Search Results (79)

Background: Hypoxic hepatitis contributes to the development and progression of multiple organ failure (MOF). We evaluated whether MOF is associated with 30-day mortality in patients with hypoxic hepatitis. Methods: This retrospective study included 1011 patients diagnosed with hypoxic hepatitis at two centers in South Korea between 2010 and 2021. Organ failure was defined as a sequential organ failure assessment score ≥ 3 for each individual organ system. Results: Circulatory failure was the most common organ failure (n = 521), followed by respiratory (n = 380), cerebral (n = 307), renal (n = 236), coagulation (n = 182), and hepatic failure (n = 73). The proportions of patients without organ failure, with single organ failure, and with MOF were 28.7%, 22.3%, and 49.1%, respectively, with corresponding 30-day mortality rates of 17.9%, 29.3%, and 70.0%. In the multivariate Cox regression model, the presence of MOF grade 1 (two organ failures), grade 2 (three organ failures), and grade 3 (≥four organ failures) increased the risk of 30-day mortality by approximately threefold, fourfold, and fivefold, respectively, compared to patients without MOF. Conclusions: MOF is frequently observed in patients with hypoxic hepatitis and is a strong independent predictor of short-term mortality. Full article

In this study, the influence of HfO₂ interlayer thickness on the performance of heteroepitaxial α-Ga₂O₃ layer-based metal–insulator–semiconductor–insulator–metal (MISIM) ultraviolet photodetectors is examined. A thin HfO₂ interlayer enhances the interface quality and reduces the density of interface traps, thereby improving the performance of UVC photodetectors. The fabricated device with a 1 nm HfO₂ interlayer exhibited a significantly reduced dark current and higher photocurrent than a conventional metal–semiconductor–metal (MSM). Specifically, the 1 nm HfO₂ MISIM device demonstrated a photocurrent of 2.3 μA and a dark current of 6.61 pA at 20 V, whereas the MSM device exhibited a photocurrent of 1.1 μA and a dark current of 73.3 pA. Furthermore, the photodetector performance was comprehensively evaluated in terms of responsivity, response speed, and high-temperature operation. These results suggest that the proposed ultra-thin HfO₂ interlayer is an effective strategy for enhancing the performance of α-Ga₂O₃-based UVC photodetectors by simultaneously suppressing dark currents and increasing photocurrents and ultimately demonstrate its potential for stable operation under extreme environmental conditions. Full article

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, treats type 2 diabetes by blocking renal glucose reabsorption and promoting urinary glucose excretion. This mechanism lowers blood glucose concentrations independently of insulin. The resulting caloric loss also contributes to weight reduction. Although these effects are well documented in patients with diabetes, their magnitude and underlying mechanisms in healthy individuals remain poorly understood. Background/Objectives: We investigated metabolic alterations after a single 10 mg dose of dapagliflozin in healthy adults with normal body-mass indices (BMIs) using untargeted metabolomics. Methods: Thirteen healthy volunteers completed this study. Plasma was collected before and 24 h after dosing. Untargeted metabolic profiling was performed with ultra-high-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry. Results: Twenty-five endogenous metabolites were annotated; ten were putatively identified. Eight metabolites increased significantly, whereas two decreased. Up-regulated metabolites included phosphatidylcholine (PC) species (PC O-36:5, PC 36:3), phosphatidylserine (PS) species (PS 40:2, PS 40:3, PS 36:1, PS 40:4), lysophosphatidylserine 22:1, and uridine. Dehydroepiandrosterone sulfate and bilirubin were down-regulated. According to the Human Metabolome Database, these metabolites participate in glycerophospholipid, branched-chain amino acid, pyrimidine, and steroid-hormone metabolism. Conclusions: Dapagliflozin may affect pathways related to energy metabolism and homeostasis beyond glucose regulation. These data provide a reference for future investigations into energy balance and metabolic flexibility in metabolic disorders. Full article

