Keimyung University

Reactive oxygen species play an integral role in physiological signaling but contribute to pathology when dysregulated. Elevated ROS levels in diseased tissues such as tumors, inflamed sites, and ischemic regions present unique biochemical triggers for targeted drug delivery. Furthermore, strategies utilizing exogenously generated ROS (e.g., via photodynamic action) provide an alternative route for spatiotemporal control. This review summarizes recent advances in ROS-responsive systems, beginning with the chemistry of ROS-cleavable linkers and the design of nanocarrier platforms capable of spatiotemporally controlled release. The integration of these carriers with theranostic functions is highlighted as a strategy to enhance selectivity and reduce systemic toxicity. Applications across oncology, inflammatory disorders, ischemia-reperfusion injury, and regenerative medicine illustrate the breadth of therapeutic potential. Key design considerations including sensitivity thresholds, payload compatibility, and surface functionalization are discussed alongside translational challenges such as stability, reproducibility, and scalability. Emerging opportunities, notably patient-specific redox profiling and biosensor-guided adaptive delivery are identified as promising routes to clinical translation. By bridging redox biology with materials science and nanomedicine, ROS-triggered drug delivery platforms demonstrate the capacity to exploit endogenous oxidative cues for improved therapeutic precision and safety, positioning them as a transformative approach in the development of next-generation controlled release systems.

BackgroundDespite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited.MethodsIn this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years. Safety was also assessed.ResultsOf 3048 patients who underwent randomization, 1526 were assigned to the intensive-targeting group and 1522 to the conventional-targeting group. The median follow-up was 3.0 years. The median LDL cholesterol level during the trial was 56 mg per deciliter (1.4 mmol per liter) in the intensive-targeting group and 66 mg per deciliter (1.7 mmol per liter) in the conventional-targeting group. A primary end-point event occurred in 100 patients (Kaplan–Meier estimate of cumulative incidence, 6.6%) in the intensive-targeting group and in 147 patients (Kaplan–Meier estimate of cumulative incidence, 9.7%) in the conventional-targeting group (hazard ratio, 0.67; 95% confidence interval, 0.52 to 0.86; P=0.002). The incidence of prespecified safety end points was similar in the two trial groups, except for a lower incidence of creatinine elevation in the intensive-targeting group.ConclusionsAmong patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter. (Funded by the Cardiovascular Research Center and Yuhan; Ez-PAVE ClinicalTrials.gov number, NCT04626973.)

In 2024, the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) approved 50 "novel" drugs, either as new molecular entities under New Drug Applications, or as new therapeutic biologics under Biologics License Applications.These drugs have never been approved or marketed in the U.S.This review presents a focused discussion on selected novel drugs used in disease conditions designated by American College of Clinical Pharmacy (ACCP) pharmacotherapy didactic curriculum toolkit.The discussed novel drugs include: vadadustat for anemia in chronic kidney disease; aprocitentan for refractory hypertension; landiolol for supraventricular tachycardia; deuruxolitinib for alopecia areata; lebrikizumab for atopic dermatitis; donanemab for both mild cognitive impairment and Alzheimer's disease; xanomeline-trospium chloride, an antipsychotic agent for schizophrenia; and ensifentrine as a maintenance therapy for COPD.This review aims to provide essential clinical pharmacology and therapeutic insights to support the pharmacy education and clinical decision-making regarding these newly approved agents.

Patients with Liver Hepatocellular carcinoma (LIHC) have a poor prognosis due to late-stage diagnosis and the limited efficacy of drug treatments. Dysregulation of nuclear pore complex (NPC) components, particularly nucleoporins (NUPs), may play a role in tumor progression. However, the specific role of NUP205 in LIHC has not been comprehensively investigated. We evaluated the expression, prognostic significance, epigenetic regulation, microRNA(miRNA) interactions, drug sensitivity, and biological functions of NUP205 in LIHC. Comprehensive bioinformatics analyses were performed using publicly available databases and web-based analysis platforms, including The Cancer Genome Atlas (TCGA), UALCAN, and the Kaplan-Meier Plotter (KM Plotter), among others. In vitro validation was performed using small interfering RNA (siRNA)-mediated knockdown of NUP205 in HepG2 cells, followed by quantitative reverse transcription PCR (RT-qPCR), apoptosis assay and wound-healing assay. NUP205 expression was significantly elevated in patients with LIHC and was associated with advanced clinicopathological features and poor prognosis. Promoter hypomethylation and miRNAs were identified as regulatory mechanisms influencing NUP205 expression. Increased NUP205 levels were associated with resistance to multiple chemotherapeutic agents. NUP205 knockdown significantly reduced messenger RNA (mRNA) expression in HepG2 and PLC/PRF/5 cells, and also reduced the expression of Transmembrane protein 209 (TMEM209) in HepG2 cells and improved sensitivity to doxorubicin. NUP205 expression was consistently associated with adverse clinicopathological features, poor prognosis, and altered drug sensitivity in LIHC. Integrative analyses suggest that NUP205 dysregulation may be linked to epigenetic and miRNA-associated regulatory mechanisms. These findings support NUP205 as a candidate prognostic biomarker and a potential regulatory factor in LIHC, warranting further mechanistic and protein-level validation. Further research is necessary to fully elucidate its underlying mechanisms and potential clinical applications.

