Article
Oncology
Pichaya Thanindratarn, Ran Wei, Dylan C. Dean, Arun Singh, Noah Federman, Scott D. Nelson, Francis J. Hornicek, Zhenfeng Duan
Summary: The study revealed that high expression of TOPK in osteosarcoma is associated with metastasis, disease status, and shorter overall survival. Silencing TOPK with siRNA or inhibiting it with the selective inhibitor OTS514 can suppress proliferation and migration of osteosarcoma cells, enhance chemotherapeutic sensitivity, and exert synergistic effects with doxorubicin or cisplatin.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Lama Alhawas, Karishma S. Amin, Bharath Salla, Partha P. Banerjee
Summary: This study highlights the significant role of the protein kinase TOPK in regulating the expression of ARv7 and driving androgen-independent growth in prostate cancer cells. Additionally, pharmacological inhibition of TOPK can suppress AR activity and stability in androgen-independent cells. Therefore, TOPK may be a potential target for overcoming resistance to anti-androgen therapies in prostate cancer.
Article
Cell Biology
Juanjuan Xiao, Lu Zhang, Huijun Yi, Ling Zou, Jianmei Mo, Feng Xue, Jinhua Zheng, Yingze Huang, Hui Lu, Hansheng Wu, Peipei Xue, Xin Zhang, Lifei He, Zhaoxin Li, Shigui Pang, Guibin Qiao, Qiuhong Duan, Feng Zhu
Summary: This study reveals the role of T-LAK cell-oriented protein kinase (TOPK) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). The researchers found that TOPK is highly expressed in ALK-positive NSCLC and identified ALK as an upstream kinase of TOPK. Moreover, they showed that inhibiting TOPK enhances tumor sensitivity to an ALK inhibitor, and the combination of alectinib and a TOPK inhibitor suppresses tumor growth and promotes apoptosis of ALK-positive NSCLC cells.
CELL DEATH & DISEASE
(2022)
Article
Biology
Soichiro Suzuki, Fumiaki Ando, Sae Kitagawa, Yu Hara, Tamami Fujiki, Shintaro Mandai, Koichiro Susa, Takayasu Mori, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Summary: Signaling through cAMP/protein kinase A (PKA) promotes endothelial barrier function to prevent plasma leakage. ZNF185, identified as a PKA substrate, interacts with PKA and colocalizes with F-actin in endothelial cells. Knockdown of ZNF185 disrupts actin filaments and promotes stress fiber formation, resulting in endothelial barrier dysfunction.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Physical
He Wang, Xun Zhu, Yizhen Zhao, Yongjian Zang, Jianwen Zhang, Ying Kang, Zhiwei Yang, Peng Lin, Lei Zhang, Shengli Zhang
Summary: This study investigated the micromechanism of TOPK, a potential target for cancer therapy, through modeling and simulation. The results showed that the ENI motif of the NTPM is regulated by the N-C interaction zone, and mutations at specific residues promote conformational changes and phosphorylation. Furthermore, allosteric effects induce structural changes that are important for activation or binding. These findings provide insights for designing inhibitors and understanding the regulatory mechanisms of TOPK monomers.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Medicine, Research & Experimental
Aneesh Bapat, Guoping Li, Ling Xiao, Ashish Yeri, Maarten Hulsmans, Jana Grune, Masahiro Yamazoe, Maximilian J. Schloss, Yoshiko Iwamoto, Justin Tedeschi, Xinyu Yang, Matthias Nahrendorf, Anthony Rosenzweig, Saumya Das, Patrick T. Ellinor, David Milan
Summary: This study validates the role of SGK1 in obesity-related atrial fibrillation using a mouse model. It demonstrates the impact of SGK1 on atrial electrophysiology, structural remodeling, inflammation, and sodium current in obesity-related AF.
