Article
Biochemistry & Molecular Biology
You Chul Chung, Chang-Gu Hyun
Summary: Pinostilbene hydrate (PH) inhibits adipogenesis in 3T3-L1 cells by reducing lipid accumulation and triglyceride content without cytotoxicity. It works through multiple pathways, including activation of the AMPK signaling pathway and inhibition of MAPK and AKT insulin-dependent signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Ignacio Niechi, Jose I. Erices, Diego Carrillo-Beltran, Atenea Uribe-Ojeda, Angelo Torres, Jose Dellis Rocha, Daniel Uribe, Maria A. Toro, Karla Villalobos-Nova, Belen Gaete-Ramirez, Gabriel Mingo, Gareth I. I. Owen, Manuel Varas-Godoy, Lilian Jara, Francisco Aguayo, Veronica A. Burzio, Claudia Quezada-Monras, Julio C. C. Tapia
Summary: Glioblastoma (GBM) is a common and aggressive brain tumor characterized by high recurrence rates. Glioblastoma stem-like cells (GSCs), which are highly resistant to anti-cancer drugs, play a key role in GBM recurrence. This study investigated the role of endothelin-converting enzyme-1 (ECE1) in promoting GSC-like traits in GBM. The researchers found that a phosphorylated variant of ECE1c (ECE1c(K6R)) increased self-renewal and stem-like characteristics in GBM cells, as well as enhanced resistance to chemotherapy drugs and invasiveness. These findings suggest that phosphorylated ECE1c may serve as a prognostic marker and potential therapeutic target for GBM.
Article
Biochemistry & Molecular Biology
Jan Pencik, Cecile Philippe, Michaela Schlederer, Emine Atas, Matteo Pecoraro, Sandra Grund-Groeschke, Wen (Jess) Li, Amanda Tracz, Isabel Heidegger, Sabine Lagger, Karolina Trachtova, Monika Oberhuber, Ellen Heitzer, Osman Aksoy, Heidi A. Neubauer, Bettina Wingelhofer, Anna Orlova, Nadine Witzeneder, Thomas Dillinger, Elisa Redl, Georg Greiner, David D'Andrea, Johnny R. Ostman, Simone Tangermann, Ivana Hermanova, Georg Schaefer, Felix Sternberg, Elena E. Pohl, Christina Sternberg, Adam Varady, Jaqueline Horvath, Dagmar Stoiber, Tim I. Malcolm, Suzanne D. Turner, Eileen E. Parkes, Brigitte Hantusch, Gerda Egger, Stefan Rose-John, Valeria Poli, Suneil Jain, Chris W. D. Armstrong, Gregor Hoermann, Vincent Goffin, Fritz Aberger, Richard Moriggl, Arkaitz Carracedo, Cathal McKinney, Richard D. Kennedy, Helmut Klocker, Michael R. Speicher, Dean G. Tang, Ali A. Moazzami, David M. Heery, Marcus Hacker, Lukas Kenner
Summary: PTEN and STAT3 are frequently co-deleted genes in metastatic prostate cancer (mPCa). STAT3 controls mPCa through the LKB1/pAMPK/mTORC1/CREB signaling pathway, and metformin can inhibit mPCa growth.
Article
Medicine, Research & Experimental
Abdulla M. A. Mahmoud, Eman M. Mantawy, Sara A. Wahdan, Ramy M. Ammar, Ebtehal El-Demerdash
Summary: This study aimed to investigate the potential neuroprotective properties of vildagliptin against cisplatin-induced neurotoxicity and elucidate the underlying molecular mechanisms. The results showed that vildagliptin could restore the impaired cognitive function, alleviate neurodegeneration and inflammation, and promote hippocampal neurogenesis and survival. These effects were mainly mediated by activating AMPK/Akt/CREB signaling cascades.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biology
Rossella Delle Donne, Rosa Iannucci, Laura Rinaldi, Luca Roberto, Maria A. Oliva, Emanuela Senatore, Domenica Borzacchiello, Luca Lignitto, Giorgio Giurato, Francesca Rizzo, Assunta Sellitto, Francesco Chiuso, Salvatore Castaldo, Giovanni Scala, Virginia Campani, Valeria Nele, Giuseppe De Rosa, Chiara D'Ambrosio, Corrado Garbi, Andrea Scaloni, Alessandro Weisz, Concetta Ambrosino, Antonella Arcella, Antonio Feliciello
Summary: The study identifies praja2 as an essential regulator of cancer cell metabolism in glioblastoma (GBM) and a potential therapeutic target to suppress GBM growth. Silencing praja2 using siRNA delivered by nanoparticles reduces tumor size in GBM-bearing mice.