Hypertensive intracerebral hemorrhage (ICH) of the basal ganglia mostly occurs unilaterally. Therefore, we describe the differences between the morphological parameters of lesional and non-lesional carotid arteries using initial computed tomography angiography. A total of 284 patients were diagnosed with nontraumatic ICH between March 2020 and October 2024. Hypertensive basal ganglia hemorrhages were included with a total of 64 patients enrolled in this study. Using an IntelliSpace portal, morphological examination was conducted on both the intracranial and extracranial segments on each side of the carotid artery (intra- and extra group). The total length, short distance, maximal diameter, and minimal diameter of each segment was calculated. In both the intra- and extra-groups, the measured variables (Tortuosity, short distance, length, Dmin, Dmax) demonstrated no statistically significant differences between the ICH and non-ICH sides. There were no statistically significant differences in the five measured parameters after adjusting for the bleeding side to compensate for left/right (Lt/Rt) anatomical differences. To evaluate age-related alterations in blood vessels, we categorized individuals into 2 groups: those aged $$\ge$$65 and $$\le$$65 years, ensuring a comparable distribution across the groups. Subsequently, we analyzed morphological alterations in the blood vessels of both groups. Significant differences in tortuosity and short distances within the Intra group were observed using paired t-tests. (tortuosity- p = 0.011, short distance- p = 0.041) Morphological analysis revealed that the bilateral carotid arteries did not differ between the intracranial and extracranial segments. However, some parameters (tortuosity and short distance) exhibited morphological changes associated with aging.

As climate change (including global warming) intensifies the frequency and intensity of extreme weather events, ambient heat (high temperature) has emerged as a key factor determining global health risks. Chronic kidney disease (CKD), which affects approximately 10% of the world's population, is an important public health challenge as it contributes significantly to comorbidities and socioeconomic burdens. The kidneys play an essential role in maintaining fluid homeostasis and electrolyte balance. However, individuals with decreased kidney function are more susceptible to physiological vulnerabilities in situations of heat stress. Although it is known that patients with CKD may be vulnerable to environmental stress factors, including heat, large-scale empirical evidence to quantify the impact of ambient high temperature exposure as a clinical risk factor is still limited.Using a national population-based dataset incorporating ERA-5 Land high-resolution reanalysis temperature data and National Health Insurance Service (NHIS) records in South Korea, this study investigated the association between extreme ambient heat and all-cause mortality in patients with CKD. Based on sex and age, 1,145,237 CKD patients with 1:1 matching with the non-CKD cohort were identified and bidirectional, time-stratified case-crossover study was conducted. Distributed Lag Non-linear Model (DLNM) was applied to capture nonlinear exposure-response relationships and lag effects (lag 0 to 6 days) together. Extreme heat was defined as the 99th percentile of the temperature distribution by district (si-gun-gu) and compared with the 75th percentile as the reference temperature (Temperature percentile was used to take into account regional temperature adaptations).Analysis of 223,949 confirmed deaths in the CKD group revealed that extreme heat exposure was significantly associated with an increased risk of all-cause mortality (Odds Ratio[OR] 1.041; 95% CI 1.002–1.081; p=0.041). On the other hand, no significant association was observed in the matched non-CKD group (OR 0.993; 95% CI 0.951–1.036). Subgroup analysis revealed greater vulnerability in females, the elderly (≥65 years), and those with hypertension. These results suggest that heat stress may exacerbate vascular endothelial dysfunction and fluid volume dysregulation, especially in patients with decreased renal concentration capacity, thereby increasing the risk of fatal outcomes. Furthermore, sensitivity analysis with various model settings (alternative reference temperature, shorter lag structures) also confirmed the robustness of the results.Taken together, this study provides a robust basis for supporting that CKD patients are disproportionately vulnerable to the negative effects of short-term extreme heat waves. From an interdisciplinary perspective, this study highlights the need for environmental risk profiling in CKD population groups. In a situation where the climate is warming more rapidly, it emphasizes the need for targeted prevention strategies such as customized heat wave-health alert systems and preemptive clinical monitoring to reduce the health burden on vulnerable CKD populations.