Article
Biochemistry & Molecular Biology
Rui Albuquerque-Martins, Dora Szakonyi, James Rowe, Alexander M. Jones, Paula Duque
Summary: By analyzing transgenic plants expressing fluorescently tagged SR45, we found that SR45, an SR protein, can reduce sensitivity to ABA during early seedling development. Exposure to ABA leads to dephosphorylation of multiple amino acid residues on SR45 and its accumulation through reduced ubiquitination and degradation. Through the study of phosphomutant and phosphomimetic transgenic lines, we demonstrate that ABA-mediated dephosphorylation of a specific residue, T264, is important in antagonizing SR45 ubiquitination and degradation to promote its function as a repressor of seedling ABA sensitivity.
PLANT COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Rosemary Lane, Chiara Cilibrasi, Jianing Chen, Kalpit Shah, Eleonora Messuti, Nektarios K. Mazarakis, Justin Stebbing, Giles Critchley, Erwei Song, Thomas Simon, Georgios Giamas
Summary: This study identifies PDGF-R alpha/beta inhibitor CP-673451 as a potential differentiation agent for GBM. In vitro experiments showed that CP-673451 promotes differentiation of GBM cells and GBM stem cells into neural-like cells, while reducing proliferation and invasion. In vivo experiments demonstrated that CP-673451 enhances the anti-tumor effects of temozolomide. Mechanistically, upregulation of phosphatase DUSP1 and downregulation of phosphorylated-p38(MAPK) may underlie the pro-differentiation effect of CP-673451 on GBM cells.
Article
Biology
Mark C. Johnson, Geylani Can, Miguel Monteiro Santos, Diana Alexander, Philip Zegerman
Summary: This study reveals that Rad53 phosphorylates the same substrates throughout the cell cycle, not just in S-phase, suggesting its roles beyond S-phase. By inhibiting 51d3 and Dbf4, Rad53 limits re-replication in G2/M, preventing gene amplification, and inhibiting these substrates in G1 prevents premature initiation at the G1/S transition. This redefinition of the 'S-phase checkpoint' has implications for understanding checkpoint function in cancers without proper cell cycle controls.
Article
Dermatology
Katrin Rietscher, Heinz-Georg Jahnke, Matthias Ruebsam, Eric W. Lin, Cristina Has, M. Bishr Omary, Carien M. Niessen, Thomas M. Magin
Summary: This study demonstrates that the multikinase inhibitor PKC412 can reduce keratin aggregation in patient-derived EBS keratinocytes and restore intercellular adhesion. The findings provide a proof of concept for the repurposing of existing drugs for the targeted treatment of EBS and pave the way for clinical trials using PKC412 in EBS patients.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Endocrinology & Metabolism
Bastian Ramms, Dennis P. Pollow, Han Zhu, Chelsea Nora, Austin R. Harrington, Ibrahim Omar, Philip L. S. M. Gordts, Matthew Wortham, Maike Sander
Summary: This study demonstrates the role of an enzyme called LSD1 in obesity-associated metabolic reprogramming. The inhibition of LSD1 reduces food intake and body weight, improves fatty liver disease, and enhances insulin sensitivity and glycemic control in obese mice. The findings suggest that targeting LSD1 could be a potential strategy for the treatment of obesity and its associated complications.
Article
Oncology
Jun Li, Nan Liu, Hong Zhou, Peng Xian, Yanping Song, Xianli Tang, Yuan Li, Michael Basler
Summary: This study found that immunoproteasome inhibition has a significant effect on suppressing the progression of castration-resistant prostate cancer (CRPC). The results showed that immunoproteasome inhibition prevents CRPC progression by suppressing inflammation and inducing apoptosis of CRPC cells through activating the unfolded protein response.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Damjan Avsec, Marja Skrlj Miklavcic, Tilen Burnik, Masa Kanduser, Marusa Bizjak, Helena Podgornik, Irena Mlinaric-Rascan
Summary: Chronic lymphocytic leukemia (CLL) is a type of hematological cancer involving B lymphocytes, and venetoclax is a commonly used targeted therapy. This study found that certain molecular mechanisms in CLL cells can lead to resistance to venetoclax, but targeting these mechanisms can overcome the resistance.
