Background: Renal function declines with age as the kidneys become more vulnerable to inflammation and cellular senescence. This study examined gene expression changes linked to renal aging and assessed whether short-term calorie restriction (CR), a known anti-aging intervention, could reverse these alterations. Methods: Using RNA-seq data, we applied bioinformatics, systems biology, and molecular biology approaches to identify differentially expressed genes during aging and under CR. Gene Ontology and pathway analyses revealed that both aging and CR altered the expression of key senescence-associated secretory phenotype (SASP) genes, including cytokines and chemokines (Il1b, Ccl3, Ccl5, Il19, and Il24) and growth factors (Timp1 and Mmp12). Results: Renal aging is also associated with an increased expression of cell cycle arrest markers (p15INK4B (Cdkn2b), p16INK4A (Cdkn2a), and p21 (Cdkn1a)), which are suppressed by CR, suggesting a link to cellular senescence. Quantitative analysis of renal tissue samples confirmed the age-associated upregulation of these genes at the transcriptional level, and CR effectively attenuated these changes. Among these genes, we focused on the members of the interleukin 20 (IL-20) family, particularly Il19 and Il24. Furthermore, experimental induction of cellular senescence using H2O2 resulted in elevated Il19 and Il24 expression alongside other senescence markers. These findings suggest that aging and short-term CR regulate the IL-20 family expression, potentially influencing cellular senescence. Conclusion Our study suggests that Il19 and Il24 are associated with age-related renal decline and may represent hypothesis-generating candidates, highlighting potential molecular targets for future mechanistic and therapeutic investigations.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Purpose: To evaluate functional and anatomical outcomes, including vessel morphology parameters on swept-source optical coherence tomography angiography (SS-OCTA), in eyes with neovascular age-related macular degeneration (nAMD) switched to brolucizumab. Methods: This retrospective study included 37 eyes with nAMD that were switched from other anti–vascular endothelial growth factor (anti-VEGF) agents to intravitreal brolucizumab. Best-corrected visual acuity (BCVA), injection intervals, central subfield thickness (CST), pigment epithelial detachment (PED), and presence of retinal fluid were compared between baseline and 12 months after switch. SS-OCTA images were analyzed to quantify macular neovascularization (MNV) area, vessel density, fractal dimension (FD), and lacunarity. Results: Switching to brolucizumab significantly extended injection intervals and reduced CST, PED height and retinal fluid, while maintaining BCVA at 12 months. Quantitative OCTA analysis showed reductions in MNV area and FD following the switch. When compared with the preceding 12 months of other anti-VEGF therapy, FD still showed a significant reduction after brolucizumab treatment (p = 0.019). Intraocular inflammation occurred in one eye and resolved with topical corticosteroids. Conclusions Intravitreal brolucizumab demonstrated favorable anatomical improvements and maintained visual outcomes over 12 months. Quantitative OCTA biomarkers, particularly FD, may serve as imaging indicators of disease activity and treatment response in eyes with nAMD undergoing a therapy switch.

Purpose: This study aimed to quantitatively evaluate longitudinal changes in drusen area and volume over 36 months in South Korean patients and to identify the factors associated with these changes and the development of advanced age-related macular degeneration (AMD). Methods: In this retrospective study, 38 eyes from 38 patients diagnosed with drusen were analyzed. The drusen area and volume were measured using spectral-domain optical coherence tomography (SD-OCT; Cirrus 5000, Carl Zeiss Meditec) with an automated retinal pigment epithelium elevation map algorithm. To minimize bias from variable follow-up intervals, an annualized classification framework was adopted. Based on percentage change in drusen area within the 5-mm circle, eyes were categorized as progressed (increase >20%), stable (change within ±20%), or regressing (decrease >20%). Results: Both drusen area and volume increased significantly up to 24 months (area, p = 0.003; volume, p = 0.028) and then showed a modest decline at 36 months, remaining above baseline levels. No significant difference in the proportions of progressed, stable, or regressing eyes was observed across 12-month intervals or compared with baseline (all p > 0.05). A larger baseline 5-mm drusen area was significantly associated with the development of advanced AMD (adjusted odds ratio, 2.818; 95% confidence interval, 1.022–7.767; p = 0.045). Eyes that exhibited at least one episode of drusen regression showed a higher incidence of advanced AMD (36.8% vs. 5.3%, p = 0.042). Conclusions Drusen in South Korean patients demonstrated dynamic morphological remodeling over time. Drusen regression was not a benign phenomenon but rather a potential high-risk marker for progression to advanced AMD. These findings highlight the importance of population-specific, quantitative SD-OCT monitoring for early risk stratification in East Asian eyes.

