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Article ; Online: Role of Ischemic Preconditioning in the Cardioprotective Mechanisms of Monomeric C-Reactive Protein-Deposited Myocardium in a Rat Model

Eun Na Kim / Jae-Sung Choi / Chong Jai Kim / So Ra Kim / Se Jin Oh

Journal of Chest Surgery, Vol 54, Iss 1, Pp 9-

2021 Volume 16

Abstract: Background: The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. Methods: We ... ...

Abstract	Background: The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. Methods: We evaluated the effects of IPC on myocardium upon which mCRP had been deposited due to IRI in a rat model. Myocardial IRI was induced via ligation of the coronary artery. Direct IPC was applied prior to IRI using multiple short direct occlusions of the coronary artery. CRP was infused intravenously after IRI. The study included sham (n=3), IRI-only (n=5), IRI+CRP (n=9), and IPC+IRI+CRP (n=6) groups. The infarcted area and the area at risk were assessed using Evans blue and 2,3,5-triphenyltetrazolium staining. Additionally, mCRP immunostaining and interleukin-6 (IL-6) mRNA reverse transcription-polymerase chain reaction were performed. Results: In the IRI+CRP group, the infarcted area and the area of mCRP deposition were greater, and the level of IL-6 mRNA expression was higher, than in the IRI-only group. However, in the IPC+IRI+CRP group relative to the IRI+CRP group, the relative areas of infarction (20% vs. 34%, respectively; p=0.079) and mCRP myocardial deposition (21% vs. 44%, respectively; p=0.026) were lower and IL-6 mRNA expression was higher (fold change: 407 vs. 326, respectively; p=0.376), although the difference in IL-6 mRNA expression was not statistically significant. Conclusion: IPC was associated with significantly decreased deposition of mCRP and with increased expression of IL-6 in myocardium damaged by IRI. The net cardioprotective effect of decreased mCRP deposition and increased IL-6 levels should be clarified in a further study.
Keywords	ischemic preconditioning ; reperfusion injury ; c-reactive protein ; myocardial infarction ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Korean Society for Thoracic & Cardiovascular Surgery
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ethical challenges regarding artificial intelligence in medicine from the perspective of scientific editing and peer review

Seong Ho Park / Young-Hak Kim / Jun Young Lee / Soyoung Yoo / Chong Jai Kim

Science Editing, Vol 6, Iss 2, Pp 91-

2019 Volume 98

Abstract: This review article aims to highlight several areas in research studies on artificial intelligence (AI) in medicine that currently require additional transparency and explain why additional transparency is needed. Transparency regarding training data, ... ...

Abstract	This review article aims to highlight several areas in research studies on artificial intelligence (AI) in medicine that currently require additional transparency and explain why additional transparency is needed. Transparency regarding training data, test data and results, interpretation of study results, and the sharing of algorithms and data are major areas for guaranteeing ethical standards in AI research. For transparency in training data, clarifying the biases and errors in training data and the AI algorithms based on these training data prior to their implementation is critical. Furthermore, biases about institutions and socioeconomic groups should be considered. For transparency in test data and test results, authors should state if the test data were collected externally or internally and prospectively or retrospectively at first. It is necessary to distinguish whether datasets were convenience samples consisting of some positive and some negative cases or clinical cohorts. When datasets from multiple institutions were used, authors should report results from each individual institution. Full publication of the results of AI research is also important. For transparency in interpreting study results, authors should interpret the results explicitly and avoid over-interpretation. For transparency by sharing algorithms and data, sharing is required for replication and reproducibility of the research by other researchers. All of the above mentioned high standards regarding transparency of AI research in healthcare should be considered to facilitate the ethical conduct of AI research.
Keywords	Artificial intelligence ; Ethics ; Research ; Publishing ; Bias ; Science (General) ; Q1-390
Subject code	170
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	Korean Council of Science Editors
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alteration of fatty acid oxidation by increased CPT1A on replicative senescence of placenta-derived mesenchymal stem cells

Jin Seok / Hyun Sook Jung / Sohae Park / Jung Ok Lee / Chong Jai Kim / Gi Jin Kim

Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-

2020 Volume 13

Abstract: Abstract Background Human placenta-derived mesenchymal stem cells (PD-MSCs) are powerful sources for cell therapy in regenerative medicine. However, a limited lifespan by senescence through mechanisms that are well unknown is the greatest obstacle. In ... ...

