1.Proteome-wide Characterization and Pathophysiology Correlation in Nonischemic Cardiomyopathies
Seonhwa LEE ; Dong-Gi JANG ; Yeon Ju KYOUNG ; Jeesoo KIM ; Eui-Soon KIM ; Ilseon HWANG ; Jong-Chan YOUN ; Jong-Seo KIM ; In-Cheol KIM
Korean Circulation Journal 2024;54(8):468-481
Background and Objectives:
Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
Methods:
Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
Results:
The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
Conclusions
Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
2.Proteome-wide Characterization and Pathophysiology Correlation in Nonischemic Cardiomyopathies
Seonhwa LEE ; Dong-Gi JANG ; Yeon Ju KYOUNG ; Jeesoo KIM ; Eui-Soon KIM ; Ilseon HWANG ; Jong-Chan YOUN ; Jong-Seo KIM ; In-Cheol KIM
Korean Circulation Journal 2024;54(8):468-481
Background and Objectives:
Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
Methods:
Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
Results:
The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
Conclusions
Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
3.Proteome-wide Characterization and Pathophysiology Correlation in Nonischemic Cardiomyopathies
Seonhwa LEE ; Dong-Gi JANG ; Yeon Ju KYOUNG ; Jeesoo KIM ; Eui-Soon KIM ; Ilseon HWANG ; Jong-Chan YOUN ; Jong-Seo KIM ; In-Cheol KIM
Korean Circulation Journal 2024;54(8):468-481
Background and Objectives:
Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
Methods:
Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
Results:
The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
Conclusions
Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
4.Postoperative Thoracic Cord Compression Induced by a Dural Sealant System (DuraSeal®): A Case Report and Literature Review
Dong Soon JANG ; Seung Hun SHEEN ; Inbo HAN ; Soo Hyun LEE ; Woo Seok CHOI ; Minsung BOCK ; Seil SOHN
The Nerve 2024;10(1):57-62
Cerebrospinal fluid (CSF) leakage is a rare complication that can occur due to dural defects during spinal surgery, hindering the improvement of the surgical site and increasing the possibility of infection. DuraSeal® is a dural sealing adhesive that prevents CSF leakage and is used as an adjunct to enable the watertight repair of dural defects when the dura is damaged during spinal surgery. In the present case, DuraSeal® was applied to repair a dural defect in the surgical area after thoracic spine surgery, and no neurological problems occurred immediately after surgery. However, a day later, the patient’s paraparesis worsened; therefore, reoperation was performed and the symptoms improved.
5.Association between Congestive Heart Failure and Ossification of the Posterior Longitudinal Ligament in Korea: A Nationwide Longitudinal Cohort Study
Dong Soon JANG ; Hakyung KIM ; Seung Hun SHEEN ; Inbo HAN ; Soo Hyun LEE ; Woo Seok CHOI ; Je Beom HONG ; Min Jai CHO ; Seil SOHN
The Nerve 2024;10(1):19-24
Objective:
The objective of this nationwide, long-term follow-up study was to explore the connection between congestive heart failure (CHF) and ossification of the posterior longitudinal ligament (OPLL) in Korea.
Methods:
Patient information was collected from the Health Screening cohort of the National Health Insurance Service. Individuals diagnosed with OPLL were identified using specific International Classification of Diseases, 10th revision codes (M48.8, M48.81, M48.82, and M48.83). A total of 1,289 OPLL patients and 6,445 controls were included in the study, selected through 1:5 age and sex matching. The data spanned from January 1, 2004 to July 31, 2015. To compute the incidence rate of CHF in each group, the Kaplan-Meier method was employed. Additionally, Cox proportional-hazards regression analysis was utilized to estimate the hazard ratio of CHF.
Results:
CHF was present in 19 patients (1.47%) in the OPLL group and 71 patients (1.10%) in the control group. After accounting for age and sex, the hazard ratio for CHF in the OPLL group was 3.164 (95% confidence interval [CI], 1.867-5.360). When additionally considering income and underlying diseases, the hazard ratio for CHF within the OPLL group was 3.355 (95% CI, 1.977-5.694). All subgroups of OPLL patients exhibited an increased risk ratio for CHF across parameters such as sex, age, diabetes, hypertension, and dyslipidemia.
Conclusion
According to this nationwide longitudinal study, an elevated incidence rate of CHF was associated with OPLL.
6.Proteome-wide Characterization and Pathophysiology Correlation in Nonischemic Cardiomyopathies
Seonhwa LEE ; Dong-Gi JANG ; Yeon Ju KYOUNG ; Jeesoo KIM ; Eui-Soon KIM ; Ilseon HWANG ; Jong-Chan YOUN ; Jong-Seo KIM ; In-Cheol KIM
Korean Circulation Journal 2024;54(8):468-481
Background and Objectives:
Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue–based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies.
