavy menstrual bleeding, with angiogenesis being implicated as a key mechanism of this condition. We compared vascular endothelial growth factor (VEGF), angiopoietin-1 (ANGPT-1), and angiopoietin-2 (ANGPT-2) expression in eutopic and ectopic endometria from patients with adenomyosis and evaluated whether the levonorgestrel intrauterine system (LNG-IUS) modulates these angiogenic markers. Methods: In a case–control analysis, specimens from patients with adenomyosis without an LNG-IUS (n = 20), those with adenomyosis with prior LNG-IUS insertion (n = 18), and controls (n = 12) were analyzed. Immunohistochemistry with H-scores was used to assess protein expression in eutopic and ectopic tissues. ANGPT1, ANGPT2, and VEGFA mRNA in eutopic endometrial tissue were quantified by qRT-PCR. Results: In untreated adenomyosis patients, ectopic endometria showed higher protein expression than eutopic tissue for ANGPT-1, ANGPT-2, and VEGF (all p ≤ 0.05). The LNG-IUS was associated with significantly lower expression of all three markers in both eutopic and ectopic tissue (all p < 0.01), with eutopic levels approaching those of controls. qRT-PCR findings corroborated the decrease in ANGPT1, ANGPT2, and VEGFA transcript levels after LNG-IUS insertion (all p < 0.05). Conclusions: Adenomyosis is characterized by upregulated angiogenic signaling in both eutopic and ectopic endometria. The LNG-IUS attenuates ANGPT-1, ANGPT-2, and VEGF expression at both the protein and transcript levels, suggesting that modulation of angiogenic pathways may contribute to its therapeutic benefit in abnormal uterine bleeding associated with adenomyosis. Full article
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15 pages, 3408 KB  
Article
Therapeutic Effects of Cephalotaxus harringtonia Leaf Extract on Hepatocellular Carcinoma via Regulation of the Intrinsic Apoptosis Pathway and Cell Cycle
by Dae-Han Park, Sonny C. Ramos, Hyun Bo Sim, Ju-Bin Lee, Ho-Yeol Jang, Beom-Gyun Jeong, Kyung-Wuk Park, Kyung-Yun Kang and Jong-Jin Kim
Curr. Issues Mol. Biol. 2025, 47(12), 994; https://doi.org/10.3390/cimb47120994 - 27 Nov 2025
Cited by 1 | Viewed by 460
Abstract
Apoptosis induction in tumor cells is a fundamental therapeutic approach in cancer treatment, with growing interest in plant-derived compounds that offer potent efficacy and reduced toxicity. Cephalotaxus harringtonia, traditionally used in East Asian medicine, contains several bioactive constituents, including homoharringtonine (HHT) and [...] Read more.
Apoptosis induction in tumor cells is a fundamental therapeutic approach in cancer treatment, with growing interest in plant-derived compounds that offer potent efficacy and reduced toxicity. Cephalotaxus harringtonia, traditionally used in East Asian medicine, contains several bioactive constituents, including homoharringtonine (HHT) and quercetin 3-β-D-glucoside (Q3G), which are known for their anticancer properties. This study investigated the anticancer effects of C. harringtonia leaf extract (CHLE) and its two major compounds, quercetin 3-β-D-glucoside (Q3G) and HHT, against human liver cancer cell lines (HepG2). CHLE exhibited selective cytotoxicity and apoptosis specifically in HepG2 cells while showing minimal toxicity toward normal kidney cells (HK-2). Mechanistic analyses revealed that CHLE induced apoptosis through a mitochondria-mediated intrinsic pathway, characterized by increased reactive oxygen species production, mitochondrial membrane depolarization, and BAX upregulation. These findings demonstrate that C. harringtonia leaf extract possesses potent, selective anticancer activity and may serve as a promising natural candidate for the prevention and therapeutic management of liver cancer. Full article
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17 pages, 2090 KB  
Article
Fermented Porcine Placenta and Its Dipeptides Modulate Cellular Senescence in Human Keratinocytes
by Yea Jung Choi, Minseo Kang, Mu Hyun Jin, Jongbae Kim, Won Kyung Lee, Seok-Seon Roh, Ki Sung Kang, Gwi Seo Hwang, Sangki Park and Sullim Lee
Curr. Issues Mol. Biol. 2025, 47(11), 941; https://doi.org/10.3390/cimb47110941 - 12 Nov 2025
Viewed by 572
Abstract
Skin aging is primarily driven by oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. This study investigated the anti-senescence effects of fermented porcine placenta (FPP) and its dipeptides, leucine–glycine (LG) and proline–hydroxyproline (PH), in human epidermal keratinocytes (HEKs), using nicotinamide mononucleotide (NMN) as [...] Read more.
