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.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.
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.Reducing Microbial Contamination in Hematopoietic Stem Cell Products and Quality Improvement Strategy: Retrospective Analysis of 1996-2021 Data
You Keun KO ; Jong Kwon LEE ; Hye Kyung PARK ; Ae Kyung HAN ; Sun Kyoung MUN ; Hye Jeong PARK ; Hae Kyoung CHOUNG ; Se Mi KIM ; Kwang Mo CHOI ; Nam Yong LEE ; Duck CHO ; Dae Won KIM ; Eun-Suk KANG
Annals of Laboratory Medicine 2023;43(5):477-484
Background:
Sterility and safety assurance of hematopoietic stem cell (HSC) products is critical in transplantation. Microbial contamination can lead to product disposal and increases the risk of unsuccessful clinical outcomes. Therefore, it is important to implement and maintain good practice guidelines and regulations for the HSC collection and processing unit in each hospital. We aimed to share our experiences and suggest strategies to improve the quality assurance of HSC processing.
Methods:
We retrospectively analyzed microbial culture results of 11,743 HSC products processed over a 25-year period (January 1996 to May 2021). Because of reorganization of the HSC management system in 2008, the 25-year period was divided into periods 1 (January 1996 to December 2007) and 2 (January 2008 to May 2021). We reviewed all culture results of the HSC products and stored aliquot samples and collected culture results for peripheral blood and catheter samples.
Results:
Of the 11,743 products in total, 35 (0.3%) were contaminated by microorganisms, including 19 (0.5%) of 3,861 products during period 1 and 16 (0.2%) of 7,882 products during period 2. Penicillium was the most commonly identified microorganism (15.8%) during period 1 and coagulase-negative Staphylococcus was the most commonly identified (31.3%) during period 2. HSC product contamination occurred most often during HSC collection and processing.
Conclusions
The contamination rate decreased significantly during period 2, when the HSC management system was reorganized. Our results imply that handling HSC products by trained personnel and adopting established protocols, including quality assurance programs, aid in decreasing the contamination risk.
7.Elderly kidney transplant recipients have favorable outcomes but increased infection-related mortality
Jeong-Hoon LIM ; Ga Young LEE ; Yena JEON ; Hee-Yeon JUNG ; Ji-Young CHOI ; Jang-Hee CHO ; Sun-Hee PARK ; Yong-Lim KIM ; Hyung-Kee KIM ; Seung HUH ; Eun Sang YOO ; Dong-Il WON ; Chan-Duck KIM
Kidney Research and Clinical Practice 2022;41(3):372-383
The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.
8.Treatment of rituximab in patients with idiopathic membranous nephropathy: a case series and literature review
Soo-Jee JEON ; Ji-Hye KIM ; Hee-Won NOH ; Ga-Young LEE ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Ji-Young CHOI ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
The Korean Journal of Internal Medicine 2022;37(4):830-840
Background/Aims:
Membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults. This study aimed to evaluate the effect of rituximab (RTX) in patients with idiopathic MN (iMN) who have a high risk of progression.
Methods:
We retrospectively analyzed data of 13 patients with iMN, who received RTX treatments from January 2014 to July 2020. RTX was indicated in patients with iMN with severe proteinuria and decreasing estimated glomerular filtration rate (eGFR) in the previous 6 months despite other immunosuppressive therapies.
Results:
The patients were predominantly males (n = 11) and with a mean age of 55.3 years; median eGFR, 37.0 mL/min/1.73 m2 (interquartile range [IQR], 26.3 to 66.5); serum albumin level, 2.6 g/dL (IQR, 1.9 to 3.1); and spot urine protein-to-creatinine ratio at baseline, 6.6 g/g (IQR, 5.7 to 12.9). In a median follow-up of 22 months, eight patients (61.5%) achieved complete or partial remission. In responder group (n = 8), median eGFR increased from 31.5 to 61.5 mL/min/1.73 m2 (p = 0.049) and serum albumin level increased from 2.3 to 4.2 g/dL (p = 0.017) from RTX initiation to last follow-up. Antiphospholipase A2 receptor antibody (anti-PLA2R-Ab) was positive in six among seven tested patients, which markedly decreased in the responder group. There were no adverse events after RTX.
Conclusions
This study suggests that RTX is a safe and effective treatment option for patients with iMN who have a high risk of progression. Individualized therapy based on anti-PLA2R-Ab titer would be needed for better outcomes.
9.Efficacy of geriatric multidisciplinary oncology clinic in the surgical treatment decision-making process for frail elderly patients with colorectal cancer
In Jun YANG ; Heung-Kwon OH ; Jeehye LEE ; Jung Wook SUH ; Hong-Min AHN ; Hye Rim SHIN ; Jin Won KIM ; Jee Hyun KIM ; Changhoon SONG ; Jung-Yeon CHOI ; Duck-Woo KIM ; Sung-Bum KANG
Annals of Surgical Treatment and Research 2022;103(3):169-175
Purpose:
Multidisciplinary care has become a cornerstone of colorectal cancer management. To evaluate the clinical efficacy of a geriatric multidisciplinary oncology clinic (GMOC), we analyzed the surgical treatment decision-making process and outcomes.
Methods:
This retrospective single-center study reviewed the data of patients aged ≥65 years who participated in the GMOC at a tertiary referral hospital between 2015 and 2021. The clinical adherence rate, comprehensive geriatric assessment, and a multidimensional frailty score (MFS) were obtained. The groups that were recommended and not recommended for surgery were compared, analyzing the factors impacting the decision and 1-year survival outcomes. Furthermore, the postoperative complications of patients who underwent surgery were evaluated.
Results:
A total of 165 patients visited the GMOC, and 74 had colorectal cancer (mean age, 85.5 years [range, 81.2–89.0 years]). Among patients with systemic disease (n = 31), 7 were recommended for surgery, and 5 underwent surgery. Among patients with locoregional disease (n = 43), 18 were recommended for surgery, and 12 underwent surgery. Patients recommended and not recommended for surgery had significantly different activities of daily living (ADL) (P = 0.024), instrumental ADL (P = 0.001), Mini-Mental State Examination (P = 0.014), delirium risk (P = 0.039), and MFS (P = 0.001). There was no difference in the 1-year overall survival between the 2 groups (P = 0.980). Of the 17 patients who underwent surgery, the median (interquartile range) of operation time was 165.0 minutes (120.0–270.0 minutes); hospital stay, 7.0 days (6.0–8.0 days); and 3 patients had wound complications.
Conclusion
Proper counseling of patients through the GMOC could lead to appropriate management and favorable outcomes.
10.A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy
Sang Youb HAN ; Chan-Young JUNG ; Sang Ho LEE ; Dong Won LEE ; Sik LEE ; Chan-Duck KIM ; Bum Soon CHOI ; Beom Seok KIM
Kidney Research and Clinical Practice 2022;41(4):452-461
It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. Methods: We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20–50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. Results: Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in the combination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of –4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and –5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was –0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. Conclusion: In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.

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