In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Background: Circulating tumor DNA (ctDNA) profiling from peripheral blood allows relatively noninvasive monitoring of solid tumors; however, its utility post-surgery or chemotherapy in colorectal cancer remains underexplored. We evaluated the clinical implications of a ctDNA next-generation sequencing (NGS) panel post-surgery or chemotherapy in patients with colorectal cancer. Methods: We collected samples from 23 patients with colorectal cancer (17 men, median age 65 yrs) at baseline and post-surgery or chemotherapy at the National Cancer Center, Korea, between January 2021 and September 2023. ctDNA was analyzed using an NGS panel including 46 genes, and variant allele frequencies (VAFs) were determined. Followup samples were analyzed using the NGS panel or droplet digital PCR (ddPCR) when probes were available. Clinical status was compared with ctDNA results, and survival was analyzed using a time-dependent Cox model. Results: Mutations were identified in 13 out of 14 patients (92.8%) with stage II/III cancer and in all nine patients (100%) with stage IV cancer. Mutations were detected in KRAS (N = 15, 65%), APC (N = 8, 35%), TP53 (N = 7, 30%), PIK3CA (N = 5, 22%), and RET (N = 4, 17%). A 1% increase in KRAS and TP53 VAFs was associated with 48% and 32% increased mortality risk, respectively. Changes in VAF correlated well with clinical findings. Conclusions The detection of and an increase in KRAS and TP53 VAFs were associated with poor prognosis. ddPCR-based ctDNA monitoring results were comparable to those obtained with the NGS panel. ctDNA monitoring during treatment is clinically informative in managing colorectal cancer.

Background: Gout is a type of inflammatory arthritis caused by monosodium urate crystal deposits, and the prevalence of this condition has been increasing. This study aimed to determine the combined effects of genetic risk factors and lifestyle habits on gout, using data from a Korean cohort study. Identifying high-risk individuals in advance can help prevent gout and its associated disorders. Methods: We analyzed data from the Korean Genome and Epidemiology Study-Urban Health Examinees cohort (KoGES-HEXA). Genetic information of the participants was collected at baseline, and gout cases were identified based on patient statements. The polygenic risk score (PRS) was calculated using nine independent genome-wide association study datasets, and lifestyle factors and metabolic syndrome status were measured for each participant using the KoGES. Logistic regression models were used to estimate the odds ratios (ORs) for gout in relation to genetic risk, lifestyle habits, and metabolic health status, after adjusting for age and sex. Results: Among 44,605 participants, 617 were diagnosed with gout. Gout was associated with older age, higher body mass index, and higher prevalence of hypertension, diabetes, and hypertriglyceridemia. High PRS, unfavorable lifestyle habits, and poor metabolic profiles were significantly associated with an increased risk of gout. Compared with that in the low-genetic-risk and healthy lifestyle group or ideal metabolic profile group, the risk of gout was increased in the high-genetic-risk plus unfavorable lifestyle (OR, 3.64; 95% confidence interval [CI], 2.32–6.03) or poor metabolic profile (OR, 7.78; 95% CI, 4.61–13.40) group.Conversely, adherence to favorable lifestyle habits significantly reduced gout risk, especially in high-genetic-risk groups. Conclusion Genetic predisposition and unhealthy lifestyle habits significantly increase the risk of gout. Promoting healthy lifestyle habits is crucial to prevent the development of gout, particularly in individuals with high genetic susceptibility.

Background: Gout is a type of inflammatory arthritis caused by monosodium urate crystal deposits, and the prevalence of this condition has been increasing. This study aimed to determine the combined effects of genetic risk factors and lifestyle habits on gout, using data from a Korean cohort study. Identifying high-risk individuals in advance can help prevent gout and its associated disorders. Methods: We analyzed data from the Korean Genome and Epidemiology Study-Urban Health Examinees cohort (KoGES-HEXA). Genetic information of the participants was collected at baseline, and gout cases were identified based on patient statements. The polygenic risk score (PRS) was calculated using nine independent genome-wide association study datasets, and lifestyle factors and metabolic syndrome status were measured for each participant using the KoGES. Logistic regression models were used to estimate the odds ratios (ORs) for gout in relation to genetic risk, lifestyle habits, and metabolic health status, after adjusting for age and sex. Results: Among 44,605 participants, 617 were diagnosed with gout. Gout was associated with older age, higher body mass index, and higher prevalence of hypertension, diabetes, and hypertriglyceridemia. High PRS, unfavorable lifestyle habits, and poor metabolic profiles were significantly associated with an increased risk of gout. Compared with that in the low-genetic-risk and healthy lifestyle group or ideal metabolic profile group, the risk of gout was increased in the high-genetic-risk plus unfavorable lifestyle (OR, 3.64; 95% confidence interval [CI], 2.32–6.03) or poor metabolic profile (OR, 7.78; 95% CI, 4.61–13.40) group.Conversely, adherence to favorable lifestyle habits significantly reduced gout risk, especially in high-genetic-risk groups. Conclusion Genetic predisposition and unhealthy lifestyle habits significantly increase the risk of gout. Promoting healthy lifestyle habits is crucial to prevent the development of gout, particularly in individuals with high genetic susceptibility.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.