Abstract	Abstract Background Human placenta-derived mesenchymal stem cells (PD-MSCs) are powerful sources for cell therapy in regenerative medicine. However, a limited lifespan by senescence through mechanisms that are well unknown is the greatest obstacle. In the present study, we first demonstrated the characterization of replicative senescent PD-MSCs and their possible mitochondrial functional alterations. Methods Human PD-MSCs were cultured to senescent cells for a long period of time. The cells of before passage number 8 were early cells and after passage number 14 were late cells. Also, immortalized cells of PD-MSCs (overexpressed hTERT gene into PD-MSCs) after passage number 14 were positive control of non-senescent cells. The characterization and mitochondria analysis of PD-MSCs were explored with long-term cultivation. Results Long-term cultivation of PD-MSCs exhibited increases of senescent markers such as SA-β-gal and p21 including apoptotic factor, and decreases of proliferation, differentiation potential, and survival factor. Mitochondrial dysfunction was also observed in membrane potential and metabolic flexibility with enlarged mitochondrial mass. Interestingly, we founded that fatty acid oxidation (FAO) is an important metabolism in PD-MSCs, and carnitine palmitoyltransferase1A (CPT1A) overexpressed in senescent PD-MSCs. The inhibition of CPT1A induced a change of energy metabolism and reversed senescence of PD-MSCs. Conclusions These findings suggest that alteration of FAO by increased CPT1A plays an important role in mitochondrial dysfunction and senescence of PD-MSCs during long-term cultivation.
Keywords	Placenta-derived mesenchymal stem cell ; Senescence ; Mitochondria ; Fatty acid ; CPT1A ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	571
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of a novel therapeutic target underlying atypical manifestation of Gaucher disease

Eun Na Kim / Hyo‐Sang Do / Hwangkyo Jeong / Taeho Kim / Sun Hee Heo / Yoo‐Mi Kim / Chong Kun Cheon / Yena Lee / Yunha Choi / In Hee Choi / Jeongmin Choi / Han‐Wook Yoo / Chong Jai Kim / Ari Zimran / Kyunggon Kim / Beom Hee Lee

Clinical and Translational Medicine, Vol 12, Iss 5, Pp n/a-n/a (2022)

2022

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Soluble Cytoplasmic Expression and Purification of Immunotoxin HER2(scFv)-PE24B as a Maltose Binding Protein Fusion

Sangsu Park / Minh Quan Nguyen / Huynh Kim Khanh Ta / Minh Tan Nguyen / Gunsup Lee / Chong Jai Kim / Yeon Jin Jang / Han Choe

International Journal of Molecular Sciences, Vol 22, Iss 6483, p

2021 Volume 6483

Abstract: Human epidermal growth factor receptor 2 (HER-2) is overexpressed in many malignant tumors. The anti-HER2 antibody trastuzumab has been approved for treating HER2-positive early and metastatic breast cancers. Pseudomonas exotoxin A (PE), a bacterial ... ...

Abstract	Human epidermal growth factor receptor 2 (HER-2) is overexpressed in many malignant tumors. The anti-HER2 antibody trastuzumab has been approved for treating HER2-positive early and metastatic breast cancers. Pseudomonas exotoxin A (PE), a bacterial toxin of Pseudomonas aeruginosa , consists of an A-domain with enzymatic activity and a B-domain with cell binding activity. Recombinant immunotoxins comprising the HER2(scFv) single-chain Fv from trastuzumab and the PE24B catalytic fragment of PE display promising cytotoxic effects, but immunotoxins are typically insoluble when expressed in the cytoplasm of Escherichia coli , and thus they require solubilization and refolding. Herein, a recombinant immunotoxin gene was fused with maltose binding protein (MBP) and overexpressed in a soluble form in E. coli . Removal of the MBP yielded stable HER2(scFv)-PE24B at 91% purity; 0.25 mg of pure HER2(scFv)-PE24B was obtained from a 500 mL flask culture. Purified HER2(scFv)-PE24B was tested against four breast cancer cell lines differing in their surface HER2 level. The immunotoxin showed stronger cytotoxicity than HER2(scFv) or PE24B alone. The IC 50 values for HER2(scFv)-PE24B were 28.1 ± 2.5 pM ( n = 9) and 19 ± 1.4 pM ( n = 9) for high HER2-positive cell lines SKBR3 and BT-474, respectively, but its cytotoxicity was lower against MDA-MB-231 and MCF7. Thus, fusion with MBP can facilitate the soluble expression and purification of scFv immunotoxins.
Keywords	protein expression ; protein purification ; immunotoxin ; HER2(scFv)-PE24B ; maltose binding protein ; trastuzumab ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole-genome sequencing reveals an association between small genomic deletions and an increased risk of developing Parkinson’s disease

