Background: Epidermal growth factor (EGF) is widely applied in dermatology for its regenerative effects; however, its clinical utility is limited by low stability and high production costs.To overcome these limitations, we developed a novel probiotic-derived epidermal growth factor (pEGF) by engineering Pediococcus pentosaceus CBT SL4 to express and secrete EGF. Objective: To investigate the anti-photoaging effects of topical pEGF in a ultraviolet B (UVB)-irradiated mice by assessing histological and molecular changes related to collagen synthesis, extracellular matrix (ECM) remodeling, oxidative stress, and inflammation. Methods: SKH1 hairless mice were exposed to UVB for twelve weeks to induce photoaging and treated with topical 10% pEGF cream from week 9 to 12. Skin samples were analyzed using dermoscopy, histology, immunohistochemistry, quantitative real-time polymerase chain reaction, western blotting, and proteomics to evaluate morphological and molecular alterations in ECM components and inflammatory markers. Results: Topical pEGF treatment improved skin texture and reduced wrinkles. Histological evaluation revealed that EGF significantly attenuated UVB-induced epidermal thickening and restored collagen density, with the strongest effects observed in the pEGF group. Molecular analysis showed downregulation of matrix metalloproteinases (MMPs; MMP-1, MMP-3), upregulation of collagen (type I collagen, type III collagen) and tissue inhibitors of metalloproteinases (TIMPs; TIMP-1, TIMP-2). Additionally, pEGF reduced pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β) and oxidative stress markers. Conclusion pEGF demonstrated potent anti-photoaging effects through ECM restoration, inflammation modulation, and barrier reinforcement. These findings support the therapeutic potential of pEGF as a stable, cost-effective alternative to conventional EGF in dermatological applications.

X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of Ecadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led todownregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2′-O-methoxyethyl andphosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin– targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.

The optimal frequency for hemodialysis in older adults with end-stage kidney disease (ESKD) has not been established. This study aims to investigate whether a twice-weekly dialysis schedule using an incremental approach can reduce hospitalization rates in the elderly with incident dialysis, compared with conventional thrice-weekly dialysis. Methods: We have designed a pragmatic randomized controlled trial to compare the effects of twice-weekly versus thrice-weekly hemodialysis in 428 ESKD individuals (dropout rate 20%) aged 60 years or older with residual kidney function (urine output, >500 mL/ day). The trial will be conducted across 18 referral hospital-based dialysis centers in Korea. Individual participants will be randomized to either a twice-weekly (with incremental approach) or thrice-weekly dialysis group and will be followed up for 24 months. The primary outcome of the study is all-cause hospitalization rate, while secondary outcomes include dialysis-specific hospitalization rates, mortality, quality of life, frailty, and cost-effectiveness. Participants have the flexibility to transfer to other dialysis centers as needed. The decision to increase dialysis frequency will be made by the treating physicians. The study is ongoing and will be completed in May 2026. Conclusion: This study will provide valuable insights into the benefits and risks of twice-weekly dialysis with an incremental approach in elderly with residual kidney function compared to thrice-weekly dialysis.

Background: The effects of perioperative ketamine and esketamine on postoperative nausea and vomiting (PONV) remain unclear. This study aimed to clarify their impact on PONV and related adverse events. Methods: We performed a meta-analysis of randomized controlled trials and observational studies comparing ketamine or esketamine with control agents. The primary outcome was a pooled analysis of PONV and nausea-only data. PONV, postoperative nausea (PON), and postoperative vomiting (POV) were also analyzed separately. Subgroup analyses were conducted by comparator type (placebo, opioid, or non-opioid) and dose categories. Meta-regression was used to assess dose-response relationships. Results: Fifty-five studies (n = 6676) were included. Ketamine and esketamine did not significantly reduce the incidence of pooled PONV risk (risk ratio [RR]: 0.95, 95% CI [0.87–1.04], P = 0.274). No benefit was found versus placebo. Compared with opioids, PONV was reduced (RR = 0.50, 95% CI [0.32–0.77], P = 0.002), but not in the pooled analysis (RR = 0.69, 95% CI [0.43–1.08], P = 0.107). Conversely, compared with non-opioid controls, ketamine/esketamine increased the pooled PONV risk (RR = 1.46, 95% CI [1.03–2.05], P = 0.032). No significant dose-response relationship was found. Both agents increased hallucinations (RR = 1.73, 95% CI [1.35–2.20], P = 0.0002) and drowsiness (RR = 2.18, 95% CI [1.13–4.21], P = 0.024). Conclusions Ketamine and esketamine did not significantly reduce PONV overall. While they showed benefits compared with opioid-based regimens, they may be less effective than non-opioid adjuvants. However, their neuropsychiatric and sedative risks warrant cautious use.

