Article
Biochemistry & Molecular Biology
Soon-Young Na, Ki-Sun Kim, Yoon Seok Jung, Don-Kyu Kim, Jina Kim, Sung Jin Cho, In-Kyu Lee, Jongkyeong Chung, Jeong-Sun Kim, Hueng-Sik Choi
Summary: In this study, we found that GSK5182 stabilizes the ERR gamma protein by inhibiting its ubiquitination and recruiting a corepressor through the AF-2 domain. These findings suggest that GSK5182 regulates ERR gamma by a unique molecular mechanism, increasing the inactive form of ERR gamma via inhibition of ubiquitination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Santanu Sasidharan, Kamalakannan Radhakrishnan, Jun-Yeong Lee, Prakash Saudagar, Vijayakumar Gosu, Donghyun Shin
Summary: In this study, long-range molecular dynamics simulations were used to explore the intrinsic dynamics of ERR gamma. The results revealed that the agonist had more hydrogen bonds with ERR gamma, but the inverse agonist 4-OHT had higher binding energy, indicating the importance of hydrophobic interactions. Furthermore, the study uncovered the intramolecular signal transduction mechanism within the ERR gamma protein. These findings have implications for the design of therapeutic compounds against ERR gamma associated diseases.
Article
Biochemistry & Molecular Biology
Semim Akhtar Ahmed, Pranamika Sarma, Sagar Ramrao Barge, Deepsikha Swargiary, Gurumayum Shalini Devi, Jagat C. Borah
Summary: This study investigated the beneficial effects of Tribulus terrestris (TT) and its active constituent, Xanthosine, on gluconeogenesis and glycogenesis in hepatic insulin resistance. Xanthosine enhanced glucose uptake and decreased glucose production in hepatocytes. It also improved insulin sensitivity, reduced fasting blood glucose levels, and improved glucose homeostasis in diabetic rats.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Endocrinology & Metabolism
Youjin Kim, Si Woo Lee, Hyejin Wang, Ryeong-Hyeon Kim, Hyun Ki Park, Hangkyu Lee, Eun Seok Kang
Summary: The study found that DA-1241 can increase glucose-dependent insulin release through stimulation of GLP-1 secretion, reduce hepatic gluconeogenesis, and block autophagy, thus improving glycemic control.
DIABETES & METABOLISM JOURNAL
(2022)
Article
Endocrinology & Metabolism
Xinyu Cao, Xiaotong Ye, Shuang Zhang, Li Wang, Yanhong Xu, Shiqiao Peng, Yang Zhou, Yue Peng, Junhua Li, Xiaoying Zhang, Xiao Han, Wen-ying Huang, Weiping Jia, Jianping Ye
Summary: The study revealed that extracellular ADP can regulate blood glucose levels in mice through various pathways, including enhancing hepatic gluconeogenesis, altering metabolite levels, and affecting the levels of gluconeogenic hormones.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Neurosciences
Mengwen Shi, Jiaxin Tang, Chengmei Yang, Guanlong Guo, Huaxing Ou, Weihai Chen
Summary: This study found that the reversal effect of 5-HT2A receptor inverse agonists on PPI deficits is achieved through modulation of the nucleus accumbens and ventral hippocampus, rather than the medial prefrontal cortex or ventral tegmental area. These findings contribute to the exploration of the antipsychotic effects of 5-HT2A receptor inverse agonists by identifying the critical brain areas involved in PPI deficits reversal.
Article
Biochemistry & Molecular Biology
Mukundan Ragavan, Marc A. McLeod, Anthony G. Giacalone, Matthew E. Merritt
Summary: Type II diabetes and pre-diabetes are common in adults and are often treated by targeting hepatic gluconeogenesis. Direct measurement of hepatic gluconeogenic capacity is difficult, but the study successfully used hyperpolarized [2-C-13]dihydroxyacetone (DHA) to detect changes in gluconeogenic potential. Using ex vivo perfused mouse livers, the study confirmed that the ratio of signal intensities of 6C to 3C in C-13 nuclear magnetic resonance spectra is sensitive to hepatic gluconeogenic state.