Methods:
Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography–mass spectrometry.Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings.
Results:
The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes.
Conclusions
Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.
7.Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke
Boyoung KIM ; Ji Sung LEE ; Hong-Kyun PARK ; Young Bok YUNG ; Ki Chang OH ; Jeong Joo PARK ; Yong-Jin CHO ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Hee-Joon BAE ; Tai Hwan PARK ; Sang-Soon PARK ; Kyung Bok LEE ; Jun LEE ; Byung-Chul LEE ; Minwoo LEE ; Joon-Tae KIM ; Kang-Ho CHOI ; Dong-Eog KIM ; Jay Chol CHOI ; Dong-Ick SHIN ; Jee-Hyun KWON ; Wook-Joo KIM ; Sung Il SOHN ; Jeong-Ho HONG ; Hyung Jong PARK ; Seong-Hwa JANG ; Kwang-Yeol PARK ; Sang-Hwa LEE ; Jong-Moo PARK ; Keun-Sik HONG
Journal of the Korean Neurological Association 2023;41(2):112-120
Background:
For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients.
Methods:
Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927).
Results:
The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]).
Conclusions
In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.
8.Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Jun-Ook PARK ; Joo Hyun KIM ; Young Hoon JOO ; Sang-Yeon KIM ; Geun-Jeon KIM ; Hyun Bum KIM ; Dong-Hyun LEE ; Hyun Jun HONG ; Young Min PARK ; Eun-Jae CHUNG ; Yong Bae JI ; Kyoung Ho OH ; Hyoung Shin LEE ; Dong Kun LEE ; Ki Nam PARK ; Myung Jin BAN ; Bo Hae KIM ; Do Hun KIM ; Jae-Keun CHO ; Dong Bin AHN ; Min-Su KIM ; Jun Girl SEOK ; Jeon Yeob JANG ; Hyo Geun CHOI ; Hee Jin KIM ; Sung Joon PARK ; Eun Kyung JUNG ; Yeon Soo KIM ; Yong Tae HONG ; Young Chan LEE ; Ho-Ryun WON ; Sung-Chan SHIN ; Seung-Kuk BAEK ; Soon Young KWON
Clinical and Experimental Otorhinolaryngology 2023;16(1):1-19
The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
9.Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample
Jina HAN ; Hye Jin BAEK ; Eunbi NOH ; Kyuhyun YOON ; Jung Ae KIM ; Sukhyun RYU ; Kay O LEE ; No Yai PARK ; Eunok JUNG ; Sangil KIM ; Hyukmin LEE ; Yoo-Sung HWANG ; Jaehun JUNG ; Hun Jae LEE ; Sung-il CHO ; Sangcheol OH ; Migyeong KIM ; Chang-Mo OH ; Byengchul YU ; Young-Seoub HONG ; Keonyeop KIM ; Sunjae JUNG ; Mi Ah HAN ; Moo-Sik LEE ; Jung-Jeung LEE ; Young HWANGBO ; Hyeon Woo YIM ; Yu-Mi KIM ; Joongyub LEE ; Weon-Young LEE ; Jae-Hyun PARK ; Sungsoo OH ; Heui Sug JO ; Hyeongsu KIM ; Gilwon KANG ; Hae-Sung NAM ; Ju-Hyung LEE ; Gyung-Jae OH ; Min-Ho SHIN ; Soyeon RYU ; Tae-Yoon HWANG ; Soon-Woo PARK ; Sang Kyu KIM ; Roma SEOL ; Ki-Soo PARK ; Su Young KIM ; Jun-wook KWON ; Sung Soon KIM ; Byoungguk KIM ; June-Woo LEE ; Eun Young JANG ; Ah-Ra KIM ; Jeonghyun NAM ; ; Soon Young LEE ; Dong-Hyun KIM
Epidemiology and Health 2023;45(1):e2023075-
OBJECTIVES:
We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea.
METHODS:
In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022.
RESULTS:
In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%.
CONCLUSIONS
The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.
10.Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation
Jun Sang SHIN ; Tae-Gyu KIM ; Young Hwa KIM ; So Yeong EOM ; So Hyun PARK ; Dong Hyun LEE ; Tae Jun PARK ; Soon Sang PARK ; Jang-Hee KIM
Journal of Pathology and Translational Medicine 2023;57(6):305-314
Background:
Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.
Methods:
Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.
Results:
Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.
Conclusions
Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

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