CELL DEATH & DISEASE
(2022)
Article
Endocrinology & Metabolism
Fernanda M. C. Sodre, Samal Bissenova, Ylke Bruggeman, Ronak Tilvawala, Dana P. Cook, Claire Berthault, Santanu Mondal, Aisha Callebaut, Sylvaine You, Raphael Scharfmann, Roberto Mallone, Paul R. Thompson, Chantal Mathieu, Mijke Buitinga, Lut Overbergh
Summary: In this study, systemic inhibition of peptidylarginine deiminases (PADs) through BB-Cl-amidine treatment prevented diabetes development in NOD mice by reducing citrullination levels in the pancreas, decreasing circulating autoantibody titers, and reducing neutrophil extracellular trap formation. Additionally, the treatment induced a shift in cytokine production and increased regulatory T cell frequency. This highlights the potential of PAD inhibition for treating autoimmune diseases like type 1 diabetes.
Article
Pharmacology & Pharmacy
Janaine P. Oliveira, Fabiula F. Abreu, Jose Marcos M. Bispo, Anderson R. A. Cerqueira, Jose Ronaldo dos Santos, Cristiane B. B. Correa, Soraia K. P. Costa, Enilton A. A. Camargo
Summary: This study evaluated the effect of myrtenol on orofacial pain and inflammation. The results showed that myrtenol can alleviate orofacial pain and inflammation and is associated with the modulation of IL-1β levels in the trigeminal pathway and p38-MAPK in the trigeminal ganglia.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ga-Eun Lee, Cheol-Jung Lee, Hyun-Jung An, Han Chang Kang, Hye Suk Lee, Joo Young Lee, Sei-Ryang Oh, Sung-Jun Cho, Dae Joon Kim, Yong-Yeon Cho
Summary: Fargesin inhibits cancer cell growth by suppressing cell cycle transition and EGF-induced cell transformation through multiple signaling pathways, including CDK/cyclin and Rb-E2F pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nuri Choi, Gabsik Yang, Joo Hyeon Jang, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Summary: The study found that loganin can prevent gout inflammation by inhibiting the NLRP3 inflammasome and reducing neutrophil recruitment. Additionally, loganin blocks mitochondrial DNA synthesis and inhibits mitochondrial damage, thus preventing the occurrence of gout inflammation.
Review
Immunology
Jin Kyung Seok, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Summary: Inflammation is a host protection mechanism that can eliminate invasive pathogens from the body, but chronic inflammation may lead to various inflammatory and autoimmune diseases. Recent studies have shown the significant contribution of the NLRP3 inflammasome to the pathology of various inflammatory diseases. Understanding the activation regulation of NLRP3 inflammasome by multiple signaling pathways, post-translational modifications, and cellular organelles is crucial for the development of therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Jin Kyung Seok, Eun-Hee Hong, Gabsik Yang, Hye Eun Lee, Sin-Eun Kim, Kwang-Hyeon Liu, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Summary: Oxidized phospholipids, such as POVPC and PGPC, are found to promote epithelial-mesenchymal transition (EMT) and autophagy in cancer cells, leading to increased migration and invasion potential. Elevated levels of these oxidized phospholipids are observed in tumor tissues and are associated with enhanced metastatic abilities.
Article
Pharmacology & Pharmacy
Ria Park, Eun Jeong Park, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Im-Sook Song, Hye Suk Lee
Summary: Tetrahydrofurofuranoid lignans, such as eudesmin and magnolin, were found to inhibit UGT1A1 and UGT1A3 activities in human liver microsomes. This suggests a potential for drug-drug interactions involving these lignans with UGT1A1 and UGT1A3 substrates in vivo.
