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Article: Curcumin Disrupts a Positive Feedback Loop between ADMSCs and Cancer Cells in the Breast Tumor Microenvironment via the CXCL12/CXCR4 Axis.

Jang, Bo-Young / Shin, Min Kyoung / Han, Dong-Hee / Sung, Jung-Suk

2023 Volume 15, Issue 11

Abstract: Adipose tissue has a significant impact on breast cancer initiation and progression owing to its substantial proportion in the breast. Adipose-derived mesenchymal stem cells (ADMSCs) are major players in the breast tumor microenvironment (TME) as they ... ...

Abstract	Adipose tissue has a significant impact on breast cancer initiation and progression owing to its substantial proportion in the breast. Adipose-derived mesenchymal stem cells (ADMSCs) are major players in the breast tumor microenvironment (TME) as they interact with cancer cells. The intricate interaction between ADMSCs and cancer cells not only drives the differentiation of ADMSCs into cancer-associated fibroblasts (CAFs) but also the metastasis of cancer cells, which is attributed to the CXCL12/CXCR4 axis. We investigated the effects of curcumin, a flavonoid known for CXCL12/CXCR4 axis inhibition, on breast TME by analyzing whether it can disrupt the ADMSC-cancer positive loop. Using MCF7 breast cancer cell-derived conditioned medium (MCF7-CM), we induced ADMSC transformation and verified that curcumin diminished the phenotypic change, inhibiting CAF marker expression. Additionally, curcumin suppressed the CXCL12/CXCR4 axis and its downstream signaling both in ADMSCs and MCF7 cells. The CM from ADMSCs, whose ADMSC-to-CAF transformation was repressed by the curcumin treatment, inhibited the positive feedback loop between ADMSCs and MCF7 as well as epithelial-mesenchymal transition in MCF7. Our study showed that curcumin is a potent anti-cancer agent that can remodel the breast TME, thereby restricting the ADMSC-cancer positive feedback loop associated with the CXCL12/CXCR4 axis.
Language	English
Publishing date	2023-11-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15112627
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Article ; Online: Evaluating the performance of thermoplastic 3D bolus used in radiation therapy.

Jung, Kyung Hwan / Han, Dong Hee / Lee, Ki Yoon / Kim, Jang Oh / Ahn, Woo Sang / Baek, Cheol Ha

Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine

2024 Volume 209, Page(s) 111329

Abstract: A 3D-printed bolus is being developed to deliver accurate doses to superficial cancers. In this study, flexible thermoplastic filaments, specifically PLA, TPU, PETG, and HIPS, were fabricated into boluses and then compared to commercial bolus for the ... ...

Abstract	A 3D-printed bolus is being developed to deliver accurate doses to superficial cancers. In this study, flexible thermoplastic filaments, specifically PLA, TPU, PETG, and HIPS, were fabricated into boluses and then compared to commercial bolus for the variation of the dose elevation region of photon beams. The experimental results indicate that the maximum dose depth is similar, and the consistent trend of the percentage depth dose confirms the potential usage as a build-up bolus.
MeSH term(s)	Printing, Three-Dimensional ; Humans ; Radiotherapy Dosage ; Plastics
Chemical Substances	Plastics
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article ; Evaluation Study
ZDB-ID	1142596-9
ISSN	1872-9800 ; 0883-2889 ; 0969-8043
ISSN (online)	1872-9800
ISSN	0883-2889 ; 0969-8043
DOI	10.1016/j.apradiso.2024.111329
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Article ; Online: Chronic Exposure to TDI Induces Cell Migration and Invasion via TGF-β1 Signal Transduction.

Han, Dong-Hee / Shin, Min Kyoung / Oh, Jin Wook / Lee, Junha / Sung, Jung-Suk / Kim, Min

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Toluene diisocyanate (TDI) is commonly used in manufacturing, and it is highly reactive and causes respiratory damage. This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. In addition, ... ...

