1.Therapeutic effects of Pueraria lobata (Willd.) Ohwi root and Hovenia dulcis Thunb. extracts on alcoholic liver disease: Network pharmacology and experimental validation
Zhendong Chen ; Yu Yue ; Hongyan An ; Haisu Yan ; Hyeok-Joo Park ; Pei Lin
Journal of Traditional Chinese Medical Sciences 2025;2025(1):100-111
Objective:
To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata (Willd.) Ohwi root (P. lobata, Ge Gen) and Hovenia dulcis Thunb. (H. dulcis, Zhi Ju Zi) against ethanol-induced liver damage in vitro, using a human hepatoma cell line G2 (HepG2) cell model.
Methods:
HepG2 cells were cultured in medium containing 4% ethanol to establish a model of alcoholic liver damage. The cells were then treated with the combined extract obtained via cryogenic extraction. Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers, antioxidant enzymes, and inflammatory cytokines. In addition, activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was examined to elucidate the mechanisms underlying the effects of the extract.
Results:
Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells; promoted the elevated expression of superoxide dismutase, catalase, and glutathione, indicating enhanced antioxidant defenses; and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals. In addition, by activating the PI3K/AKT pathway, treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets, subsequently inhibiting apoptosis. Moreover. inflammatory responses were mitigated, as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6, and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase, thereby indicating hepatoprotective effects.
Conclusion
The combined P. lobata root and H. dulcis extract was established to have notable antioxidative and anti-inflammatory properties, effectively alleviating ethanol-induced liver damage in vitro. These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.
2.Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study
Dong Kee JANG ; So Jeong KIM ; Hwe Hoon CHUNG ; Jae Min LEE ; Seung Bae YOON ; Jong-Chan LEE ; Dong Woo SHIN ; Jin-Hyeok HWANG ; Min Kyu JUNG ; Yoon Suk LEE ; Hee Seung LEE ; Joo Kyung PARK ;
Gut and Liver 2024;18(4):729-736
Background/Aims:
Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA.
Methods:
Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed.
Results:
Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA.
Conclusions
While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.
3.A Case of Breast Carcinoma en Cuirasse in Male
Jin Hyeok HYEONG ; Soo Hyun JEONG ; Eun Joo PARK ; Kwang Joong KIM ; Kwang Ho KIM
Annals of Dermatology 2023;35(Suppl2):S323-S326
A 63-year-old male presented with a painful skin lesion on the left side of the neck and upper chest approximately two months prior to presentation. Diffuse erythematous to purplish-colored sclerotic patches were observed. He had been treated with intravenous antibiotics for two weeks for cellulitis, but the lesion did not improve. Punch biopsy, and neck computed tomography (CT) with contrast enhancement were performed to differentiate between cellulitis and scleroderma. Histopathological examination revealed infiltration of pleomorphic and poorly differentiated tumor cells extending into thickened collagen bundles, and mitotic activity. Based on histologic and radiologic findings, the patient was suspected to have poorly differentiated carcinoma, and further evaluation of the origin of the carcinoma was performed. A subareolar mass on the left breast was observed on chest CT, and a needle biopsy was performed; results were consistent with findings from the skin biopsy. Finally, the patient was diagnosed with carcinoma en cuirasse, a subtype of cutaneous metastasis of breast cancer, was transferred to oncology, and underwent palliative chemotherapy.
4.Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study
Jong-In CHANG ; Jung Hee KIM ; Dong Hyun SINN ; Ju-Yeon CHO ; Kwang Min KIM ; Joo Hyun OH ; Yewan PARK ; Won SOHN ; Myung Ji GOH ; Wonseok KANG ; Geum-Youn GWAK ; Yong-Han PAIK ; Moon Seok CHOI ; Joon Hyeok LEE ; Kwang Cheol KOH ; Seung-Woon PAIK
Gut and Liver 2023;17(4):620-628
Background/Aims:
The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted.
Methods:
A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated.
Results:
After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCAresponse rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41(n=97). The area under the receiver operating characteristic curve of URS in predicting UDCAresponse was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed accordingto the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005).