Article
Biochemistry & Molecular Biology
Yoshinori Takeuchi, Yuki Murayama, Yuichi Aita, Zahra Mehrazad Saber, Samia Karkoutly, Duhan Tao, Kyoka Katabami, Chen Ye, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
Summary: This study reveals the mechanism by which the glucocorticoid receptor (GR) regulates hepatic lipogenesis through the KLF15-SREBP-1 pathway during fasting. It emphasizes the importance of the hypothalamic-pituitary-adrenal (HPA) axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.
Article
Chemistry, Medicinal
Giuseppe Faudone, Rezart Zhubi, Fatih Celik, Stefan Knapp, Apirat Chaikuad, Jan Heering, Daniel Merk
Summary: TLX is a master regulator of neurogenesis and acts as a transcriptional repressor of tumor suppressor genes to maintain neuronal stem cell homeostasis. The development of a potent TLX agonist, with submicromolar potency and high selectivity, has been reported, providing a valuable tool for functional studies on TLX.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Takumi Kouketsu, Rina Monma, Yuri Miyairi, Shun Sawatsubashi, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara, Atsushi Yokoyama
Summary: This study investigates the interaction between HNF4α and IRF2BP2 and their regulatory effects on gluconeogenic gene expression. The experiments reveal that IRF2BP2 functions as a novel co-repressor of HNF4α, suppressing its transcriptional activity through its E3 ubiquitin ligase activity. This finding uncovers a new characteristic of nuclear receptor co-regulators.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biology
Peter M. Masschelin, Pradip Saha, Scott A. Ochsner, Aaron R. Cox, Kang Ho Kim, Jessica B. Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L. Lorenzi, Alli M. Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D. Moore, Scott A. Summers, Neil J. McKenna, Sean M. Hartig
Summary: Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions for cellular energy demands. Depleting FAD pools in mice causes phenotypes associated with organic acidemias and other inborn errors of metabolism (IEMs), such as reduced body weight, hypoglycemia, and fatty liver disease. The study reveals that B2D inhibits fasting activation of PPAR alpha target genes and downregulates gluconeogenesis genes. Knockdown of PPAR alpha in the liver recapitulates B2D effects, while treatment with the PPAR alpha agonist fenofibrate rescues fasting glucose availability and overcomes B2D phenotypes.
Article
Biochemistry & Molecular Biology
Bo-Eun Kim, Byungyoon Choi, Woo-Ram Park, Yu-Ji Kim, In-Young Kim, Yoon Seok Jung, Yong-Hoon Kim, Chul-Ho Lee, Hueng-Sik Choi, Don-Kyu Kim
Summary: This study elucidated the detailed molecular mechanism of hepatic TFR2 gene expression involving ERR gamma in response to the endocannabinoid 2-arachidonoylglycerol (2-AG). The results showed that ERR gamma overexpression was sufficient to induce TFR2 expression, while ERR gamma knockdown significantly decreased 2-AG or alcohol-mediated TFR2 gene expression. These findings reveal a previously unrecognized role of ERR gamma in the transcriptional regulation of TFR2 gene expression in response to alcohol.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gyun-Sik Oh, Si-Ryong Kim, Eun-Sook Lee, Jin Yoon, Min-Kyung Shin, Hyeon Kyoung Ryu, Dong Seop Kim, Seung-Whan Kim
Summary: NCOA6 is a transcriptional coactivator of nuclear receptors and other transcription factors. It regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.
MOLECULES AND CELLS
(2022)
Review
Cell Biology
Eun Young Kim, Jae Man Lee
Summary: Autophagy is an important cellular process involved in the degradation of cellular components and dysfunctions in autophagy are associated with various diseases. Nuclear receptors, as transcription factors, play a role in regulating autophagy and can be utilized for the treatment of liver diseases.
Article
Chemistry, Multidisciplinary
Sabine Willems, Julian A. Marschner, Whitney Kilu, Giuseppe Faudone, Romy Busch, Silke Duensing-Kropp, Jan Heering, Daniel Merk
Summary: The ligand-sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies. Statins can modulate the activity of Nurr1, demonstrating clinically relevant neuroprotective effects.