Abstract	Toluene diisocyanate (TDI) is commonly used in manufacturing, and it is highly reactive and causes respiratory damage. This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. In addition, transcriptome analysis results confirmed that TDI increases transforming growth factor-beta 1 (TGF-β1) expression and regulates genes associated with cancerous characteristics in bronchial cells. Our chronically TDI-exposed model exhibited elongated spindle-like morphology, a mesenchymal characteristic. Epithelial-mesenchymal transition (EMT) was evaluated following chronic TDI exposure, and EMT biomarkers increased concentration-dependently. Furthermore, our results indicated diminished cell adhesion molecules and intensified cell migration and invasion. In order to investigate the cellular regulatory mechanisms resulting from chronic TDI exposure, we focused on TGF-β1, a key factor regulated by TDI exposure. As predicted, TGF-β1 was significantly up-regulated and secreted in chronically TDI-exposed cells. In addition, SMAD2/3 was also activated considerably as it is the direct target of TGF-β1 and TGF-β1 receptors. Inhibiting TGF-β1 signaling through blocking of the TGF-β receptor attenuated EMT and cell migration in chronically TDI-exposed cells. Our results corroborate that chronic TDI exposure upregulates TGF-β1 secretion, activates TGF-β1 signal transduction, and leads to EMT and other cancer properties.
MeSH term(s)	Transforming Growth Factor beta1/metabolism ; Cell Line, Tumor ; Toluene 2,4-Diisocyanate ; Signal Transduction ; Cell Movement ; Epithelial-Mesenchymal Transition
Chemical Substances	Transforming Growth Factor beta1 ; Toluene 2,4-Diisocyanate (17X7AFZ1GH)
Language	English
Publishing date	2023-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076157
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Article ; Online: Regulation of base excision repair during adipogenesis and osteogenesis of bone marrow-derived mesenchymal stem cells.

Kim, Min / Jang, Hyun-Jin / Baek, Song-Yi / Choi, Kyung-Jin / Han, Dong-Hee / Sung, Jung-Suk

Scientific reports

2023 Volume 13, Issue 1, Page(s) 16384

Abstract: Bone marrow-derived human mesenchymal stem cells (hMSCs) can differentiate into various lineages, such as chondrocytes, adipocytes, osteoblasts, and neuronal lineages. It has been shown that the high-efficiency DNA-repair capacity of hMSCs is decreased ... ...

Abstract	Bone marrow-derived human mesenchymal stem cells (hMSCs) can differentiate into various lineages, such as chondrocytes, adipocytes, osteoblasts, and neuronal lineages. It has been shown that the high-efficiency DNA-repair capacity of hMSCs is decreased during their differentiation. However, the underlying its mechanism during adipogenesis and osteogenesis is unknown. Herein, we investigated how alkyl-damage repair is modulated during adipogenic and osteogenic differentiation, especially focusing on the base excision repair (BER) pathway. Response to an alkylation agent was assessed via quantification of the double-strand break (DSB) foci and activities of BER-related enzymes during differentiation in hMSCs. Adipocytes showed high resistance against methyl methanesulfonate (MMS)-induced alkyl damage, whereas osteoblasts were more sensitive than hMSCs. During the differentiation, activities, and protein levels of uracil-DNA glycosylase were found to be regulated. In addition, ligation-related proteins, such as X-ray repair cross-complementing protein 1 (XRCC1) and DNA polymerase β, were upregulated in adipocytes, whereas their levels and recruitment declined during osteogenesis. These modulations of BER enzyme activity during differentiation influenced DNA repair efficiency and the accumulation of DSBs as repair intermediates in the nucleus. Taken together, we suggest that BER enzymatic activity is regulated in adipogenic and osteogenic differentiation and these alterations in the BER pathway led to different responses to alkyl damage from those in hMSCs.
MeSH term(s)	Humans ; Adipogenesis/genetics ; Osteogenesis/physiology ; Bone Marrow/metabolism ; Cells, Cultured ; Cell Differentiation/physiology ; DNA Repair ; Mesenchymal Stem Cells ; X-ray Repair Cross Complementing Protein 1/metabolism
Chemical Substances	XRCC1 protein, human ; X-ray Repair Cross Complementing Protein 1
Language	English
Publishing date	2023-09-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-43737-z
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Article ; Online: Quercetin and Isorhamnetin Reduce Benzo[a]pyrene-Induced Genotoxicity by Inducing RAD51 Expression through Downregulation of miR-34a.

Kim, Min / Jee, Seung-Cheol / Shin, Min-Kyoung / Han, Dong-Hee / Bu, Kyung-Bin / Lee, Seung-Cheol / Jang, Bo-Young / Sung, Jung-Suk

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated ... ...

