Search Results (289)

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article

Background: High-density lipoprotein cholesterol (HDL-C) is known for its cardiovascular and neuroprotective effects, but its association with cognitive function remains unclear, particularly in relation to genetic factors such as apolipoprotein E ε4 (APOE4). We aimed to investigate the association between serum HDL-C levels and cognition and to examine the moderating effect of APOE4 on this relationship. Methods: This cross-sectional study included 196 dementia-free older adults (aged 65–90) recruited from a memory clinic and the community. Cognitive function was assessed across multiple domains using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery. Serum HDL-C levels were measured, and APOE4 genotyping was performed. Multiple linear regression analyses were conducted, adjusting for age, sex, APOE4 status, education, diagnosis, vascular risk, nutritional status, physical activity, and blood biomarkers. Results: Higher HDL-C levels were significantly associated with better episodic memory (B = 0.109, 95% confidence interval [CI]: 0.029–0.189, p = 0.008) and global cognition (B = 0.130, 95% CI: 0.001–0.261, p = 0.049). These associations were significantly moderated by APOE4 status. In APOE4-positive individuals, HDL-C was strongly associated with both episodic memory (B = 0.357, 95% CI: 0.138–0.575, p = 0.003) and global cognition (B = 0.519, 95% CI: 0.220–0.818, p = 0.002), but no such associations were observed in APOE4-negative participants. Conclusions: This study indicates a significant association between serum HDL-C levels and cognitive function, particularly in episodic memory and global cognition, with APOE4 status potentially moderating this relationship. While these findings may suggest a protective role of HDL-C in individuals at increased genetic risk due to APOE4, they should be interpreted with caution given the cross-sectional design. Future longitudinal and mechanistic studies are warranted to clarify causality and potential clinical implications. Full article

This study examined the relationships between mid-arm circumference (MAC) and calf circumference (CC) with cognitive performance, considering the moderating effect of apolipoprotein E ε4 allele (APOE4) status. Data from 196 older adults (65–90 years) in the General Lifestyle and AD (GLAD) study were analyzed. Cognitive performance was assessed using the CERAD neuropsychological battery, with episodic memory score (EMS) and non-memory score (NMS) as primary outcomes. Multiple linear regression analyses examined associations between MAC, CC, and waist circumference (WC) with cognition, adjusting for key covariates. Interaction effects with APOE4 status were also explored. Higher MAC (or MAC/WC) significantly correlated with better EMS, while higher CC (or CC/WC) correlated with better NMS, even after Bonferroni correction (P_B < 0.0125). These associations were stronger in APOE4-negative individuals but not significant in APOE4-positive participants. WC was not associated with cognitive measures. The results suggest that Upper- and lower-limb musculature may play distinct roles in cognitive function, with MAC linked to episodic memory and CC to non-memory cognition, particularly in APOE4-negative individuals. These findings highlight the potential of muscle health maintenance as a strategy for preserving cognitive function in aging populations. Full article

This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from Styphnolobium japonicum L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using Lactobacillus plantarum to model intestinal biotransformation, we compared glycoside-rich (Rex) and aglycone-rich (Rex-AG) extracts in ovariectomized rats. Both treatments significantly reduced weight gain and alleviated vaginal dryness, with Rex demonstrating superior thermoregulatory stabilization. Histological and molecular analyses revealed preserved trabecular bone integrity through the downregulation of RANKL and upregulation of TGF-β. Both extracts exhibited potent anti-inflammatory effects in adipose tissue, suppressing IL-6 and TNF-α, while regulating adipogenesis markers (FABP4, KLF, leptin, PPARγ) more effectively than 17β-estradiol. Serum genistein concentrations confirmed its efficient biotransformation and systemic bioavailability. Importantly, the treatments showed favorable safety profiles with no adverse effects on organ weight. These findings establish S. japonicum L. fruit-derived phytoestrogens as promising candidates for the comprehensive management of postmenopausal symptoms, offering an efficacious and safer alternative to conventional hormone therapy. Full article