Skin aging is primarily driven by oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. This study investigated the anti-senescence effects of fermented porcine placenta (FPP) and its dipeptides, leucine–glycine (LG) and proline–hydroxyproline (PH), in human epidermal keratinocytes (HEKs), using nicotinamide mononucleotide (NMN) as a reference for nicotinamide adenine dinucleotide (NAD+)-related pathways. FPP suppressed senescence-associated β-galactosidase (SA-β-gal) activity and Cyclin-dependent kinase inhibitor 2A (p16) expression while enhancing adenosine triphosphate (ATP) production and sirtuin 1 (SIRT1)–peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling. LG and PH exhibited distinct actions: LG improved redox balance by increasing the NAD+/NADH ratio and NAD(P)H quinone oxidoreductase 1 (NQO1) activity, whereas PH modulated cell cycle regulators and upregulated sirtuin 3 (SIRT3) expression. Although both peptides contributed to FPP’s effects, their combination did not fully replicate its overall activity, suggesting synergistic roles of multiple bioactive constituents. These findings highlight FPP as a multifactorial modulator of keratinocyte senescence, acting via mitochondrial and redox-related mechanisms. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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14 pages, 2377 KB  
Article
Multifunctional Effects of N-Carbamylglutamate on Skin-Related Cells: Antioxidant, Anti-Aging, Anti-Melanogenic and Anti-Inflammatory Activities
by Sa Rang Choi, Nu Ri Song, Seo Yeon Shin, Ki Min Kim, Jae Hee Byun, Seon Ju Kim, Dai Hyun Jung, Su Jung Kim and Kyung Mok Park
Cosmetics 2025, 12(6), 250; https://doi.org/10.3390/cosmetics12060250 - 7 Nov 2025
Viewed by 1041
Abstract
Skin aging is accelerated by both environmental factors—including ultraviolet (UV) radiation and pollution—and intrinsic processes such as chronic inflammaging. N-carbamylglutamate (NCG), an arginine precursor known for its benefits for gut and reproductive health, has not been extensively studied in dermatological applications. To explore [...] Read more.
Skin aging is accelerated by both environmental factors—including ultraviolet (UV) radiation and pollution—and intrinsic processes such as chronic inflammaging. N-carbamylglutamate (NCG), an arginine precursor known for its benefits for gut and reproductive health, has not been extensively studied in dermatological applications. To explore its suitability as a multifunctional cosmetic ingredient, this study examines the protective role of NCG in counteracting UV-stimulated oxidative and inflammatory responses in skin cells. NCG significantly reduced UV-induced reactive oxygen species (ROS), indicating strong antioxidant properties. It also inhibited matrix metalloproteinase (MMP) activity, preserving collagen integrity and reducing wrinkle formation. In addition, NCG suppressed nitric oxide (NO) production and downregulated key inflammatory mediators—including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)—highlighting its anti-inflammatory potential. Furthermore, NCG reduced melanin production and the expression of melanogenesis-related factors such as the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1), and TRP-2. These findings support the role of NCG as a promising multifunctional cosmetic ingredient with antioxidant, anti-inflammatory, anti-wrinkle, and skin-brightening properties. Full article
(This article belongs to the Special Issue Skin Anti-Aging Strategies)
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17 pages, 2409 KB  
Article
Immunogenicity and Contraceptive Potential of a Classical Swine Fever Viral Vector Live Vaccine Strain Containing Pig Gonadotropin-Releasing Hormone
by Dong-Jun An, Ji-Hee Shin, SeEun Choe, Young-Hyeon Lee, Min-Kyung Jang, Byung-Hyun An, Gyu-Nam Park, Yun-Sang Cho and Kyung-Soo Chang
Vaccines 2025, 13(10), 1048; https://doi.org/10.3390/vaccines13101048 - 12 Oct 2025
Viewed by 1314
Abstract
Background: Classical swine fever virus (CSFV) is a highly contagious and fatal disease in pigs and wild boars. While hunting and bait vaccination are effective for CSFV eradication, additional strategies are needed to control wild boar populations. This study aimed to develop an [...] Read more.