Abstract	Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a]P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole-transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a]P-treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH
MeSH term(s)	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/toxicity ; Benzo(a)pyrene/toxicity ; Quercetin/pharmacology ; Down-Regulation ; DNA Damage ; DNA Adducts ; Mutagens/toxicity ; MicroRNAs/genetics
Chemical Substances	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (55097-80-8) ; Benzo(a)pyrene (3417WMA06D) ; 3-methylquercetin (07X3IB4R4Z) ; Quercetin (9IKM0I5T1E) ; DNA Adducts ; Mutagens ; MicroRNAs
Language	English
Publishing date	2022-10-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232113125
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Article ; Online: Daily injection of melatonin inhibits insulin resistance induced by chronic mealtime shift.

Park, Jihyun / Kim, Jichul / Yun, Yejin / Han, Dong-Hee / Kim, Kyungjin / Hong, Jongki / Cho, Sehyung

Physiological reports

2022 Volume 10, Issue 6, Page(s) e15227

Abstract: Shift work disorders have become an emerging concern worldwide. Shift disorders encompass a wide range of illnesses that have yet to be identified. The study focused on the relationship between shift work disorders and insulin resistance. Previously, it ... ...

Abstract	Shift work disorders have become an emerging concern worldwide. Shift disorders encompass a wide range of illnesses that have yet to be identified. The study focused on the relationship between shift work disorders and insulin resistance. Previously, it was reported that advancing the usual mealtime of mice triggered insulin resistance. Here, the hypothesis that chronic mealtime shifts induce oxidative damage leading to chronic diseases such as type 2 diabetes was tested. It was found that mealtime shift causes imbalances between anti-oxidative capacity and reactive oxygen species (ROS) levels, indicating increased oxidative damage during the light/rest phase. This study further demonstrated that daily supplementation of antioxidants at the appropriate time of day inhibited insulin resistance caused by chronic mealtime shifts, suggesting significant and chronic health implications for shift workers. In conclusion, it was confirmed that increased ROS levels caused by mealtime shift induce insulin resistance, which is inhibited by the antioxidant melatonin.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2 ; Insulin Resistance ; Meals ; Melatonin/pharmacology ; Mice ; Reactive Oxygen Species
Chemical Substances	Reactive Oxygen Species ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15227
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Article ; Online: De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity.

Shin, Min Kyoung / Jang, Bo-Young / Bu, Kyung-Bin / Lee, Seung-Ho / Han, Dong-Hee / Oh, Jin Wook / Sung, Jung-Suk

International journal of molecular sciences

2022 Volume 23, Issue 24

Abstract: Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their ...

Abstract	Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach.
Language	English
Publishing date	2022-12-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232415594
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Article ; Online: Mealtime shift delays conception in mice.

Park, Jihyun / Kim, Mi-Hee / Han, Dong-Hee / Noh, Jong-Yun / Ji, Eun-Sang / Lee, Sung-Ho / Kim, Chang-Ju / Cho, Sehyung

Reproduction (Cambridge, England)

2022 Volume 163, Issue 5, Page(s) 323–331

Abstract: The physiological processes of organisms in this rotating planet can adjust according to the time of day via built-in circadian clocks. However, more people are having different shift works, which can increase the risk of pathological conditions ... ...

Abstract	The physiological processes of organisms in this rotating planet can adjust according to the time of day via built-in circadian clocks. However, more people are having different shift works, which can increase the risk of pathological conditions including altered reproductive function. Thus, circadian rhythm disturbance has become prevalent in the modern society. Specifically, epidemiological evidence has shown that shift-working women are at high risk of spontaneous abortions, irregular menstrual cycles, and low-birth-weight babies. The current study aimed to investigate the effects of circadian rhythm disturbances on the reproductive function of mice caused by dietary time shift, which is common among night-shift workers. According to the schedule of restricted feeding, the mice were classified into the free feeding, daytime feeding, and night feeding groups. The fertility indices of each group were then evaluated. Activity monitoring was performed to determine whether pregnancy delay might be attributed to mealtime shift. Moreover, the estrous cycle of female mice and the reproductive phenotype of male mice were investigated. Results showed that a 12-h mealtime shift significantly delayed successful conception, which could be attributed to a disrupted estrous cycle, in adult female mice.
MeSH term(s)	Animals ; Circadian Rhythm ; Female ; Humans ; Male ; Meals ; Menstruation Disturbances ; Mice ; Pregnancy ; Reproduction ; Work Schedule Tolerance
Language	English
Publishing date	2022-04-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-21-0336
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Article ; Online: Alternating mealtimes during pregnancy and weaning triggers behavioral changes in adult offspring.