Dry eye disease (DED) is characterized by tear film instability and oxidative stress-induced epithelial damage. This study was conducted to compare the therapeutic effects of 2% rebamipide (REB) and 3% diquafosol (DQS) on oxidative stress-related apoptotic damage of the ocular surface in DED. Human corneal epithelial cells (HCECs) were exposed to hyperosmotic stress in vitro and treated with REB or DQS. Cell viability and cleaved caspase-3 expression were evaluated using the MTT assay and Western blotting. DED was induced in vivo in C57BL/6 mice using subcutaneous scopolamine injection. Thereafter, the mice were assigned to normal control (NC), dry eye (DE), DQS-treated (DQS), or REB-treated (REB) groups. Clinical evaluations, including measurement of tear film break-up time, corneal smoothness, and the lipid layer, were performed on days 7 and 14. In addition, CD4⁺ IFN-γ⁺ T cells, inflammatory cytokines, reactive oxygen species (ROS), lipid peroxidation markers, and corneal apoptosis were analyzed on day 14. Glycocalyx integrity and goblet cell density were also evaluated. The results indicate that REB improved HCEC survival and suppressed cleaved caspase-3 expression more effectively than DQS (p < 0.05). Both treatments improved clinical outcomes in the murine dry eye model; however, REB showed superior efficacy in reducing ROS levels, lipid peroxidation, and apoptosis, and in preserving corneal glycocalyx integrity and conjunctival goblet cell density. These findings highlight the therapeutic potential and protective effects of REB against oxidative stress-related damage and apoptosis in DED. Full article

Background/Objectives: Fluoroscopy has been widely adopted in interventional pulmonology, as it facilitates real-time visualization of the bronchoscope, endobronchial ultrasound, and biopsy tools during procedures. The purpose of this study was to evaluate the effectiveness of radiation shields in minimizing scattered X-ray dose to the bronchoscopist in a phantom study and to determine the dose of scattered X-ray dose to medical staff with radiation shields in clinical application. Methods: An anthropomorphic torso phantom was positioned on the fluoroscopic table between the C-arm X-ray tube and the image detector to mimic bronchoscopic operations. Upper and lower body lead shields were used to examine the effectiveness of radiation shielding. Scatter radiation rates were assessed at a first operator location using real-time dosimeters with and without protective devices. In clinical application, the scattered X-ray dose of the first operator and main assistant was measured using wearable radiation dosimeters during 20 procedures. Results: In the phantom study, scattered radiation without shielding was 266.34 ± 8.86 μSv/h (glabella), 483.90 ± 8.01 μSv/h (upper thorax), 143.97 ± 8.20 μSv/h (hypogastrium), and 7.22 ± 0.28 μSv/h (ankle). The combination of upper and lower body lead shields reduced the scattered X-ray dose by 98.7%, 98.3%, 66.2%, and 79.9% at these levels, respectively. In clinical application, mean scattered X-ray dose rates were 0.14 ± 0.05 μSv/procedure (eye), 0.46 ± 0.51 μSv/procedure (chest), 0.67 ± 0.50 μSv/procedure (hypogastrium), and 1.57 ± 2.84 μSv/procedure (assistant’s wrist). Conclusions: The combination of radiation shields significantly reduced the scattered X-ray dose at the operator site in the phantom study. The scattered X-ray dose to medical staff during bronchoscopy can be kept at a low level with the aid of a shielding system. Full article

In regard to both natural aging and photoaging caused by UV radiation, a decrease in skin collagen and elastin fibers results in the loss of soft tissue volume. Biodegradable polymer fillers have been used to overcome this problem, but the slow rate of reconstruction and particle agglomeration has limited this approach. The DMSB01 filler, which consists of poly d-l-lactic acid (PDLLA) with a methoxy polyethylene glycol (mPEG) initiator, was created to address this issue. In this study, we assessed the reconstruction and dispersion of the DMSB01 filler in vitro, as well as its effect on collagen expression in rats. DMSB01 showed rapid reconstruction and excellent dispersion stability; gelation occurred within 5 min at 37 °C and remained stable. In an animal model, DMSB01 induced M2 macrophages, Transforming growth factor beta (TGF-β) expression, and significantly increased collagens I and III. Collagen recovery and wrinkle improvement were confirmed by the aging and photoaging models, and hematoxylin and eosin (H&E) staining was used to demonstrate the safety and biodegradability of DMSB01. DMSB01 was effective in terms of inducing collagen production and improving skin aging, and shows promise as an innovative ingredient to overcome the limitations of existing fillers. Full article

