Search Results (129)

Vascular calcification significantly contributes to cardiovascular complications and limb loss in chronic kidney disease (CKD). To establish an optimal rat model for vascular calcification, we tested varying adenine concentrations and feeding durations in Sprague–Dawley rats (n = 72), divided into six groups (n = 12 each). The control group received a standard diet for 18 weeks. Group 1 was given 0.5% adenine for 4 weeks, followed by a standard diet. Group 2 received 0.5% adenine for 4 weeks, then 0.25% for 14 weeks. Group 3A received 0.5% adenine for 12 weeks and then standard diet; group 3B received 0.5% adenine for 12 weeks, followed by 0.25% for 6 weeks; group 3C received 0.5% adenine for 18 weeks. At week 18, vascular calcification was absent in the control and group 1. Groups 2 and 3A showed low incidence (12.5%), while groups 3B and 3C showed high incidence (66.7%). However, survival rates differed: 75.0% in 3B and 50.0% in 3C after 12 wk. Thus, 0.5% adenine for 12 weeks followed by 0.25% for 6 weeks effectively induced vascular calcification while maintaining acceptable survival, providing a practical model for studying CKD-related vascular pathology. Full article

Introduction: In Haemophilia B, guideline-level factor IX (FIX) prophylaxis is recommended, but real-world dosing and adherence vary. Aim: To assess treatment patterns, adherence, FIX dosing, and their associations with bleeding events in Korean patients. Methods: We conducted a retrospective chart review and one-time survey of 130 Korean patients with haemophilia B treated with FIX for ≥12 months at 12 centers (June 2022–May 2023). A total of forty-seven patients (36.2%) received prophylaxis (≥90 IU/kg/week for ≥45 weeks); the remainder were managed non-prophylactically. Annualized bleeding events (ABEs) were analyzed using negative binomial regression, and monthly bleeds with a generalized linear mixed model. Covariates with p < 0.10 and clinical relevance were included in multivariable models. Results: The prophylaxis group showed significantly fewer ABEs (incidence rate ratio [IRR]: 0.383, p = 0.011). Each 100 IU/kg monthly dose increment reduced bleed risk (IRR: 0.692, p < 0.001). Adherence showed no independent association with bleeding in adjusted models. Conclusions: Bleed prevention in haemophilia B is driven more by delivered FIX exposure than by regimen label. Study-defined sustained prophylaxis remains underused and under-dosed. Individualized dosing and continuous adherence monitoring are essential to close this treatment gap and improve outcomes. Full article

Background/Objectives: Karyomapping, a genome-wide SNP analysis, has drastically changed the approach to preimplantation genetic testing for monogenic disorders (PGT-M). However, there are cases in which karyomapping cannot be applied due to an insufficient number of informative SNPs. In this study, we aimed to analyze for the first time whether an insufficient number of informative SNPs is related to the family member used as a reference. Methods: For the karyomapping pre-clinical test, in addition to the couple, one of the DNA samples from an additional family member (children, parent, sibling) is used as a reference for phasing the SNP allele. We analyzed 263 couples who underwent karyomapping for PGT-M at the CHA Fertility Center from May 2020 to December 2022. karyomapping data was scanned on an Illumina NextSeq and analyzed through the BlueFuse Multi software version 4.5. Results: Preclinical karyomapping tests were performed in 263 couples with 58 monogenic diseases. Karyomapping was applicable to PGT-M for 241 (91.6%) couples and not applicable for 22 (8.4%) couples. The percentages of “not applicable” cases according to the reference family member were 1.3% (1/80) in the children group, 5.4% (8/148) in the parent group, and 37.1% (13/35) in the sibling group. Among the genetic diseases studied, couples with neurofibromatosis type 1 (6/27, 22.2%) and Kennedy disease (5/5, 100%) had the highest rate of non-applicable cases. Conclusions: Our results suggest that a child or parent may be better than the sibling for karyomapping in PGT-M. These data provide useful information for selecting a reference among the family members for preclinical karyomapping tests. Full article

