1.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
2.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
3.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
4.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.
5.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
6.Postmortem Computed Tomography – Based Body Weight Estimation in Korean Infants Using Volume and Multiplication Factors
Jin-Haeng HEO ; Seon Jung JANG ; Jeong-hwa KWON ; Sang-Beom IM ; Joo-Young NA ; Yongsu YOON ; Young San KO ; Minju LEE ; Se-Min OH ; Sung Wook CHOI ; Sookyoung LEE
Korean Journal of Legal Medicine 2024;48(3):55-60
Postmortem computed tomography (PMCT) is used in forensic medicine worldwide due to its ability to non-invasively visualize injuries, hemorrhage, and estimate volume. In the autopsy of infants, assessing nutritional conditions such as weight is crucial for identifying neglect. This study aims to evaluate the usefulness of retrospectively estimating the weight of Korean infants using PMCT-based volume and multiplication factors, even when the body has been cremated. A total of 44 cases of infant death (under 12 months) were analyzed. PMCT images were obtained before autopsy. Autopsy records and documentation provided by the police at the time of autopsy were reviewed to determine the weight (g) of the infant. PMCT-based infant volumes (mL) were estimated using a three-dimensional semi-automatic segmentation method. Multiplication factors (g/mL) were calculated by dividing the weight recorded at autopsy by the PMCT-based volume, yielding a mean of 1.047 g/mL, ranging from 1.014 g/mL to 1.085 g/mL. The mean absolute error compared to weights recorded at autopsy was 95 g. Significant discrepancies were observed between weights recorded at the scene or medical center and those measured at autopsy. This study demonstrates that PMCT-based weight estimation for Korean infants is a reliable method and has the potential for retrospectively validating incorrect weight measurements and addressing inconsistencies in recorded weight data.
7.Effect of Paxlovid in COVID-19 treatment during the periods of SARS-CoV-2 Omicron BA.5 and BN.1 subvariant dominance in the Republic of Korea: a retrospective cohort study
Dong-Hwi KIM ; Min-Gyu YOO ; Na-Young KIM ; So Young CHOI ; Minjeong JANG ; Misuk AN ; Se-Jin JEONG ; Jungyeon KIM
Osong Public Health and Research Perspectives 2024;15(2):137-149
Objectives:
This study was conducted to assess the efficacy of nirmatrelvir/ritonavir treatment in patients with coronavirus disease 2019 (COVID-19), particularly those aged 60 years and older. Using real-world data, the period during which the BN.1 Omicron variant was dominant was compared to the period dominated by the BA.5 variant.
Methods:
In this retrospective cohort study, data were collected regarding 2,665,281 patients infected with severe acute respiratory syndrome coronavirus 2 between July 24, 2022, and March 31, 2023. Propensity score matching was utilized to match patients who received nirmatrelvir/ritonavir in a 1:4 ratio between BN.1 and BA.5 variant groups. Multivariable logistic regression analysis was employed to assess the effects of nirmatrelvir/ritonavir within these groups.
Results:
Compared to the prior period, the efficacy of nirmatrelvir/ritonavir did not significantly differ during the interval of Omicron BN.1 variant dominance in the Republic of Korea. Among patients treated with nirmatrelvir/ritonavir, a significantly lower risk of mortality was observed in the BN.1 group (odds ratio [OR], 0.698; 95% confidence interval [CI], 0.557–0.875) compared to the BA.5 group. However, this treatment did not significantly reduce the risk of severe or critical illness, including death, for those in the BN.1 group (OR, 0.856; 95% CI, 0.728–1.007).
Conclusion
Nirmatrelvir/ritonavir has maintained its effectiveness against COVID-19, even with the emergence of the BN.1 Omicron subvariant. Consequently, we strongly recommend the administration of nirmatrelvir/ritonavir to patients exhibiting COVID-19-related symptoms, irrespective of the dominant Omicron variant or their vaccination status, to mitigate disease severity and decrease the risk of mortality.
8.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.
9.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
10.Revolutionizing Non–Small Cell Lung Cancer Diagnosis: Ultra-High-Sensitive ctDNA Analysis for Detecting Hotspot Mutations with Long-term Stored Plasma
Ji-Young LEE ; Seyeon JEON ; Ha Ra JUN ; Chang Ohk SUNG ; Se Jin JANG ; Chang-Min CHOI ; Sung-Min CHUN
Cancer Research and Treatment 2024;56(2):484-501
Purpose:
Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting BRAF, KRAS, and EGFR hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%).
Materials and Methods:
Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA.
Results:
The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with EGFR mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84).
Conclusion
Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.

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