Background and Objectives: Peritoneal dialysis (PD) requires well-functioning medical devices (MDs). PD complications can result in significant adverse events, including the discontinuation of PD, hospitalization, and death. This study aimed to evaluate the feasibility of detecting various PD complications and data related to MDs. Materials and Methods: A retrospective study was conducted on patients who received PD catheter insertions between January 2001 and March 2021 to evaluate PD-related complications. PD complications were evaluated through diagnostic, procedural, and MD codes using a common data model (CDM) and were compared with those from electronic health records (EHRs). The results from one CDM database were compared with those from another CDM database. Results: A total of 342 patients were enrolled. One hundred and ninety-five patients experienced PD complications more than once. Nineteen prescription codes and twenty diagnostic codes from the EHR were identified, covering 11 procedures, three MDs, and seven complications related to PD. Infectious complications were detected using the CDM, whereas mechanical complications were missed. Although data on PD catheters and adaptors were available in the EHR, they were not detected via the CDM. Some infectious and mechanical complications were identified via the CDM in the other database. After implementing amended matching, these data were detected. Conclusions: While some PD-related medical data recorded in EHRs were misrepresented or omitted during the CDM database extraction, transformation, and loading process, the CDM shows potential to serve as a source of real-world data for active surveillance. Full article

Articular cartilage has limited regenerative potential due to its anatomical characteristics, making complete recovery from damage challenging. Microfracture (MFx) is a widely used technique to promote cartilage healing, often enhanced with scaffolds to improve outcomes. In this study, we compared the efficacy of bilayer atelocollagen and standard collagen scaffolds combined with MFx in treating osteochondral defects in a rabbit model. Three articular cartilage defects were created in the femoral condyle of each rabbit and treated with either MFx plus a bilayer atelocollagen scaffold (test group), MFx plus a standard collagen scaffold (positive group), or MFx alone (negative group). Macroscopic and histological assessments were performed at 3, 6, and 12 weeks. By week 12, macroscopic examination showed hyaline-like cartilage restoration in the test group, while the positive group exhibited restoration with some overgrowth, and the negative group showed no restoration. Histological analysis revealed significantly better restoration in the test group than in the negative group, with comparable outcomes between the test and positive groups. These findings suggest that bilayer atelocollagen scaffold implantation following MFx is a promising treatment for articular cartilage defects and may provide a viable therapeutic option for patients with cartilage damage. Full article

This study proposes an optimal resonant network design for an 11.1 kW wireless power transfer (WPT) system with a double-sided LCC compensation circuit, targeting 800 V class battery applications. Conventional WPT circuit topologies and design parameters specified in existing standards, such as SAE J2954, are unsuitable for 800 V class battery systems because they impose excessive voltage and current stresses on the resonant network components. To address this, the proposed design focuses on minimizing component stresses while ensuring compliance with the output voltage requirements for 800 V battery charging. A switched capacitor technique is integrated into the resonant network to dynamically adjust the compensation capacitance, enabling seamless adaptation to the constant current–constant voltage charging profile. The feasibility of the WPT system is validated through simulations and experiments, demonstrating an input voltage of 400 VDC, an output voltage range of 560–820 VDC, and a rated power capacity of 11.1 kW. Under rated conditions, the system achieves a peak efficiency of 95%, underscoring its practicality for high-voltage electric vehicle charging applications. Full article

Background and Objectives: Preterm birth (PTB), defined as delivery before 37 weeks of gestation, remains a significant public health concern due to its association with neonatal morbidity and mortality. Although studies have suggested that microbial factors in vaginal microbiota (VMB) influence PTB, longitudinal research on Korean women is limited. This study aimed to analyze VMB differences between term and preterm pregnancies in Korean women and their correlation with the cervical length (CL). Materials and Methods: A cohort of 60 pregnant Korean women (40 who had a term birth (TB) and 20 who had a PTB) was recruited. Vaginal samples were collected at five time points (first, second, and third trimester; 1–2 weeks postpartum; 1–2 months postpartum). Microbial DNA was extracted and analyzed using quantitative PCR targeting 12 bacterial species. The CL was measured in the second and third trimesters. Results: Lactobacillus crispatus was consistently dominant in the TB group, whereas PTB cases exhibited greater microbial diversity with elevated levels of Prevotella salivae and Ureaplasma species. The CL was significantly shorter in PTB cases, correlating with shifts in the VMB composition. Conclusions: A stable, Lactobacillus-dominant microbiome is protective in pregnancy, while increased diversity in PTB cases suggests microbial biomarkers for early risk prediction. Combining VMB profiling with CL measurement may enhance early, non-invasive PTB risk assessments. Full article

