2.Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats
Ki Tae YOON ; Hongqun LIU ; Jing ZHANG ; Sojung HAN ; Samuel S. LEE
Clinical and Molecular Hepatology 2022;28(2):232-241
Background/Aims:
Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.
Methods:
Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.
Results:
Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.
Conclusion
Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.
3.Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified
Bogyeong HAN ; Sojung LIM ; Jeemin YIM ; Young Keun SONG ; Jiwon KOH ; Sehui KIM ; Cheol LEE ; Young A KIM ; Yoon Kyung JEON
Journal of Pathology and Translational Medicine 2024;58(2):59-71
Background:
The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear.
Methods:
Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)odal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-TfhTFHL–not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed.
Results:
TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-TfhTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054).
Conclusions
The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.
4.Usefulness of the Patient Health Questionnaire-2 in Screening for Depression
Minkyeung JO ; Hye Yeon KOO ; In Young CHO ; Yoojin LEE ; Sojung YOON ; Yeseul YANG ; Ju Young KIM ; Kiheon LEE ; Kee Hyuck LEE ; Se Young JUNG ; Hyejin LEE ; Jong Soo HAN ; Sarah KIM ; Woo Kyung BAE
Korean Journal of Family Practice 2019;9(4):336-340
BACKGROUND: While various screening tools are available for depression, they are not feasible in clinical practice because of their excessive number of questions. The Patient Health Questionnaire-2 (PHQ-2) consists of two questions gauging the frequency of depressed mood and anhedonia over the past two weeks. This study aimed to assess the usefulness of the PHQ-2 as a brief screening tool for depression.METHODS: This study used Korean National Health and Nutrition Examination Survey data from 2014, and the study population consisted of 4,946 individuals. We analyzed the validity of the PHQ-2 compared with ‘depression by PHQ-9,’ and obtained the optimal cut point for screening depression. The agreement between PHQ-2 and depression by PHQ-9 and the agreement between PHQ-2 and ‘currently diagnosed as depression’ were analyzed using Cohen's kappa. The correlation between EuroQol-5D (EQ-5D) index scores and PHQ-2 scores was analyzed using Student's t-test.RESULTS: Using ‘depression by PHQ-9’ as the criterion standard, PHQ-2 scores ≥2 had a sensitivity of 89% and a specificity of 87%, and a receiver operating characteristic analysis identified PHQ-2≥2 as the optimal cut point for screening. The agreement between PHQ-2 and depression by PHQ-9 was 0.430 when PHQ-2 ≥2 was used as a cut point. The agreement between PHQ-2 and ‘depression by questionnaire’ was poor. The EQ-5D index score of the depressive group was significantly lower than that of the normal group.CONCLUSION: The PHQ-2 is an effective measure for screening depression and is expected to be useful in busy clinical settings.
Anhedonia
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Depression
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Humans
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Mass Screening
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Nutrition Surveys
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ROC Curve
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Sensitivity and Specificity
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Surveys and Questionnaires
5.Sorafenib for 9,923 Patients with Hepatocellular Carcinoma:An Analysis from National Health Insurance Claim Data in South Korea
Sojung HAN ; Do Young KIM ; Ho Yeong LIM ; Jung-Hwan YOON ; Baek-Yeol RYOO ; Yujeong KIM ; Kookhee KIM ; Bo Yeon KIM ; So Young YI ; Dong-Sook KIM ; Do-Yeon CHO ; Jina YU ; Suhyun KIM ; Joong-Won PARK
Gut and Liver 2024;18(1):116-124
Background/Aims:
Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea.
Methods:
This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study.
Results:
Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib;2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400–600 mg (9.6 months).
Conclusions
Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.