The Wikstroemia genus is highly regarded in traditional Asian medicine for its diverse therapeutic applications, including the treatment of inflammatory and infectious conditions. Among its members,Wikstroemia trichotoma (Thunb.) Makino remains a promising medicinal resource which is yet to be chemicallycharacterized. To ensure the chemical consistency of W. trichotoma, we developed and validated the first HPLC method for the simultaneous quantification of three major marker compounds: chlorogenic acid (1), miconioside B (2), and matteucinol 7-O-apiofuranosyl(1→6)-glucopyranoside (3). Chromatographic separation was achieved on a C18 column using a gradient elution system of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection was optimized using a photodiode array (PDA) detector at 280 and 325 nm, based on the absorption maxima of the markers. The method was validated in accordance with the International Council for Harmonisation (ICH) and the Ministry of Food and Drug Safety (MFDS) guidelines. The results demonstrated high linearity (r2 > 0.999), with limits of detection and quantitation ranging from 4.28–6.42 and 12.97–19.47 μg/ mL, respectively. Intra- and inter-day precision (% RSD ≤ 1.83%) and accuracy (recoveries of 92.5–101.7%) were within acceptable limits. Quantitative analysis revealed the contents of 1, 2, and 3 in the W. trichotoma extract to be 19.9, 139.8, and 264.9 mg/g, respectively. This study provides a reliable analytical framework for the standardization, quality control, and future pharmacological evaluation of W. trichotoma.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background: Biologics effectively improve psoriatic skin lesions, but their impact on itch relief remains unclear. Objective: To evaluate itch improvement in severe psoriasis patients treated with ustekinumab or guselkumab. Methods: This retrospective study analyzed patients with severe psoriasis who completed initial efficacy evaluations after treatment with either biologic. Itch severity was assessed using numerical rating scale (NRS), visual analog scale, and verbal rating scale. NRS improvement was evaluated after three injections. Results: Among 108 patients (74 on ustekinumab, 34 on guselkumab), 77 (71.3%) had moderate-to-severe itch (NRS ≥4) at baseline. Of these, 63 (81.8%) achieved an NRS improvement of ≥4 points. Ustekinumab showed greater itch relief compared to guselkumab in NRS (p=0.033). On the other hand, guselkumab showed more reduction for psoriatic skin lesions than ustekinumab in the Psoriasis Area and Severity Index (p=0.040). In the moderate-to-severe itch group, patients with large plaques experienced significantly greater improvement in NRS than those with small plaques (p=0.012). Conclusion While guselkumab is generally preferred for psoriatic skin lesions, ustekinumab may provide superior itch relief.

Purpose: Biliary atresia (BA) is a rare but progressive cholangiopathy and the leading cause of pediatric liver transplantation worldwide. The Korean Association of Pediatric Surgeons (KAPS) has conducted three national surveys (2001, 2011, and 2023) to assess long-term trends in the diagnosis, treatment, and outcomes of BA. This study provides a comparative analysis of the 2nd and 3rd national surveys, with reference to selected findings from the 1st survey. Methods: This study included 453 patients from the 3rd national survey (2011–2021) and 435 patients from the 2nd survey (2001–2010), all of whom underwent Kasai portoenterostomy. Data were collected via electronic case report forms from pediatric surgical centers nationwide. Comparisons were made regarding demographics, clinical features, diagnostic patterns, operative details, follow-up outcomes, and survival. Kaplan–Meier analysis was used to evaluate long-term survival. Results: The mean number of BA patients per year remained stable between surveys (43.5 in the 2nd, 41.18 in the 3rd), though centralization of care increased, with 61.5% of cases managed by two major institutions in the 3rd survey. The median age at surgery decreased, and the use of preoperative imaging (especially magnetic resonance cholangiopancreatography) increased. The 10-year native liver survival rate declined from 59.8% to 53.7%, while overall 10-year survival improved slightly (92.9% to 93.2%). Postoperative complications, such as cholangitis and liver failure, persisted but were better categorized. The 3rd survey also reported improved mortality (4.9%) and reduced follow-up loss (11.5%) compared to the 2nd survey. Conclusion While overall survival after Kasai operation has remained high and even improved, native liver survival has slightly declined. The findings reflect earlier diagnosis, more consistent diagnostic imaging, and increasing centralization of care. These trends underscore the importance of long-term nationwide data collection in guiding future strategies for BA management in Korea.