Background/Objectives: Cannabis sativa has been utilized for medical purposes for thousands of years. It continues to be recognized as a plant with an extensive variety of medicinal and nutraceutical uses today. In this study, a chemical investigation of the flowers of C. sativa isolated by using a variety of chromatographic techniques led to the isolation of eleven compounds. These purified compounds were evaluated for antitumor activity against SK-N-SH neuroblastoma cells. Methods: The compounds were isolated by using chromatographic techniques. Their structures were identified by the examination of spectroscopic methods, including 1D (¹H, ¹³C, and DEPT) and 2D (COSY, HSQC, HMBC, and NOESY) nuclear magnetic resonance (NMR) spectra and mass spectrum, together with the comparison to those reported previously in the literature. The evaluation of toxicity on SK-N-SH cells was performed by the MTT method. Results: Eleven compounds were isolated from the flowers of C. sativa, including two new compounds, namely cannabielsoxa (1), 13²-hydroxypheophorbide c ethyl ester (2), and six known cannabinoids (6–11), together with the first isolation of chlorin-type compounds: pyropheophorbide A (3), 13²-hydroxypheophorbide b ethyl ester (4), and ligulariaphytin A (5) from this plant. The results also demonstrated that cannabinoid compounds had stronger inhibitory effects on neuroblastoma cells than chlorin-type compounds. Conclusions: The evaluation of the biological activities of compounds showed that compounds 4–10 could be considered as the potential compounds for antitumor effects against neuroblastomas. This is also highlighted by using docking analysis. Additionally, the results of this study also suggest that these compounds have the potential to be developed into antineuroblastoma products. Full article

This study aimed to develop new parameters for electromyography (EMG)-based muscle fatigue assessments. First, various combinations of frequency band parameters, including the high-frequency band (HFB: >95 Hz), medium-frequency band (MFB: 46–95 Hz), and low-frequency band (LFB: 15–45 Hz), were assessed to evaluate the fatigue detection performance of individual parameters during isometric muscle contractions. The experimental design involved applying three force levels (30%, 40%, and 50% of the maximum voluntary contraction) and targeting three muscles (upper trapezius, mid-deltoid, and pectoralis major) due to their relevance in shoulder load postures associated with musculoskeletal disorders. A total of 15 participants were involved in this study. The effectiveness of each parameter was assessed through response sensitivity evaluations. Through these evaluations, we confirmed that the previously mentioned individual frequency bands, along with the proposed H/(M + L) frequency band, exhibited high statistical significance and sensitivity under various experimental conditions. Specifically, our findings demonstrated that the H/(M + L) frequency band effectively assessed fatigue levels with high sensitivity and accuracy at low force levels during static isometric contractions. Overall, these results are expected to improve the accuracy of evaluations of individual shoulder muscle fatigue, thereby reducing the risk of shoulder injuries. Full article

Background: Cardiogenic shock (CS) frequently leads to multiorgan failure, often necessitating continuous renal replacement therapy (CRRT) or extracorporeal membrane oxygenation (ECMO). We evaluated the association between CRRT, ECMO, and its prognostic implication in patients with CS. Methods: A total of 1247 patients with CS were enrolled from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients with Cardiogenic Shock) registry between January 2014 and December 2018. The primary outcomes, including the 72 h and 30-day all-cause mortality rates, were analyzed in relation to the use of ECMO and CRRT among CS patients. Results: Among 751 non-ECMO patients, 90 (12%) underwent CRRT, while among 496 ECMO patients, 195 (39.3%) underwent CRRT. Overall, CRRT was associated with higher 30-day mortality. However, among ECMO patients, CRRT was linked to lower 72 h mortality (19.6% versus 12.3%; p = 0.045). Multivariate analysis showed that CRRT reduced 72 h mortality in ECMO patients (hazard ratio: 0.44; 95% confidence interval: 0.21–0.91; p = 0.027). Independent predictors for CRRT included an estimated GFR < 44 mL/min/1.73 m², mechanical ventilation, ECMO use, IABP use, and increased lactate. Conclusions: CS patients receiving CRRT had higher 30-day mortality. Nonetheless, CRRT administration was more common in ECMO patients, potentially improving early in-hospital clinical outcomes. Full article