COMMUNICATIONS BIOLOGY
(2022)
Article
Plant Sciences
Xiaoqiong Liu, Lingling Fan, Jian Li, Ziyu Bai, Yue Wang, Yafang Liu, Hong Jiang, Anhua Tao, Xiang Li, Hui Zhang, Ninghua Tan
Summary: The study aimed to investigate the relationship between neuroprotection and apoptosis for clarifying the mechanism of Mailuoning oral liquid (MLN O) in the recovery phase of ischemic stroke. The results showed that MLN O significantly reduced brain infarct volume and neurological deficit scores, inhibited inflammatory cell infiltration and neuronal apoptosis, and promoted gliosis, neuronal survival, and neuroprotection. Furthermore, MLN O improved cell viability, restored cell morphology, and attenuated cell damage, while inhibiting neuronal apoptosis. MLN O inhibited AMPK/mTOR activity and activated CREB/BDNF signaling pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Physiology
Raquel Gonzalez-Blazquez, Marta Gil-Ortega, Martin Alcala, Daniel Gonzalez-Moreno, Marta Viana, Julie A. Chowen, Marta Sanz-Gomez, Maria S. Fernandez-Alfonso, Beatriz Somoza
Summary: This study aimed to investigate if replacing a high-fat diet with a standard diet for a short period could reverse obesity-induced endothelial dysfunction through AMPK-CREB activation. The results showed that improving dietary intake significantly improved vascular function and the antioxidant system mediated by the AMPK/CREB signaling pathway.
Review
Biochemistry & Molecular Biology
Mehdi Sanati, Samaneh Aminyavari, Hamid Mollazadeh, Ali Motamed-Sanaye, Bahram Bibak, Elmira Mohtashami, Yong Teng, Amir R. R. Afshari, Amirhossein Sahebkar
Summary: This research reviewed the literature to assess the connection between metformin's anticancer properties and the development of glioblastoma multiforme (GBM). The comprehensive review found that metformin not only inhibits tumor growth by activating the AMPK pathway, but also induces cell apoptosis, inhibits cell proliferation and metastasis, and enhances chemo-radio-sensitizing behavior against GBM through other mechanisms. Further research is needed to explore the potential of metformin-based therapeutics for GBM and the challenges they may face.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Neurosciences
Qiang Dong, Degui Wang, Lanlan Li, Jie Wang, Qiao Li, Lei Duan, Hang Yin, Xiaoqing Wang, Yang Liu, Guoqiang Yuan, Yawen Pan
Summary: The study found that BCA can effectively enhance sensitivity of GBM to TMZ by inhibiting autophagy, mediated through interaction with AMPK residues. This discovery sheds new light on the potential therapeutic role of BCA in sensitizing chemoresistant GBM to TMZ.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Oncology
Hongying Zhang, Songpeng Yang, Jiao Wang, Yangfu Jiang
Summary: Aspirin can enhance the anti-cancer effect on hepatocellular carcinoma (HCC) by activating signaling pathways, while the combination with the natural agent berbamine can improve the sensitivity of HCC to aspirin. Targeting the cAMP-PKA-CREB/ATF1 signaling pathway may represent a novel strategy to enhance the therapeutic effects of aspirin on HCC.
Article
Oncology
Mengting Yang, Xi Chen, Junyao Zhang, Ermeng Xiong, Qianqian Wang, Wenjing Fang, Li Li, Fei Fei, Aihua Gong
Summary: ME2 is significantly upregulated in GBM compared to normal brain tissues and negatively correlates with patient survival. It promotes proliferation, migration, and invasion of glioma cells, as well as proneural-mesenchymal transition and lipogenesis in GBM through AMPK-SREBP-1-ACSS2 signaling.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Chen Jie, Wang Xuan, Han-Dong Feng, Ding-Mao Hua, Wang Bo, Sun Fei, Zhang Hao
Summary: AdipoR2 expression correlates with glioma grade and has antiproliferative effects in U251 cells. Analysis of gene expression profiles revealed AdipoR2 is associated with cell cycle, and the AMPK/mTOR signaling pathway is involved in AdipoR2-induced cell cycle arrest.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2021)
Article
Environmental Sciences
Tong Zhang, Yue Wang, Wenxue Yao, Yangyang Chen, Dan Zhang, Ying Gao, Shuo Jin, Lina Li, Shikuan Yang, Yonghui Wu
Summary: Nickel compounds in the industrial environment increase the risk of lung inflammation and lung cancer. This study found that Nickel-refining fumes (NiRF) can induce cell pyroptosis and oxidative stress, while metformin treatment alleviates these damages. Metformin suppresses NiRF-induced pyroptosis by regulating AMPK/CREB/Nrf2 signaling pathway, providing pulmonary protection.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Cell Biology
Katharina M. Eyme, Alessandro Sammarco, Roshani Jha, Hayk Mnatsakanyan, Caline Pechdimaljian, Litia Carvalho, Rudolph Neustadt, Charlotte Moses, Ahmad Alnasser, Daniel F. Tardiff, Baolong Su, Kevin J. Williams, Steven J. Bensinger, Chee Yeun Chung, Christian E. Badr