Objective: Cognitive impairment is common in patients with Parkinson’s disease (PD), and few pharmacological options are available for treating this condition. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), which was previously shown to be effective in populations at risk of Alzheimer’s disease, on cognitive function in individuals with PD. Methods: Twenty-three individuals with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to the intervention (n=16) or control (n=7) groups. The intervention group completed a 12-week, home-based, tablet-based cognitive training program (25–30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention. Results: The adherence rate was 79.36%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and the Controlled Oral Word Association Test, while no changes were observed in the control group. Analysis of covariance confirmed greater SVLT improvement in the intervention group (F statistic=7.15, p=0.015, partial η2=0.28). Conclusion SUPERBRAIN is feasible and can improve cognitive function in individuals with PD-MCI.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

Purpose: Prostate cancer ranks as the second most common cancer in men globally, representing a significant cause of cancer-related mortality. Metastasis, the spread of cancer cells from the primary site to distant organs, remains a major challenge in managing prostate cancer. Pyruvate dehydrogenase kinase 4 (PDK4) is implicated in the regulation of aerobic glycolysis, emerging as a potential player in various cancers. However, its role in prostate cancer remains unclear. This study aims to analyze PDK4 expression in prostate cancer cells and human samples, and to explore the gene's clinical significance. Materials and Methods: PDK4 expression was detected in cell lines and human tissue samples. Migration ability was analyzed using Matrigel-coated invasion chambers. Human samples were obtained from the Kyungpook National University Chilgok Hospital. Results: PDK4 expression was elevated in prostate cancer cell lines compared to normal prostate cells, with particularly high levels in DU145 and LnCap cell lines. PDK4 knockdown in these cell lines suppressed their invasion ability, indicating a potential role of PDK4 in prostate cancer metastasis. Furthermore, our results revealed alterations in epithelial-mesenchymal transition markers and downstream signaling molecules following PDK4 suppression, suggesting its involvement in the modulation of invasion-related pathways. Furthermore, PDK4 expression was increased in prostate cancer tissues, especially in castration-resistant prostate cancer, compared to normal prostate tissues, with PSA and PDK4 expression showing a significantly positive correlation. Conclusions PDK4 expression in prostate cancer is associated with tumor invasion and castration status. Further validation is needed to demonstrate its effectiveness as a therapeutic target.

Purpose: Emphysematous pyelonephritis (EPN) is a life-threatening disease requiring immediate treatment. This multicenter retrospective cohort study aimed to analyze the mortality rate and risk factors associated with EPN. Materials and Methods: Between January 2011 and February 2021, 217 patients diagnosed with EPN via computed tomography who visited 14 teaching hospitals were retrospectively analyzed. Clinical data, including age, sex, comorbidities, Huang and Tseng classification, hydronephrosis, acute kidney injury, blood and urine tests, surgical interventions, percutaneous drainage, and conservative treatments, were compared between the survival and death groups. Risk factors for mortality due to EPN were analyzed using univariate and multivariate methods. Results: The mean age of survivors and deceased patients was 67.8 and 69.0 years, respectively (p=0.136). The sex distribution (male/female) was 48/146 and 8/15, respectively (p=0.298). Of the 217 patients, 23 died, resulting in a mortality rate of 10.6%. In univariate analysis, the Huang and Tseng classification (p=0.004), platelet count (p=0.005), and acute kidney injury (p=0.007) were significantly associated with mortality from EPN. In multivariate analysis, only the Huang and Tseng classification (p=0.029) was identified as a risk factor. Mortality rates according to the Huang and Tseng classification were as follows: class I (5.88%), class II (7.50%), class IIIa (14.28%), class IIIb (25.00%), and class IV (23.07%). Conclusions EPN is associated with a high mortality rate. Among various clinical factors, the Huang and Tseng classification was the most significant indicator for predicting mortality.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.