As the global transition to carbon neutrality accelerates, hydrogen energy has emerged as a key alternative to fossil fuels due to its potential to reduce carbon emissions. Many countries, including Korea, are constructing hydrogen refueling stations; however, safety concerns persist due to accidents caused by equipment failures and human errors. While various accident analysis models exist, the application of the root cause analysis (RCA) technique to hydrogen refueling station accidents remains largely unexplored. This study develops an RCA modeling map specifically for hydrogen refueling stations to identify not only direct and indirect causes of accidents, but also root causes, and applies it to actual accident cases to provide basic data for identifying the root causes of future hydrogen refueling station accidents. The RCA modeling map developed in this study uses accident cause investigation data from accident investigation reports over the past five years, which include information on the organizational structure and operational status of hydrogen refueling stations, as well as the RCA handbook. The primary defect sources identified were equipment defect, personal defect, and other defects. The problem categories, which were the substructures of the primary defect source “equipment defect,” consisted of four categories: the equipment design problem, the equipment installation/fabrication problem, the equipment reliability program problem, and the equipment misuse problem. Additionally, the problem categories, which were the substructures of the primary defect source “personal defect,” consisted of two categories: the company employee problem and the contract employee problem. The problem categories, which were the substructures of the primary defect source “other defects,” consisted of three categories: sabotage/horseplay, natural phenomena, and other. Compared to existing accident investigation reports, which identified only three primary causes, the RCA modeling map revealed nine distinct causes, demonstrating its superior analytical capability. In conclusion, the proposed RCA modeling map provides a more systematic and comprehensive approach for investigating accident causes at hydrogen refueling stations, which could significantly improve safety practices and assist in quickly identifying root causes more efficiently in future incidents. 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

Anthropogenic influence has altered watershed environments and hydrological processes, leading to increased occurrences of impaired streams and negative impacts on benthic invertebrates. While individual environmental factors affecting benthic macroinvertebrates have been studied, the cascading effects of land use change and hydrological alterations remain unclear. This study employed structural equation modeling (SEM) to analyze the interactions among land use proportion, hydrological characteristics, substrate composition, and water quality and their influence on benthic macroinvertebrate communities in impaired streams upstream of the Paldang Dam in the Han River Basin, South Korea. Analysis of data from 24 streams surveyed between 2018 and 2022—3 or 6 streams per year—under the Impaired Stream Diagnosis Program indicated that urban and agricultural land cover, low substrate diversity, high pollutant concentrations, and altered flow conditions (low velocity and discharge) were associated with decreased pollution-sensitive Ephemeroptera, Plecoptera, and Trichoptera (EPT) taxa and increased pollution-tolerant and collector–gatherer taxa. These findings highlight the role of land use-driven hydrological changes in stream ecosystem degradation and underscore the need for targeted restoration strategies, such as riparian buffer zones, substrate enhancement, and hydrological flow restoration, to mitigate these impacts and improve benthic macroinvertebrate habitats. Full article

Background/Objectives: Rare diseases often present challenges in obtaining reliable and accurate information than common diseases owing to their low prevalence. Patients and families often rely on self-directed learning, but understanding complex medical information can be difficult, increasing the risk of misinformation. This study aimed to evaluate whether generative artificial intelligence (AI) provides accurate and non-harmful answers to rare disease-related questions and assesses its utility in supporting patients and families requiring genetic counseling. Methods: We evaluated four generative AI models available between 22 September and 4 October 2024: ChatGPT o1-Preview, Gemini advanced, Claude 3.5 sonnet, and Perplexity sonar huge. A total of 102 questions targeting four rare diseases, covering general information, diagnosis, treatment, prognosis, and counseling, were prepared. Four evaluators scored the responses for professionalism and accuracy using the Likert scale (1: poor, 5: excellent). Results: The average scores ranked the AI models as: ChatGPT (4.24 ± 0.73), Gemini (4.15 ± 0.74), Claude (4.13 ± 0.82), and Perplexity (3.35 ± 0.80; p < 0.001). Perplexity had the highest proportion of scores of 1 (very poor) and 2 (poor) (7.6%, 31/408), followed by Gemini (2.0%, 8/408), Claude (1.5%, 6/408), and ChatGPT (1.5%, 6/408). The accuracy of responses in the counseling part across all four diseases was significantly different (p < 0.001). Conclusions: The four generative AI models generally provided reliable information. However, occasional inaccuracies and ambiguous references may lead to confusion and anxiety among patients and their families. To ensure its effective use, recognizing the limitations of generative AI and providing guidance from experts regarding its proper utilization is essential. Full article