Purpose: To investigate long-term topographic progression of the geographic atrophy (GA) area based on location and analyze its correlation with visual acuity in patient with GA secondary to non-neovascular age-related macular degeneration in South Korean patient cohort. Methods: Medical records and imaging data of 58 eyes from 34 patients with GA were retrospectively reviewed using fundus autofluorescence (FAF). Regions of interest were defined as concentric ring-shaped zones with diameters of 1, 2, 3, and 4 mm centered on the fovea (zones 0–3), each subdivided into superior, temporal, inferior, and nasal sectors. The foveal center was determined using optical coherence tomography, and sectoral GA areas were measured on FAF with the semiautomated software (RegionFinder ver. 2.6.2.0). Correlations among GA area enlargement, GA growth rate, and changes in best-corrected visual acuity (BCVA) were evaluated. Results: The mean GA area enlarged from 4.10 to 16.57 mm2 and mean BCVA decreased from 0.34 to 1.06 logMAR at 5 years of follow-up. The mean overall GA area growth rate was 1.96 mm2/yr. During yearly follow-up from baseline to 5 years, there were significant differences in GA growth rate of zone 3 inferior (p < 0.005). The GA area changes of zone 3 inferior was significantly correlated with BCVA. In the subgroup with BCVA decreased under 1.0 logMAR during follow-up, there was a higher growth rate in zone 2 nasal sector, 2 to 3 years before. Conclusions The overall GA growth rate was 1.96 mm2/yr in the 5-year follow-up of our cohort. Changes in the GA growth rate in the nasal perifoveal region (zone 2) may be associated with subsequent clinically meaningful visual decline.

Objectives: This pilot study examined the preliminary findings associated with a cognitive-load-controlled structured psychodrama program on affect, fear of negative evaluation, and general psychopathology in long-term psychiatric inpatients, most of whom had schizophrenia spectrum disorders. Methods: A single-group pre-post design was used. A total of 125 stabilized long-term psychiatric inpatients participated in a 25-session structured psychodrama program. To enhance measurement validity in consideration of participants’ cognitive characteristics, self-report measures were administered in small-group sessions with individualized explanation. Primary outcomes (Positive and Negative Affect Schedule [PANAS], Affect Balance Scale [ABS], and Brief Fear of Negative Evaluation [BFNE]) were assessed in 125 participants, and the secondary outcome (Brief Psychiatric Rating Scale [BPRS]) was assessed in a randomly selected subgroup of 53 participants. Results: After the intervention, positive affect significantly increased, whereas negative affect significantly decreased on both the PANAS and ABS (all p＜0.001). BFNE scores significantly decreased from 43.14 to 28.94 (p＜0.001). Total BPRS scores also significantly decreased from 47.49 to 34.76 (p＜0.001), with notable improvements in depressive mood, anxiety, tension, somatic concern, and emotional withdrawal. Conclusion A structured psychodrama program may be a feasible and potentially beneficial psychosocial intervention for long-term psychiatric inpatients. However, given the single-group pre-post design and other methodological limitations, the magnitude of the observed changes should be interpreted cautiously. These findings may serve as preliminary data for future controlled trials.

Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

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.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.