Ji-Hye Oh / Sungyang Jo / Kye Won Park / Eun-Jae Lee / Seung Hyun Lee / Yun Su Hwang / Ha Ra Jeon / Yeonjin Ryu / Hee Jeong Yoon / Sung-Min Chun / Chong Jai Kim / Tae Won Kim / Chang Ohk Sung / Sehyun Chae / Sun Ju Chung

Experimental and Molecular Medicine, Vol 55, Iss 3, Pp 555-

2023 Volume 564

Abstract: Parkinson’s disease: genetic risk factors in a Korean population A whole-genome sequencing study of Korean individuals with Parkinson’s disease (PD) has identified several new genetic risk factors, ranging from single nucleotide variations (SNVs) to ... ...

Abstract	Parkinson’s disease: genetic risk factors in a Korean population A whole-genome sequencing study of Korean individuals with Parkinson’s disease (PD) has identified several new genetic risk factors, ranging from single nucleotide variations (SNVs) to larger DNA deletions. PD is the second most prevalent neurodegenerative disease globally, but most studies have focused on SNVs in European populations. Using whole-genome sequencing, Ji-Hye Oh at the University of Ulsan, Seoul, South Korea, and co-workers were able to identify genetic differences between PD patients and healthy controls, including deletions, gains, and several new SNVs. In particular, deletions of small non-coding regions that regulate gene expression may be key contributors to PD. These results provide a whole-genome perspective on genetic risk factors for PD in a Korean population, and illuminate how a whole-genome sequencing approach may be helpful in identifying genetic factors underlying other diseases.
Keywords	Medicine ; R ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b′a′ Domain

Thi Kieu Oanh Nguyen / Thi Luong Vu / Minh Quan Nguyen / Huynh Kim Khanh Ta / Kyoung Sun Park / Soo Hyeon Kim / Chong Jai Kim / Yeon Jin Jang / Han Choe

International Journal of Molecular Sciences, Vol 22, Iss 5267, p

2021 Volume 5267

Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as ... ...

Abstract	Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes. In our present study, the solubility of hGM-CSF was examined when combined with three N-terminal fusion tags in five E. coli strains at three different expression temperatures. In the five E. coli strains BL21 (DE3), ClearColi BL21 (DE3), LOBSTR, SHuffle T7 and Origami2 (DE3), the hexahistidine-tagged hGM-CSF showed the best expression but was insoluble in all cases at each examined temperature. Tagging with the maltose-binding protein (MBP) and the b′a′ domain of protein disulfide isomerase (PDIb′a′) greatly improved the soluble overexpression of hGM-CSF at 30 °C and 18 °C. The solubility was not improved using the Origami2 (DE3) and SHuffle T7 strains that have been engineered for disulfide bond formation. Two conventional chromatographic steps were used to purify hGM-CSF from the overexpressed PDIb′a′-hGM-CSF produced in ClearColi BL21 (DE3). In the experiment, 0.65 mg of hGM-CSF was isolated from a 0.5 L flask culture of these E. coli and showed a 98% purity by SDS-PAGE analysis and silver staining. The bioactivity of this purified hGM-CSF was measured at an EC 50 of 16.4 ± 2 pM by a CCK8 assay in TF-1 human erythroleukemia cells.
Keywords	hGM-CSF ; MBP ; PDI ; ClearColi ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm.

Eun Na Kim / Jiyoung Yu / Joon Seo Lim / Hwangkyo Jeong / Chong Jai Kim / Jae-Sung Choi / So Ra Kim / Hee-Sung Ahn / Kyunggon Kim / Se Jin Oh

PLoS ONE, Vol 16, Iss 8, p e

2021 Volume 0245361

Abstract: Objective The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; ...

Abstract	Objective The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways. Methods Twenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n = 7) and those with weak, focal, and junctional CRP immunopositivity (n = 3). Results mCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity. Conclusions AAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel Bacterial Production of Two Different Bioactive Forms of Human Stem-Cell Factor

Eunyoung Lee / Michelle Novais de Paula / Sangki Baek / Huynh Kim Khanh Ta / Minh Tan Nguyen / Taeck-Hyun Jeong / Chong Jai Kim / Yeon Jin Jang / Han Choe

International Journal of Molecular Sciences, Vol 22, Iss 6361, p

2021 Volume 6361

Abstract: Human stem-cell factor (hSCF) stimulates the survival, proliferation, and differentiation of hematopoietic cells by binding to the c-Kit receptor. Various applications of hSCF require the efficient and reliable production of hSCF. hSCF exists in three ... ...