Article
Environmental Sciences
Jae Kwon Lee, Jin Kyung Seok, Ilyoung Cho, Gabsik Yang, Kyu-Bong Kim, Seung Jun Kwack, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Summary: The study showed that celastrol inhibited TSLP production by mouse keratinocyte cells and improved atopic dermatitis symptoms induced by house dust mite in mice. Celastrol reduced TSLP levels and Th2 cytokines, as well as decreased ILC2 population in atopic dermatitis skin lesions. These findings suggest that celastrol may alleviate atopic dermatitis symptoms by regulating TSLP levels and immune responses.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2021)
Article
Environmental Sciences
Ria Park, Won-Gu Choi, Min Seo Lee, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Chang Hwan Sohn, Im-Sook Song, Hye Suk Lee
Summary: This study aimed to determine the pharmacokinetics of alpha-amanitin in mice after intravenous or oral administration. Results showed rapid clearance and major excretion via the renal route after intravenous injection, and low bioavailability and high recovery from feces after oral administration. The distribution to intestine, kidneys, and liver was consistent with previously reported major intoxicated organs. Data also suggested potential remote drug interaction with alpha-amanitin exposure.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2021)
Article
Chemistry, Medicinal
Juhee Park, Ga-Eun Lee, Hyung-Jung An, Cheol-Jung Lee, Eun Suh Cho, Han Chang Kang, Joo Young Lee, Hye Suk Lee, Jin-Sung Choi, Dae Joon Kim, Jong-Soon Choi, Yong-Yeon Cho
Summary: Kaempferol targeting RSKs may be a strategy to reduce oxaliplatin-resistant colon cancer cells. The study provides evidence that molecular mechanisms for drug resistance in human cancer are crucial in overcoming this challenge.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Engineering, Biomedical
Yeon Su Choi, Hana Cho, Won-Gu Choi, Sung Su Lee, Kang Moo Huh, Min Suk Shim, In Suh Park, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee, Han Chang Kang
Summary: This study investigates small hydrophilic molecule-stabilized nanoparticles for effective intra-cellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione.
Article
Biochemistry & Molecular Biology
Hyun-Jung An, Cheol-Jung Lee, Ga-Eun Lee, Youngwon Choi, Dohyun Jeung, Weidong Chen, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Dae Joon Kim, Jin-Sung Choi, Eun Suh Cho, Jong-Soon Choi, Yong-Yeon Cho
Summary: FBXW7 regulates ERK3 stability by promoting its ubiquitination and degradation, thereby suppressing lung cancer cell proliferation.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Chemistry, Medicinal
Gabsik Yang, Hye Eun Lee, Jin Kyung Seok, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Summary: Inflammation and immunity are closely linked to obesity and metabolic disorders. The study found that RIG-I deficiency promotes obesity and insulin resistance induced by a high-fat diet, revealing a novel role of RIG-I in the development of obesity and metabolic disorders.
Article
Pharmacology & Pharmacy
Young Yoon Bang, Im-Sook Song, Min Seo Lee, Chang Ho Lim, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang, Hye Suk Lee
Summary: The toxicokinetics of beta-amanitin, a toxic compound found in Amanitaceae mushrooms, were studied in mice. The compound was rapidly eliminated from plasma and mainly excreted through feces after oral administration. It distributed predominantly in the intestines and stomach.
Review
Biochemistry & Molecular Biology
Ga-Eun Lee, Jiin Byun, Cheol-Jung Lee, Yong-Yeon Cho
Summary: The integrity of the nuclear membrane is crucial for cellular function and disease pathogenesis. While there has been extensive research on nuclear membrane assembly, disassembly, and interactions with other cellular components, less emphasis has been placed on the regulation of nuclear morphology through nuclear membrane integrity. This review aims to shed light on the biomolecules responsible for maintaining nuclear membrane integrity and explore the role of type II membrane protein transcription factors in this context.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Jin Kyung Seok, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee
Summary: Inflammasomes are critical cytosolic receptors that play key roles in immunity and tissue repair. The NLRP3 inflammasome is well-known for its involvement in inflammatory diseases and efforts are being made to develop therapeutic applications targeting it. Small molecule inhibitors are being developed to provide new opportunities for treating NLRP3 inflammasome-related diseases.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Yeon Su Choi, Kang Moo Huh, Min Suk Shim, In Suh Park, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee, Han Chang Kang
Summary: This study investigates the release of therapeutics in the cytosol using a diselenide-based drug carrier, identifying GSH as the major trigger for diselenide cleavage and demonstrating synergistic anticancer effects when combining the carrier with an anticancer drug. The research shows that the combined use of diselenide-based drug carrier and drug has a significant inhibitory effect on tumor growth in vivo.
ADVANCED FUNCTIONAL MATERIALS
(2021)