Conclusions
URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.
5.Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease
Hyoungnae KIM ; Young Youl HYUN ; Hae-Ryong YUN ; Young Su JOO ; Yaeni KIM ; Ji Yong JUNG ; Jong Cheol JEONG ; Jayoun KIM ; Jung Tak PARK ; Tae-Hyun YOO ; Shin-Wook KANG ; Kook-Hwan OH ; Seung Hyeok HAN ;
Kidney Research and Clinical Practice 2023;42(4):501-511
The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods: This study included 2,149 patients with CKD G1–G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922–0.960) and eGFRcr (0.941; 95% CI, 0.922–0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.
6.An Autopsy Confirmed Case of Amyotrophic Lateral Sclerosis with TDP Pathology
Yu-Ri JE ; Soo-Yeon KIM ; Jung-Joon SUNG ; Myung Jun LEE ; Na-Yeon JUNG ; Jae-Hyeok LEE ; Jin-Hong SHIN ; Young Min LEE ; Jin A YOON ; Kyoungjune PARK ; Junkyeung KO ; Jae Meen LEE ; Chungsu HWANG ; Jae Woo AHN ; Suk SUNG ; Kyung-Un CHOI ; Gi Yeong HUH ; Eun-Joo KIM
Journal of the Korean Neurological Association 2022;40(2):164-167
The phosphorylated 43-kDa transactive response DNA-binding protein (TDP-43) was identified as a major disease protein in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We present a case with progressive muscle weakness who was diagnosed with sporadic ALS. On postmortem examination, TDP-43 immunoreactive neuronal cytoplasmic inclusions were noted in motor cortex, hippocampus and anterior horns of spinal cord, which was compatible with ALS-TDP, stage 4. This is the first documented autopsy-confirmed ALS case with ALS-TDP pathology in Korea.
7.Elevated On-Treatment Diastolic Blood Pressure and Cardiovascular Outcomes in the Presence of Achieved Systolic Blood Pressure Targets
Dae-Hee KIM ; In-Jeong CHO ; Woohyeun KIM ; Chan Joo LEE ; Hyeon-Chang KIM ; Jeong-Hun SHIN ; Si-Hyuck KANG ; Mi-Hyang JUNG ; Chang Hee KWON ; Ju-Hee LEE ; Hack Lyoung KIM ; Hyue Mee KIM ; Iksung CHO ; Dae Ryong KANG ; Hae-Young LEE ; Wook-Jin CHUNG ; Kwang Il KIM ; Eun Joo CHO ; Il-Suk SOHN ; Sungha PARK ; Jinho SHIN ; Sung Kee RYU ; Seok-Min KANG ; Wook Bum PYUN ; Myeong-Chan CHO ; Ju Han KIM ; Jun Hyeok LEE ; Sang-Hyun IHM ; Ki-Chul SUNG
Korean Circulation Journal 2022;52(6):460-474
Background and Objectives:
This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP).
Methods:
A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg).
Results:
During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort.
Conclusion
Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.
8.Comparative Clinicopathological Analysis of Primary Neutrophilic Scarring Alopecia:Folliculitis Decalvans and Dissecting Cellulitis
Eun Joo BAEK ; Jin Hyeok HYEONG ; Eun Joo PARK ; Kwang Joong KIM ; Kwang Ho KIM
Korean Journal of Dermatology 2022;60(3):167-172
Background:
Folliculitis decalvans and dissecting cellulitis are types of primary neutrophilic cicatricial alopecia characterized by permanent hair loss. Clinicopathological differentiation is poorly described in literature.
Objective:
This study aimed to determine the clinicopathological distinction between folliculitis decalvans and dissecting cellulitis.
Methods:
A retrospective review was conducted in 45 patients diagnosed with dissecting cellulitis and folliculitis decalvans between 2011 and 2021. We reviewed the clinical features using electronic medical records, clinical photographs, and histopathologic features.
