1.Aβ₁₋₄₀ Enhances Platelet Sensitivity to Thrombin via NADPHOxidase–ROS Signaling and Integrin α IIb β₃ Engagement
Been KIM ; Bo Kyung LEE ; Jung-Ae KIM ; Yi-Sook JUNG
Biomolecules & Therapeutics 2026;34(2):365-378
Alzheimer’s disease (AD) is increasingly recognized as a disorder with significant vascular involvement, with microvascular damage and thromboinflammation often preceding classical amyloid pathology by several years. Elevated levels of prothrombin and thrombin, along with aberrant platelet activation, have been reported in individuals with AD. We hypothesized that platelet hyperactivity in AD results from an exaggerated response to thrombin in the presence of elevated amyloid beta 1-40 (Aβ₁₋₄₀), a peptide that accumulates during the early stages of AD. Platelet activation in response to Aβ₁₋₄₀ and thrombin was assessed using aggregation assays with an aggregometer, adhesion measurements by confocal microscopy, and spreading via both confocal microscopy and scanning electron microscopy. Reactive oxygen species (ROS) production and integrin α IIbβ 3 activation were quantified by flow cytometry. The roles of NADPH oxidase (NOX), ROS, and integrin signaling were examined using selective inhibitors. Aβ₁₋₄₀ significantly enhanced thrombin-induced platelet adhesion, aggregation, and spreading via NOX-derived ROS and integrin α IIbβ 3 activation. Aβ₁₋₄₀ also promoted platelet binding to fibrinogen and cerebrovascular endothelial cells, accompanied by distinct morphological changes. Inhibition of NOX or integrin α IIbβ 3 significantly reduced these effects. These findings identify a novel Aβ₁₋₄₀–NOX–ROS–integrin α IIbβ 3 axis that drives platelet hyperactivation and cerebrovascular interactions in AD.Targeting this pathway with antithrombotic or antioxidative strategies may offer therapeutic potential in mitigating AD-associated vascular pathology.
2.Outcomes of oral antidiabetic drugs in metabolic dysfunction-associated steatotic liver disease: a nationwide target trial emulation study
Heejoon JANG ; Yeonjin KIM ; Yoo Kyoung LIM ; Dong Hyeon LEE ; Sae Kyung JOO ; Bo Kyung KOO ; Gi-Ae KIM ; Woojoo LEE ; Stefano ROMEO ; Won KIM ;
Clinical and Molecular Hepatology 2026;32(2):737-750
Background/Aims:
Patients with concurrent type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) face elevated cardiovascular risks. However, optimal oral antidiabetic drug (OAD) selection for this population remains unclear.
Methods:
Using the Korean National Health Information Database, we conducted a target trial emulation comparing cardiovascular outcomes among patients with T2DM and MASLD (defined by fatty liver index ≥30) who initiated sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas with metformin. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke.
Results:
Among 71,071 patients (331,726 person-years), SGLT2 inhibitor users experienced a significantly lower MACE risk compared to sulfonylurea users (adjusted subdistribution hazard ratio [aSHR], 0.44; 95% confidence interval [CI], 0.31–0.62). SGLT2 inhibitors also demonstrated a lower MACE risk compared to thiazolidinediones (aSHR, 0.61; 95% CI, 0.39–0.96) and DPP-4 inhibitors (aSHR, 0.59; 95% CI, 0.42–0.96). Cardiovascular mortality risk was notably reduced with SGLT2 inhibitors compared to sulfonylureas (aSHR, 0.13; 95% CI, 0.03–0.50), thiazolidinediones (aSHR, 0.19; 95% CI, 0.04–0.86), and DPP-4 inhibitors (aSHR, 0.22; 95% CI, 0.06–0.84). Mediation analysis revealed that MASLD regression accounted for 8.7% of the total cardiovascular benefit when comparing SGLT2 inhibitors to sulfonylureas.
Conclusions
In patients with concurrent T2DM and MASLD, SGLT2 inhibitors demonstrated better cardiovascular outcomes compared to other OADs. These findings suggest that SGLT2 inhibitors may be the preferred OAD choice for cardiovascular risk reduction in this high-risk population.
3.Comparison of the Gut Microbiota of Preterm Infants Born before 32-Week Gestation with Feeding Intolerance
Bo Kyeong JIN ; Hyunsu KIM ; Cho Ae LEE ; Hye-Rim KIM
Neonatal Medicine 2025;32(1):21-29
Purpose:
Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation.
Methods:
Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles.
Results:
Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points.
Conclusion
Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.
4.Korean Guidelines for the Management and Antibiotic Therapy in Adult Patients with Hospital-Acquired Pneumonia
Hayoung CHOI ; Kyung Hoon MIN ; Young Seok LEE ; Youjin CHANG ; Bo Young LEE ; Jee Youn OH ; Ae-Rin BAEK ; Jongmin LEE ; Kyeongman JEON
Tuberculosis and Respiratory Diseases 2025;88(1):69-89
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.
5.Korean Guidelines for the Management and Antibiotic Therapy in Adult Patients with Hospital-Acquired Pneumonia
Hayoung CHOI ; Kyung Hoon MIN ; Young Seok LEE ; Youjin CHANG ; Bo Young LEE ; Jee Youn OH ; Ae-Rin BAEK ; Jongmin LEE ; Kyeongman JEON
Tuberculosis and Respiratory Diseases 2025;88(1):69-89
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.
6.Comparison of the Gut Microbiota of Preterm Infants Born before 32-Week Gestation with Feeding Intolerance
Bo Kyeong JIN ; Hyunsu KIM ; Cho Ae LEE ; Hye-Rim KIM
Neonatal Medicine 2025;32(1):21-29
Purpose:
Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation.
Methods:
Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles.
Results:
Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points.
Conclusion
Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.
7.Korean Guidelines for the Management and Antibiotic Therapy in Adult Patients with Hospital-Acquired Pneumonia
Hayoung CHOI ; Kyung Hoon MIN ; Young Seok LEE ; Youjin CHANG ; Bo Young LEE ; Jee Youn OH ; Ae-Rin BAEK ; Jongmin LEE ; Kyeongman JEON
Tuberculosis and Respiratory Diseases 2025;88(1):69-89
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.
8.Comparison of the Gut Microbiota of Preterm Infants Born before 32-Week Gestation with Feeding Intolerance
Bo Kyeong JIN ; Hyunsu KIM ; Cho Ae LEE ; Hye-Rim KIM
Neonatal Medicine 2025;32(1):21-29
Purpose:
Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation.
Methods:
Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles.
Results:
Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points.
Conclusion
Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.
9.Korean Guidelines for the Management and Antibiotic Therapy in Adult Patients with Hospital-Acquired Pneumonia
Hayoung CHOI ; Kyung Hoon MIN ; Young Seok LEE ; Youjin CHANG ; Bo Young LEE ; Jee Youn OH ; Ae-Rin BAEK ; Jongmin LEE ; Kyeongman JEON
Tuberculosis and Respiratory Diseases 2025;88(1):69-89
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.
10.Korean Guidelines for the Management and Antibiotic Therapy in Adult Patients with Hospital-Acquired Pneumonia
Hayoung CHOI ; Kyung Hoon MIN ; Young Seok LEE ; Youjin CHANG ; Bo Young LEE ; Jee Youn OH ; Ae-Rin BAEK ; Jongmin LEE ; Kyeongman JEON
Tuberculosis and Respiratory Diseases 2025;88(1):69-89
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.

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