Background: Classical swine fever virus (CSFV) is a highly contagious and fatal disease in pigs and wild boars. While hunting and bait vaccination are effective for CSFV eradication, additional strategies are needed to control wild boar populations. This study aimed to develop an oral vaccine, Flc-LOM-GnRHx3, by inserting gonadotropin-releasing hormone (GnRH) epitopes into the Flc-LOM clone. Methods: The Flc-LOM-GnRHx3 strain was rescued from CPK cells and propagated to high titers in MDBK cells. Male boars (20 weeks old) received three doses (105.0 TCID50/ml/dose) of Flc-LOM-GnRHx3 either orally or intramuscularly at 2-week intervals. Anti-CSFV E2 antibodies were detected via immunofluorescence and Western blotting. Results: Both vaccination routes induced anti-GnRH antibodies and reduced testosterone levels. Testis size and weight were slightly lower than controls, with seminiferous tubule and spermatid deformities observed in 52.5% of intramuscularly vaccinated pigs and 20.8% of orally vaccinated pigs. Conclusions: Flc-LOM-GnRHx3 demonstrates potential as a dual-function oral vaccine that can eradicate CSFV and impair reproductive capacity in wild boars, offering a novel approach for integrated disease control and population management. Full article
(This article belongs to the Special Issue Classical Swine Fever Virus Vaccines)
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19 pages, 4737 KB  
Article
Myeloid-Specific STAT3 Deletion Aggravates Liver Fibrosis in Mice Fed a Methionine- and Choline-Deficient Diet via Upregulation of Hepatocyte-Derived Lipocalin-2
by Kyung Eun Kim, Hyun Joo Shin, Hyeong Seok An, Eun Ae Jeong, Yundong Sun, Jiwon Oh, Jiwoo Park, Jaewoong Lee, Seung-Soon Im and Gu Seob Roh
Cells 2025, 14(19), 1522; https://doi.org/10.3390/cells14191522 - 29 Sep 2025
Viewed by 1207
Abstract
The signal transducer and activator of transcription 3 (STAT3) in myeloid cells suppresses proinflammatory cytokine production and reduces collagen deposition. However, its role in methionine- and choline-deficient (MCD) diet-fed mice remains unclear. This study investigates the effects of myeloid-specific STAT3 deficiency on hepatic [...] Read more.
The signal transducer and activator of transcription 3 (STAT3) in myeloid cells suppresses proinflammatory cytokine production and reduces collagen deposition. However, its role in methionine- and choline-deficient (MCD) diet-fed mice remains unclear. This study investigates the effects of myeloid-specific STAT3 deficiency on hepatic inflammation and fibrosis in MCD diet-fed mice. Myeloid-specific STAT3 knockout (mSTAT3KO) mice were fed the MCD diet for four weeks to induce metabolic dysfunction-associated steatohepatitis (MASH). MCD diet-fed mice displayed MASH-like pathological phenotypes, including hepatic steatosis, inflammation, and fibrosis. Compared with MCD diet-fed WT mice, mSTAT3KO mice fed the MCD diet exhibited reduced hepatic lipid accumulation but increased fibrosis. Notably, mSTAT3KO mice showed elevated hepatic STAT3 and lipocalin-2 (LCN2) protein levels in hepatocytes. Some proinflammatory cytokines were increased by the MCD diet in mSTAT3KO mice, which also exhibited increased hepatocyte apoptosis. Conversely, MCD diet-induced CD36, perilipin-2, acyl-CoA thioesterase 2, and 4-hydroxynonenal proteins were reduced by mSTAT3KO. Myeloid-specific STAT3 deficiency may induce a compensatory STAT3/LCN2 axis in hepatocytes, thereby exacerbating MASH progression. Full article
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18 pages, 3381 KB  
Article
EPDR1 Links Fibroblast Dysfunction to Disease Severity in Idiopathic Pulmonary Fibrosis
by Jong-Uk Lee, Seung-Lee Park, Min Kyung Kim, Eunjeong Seo, Hun-Gyu Hwang, Jung Hyun Kim, Hun Soo Chang and Choon-Sik Park
Cells 2025, 14(19), 1515; https://doi.org/10.3390/cells14191515 - 28 Sep 2025
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Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by aberrant fibroblast activation, lysosomal dysfunction, and cellular senescence. Transcriptomic analyses have identified ependymin-related 1 (EPDR1) as a fibroblast-enriched gene in IPF, but its biological function remains unclear. EPDR1 expression was assessed in [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by aberrant fibroblast activation, lysosomal dysfunction, and cellular senescence. Transcriptomic analyses have identified ependymin-related 1 (EPDR1) as a fibroblast-enriched gene in IPF, but its biological function remains unclear. EPDR1 expression was assessed in lung fibroblasts, lung tissues, bronchoalveolar lavage fluid (BALF), and serum from IPF patients and controls using qPCR, Western blotting, ELISA, and immunohistochemistry. Lysosomal function, autophagic flux, and senescence markers were analyzed in primary fibroblasts following siRNA-mediated EPDR1 knockdown. EPDR1 was significantly upregulated in IPF-derived fibroblasts and localized to fibrotic regions enriched with α-SMA+, COL1A1+, and FN1+ myofibroblasts of IPF-derived lung tissues. EPDR1 levels were markedly elevated in the BALF and serum of IPF patients and correlated with increased mortality. IPF fibroblasts exhibited reduced lysosomal acidification and impaired autophagic flux, indicated by p62 and LC3B accumulation. EPDR1 knockdown restored lysosomal function; enhanced autophagic degradation; and reduced senescence markers, including p21, p16, and SA-β-gal activity. EPDR1 drives lysosomal dysfunction and fibroblast senescence in IPF. Its elevated expression in lung tissue and biological fluids, together with its association with prognosis, highlights EPDR1 as a potential biomarker and therapeutic target in IPF. Full article
(This article belongs to the Special Issue Advances in Pulmonary Fibrosis)
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