Background/Objectives: Foot-and-mouth disease (FMD) is a highly contagious class 1 animal disease that affects cloven-hoofed animals, such as cattle, pigs, and goats. Diagnosis and research on live FMD virus (FMDV) typically require biosafety level 3 facilities, which are challenging to maintain due to strict protocols and high costs. The development of NanoBiT-based assays has accelerated in response to the coronavirus disease pandemic, providing safer alternatives for viral research, and is now applicable for general laboratories. This study aimed to develop a NanoBiT-based virus-like particle (VLP) assay for the rapid and safe screening of neutralizing antibodies against FMDV Asia1 Shamir (AS). Methods: We developed an AS VLP with an inserted HiBiT tag that enabled the detection of entry into LgBiT cells through luminescence signals. Results: HiBiT-tagged AS VLPs mixed with anti-serum and introduced into LgBiT-expressing cells led to a reduction in luciferase activity. Therefore, we established a NanoBiT-based viral neutralizing antibody test (VNT) that demonstrated a high correlation (R² = 0.881) with the traditional gold standard VNT. Conclusions: The assay demonstrated high sensitivity and could be performed in BL-2 facilities, offering a safer and more efficient alternative to traditional assays while reducing the need to handle live viruses in high-containment facilities. This method provides a valuable tool for rapid screening of neutralizing antibodies and can be adapted for broader applications in FMDV research. Full article

Background/Objectives: C24 ceramide plays a crucial role in skin regeneration and wound healing; however, its hydrophobic nature limits its application in therapeutic formulations. This study aims to enhance the bioavailability and efficacy of C24 ceramide by developing ceramide-based lipid nanoparticles (C24-LNP) and evaluate their impact on skin regeneration and wound healing. Methods: C24-LNP was synthesized and characterized for aqueous stability and bioavailability. In vitro experiments were conducted to assess its effects on keratinocyte proliferation and migration. Molecular biological analysis examined key signaling pathways, including AKT and ERK1/2 phosphorylation. Additionally, an in vivo mouse wound model was utilized to evaluate wound healing efficacy, with histological analysis performed to assess epidermal and dermal regeneration. Results: C24-LNP exhibited improved aqueous stability and bioavailability compared to free C24 ceramide. In vitro studies demonstrated that C24-LNP significantly promoted keratinocyte proliferation and migration. Molecular analysis revealed activation of the AKT and ERK1/2 signaling pathways, which are critical for cell growth and skin regeneration. In vivo wound healing experiments showed that C24-LNP accelerated wound closure compared to the control group. Histological analysis confirmed enhanced epidermal and dermal regeneration, leading to improved structural and functional skin repair. Conclusion: The lipid nanoparticle formulation of C24 ceramide effectively increases its bioavailability and enhances its therapeutic efficacy in skin regeneration and wound healing. C24-LNP presents a scalable and cost-effective alternative to traditional growth factor-based therapies, offering significant potential for clinical applications in wound care and dermatological treatments. Full article

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is highly toxic with potential impacts on aging. While previous studies have linked TCDD exposure to reduced telomere length and altered sperm DNA methylation (DNAm) age, its relationship with epigenetic aging remains unclear. This study investigated the association between serum TCDD levels and epigenetic clocks derived from DNAm in whole blood in older adults. Using data from the 1999–2002 National Health and Nutrition Examination Survey, we analyzed 589 participants aged 50 to 79 years with available blood TCDD and DNA methylation measures. Blood TCDD levels were measured by high-resolution gas chromatography/isotope-dilution high-resolution mass spectrometry. The six DNAm-based epigenetic clocks included Horvath Age, Hannum Age, SkinBlood Age, Pheno Age, Grim Age, and Grim Age2. Multivariable regression analysis showed significant associations between TCDD levels and Horvath Age, Hannum Age, Pheno Age, Grim Age, and Grim Age2. However, when using lipid-adjusted TCDD levels, significant associations remained only for PhenoAge (β = 0.73; SE, 0.31; p = 0.0258) and Grim Age2 (β = 0.44; SE, 0.21; p = 0.0472). The strongest non-linear trends were observed for PhenoAge, Grim Age, and Grim Age2, suggesting a threshold-dependent impact of TCDD on DNAm aging processes. Our findings suggest that TCDD exposure is associated with accelerated epigenetic aging, particularly in mortality-related clocks, with a dose-dependent and non-linear pattern. Full article

Background/Objectives: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Methods: Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Results: Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control (p < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups (p < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups (p < 0.05). Conclusions: Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye. Full article