Background/Objectives: Regulation of acute inflammatory responses is crucial for host mortality and morbidity induced by pathogens. The pathogenesis of acute respiratory distress syndrome (ARDS) and sepsis are associated with systemic inflammation. p38 MAPK is a crucial regulator of inflammatory responses and is a potential target for acute inflammatory diseases, including ARDS and sepsis. We investigated the therapeutic effects of the TAT-TN13 peptide (TN13) on severe inflammatory diseases, including ARDS and sepsis, in vivo. Methods: To establish the ARDS model, C57BL/6 mice were intranasally (i.n.) administered lipopolysaccharide (LPS; 5 mg/kg, 40 µL) to induce lung inflammation. As a positive control, dexamethasone (DEX; 0.2 mg/kg) was administered intraperitoneally (i.n.) 1 h post-LPS exposure. In the experimental groups, TN13 was administered intranasally (i.n.) at doses of 2.5 mg or 5 mg/kg at the same time point. In the LPS-induced sepsis model, mice received an intraperitoneal injection of LPS (20 mg/kg) to induce systemic inflammation. TN13 (25 mg/kg, i.p.) was administered 1 h after LPS treatment. Control mice received phosphate-buffered saline (PBS). Lung histopathology, inflammatory cell infiltration, cytokine levels, and survival rates were assessed to evaluate TN13 efficacy. Results: TN13 significantly reduced inflammatory cell recruitment and cytokine production in the lungs, thereby mitigating LPS-induced ARDS. In the sepsis model, TN13 treatment improved survival rates by suppressing inflammatory responses. Mechanistically, TN13 exerted its effects by inhibiting the p38 MAPK/NF-κB signaling pathway. Conclusions: These results collectively suggested that TN13 could be an effective treatment option for severe inflammatory diseases. Full article

Background: As the population ages, enhancing immune function is crucial to mitigating age-related physiological decline. Since immunostimulant drugs are known to have potential side effects, medicinal plants emerge as promising candidates offering a safer alternative. To leverage the advantages of medicinal plants with fewer side effects and develop a potent immune-enhancing agent, we investigated the efficacy of a novel immunomodulatory candidate derived from the combination of Angelica gigas and Pueraria lobata (CHL). Methods: In vitro, CHL was treated in RAW 264.7 macrophages at various time points, and the experiments conducted in the study were performed using ELISA, Western blot, and RT-qPCR analysis. In vivo, C57BL/6 mice were administrated CHL for 16 days (p.o.) and CTX on the three days (i.p.), and experiments were conducted with ELISA, western blot, RT-qPCR analysis, H&E staining, flow cytometry, gut microbiome, and correlation analysis. Results: In vitro, CHL has upregulated NO and cytokines expression, substantially enhancing the NF-κB and MAPK activation. Furthermore, CHL promoted the TAK1, TRAF6, and MyD88 via TLR2/6 signaling. In vivo, the CHL improved the reduced body weight and immune organs’ indices and recovered various cytokines expression, NK cell cytotoxicity activity, and immune cell population. CHL also improved the histological structure and tight junction markers, mucin-2, and TLR2/6 in the intestines of CTX-induced mice. Conclusions: Overall, CHL demonstrated immunostimulatory potential by enhancing immune responses and restoring immune function, suggesting its promise as a safe and effective immune-enhancing agent. Full article