Background: Probiotics have been shown to enhance cognitive function in individuals with mild cognitive impairment (MCI), but their efficacy varies, depending on the strain and dosage. Objectives: Clinical investigations are crucial to confirm their safety, efficacy, and mechanism of action. This study was designed to assess the effective dosage, safety, and efficacy of MH-Pro, a test product containing Lacticaseibacillus rhamnosus CBT-LR5 (LR5) and skim milk (non-fat dry milk), in improving cognitive function and related physiological changes in older adults suspected of MCI over 12 weeks. Methods: In total, 20 participants (mean age: 68.9 years) were randomly assigned in a 1:1 ratio to either a low-dose group (1 × 10¹⁰ CFU LR5 with 1622 mg) or a high-dose group (1 × 10¹⁰ CFU LR5 with 4055 mg skim milk) in a double-blind, parallel-group clinical trial. Results: After 12 weeks, the low-dose group showed significant improvements in the MOCA-K subdomains, specifically in naming (p = 0.01) and delayed recall (p = 0.003). Additionally, levels of amyloid-β1 40/42 in the blood significantly decreased (p = 0.03) following supplementation in the low-dose group. The high-dose group exhibited significant improvement in orientation (p = 0.05). Moreover, overall cognitive enhancement was observed in the low-dose group (p = 0.003), while the high-dose group showed a trend toward improvement (p = 0.06). Fecal analysis revealed significant changes in bacterial composition, with an increase in Lacticaseibacillus after 12 weeks of MH-Pro consumption. Together, these findings provide foundational evidence suggesting that MH-Pro supplementation may serve as a potential intervention for enhancing cognitive function through gut–brain axis pathways in the elderly population. However, given the small sample size and the predominance of female participants, the impact of the outcome may be limited. Further large-scale studies are necessary to validate these preliminary results. Conclusions: This study provides foundational evidence to recognize the use of LR5 and skim milk to prepare a probiotic supplement that enhances cognitive function in the aging population. Full article

Background: Selenium (Se), a vital trace element, plays a neuroprotective role by mitigating oxidative stress through selenoproteins and regulating metal balance. The apolipoprotein E ε4 allele (APOE4), a significant genetic risk factor for Alzheimer’s disease (AD), has been linked to reduced Se levels and weakened antioxidant capacity. This research explores the association between serum Se concentrations and cognitive performance, with an emphasis on how APOE4 status influences this relationship. Methods: This study included 196 older adults from community and memory clinic settings, who underwent assessments for episodic memory, global cognition, and non-memory functions using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery, with serum selenium levels analyzed via inductively coupled plasma–mass spectrometry (ICP-MS) and APOE genotyping conducted to determine allele status. Results: Higher serum Se levels were associated with better episodic memory score (EMS) (B = 0.065, 95% CI = 0.020–0.110, p = 0.005) and CERAD total score (TS) (B = 0.119, 95% CI = 0.046–0.193, p = 0.002). However, the interaction between Se and APOE4 status significantly affected EMS (B = −0.074, 95% CI = −0.109 to −0.039, p < 0.001), with significant benefits observed in APOE4-negative participants. Conclusions: This study highlights the genotype-specific impact of Se on cognitive health, emphasizing the need for personalized nutritional interventions targeting Se levels, particularly for APOE4-negative individuals. Future research should further elucidate the mechanisms of Se’s effects and assess its therapeutic potential in aging populations. Full article

Road markings, such as lane dividers and pedestrian crossings, are integral in ensuring the safety of road users. However, traditional markings frequently exhibit limitations, including short lifespans, diminished visibility, and significant maintenance costs, particularly as traffic volumes increase. To address these persistent challenges, this study presents a thermoplastic road marking system that combines material innovation and advanced application techniques. Central to this approach is the portable heating system, equipped with ceramic heaters and precise temperature controls, which facilitates uniform heating while mitigating fire risks. The thermoplastic blend, processed into pre-formed sheets, was integrated with this heating technology. Together, these components enabled a two-phase process, engraving asphalt surfaces followed by sheet integration, that ensured robust adhesion and seamless bonding. Field trials conducted on various asphalt types validated the system’s reliability, demonstrating its durability under traffic loads and consistent visibility. By integrating durable materials with advanced application methods, this methodology significantly enhances the efficiency, longevity, and safety of road markings. It presents a practical and scalable solution for modern infrastructure needs. Future research will focus on evaluating the system’s long-term performance under extreme weather conditions to further optimize its applicability. Full article