Kim, Mi-Hee / Park, Jihyun / Han, Dong-Hee / Noh, Jong-Yun / Ji, Eun-Sang / Lee, Sung-Ho / Kim, Chang-Ju / Cho, Sehyung

Reproduction (Cambridge, England)

2022 Volume 165, Issue 1, Page(s) 135–146

Abstract: In brief: Mealtime changes in pregnant mice revealed impaired neurobehavioral development in mouse offspring. This study is the basis for investigating diseases associated with neurobehavioral development of adult offspring of pregnant shift-working ... ...

Abstract	In brief: Mealtime changes in pregnant mice revealed impaired neurobehavioral development in mouse offspring. This study is the basis for investigating diseases associated with neurobehavioral development of adult offspring of pregnant shift-working women. Abstract: Most organisms on Earth have a biological clock, and their physiological processes are regulated by a 1-day cycle. In modern society, several factors can disturb these biological clocks in humans; in particular, individuals working in shifts are exposed to stark environmental changes that interfere with their biological clock. They have a high risk of various diseases. However, there are scarce experimental approaches to address the reproductive and health consequences of shift work in the offspring of exposed individuals. In this study, considering the fact that shift workers usually have their meals during their adjusted working time, we aimed to examine the effects of a 12-h shift with usual mealtime as a plausible night work model on the neurobehavioral development of adult mouse offspring. In these offspring, early exposure to this mealtime shift differentially affected circadian rhythmic variables and total locomotor activity depending on the timing and duration of restrictive feeding. Moreover, neurobehavioral alterations such as declined short-term memory and depressive-like behavior were observed in adulthood. These results have implications for the health concerns of shift-working women and their children.
MeSH term(s)	Humans ; Pregnancy ; Adult ; Child ; Animals ; Female ; Mice ; Adult Children ; Circadian Rhythm/physiology ; Weaning ; Behavior, Animal ; Reproduction
Language	English
Publishing date	2022-12-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-22-0164
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Article: The Identification of a Novel Spider Toxin Peptide, Lycotoxin-Pa2a, with Antibacterial and Anti-Inflammatory Activities.

Shin, Min Kyoung / Hwang, In-Wook / Jang, Bo-Young / Bu, Kyung-Bin / Han, Dong-Hee / Lee, Seung-Ho / Oh, Jin Wook / Yoo, Jung Sun / Sung, Jung-Suk

Antibiotics (Basel, Switzerland)

2023 Volume 12, Issue 12

Abstract: With the increasing challenge of controlling infectious diseases due to the emergence of antibiotic-resistant strains, the importance of discovering new antimicrobial agents is rapidly increasing. Animal venoms contain a variety of functional peptides, ... ...

Abstract	With the increasing challenge of controlling infectious diseases due to the emergence of antibiotic-resistant strains, the importance of discovering new antimicrobial agents is rapidly increasing. Animal venoms contain a variety of functional peptides, making them a promising platform for pharmaceutical development. In this study, a novel toxin peptide with antibacterial and anti-inflammatory activities was discovered from the spider venom gland transcriptome by implementing computational approaches. Lycotoxin-Pa2a (Lytx-Pa2a) showed homology to known-spider toxin, where functional prediction indicated the potential of both antibacterial and anti-inflammatory peptides without hemolytic activity. The colony-forming assay and minimum inhibitory concentration test showed that Lytx-Pa2a exhibited comparable or stronger antibacterial activity against pathogenic strains than melittin. Following mechanistic studies revealed that Lytx-Pa2a disrupts both cytoplasmic and outer membranes of bacteria while simultaneously inducing the accumulation of reactive oxygen species. The peptide exerted no significant toxicity when treated to human primary cells, murine macrophages, and bovine red blood cells. Moreover, Lytx-Pa2a alleviated lipopolysaccharide-induced inflammation in mouse macrophages by suppressing the expression of inflammatory mediators. These findings not only suggested that Lytx-Pa2a with dual activity can be utilized as a new antimicrobial agent for infectious diseases but also demonstrated the implementation of in silico methods for discovering a novel functional peptide, which may enhance the future utilization of biological resources.
Language	English
Publishing date	2023-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12121708
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