Background: Allergic rhinitis is an IgE-mediated condition of nasal congestion, runny nose, and sneezing which significantly impairs the quality of life. Current treatments, including antihistamines, often have long-term side effects, leading patients to seek safer alternatives. Objectives: Therefore, in this study, we aimed to evaluate the symptom relief efficacy of immature sword bean pod (SBP) extract, a natural material, in patients with allergic rhinitis, explore the mechanisms by which SBP regulates allergic immune responses, and evaluate its efficacy and safety as a functional ingredient in the management of allergic rhinitis. Methods: In a double-blind, placebo-controlled, randomized trial involving 64 participants with perennial allergic rhinitis, the subjects were assigned to receive either SBP or placebo orally for six weeks. Results: The SBP group exhibited significant improvements in nasal congestion (interaction p = 0.031), RQLQ (interaction p = 0.001), sleep (interaction p = 0.004), systemic reaction (interaction p = 0.002), daily life (interaction p = 0.047), and nasal symptoms (interaction p = 0.002). SBP treatment in EoL-1 and HMC-1 cells also led to a notable reduction in eosinophil cationic protein levels (p < 0.05), a key biomarker of allergic inflammation, by inhibiting PI3K/Akt/mTOR activation, resulting in decreased eosinophil activity. Conclusions: These findings suggest that the SBP extract is a promising natural treatment for allergic rhinitis, offering both efficacy and safety by improving key symptoms and reducing inflammatory responses. Full article

Background/Objectives: Although preeclampsia (PE) and small for gestational age (SGA) are known to come from impaired placentation during the first trimester, prior studies have focused mostly on Doppler findings in the second trimester. Methods: In this retrospective pilot study, we enrolled 628 singleton pregnant women who underwent ultrasound in both the first and second trimesters and blood test. For SGA correlation, we further excluded 12 subjects with PE because PE may be the cause of SGA. We first presented the reference range of parameters of uterine artery Doppler in the first trimester and then grouped the subjects according to the presence of SGA (presence = 104, absence = 512) or PE (presence = 12, absence = 616) and investigated the association of uterine artery Doppler findings and serum markers in the first trimester with the occurrence of SGA or PE. Results: The uterine artery pulsatility index and the resistance index and the proportion of uterine artery notch decreased progressively in the first trimester. A lower serum beta-hCG level in the first trimester predicted the occurrence of SGA (adjusted odds ratio [AOR] = 0.53, p = 0.019), while the presence of the uterine artery notch in the first trimester predicted the development of PE (notch at least on one side: AOR = 8.65, p = 0.045 and notch on both sides: AOR = 8.91, p = 0.047). Regardless of whether a notch was present in the second trimester, a uterine artery notch in the first trimester was associated with an excellent negative predictive value (99.6%) for PE. Conclusions: This study suggests the clinical importance of assessing serum beta-hCG and the uterine artery notch in the first trimester to predict SGA and PE. Full article

Mitochondrial dysfunction and macrophage dysregulation are well recognized as significant contributors to the pathogenesis of autoimmune diseases. However, the detailed mechanisms connecting these two factors remain poorly understood. This study hypothesizes that low but chronic interferon-gamma (IFN-γ) plays a critical role in these processes. To explore this, we utilized ARE-Del mice, a model characterized by sustained low-level IFN-γ expression and lupus nephritis (LN)-like symptoms. Age- and tissue-dependent gene expression analyses in ARE-Del mice revealed significant suppression of mitochondrial complex I components and activities, particularly in the kidneys. The genotype-dependent suppression of mitochondrial complex I indicates early disruption, which leads to macrophage dysfunction. Notably, remission restored gene expression of mitochondrial complex I and macrophage dysfunction in isolated renal macrophages from NZB/W lupus-prone mice. These findings suggest that chronic low-level IFN-γ disrupts mitochondrial complex I activity in macrophages, highlighting its role in the early pathogenesis of autoimmune diseases like lupus nephritis. This provides new insights into the molecular interactions underlying autoimmune pathogenesis and suggests potential targets for therapeutic intervention. Full article