Purpose: This study aims to investigate and compare the incidence, demographic characteristics, clinical manifestations, preoperative diagnostic methods, anatomical classifications, associated anomalies, operative treatments, and postoperative outcomes of patients with intestinal atresia treated by the members of the Korean Association of Pediatric Surgeons (KAPS) through three nationwide surveys. Methods: KAPS conducted 3 national surveys in 1998, 2010, and 2024 to examine the patients diagnosed with intestinal atresia. In preparation for the survey, we developed a customized case registration form to obtain data on patient sex, birth weight, gestational age, clinical manifestations, preoperative diagnostic methods, anatomical types, associated anomalies, operative treatments, and postoperative outcomes. Authorized KAPS members completed the case registration form. Results: The first, second, and third national surveys included 218, 222, and 236 individuals diagnosed with intestinal atresia, respectively. The male-to-female ratios were 1.5:1, 1.1:1, and 1.1:1, respectively. The first, second, and third national surveys revealed that 34.3%, 43.3%, and 53.4% of patients were born before 37 weeks of gestation, respectively. Additionally, 28.7%, 32.0%, and 40.7% of patients had a birth weight under 2,500 g. In the third national survey, duodenoduodenostomy was the most common procedure, performed in 70 out of 82 patients diagnosed with duodenal atresia. Resection and anastomosis were the main surgical procedures conducted in 47 out of 54 cases of jejunal atresia and 74 out of 92 cases of ileal atresia. The mortality rates in the first, second, and third national surveys were 13.8%, 3.6%, and 1.3% respectively, with the lowest rate observed in the third national survey. Conclusion These national surveys offer valuable insights into the current state of intestinal atresia, including specific surgical interventions and postoperative outcomes in South Korea. For pediatric surgeons aiming to enhance their understanding of intestinal atresia and its treatment options, these surveys could be an indispensable resource and guide.

Transcription factor CP2-like protein 1 (Tfcp2l1), a naïve pluripotency transcription factor, is expressed in both early embryonic and adult tissues, where it enforces pluripotency of embryonic stem cells (ESCs) and stemness features of cancer cells, respectively. However, the detailed molecular pathways by which Tfcp2l1 is regulated in early embryonic development and cancer cells remain unknown. Here, we identified the pseudophosphatase dual specificity phosphatase 27 (Dusp27), also known as serine/threonine/tyrosine-interacting like-2, as a novel Tfcp2l1-interacting protein through a sterile alpha motif-like domain in the C-terminus of Tfcp2l1 in murine ESCs. The interaction between Dusp27 and Tfcp2l1 was dependent on the cell cycle status and increased during mitosis. Expression of Dusp27 was upregulated during naïve pluripotency and repressed during spontaneous differentiation of murine ESCs. Ectopic expression of Dusp27 enhanced the transcriptional activity of Tfcp2l1 and promoted features associated with the naïve pluripotent state, while suppressing meso-endodermal lineage differentiation. The present study demonstrates that Dusp27 is a novel positive regulator of Tfcp2l1 through a physical interaction and thereby fine-tunes the pluripotency status and meso-endodermal differentiation of murine ESCs.

A rare disease is generally defined as a medical condition that affects a small proportion of the population, though specific thresholds vary across countries. Despite regional differences, these definitions consistently reflect the low prevalence of such conditions, the limited availability of effective treatments, and the pressing need for targeted research and regulatory support. As a result of their rarity and low commercial potential, rare diseases have historically represented an area of market failure, where investment and research have been limited and often neglected. However, since the 1990s, each country has guaranteed continuous support to research and development projects to promote the advancements of rare disease treatments, achieving a growth rate greater than that of the entire pharmaceutical industry. In this review, we examine the status of orphan drug development using an advanced therapy medicinal product (ATMP) approach in the growing rare disease market, with a particular focus on cell therapies and gene therapies, which constitute the most actively developed and clinically applied categories within ATMPs. We also explore strategic approaches through which the orphan drug industry can utilize ATMPs, especially these two modalities, to enhance its competitiveness.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. Tomitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. No-tably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.