Results:
Clinically, middle-aged men with folliculitis decalvans showed polytrichia (80%) and papulopustules (55%), while young men with dissecting cellulitis had deeply seated nodules (84%). Histopathologically, follicular plugging was more frequently observed in dissecting cellulitis (80%) than in folliculitis decalvans (50%). There was a difference in the depth of inflammation between the two types.
Conclusion
A difference in clinical manifestations was observed according to the depth of inflammation. These findings may contribute to the differential diagnosis of primary neutrophilic cicatricial alopecia.
9.Associations among Alzheimer disease, depressive disorder, and risk of end-stage kidney disease in elderly people
Shin Chan KANG ; Hee Byung KOH ; Hyung Woo KIM ; Young Su JOO ; Seung Hyeok HAN ; Tae-Hyun YOO ; Shin-Wook KANG ; Jung Tak PARK
Kidney Research and Clinical Practice 2022;41(6):753-763
Alzheimer disease (AD) and depressive disorder (DD) are prevalent among elderly end-stage kidney disease (ESKD) patients. However, whether preexisting mental health disorders increase the risk of ESKD is not well understood. The risk of incident ESKD in patients with or without underlying AD or DD was evaluated in a nationwide cohort of elderly people in Republic of Korea. Methods: This study used data from the National Health Insurance Service-Senior cohort in Republic of Korea. Among the 558,147 total subjects, 49,634 and 54,231 were diagnosed with AD (AD group) or DD (DD group), respectively, during the follow-up period. Propensity score matching was conducted to create non-AD and non-DD groups of subjects. AD and DD diagnoses were analyzed as time-varying exposures, and the study outcome was development of ESKD. Results: The incidence rates of ESKD were 0.36 and 1.17 per 1,000 person-years in the non-AD and AD groups, respectively. After adjustment for clinical variables and competing risks of death, the risk of incident ESKD was higher in the AD group than in the nonAD group (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.34–2.08). The incidence rates of ESKD in the non-DD and DD groups were 0.36 and 0.91 per 1,000 person-years, respectively. The risk of ESKD development was also higher in the DD group than the non-DD group (HR, 1.44; 95% CI, 1.19–1.76). Conclusion: The risk of ESKD development was higher in subjects diagnosed with AD or DD, suggesting that central nervous system diseases can adversely affect kidney function in elderly people.
10.External validation of the international prediction tool in Korean patients with immunoglobulin A nephropathy
Young Su JOO ; Hyung Woo KIM ; Chung Hee BAEK ; Jung Tak PARK ; Hajeong LEE ; Beom Jin LIM ; Tae-Hyun YOO ; Kyung Chul MOON ; Ho Jun CHIN ; Shin-Wook KANG ; Seung Hyeok HAN
Kidney Research and Clinical Practice 2022;41(5):556-566
The International IgA Nephropathy Prediction Tool has been recently developed to estimate the progression risk of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the clinical performance of this prediction tool in a large IgAN cohort in Korea. Methods: The study cohort was comprised of 2,064 patients with biopsy-proven IgAN from four medical centers between March 2012 and September 2021. We calculated the predicted risk for each patient. The primary outcome was occurrence of a 50% decline in estimated glomerular filtration rate (eGFR) from the time of biopsy or end-stage kidney disease. The model performance was evaluated for discrimination, calibration, and reclassification. We also constructed and tested an additional model with a new coefficient for the Korean race. Results: During a median follow-up period of 3.8 years (interquartile range, 1.8–6.6 years), 363 patients developed the primary outcome. The two prediction models exhibited good discrimination power, with a C-statistic of 0.81. The two models generally underestimated the risk of the primary outcome, with lesser underestimation for the model with race. The model with race showed better performance in reclassification compared to the model without race (net reclassification index, 0.13). The updated model with the Korean coefficient showed good agreement between predicted risk and observed outcome. Conclusion: In Korean IgAN patients, International IgA Nephropathy Prediction Tool had good discrimination power but underestimated the risk of progression. The updated model with the Korean coefficient showed acceptable calibration and warrants external validation.


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