Background/Objectives: Sensitivity to ocular irritation varies among individuals, being influenced by clinical, subjective, and biochemical factors. This study aimed to evaluate individual variability in ocular irritation sensitivity, focusing on clinical parameters, pain perception, and tear neuromediator profiles. Methods: Sixty female participants aged 20–40 were classified into high-sensitivity and low-sensitivity groups based on their response to an irritant (Tween20). Clinical assessments included the ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer test, and corneal touch threshold measured with the Cochet–Bonnet esthesiometer. Pain sensitivity was assessed using the pain sensitivity questionnaire (PSQ), and tear neuromediators were quantified in tear samples before and after stimulation. The concentrations of calcitonin gene-related peptide (CGRP), nerve growth factor, neuropeptide Y, vasoactive intestinal peptide (VIP), and substance P were measured using an enzyme-linked immune sorbent assay (ELISA). Results: The high-sensitivity group exhibited significantly higher OSDI scores (p = 0.038). No significant differences were observed in TBUT, corneal staining scores, or Schirmer’s test results. The PSQ results revealed that the high-sensitivity group had lower total and moderate pain scores (p = 0.037 and p = 0.040, respectively). An analysis of the tear neuromediator showed elevated baseline CGRP levels (p = 0.017) and a significant post-stimulation increase in substance P (p = 0.021) in the high-sensitivity group. Conclusions: These findings emphasize the value of combining clinical, subjective, and biochemical measures to understand sensitivity to ocular irritation. This comprehensive approach may guide the development of safer cosmetic formulations and improve safety assessment protocols. Full article

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression. Full article

Reactive oxygen species (ROS)-mediated damage to macromolecules and cellular organelles is one of the major causes of senescence. Therapeutic strategies that lower ROS levels have been proposed as important treatments for senescence, but effective mechanisms for reducing ROS levels have not been discovered. Here, we aimed to find a combination that has a synergistic effect on ROS reduction using senomorphics known to reduce ROS. Combination treatment with BRAF inhibitor SB590885 and p38 MAPK inhibitor SB203580 showed a synergistic effect on ROS reduction compared to treatment with either drug alone. The synergistic effect of ROS reduction through this combination led to a synergistic effect that restored mitochondrial function and ameliorated senescence-associated phenotypes. To elucidate the underlying mechanism by which the synergistic effect of the two drugs reverses senescence, we performed RNA sequencing and identified metallothionein 2A (MT2A) as a key gene. MT2A was upregulated in response to combination therapy, and overexpression of MT2A led to a decrease in ROS and subsequent recovery of senescence-associated phenotypes, similar to the effects of combination therapy. Taken together, we found a drug combination that showed synergistic effects on ROS reduction, which contributed to the recovery of senescence-associated phenotypes through MT2A gene regulation. This study opens up a new avenue in aging research by demonstrating that combination therapy with existing senomorphics can enhance the ability to reverse senescence and that similar reversal effects can be achieved through gene regulation regulated by combination therapy. Full article

Background/Objectives: Intestinal Behçet’s disease (iBD) often requires surgical intervention, with a significant proportion of patients needing reoperation. This study aimed to investigate the risk factors associated with reoperation in patients with iBD who underwent initial bowel resection and to evaluate the perioperative and long-term outcomes in these patients. Methods: This was a retrospective case-control study analyzing patients who underwent their initial bowel resection due to iBD between 2005–2021 at a tertiary referral hospital. Reoperation was considered a surgery due to postoperative complications (within 30 days of the initial surgery) or disease progression. Results: A total of 81 patients were included. The median follow-up duration was 107.1 months, during which 26 patients (32%) underwent reoperation. Multivariable analysis showed that the presence of hematological disorders (hazards ratio [HR], 9.13; 95% confidence interval [CI], 3.79–22.02, p < 0.001), higher c-reactive protein (CRP) levels before the initial surgery (HR, 1.01; 95% CI, 1.01–1.02, p < 0.001), and a shorter specimen resection length (HR, 0.96; 95% CI, 0.93–0.99, p = 0.011) were risk factors for reoperation. Patients who underwent reoperation had higher rates of postoperative complications (69.2% vs. 43.6%, p = 0.031), required longer antibiotic use (12 vs. 7 days, p = 0.012), and had extended hospital stays (18 vs. 9 days, p = 0.011). They also had worse 5-year survival rates than those who did not undergo reoperation (83.5% vs. 98.4%, p = 0.012). Conclusions: Concurrent hematological disorders, high preoperative CRP levels, and short specimen resection were associated with an increased risk of reoperation in patients with iBD who underwent their initial bowel resections. They also had worse perioperative and long-term outcomes. Full article

This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4⁺ IFN-γ⁺ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression (p < 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4⁺ IFN-γ⁺ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure. Full article