Abstract	Human stem-cell factor (hSCF) stimulates the survival, proliferation, and differentiation of hematopoietic cells by binding to the c-Kit receptor. Various applications of hSCF require the efficient and reliable production of hSCF. hSCF exists in three forms: as two membrane-spanning proteins hSCF248 and hSCF229 and truncated soluble N -terminal protein hSCF164. hSCF164 is known to be insoluble when expressed in Escherichia coli cytoplasm, requiring a complex refolding procedure. The activity of hSCF248 has never been studied. Here, we investigated novel production methods for recombinant hSCF164 and hSCF248 without the refolding process. To increase the solubility of hSCF164, maltose-binding protein (MBP) and protein disulfide isomerase b’a’ domain (PDIb’a’) tags were attached to the N -terminus of hSCF164. These fusion proteins were overexpressed in soluble form in the Origami 2(DE3) E. coli strain. These solubilization effects were enhanced at a low temperature. His-hSCF248, the poly-His tagged form of hSCF248, was expressed in a highly soluble form without a solubilization tag protein, which was unexpected because His-hSCF248 contains a transmembrane domain. hSCF164 was purified using affinity and ion-exchange chromatography, and His-hSCF248 was purified by ion-exchange and gel filtration chromatography. The purified proteins stimulated the proliferation of TF-1 cells. Interestingly, the EC 50 value of His-hSCF248 was 1 pg/mL, 100-fold lower than 9 ng/mL hSCF164. Additionally, His-hSCF248 decreased the doubling time, increased the proportion of S and G2/M stages in the cell cycle, and increased the c-Myc expression at a 1000-fold lower concentration than hSCF164. In conclusion, His-hSCF248 was expressed in a soluble form in E. coli and had stronger activity than hSCF164. The molecular chaperone, MBP, enabled the soluble overexpression of hSCF164.
Keywords	human stem-cell factor ; hSCF248 ; hSCF164 ; MBP ; recombinant protein ; soluble protein ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antinociceptive and Anti-Inflammatory Effects of Recombinant Crotamine in Mouse Models of Pain

Jong Yeon Park / Bich Hang Do / Ju-Seung Lee / Hyun Cheol Yang / Anh Ngoc Nguyen / Martin Krupa / Chong Jai Kim / Yeon Jin Jang / Han Choe

Toxins, Vol 13, Iss 707, p

2021 Volume 707

Abstract: Crotamine, a toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus , has been reported to have antinociceptive effects. We purified recombinant crotamine expressed in Escherichia coli and investigated its antinociceptive ...

Abstract	Crotamine, a toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus , has been reported to have antinociceptive effects. We purified recombinant crotamine expressed in Escherichia coli and investigated its antinociceptive and anti-inflammatory effects using the hot-plate test, acetic-acid-induced writhing method, and formalin test in mice. Recombinant crotamine was administered intraperitoneally (0.04–1.2 mg kg −1 ) or intraplantarly (0.9–7.5 μg 10 μL −1 ) before the tests. The paw volume was measured with a plethysmometer. To evaluate the antagonistic and anti-inflammatory effects of naloxone, subcutaneous naloxone (4 mg kg −1 ) or intraplantar naloxone (5 μg 10 μL −1 ) was administered before recombinant crotamine. For tumor necrosis factor (TNF)-α assays, blood was drawn 3 h after formalin injection and measured using enzyme-linked immunosorbent assay. Intraperitoneal and intraplantar recombinant crotamine had antinociceptive and anti-inflammatory effects, neither of which were affected by pre-treatment with naloxone. The mean serum TNF-α levels were significantly lower in the intraperitoneal recombinant crotamine (0.4 and 1.2 mg kg −1 ) or intraplantar (2.5 and 7.5 μg 10 μL −1 ) recombinant crotamine groups than in the saline group and were not affected by naloxone pre-treatment. In conclusion, recombinant crotamine possesses significant antinociceptive and anti-inflammatory effects that do not appear to be related to the opioid receptor. The antinociceptive and anti-inflammatory effects of intraperitoneal or intraplantar recombinant crotamine are related to TNF-α.
Keywords	crotamine ; nociception ; inflammation ; naloxone ; tumor necrosis factor-α ; Medicine ; R
Subject code	333
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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