Article
Chemistry, Multidisciplinary
Hanjun Hwangbo, Hyeongjin Lee, Eun-Ju Jin, Yunju Jo, Jigyeong Son, Han Min Woo, Dongryeol Ryu, Geun Hyung Kim
Summary: Tissue engineering strategies using cell-laden constructs have shown promise in treating damaged tissues. However, oxygen delivery to 3D cell-constructs for regenerating skeletal muscle tissue remains a challenge. To overcome this, a photosynthetic cyanobacterium is used in a bioink and electric field stimulation is used to fabricate cell-laden scaffolds. This results in highly aligned myofibers and upregulation of myogenic genes, leading to muscle regeneration in vivo.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Gastroenterology & Hepatology
Ah-Reum Oh, Yelin Jeong, Junjie Yu, Dao Thi Minh Tam, Jin Ku Kang, Young Hoon Jung, Seung-Soon Im, Sang Bae Lee, Dongryeol Ryu, Utpal B. Pajvani, KyeongJin Kim
Summary: This study found that obesity leads to type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), but the underlying mechanisms are not fully understood. The levels of potassium channel tetramerization domain-containing protein 17 (Kctd17) are increased in livers from obese mice and humans. The research investigated the mechanism of increased Kctd17 and found that it may play a causative role in obesity-induced metabolic complications. The study also identified Kctd17 as a potential therapeutic target for obesity-induced T2D and NAFLD.
Article
Chemistry, Multidisciplinary
Wansang Cho, Solchan Won, Yoona Choi, Sihyeong Yi, Jong Beom Park, Jun-Gyu Park, Caroline E. Kim, Chintam Narayana, Ju Hee Kim, Junhyeong Yim, Young Il Choi, Dong-Sup Lee, Seung Bum Park
Summary: Modulating target proteins via the ubiquitin-proteasome system has expanded the scope of pharmacological inventions. STING, an auspicious target for immunotherapy, has been found to have importance as well as utility in immunotherapy outcomes. The proposed UPPRIS strategy utilizing the small molecule SB24011 enhances STING immunity and potentiates the efficacy of immunotherapy, suggesting targeted protein upregulation as a promising approach for immuno-oncology.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Cell Biology
Mohamed Asrih, Shibo Wei, Thanh T. Nguyen, Hyon-Seung Yi, Dongryeol Ryu, Karim Gariani
Summary: Growth and differentiation factor 15 (GDF15) is a member of the transforming growth factor-beta (TGF-beta) superfamily and has been associated with metabolic syndrome pathologies such as obesity and cardiovascular diseases. The receptor for GDF15, Glial cell-derived neurotrophic factor family receptor alpha-like (GRAL), has been identified in the hindbrain and signals through the coreceptor receptor tyrosine kinase (RET). Preclinical studies have shown that GDF15 analogues can induce weight loss through a reduction in food intake, making it a potential target for addressing the global obesity epidemic.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Cell & Tissue Engineering
SeoYul Jo, JiUn Lee, Hyeongjin Lee, Dongryeol Ryu, GeunHyung Kim
Summary: This study proposes a versatile handheld 3D printer for the fabrication of porous cell-laden methacrylated gelatin (GelMa) with high porosity. The printer utilizes air injection and a bubble-making system using mesh filters to pass a mixture of air/GelMa bioink. The cell constructs' pore size and foamability can be manipulated by adjusting various processing parameters. In vitro and in vivo tests demonstrate the viability and efficacy of the printed cell constructs for muscle regeneration.
NPJ REGENERATIVE MEDICINE
(2023)
Article
Cell & Tissue Engineering
JaeYoon Lee, Hyeongjin Lee, Eun-Ju Jin, Dongryeol Ryu, Geun Hyung Kim
Summary: Optic-fiber-assisted bioprinting is an effective technique for fabricating cell-loaded structures. By selecting appropriate processing conditions, biofunctional cell-laden structures including methacrylated gelatin, collagen, and decellularized extracellular matrix can be fabricated. This process shows great potential in skeletal muscle regeneration.
NPJ REGENERATIVE MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Kannan Vaithegi, Sihyeong Yi, Ji Hyae Lee, Begur Vasanthkumar Varun, Seung Bum Park
Summary: Substituted pyridines with diverse functional groups are important in bioactive molecules. This study reports a method for introducing multiple functional groups to pyridine via ring cleavage reaction. The robustness of the methodology was demonstrated by synthesizing a variety of 5-aminoaryl and 5-phenol pyridines, and the application of the methodology provided a privileged pyridine scaffold for drug conjugation.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Biology
Jinjoo Jung, Jongbeom Park, Mingi Kim, Jaeyoung Ha, Hana Cho, Seung Bum Park
Summary: The small molecule SB2301 activates lipophagy and alters lipid droplet membrane composition, with the ethanolamine-phosphate cytidylyltransferase 2 (PCYT2) being a potential target of the compound. The excessive accumulation of lipid droplets is associated with various diseases, and understanding the molecular mechanism of LD degradation is important for academic and industrial research. Lipophagy, a selective autophagy process, has gained attention in the research community. This study reveals a novel lipophagy mechanism through the use of SB2301, which activates ubiquitin-mediated lipophagy. The potential target protein PCYT2 is identified, and SB2301 induces PCYT2 translocation to the LD surface and alters the LD membrane composition, leading to the activation of the lipophagy process.