Introduction: The immune system’s defense against pathogens involves innate and adaptive responses, crucial in maintaining overall health. Immunosuppressed states render individuals more susceptible to potential diseases, indicating the need for effective strategies to bolster immune functions. Objectives: Although the immunostimulatory effects of various probiotics have been studied, the specific effects and molecular mechanisms of Lactococcus lactis OTG1204 (OTG1204) remain unknown. In this study, the aim was to investigate the molecular mechanisms of OTG1204 in RAW 264.7 macrophages, the key effector cells of the innate immune system involved in host defense and inflammatory responses. Additionally, in this study, the effects of OTG1204 on cyclophosphamide (CTX)-induced immunosuppression states were investigated, thereby demonstrating its potential as an immune stimulant. Methods: To assess the macrophage activation ability and underlying mechanisms of OTG1204, RAW 264.7 cells were utilized with transfection, enzyme-linked immunosorbent assay, and quantitative real-time PCR analyses. Furthermore, to evaluate the immunostimulatory effects under immunosuppressed conditions, CTX-induced immunosuppression mice model was employed, and analyses were performed using hematoxylin and eosin staining, flow cytometry, and microbiota examination. Results: OTG1204 activated RAW 264.7 macrophages, leading to increased production of nitric oxide, prostaglandin E2, and cytokines. This immune activation was mediated through the upregulation of toll-like receptor 2, which subsequently activated the nuclear factor-κB (NF-kB) and mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathways, thereby stimulating the immune response. In CTX-treated mice, OTG1204 recovered body weight, spleen, and mesenteric lymph node indices, and natural killer cell activity. It re-established populations of innate and adaptive immune cells and activated T cells to secrete cytokines. We also examined the gut barrier integrity and microbiota composition to assess OTG1204’s impact on intestinal health, as these factors play a significant role in immune enhancement. OTG1204 enhanced gut barrier integrity by upregulating mucin 2 and tight junction proteins and modulated the gut microbiota by restoring the Firmicutes/Bacteroidetes balance and reducing the abundance of Actinobacteria and Tenericutes. Conclusion: These results suggest that OTG1204 may serve as an effective probiotic for immune enhancement and gut health management by targeting the NF-κB and MAPK/AP-1 pathways, with minimal side effects. Full article

Conventional biochemical methods for studying cellular signaling cascades have relied on destructive cell disruption. In contrast, the live cell imaging of fluorescent-tagged transfected proteins offers a non-invasive approach to understanding signal transduction events. One strategy involves monitoring the phosphorylation-dependent shuttling of a fluorescent-labeled kinase between the nucleus and cytoplasm using nuclear localization, export signals, or both. In this paper, we introduce a simple method to visualize intracellular signal transduction in live cells by exploring the translocation properties of PKC from the cytoplasm to the membrane. We fused bait protein to PKC, allowing the bait (RFP-labeled) and target (GFP-labeled) proteins to co-translocate from the cytoplasm to the membrane. However, in non-interacting protein pairs, only the bait protein was translocated to the plasma membrane. To verify our approach, we examined the Raf–MEK–ERK signaling cascade (ERK pathway). We successfully visualized direct Raf1/MEK2 interaction and the KSR1-containing ternary complex (Raf1/MEK2/KSR1). However, the interaction between MEK and ERK was dependent on the presence of the KSR1 scaffold protein under our experimental conditions. Full article

Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including glutathione. Fermented fish collagen (FC) contains glycine; thus, we evaluated the effect of FC on decreasing melanogenesis via decreasing oxidative stress. The glycine receptor (GlyR) and glycine transporter-1 (GlyT1) levels were decreased in UV-irradiated keratinocytes; however, the expression levels of these proteins increased upon treatment with FC. The FC decreased oxidative stress, as indicated by the decreasing expression of NOX1/2/4, increased expression of GSH/GSSG, increased SOD activity, and decreased 8-OHdG expression in UV-irradiated keratinocytes. Administration of conditioned media from FC-treated keratinocytes to melanocytes led to decreased p38, PKC, MITF, TRP1, and TRP2 expression. These changes induced by the FC were also observed in UV-irradiated animal skin. FC treatment increased the expression of GlyR and GlyT, which was accompanied by decreased oxidative stress in the UV-irradiated skin. Moreover, the FC negatively regulated the melanogenesis signaling pathways, leading to decreased melanin content in the UV-irradiated skin. In conclusion, FC decreased UV-induced oxidative stress and melanogenesis in melanocytes and animal skin. FC could be used in the treatment of UV-induced hyperpigmentation problems. Full article