COMMUNICATIONS BIOLOGY
(2023)
Article
Integrative & Complementary Medicine
Min Kyoung Cho, Jung-Sook Jin, Yunju Jo, Jung Ho Han, Su Shin, Sung-Jin Bae, Dongryeol Ryu, Jongkil Joo, Jang-Kyung Park, Ki-Tae Ha
Summary: This study investigated the effects of frankincense on endometriosis. The results showed that frankincense can alleviate the symptoms of endometriosis, suggesting its potential as an effective and safe treatment option.
INTEGRATIVE MEDICINE RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Dahham Kim, Hayoung Son, Seung Bum Park
Summary: This study synthesized a series of BODIPY-Tz probes for bioorthogonal cellular imaging and discovered their unique fluorescence behavior on BCN and TCO. Additionally, dual-color bioorthogonal cellular imaging with a single probe was achieved for the first time.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Medicine, Research & Experimental
Soo Yeon Baek, Jeehee Lee, Taegwan Kim, Hyelim Lee, Hoon-Seong Choi, Hahnbeom Park, Minseob Koh, Eunha Kim, Michael E. Jung, Dimitrios Iliopoulos, Jeong-Yeon Lee, Jonghoon Kim, Sanghee Lee
Summary: In this study, a novel HDAC inhibitor, 5, was developed and shown to suppress microglial activation and alleviate depression-like behavior by inducing autophagy and inhibiting nitric oxide production. These findings suggest HDAC11 as a potential therapeutic target for depressive disorder.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Editorial Material
Chemistry, Medicinal
Wansang Cho, Jung Ho Lee, Seung Bum Park
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Yikun Jiang, Shibo Wei, Jin-Mo Koo, Hea-Ju Kim, Wonyoung Park, Yan Zhang, He Guo, Ki-Tae Ha, Chang-Myung Oh, Jong-Sun Kang, Jee-Heon Jeong, Dongryeol Ryu, Kyeong-Jin Kim, Yunju Jo
Summary: HCC is a major contributor to cancer-related mortality worldwide, and the limited availability of effective treatments for advanced cases highlights the need for novel therapeutic targets. This study evaluated the role of PRMTs in HCC patients and found a significant association between PRMTs and prognosis, suggesting their potential as prognostic biomarkers. Specifically, PRMT1 was found to play a pivotal role in HCC progression, particularly in the context of Tex.
Article
Biochemistry & Molecular Biology
Hana Cho, Bo Young Choi, Young-Hee Shin, Sang Won Suh, Seung Bum Park
Summary: In this study, we investigated the neuroprotective function of SB1617 against tau aggregation mediated by microglia. Our findings showed that SB1617 deactivated pathogenic M1-like microglia, reduced the secretion of pro-inflammatory cytokines, induced microglial polarization towards the M2 phenotype, and enhanced phagocytic function. In addition, we observed the clearance of extracellular pathogenic tau aggregates through LC3-associated phagocytosis. Furthermore, in vivo experiments confirmed the neuroprotective effects of SB1617 in a mouse model of traumatic brain injury by reducing pathogenic tau levels through microglia-mediated anti-inflammatory activity. Our results indicate that SB1617-mediated microglial surveillance with LC3-associated phagocytosis is a critical molecular mechanism in the regulation of tau proteostasis.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Eun-Ju Jin, Shibo Wei, Yunju Jo, Thanh T. Nguyen, Moongi Ji, Man-Jeong Paik, Jee-Heon Jeong, Se Jin Im, Dongryeol Ryu
Summary: This study found that oral supplementation of ginseng berry extracts in mice had an impact on lactate metabolism and mitochondrial function, resulting in a significant reduction in blood lactate levels after exercise.