Summary: Deregulated de novo lipid synthesis (DNLS) is a potential target for therapeutic intervention in glioblastoma (GBM), but the mechanisms underlying susceptibility to DNLS-targeted therapies are unknown and brain-penetrant inhibitors of DNLS are lacking.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Viridiana Alcantara-Alonso, Robert Dallmann, Hendrik Lehnert, Patricia de Gortari, Dimitris K. Grammatopoulos
Summary: The hypothalamic CRH-R2 plays critical roles in stress recovery and feeding regulation. While it promotes adaptive responses and feeding inhibition during acute stress, chronic stress can lead to resistance and increased food intake. The molecular mechanisms underlying these altered responses are not well understood.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Min Tang, Qi Xie, Ryan C. Gimple, Zheng Zhong, Trevor Tam, Jing Tian, Reilly L. Kidwell, Qiulian Wu, Briana C. Prager, Zhixin Qiu, Aaron Yu, Zhe Zhu, Pinar Mesci, Hui Jing, Jacob Schimelman, Pengrui Wang, Derrick Lee, Michael H. Lorenzini, Deobrat Dixit, Linjie Zhao, Shruti Bhargava, Tyler E. Miller, Xueyi Wan, Jing Tang, Bingjie Sun, Benjamin F. Cravatt, Alysson R. Muotri, Shaochen Chen, Jeremy N. Rich
Article
Oncology
Deobrat Dixit, Briana C. Prager, Ryan C. Gimple, Hui Xian Poh, Yang Wang, Qiulian Wu, Zhixin Qiu, Reilly L. Kidwell, Leo J. Y. Kim, Qi Xie, Kristoffer Vitting-Seerup, Shruti Bhargava, Zhen Dong, Li Jiang, Zhe Zhu, Petra Hamerlik, Samie R. Jaffrey, Jing Crystal Zhao, Xiuxing Wang, Jeremy N. Rich
Summary: Research reveals that m6A mRNA modifications are upregulated in glioblastoma stem cells, with the key m6A reader YTHDF2 stabilizing important transcripts such as MYC. Targeting the YTHDF2-MYC-IGFBP3 axis could potentially be a novel therapeutic approach for glioblastoma. Epitranscriptomics have the potential to reveal specific vulnerabilities in cancer cells that can be targeted for treatment.
Review
Oncology
Fahim Ahmad, Murali Krishna Cherukuri, Peter L. Choyke
Summary: While low-risk localized prostate cancer has a good prognosis with effective treatments, metastatic prostate cancer remains incurable and treatment resistance is a major issue. Resistance is primarily driven by tumor heterogeneity, altered genetic signatures, and metabolic reprogramming enabling tumors to adapt to drugs. Understanding prostate cancer metabolism may offer insights into therapy-induced adaptive responses and more durable therapeutic outcomes.
BRITISH JOURNAL OF CANCER
(2021)
Article
Cell Biology
Pruthvi Gowda, Shruti Patrick, Shanker Datt Joshi, Rajesh Kumar Kumawat, Ellora Sen
Summary: SARS-CoV-2 infection is associated with uncontrolled inflammation and loss of ACE2 function, similar to characteristics seen in lung cancer. Analysis showed an inverse correlation between ACE2 and IL6 in lung adenocarcinoma, and treatment with MTx dampened the inflammatory response while restoring ACE2 expression in CoV-2-SRBD transfected cells. Repurposing MTx as a therapy against inflammation regulators in SARS-CoV-2 infection is worthy of investigation.
Article
Cell Biology
Shruti Patrick, Pruthvi Gowda, Kirti Lathoria, Vaishali Suri, Ellora Sen
Summary: The mutation of the IDH1 gene results in decreased nuclear levels of YAP1 and TFAM, leading to mitochondrial fragmentation and ROS generation, as well as altered localization of TERT in mitochondria, which ultimately affects cell apoptosis. Treatment with the Src kinase inhibitor bosutinib further enhances ROS production and induces apoptosis, indicating a crucial role of YAP1 in regulating redox homeostasis through mitochondrial dysfunction and TERT shuttling.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Pruthvi Gowda, Kirti Lathoria, Sonia B. Umdor, Ellora Sen
Summary: The ATPase domain of BRG1 plays a crucial role in regulating redox homeostasis and sensitivity to oxidative stressors in glioma cells. BRG1 mutation creates vulnerability to elevated ROS levels, which can be therapeutically exploited, with ROS stressors as a promising therapeutic target for the treatment of BRG1-mutant cancers.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Cell Biology
Deobrat Dixit, Briana C. Prager, Ryan C. Gimple, Tyler E. Miller, Qiulian Wu, Shira Yomtoubian, Reilly L. Kidwell, Deguan Lv, Linjie Zhao, Zhixin Qiu, Guoxin Zhang, Derrick Lee, Donglim Esther Park, Robert J. Wechsler-Reya, Xiuxing Wang, Shideng Bao, Jeremy N. Rich
Summary: In this study, DPY30 was identified as an in vivo-specific glioblastoma dependency using in vivo genetic screening. By examining the chromatin characteristics of glioblastoma stem cells, DPY30 was found to regulate angiogenesis and hypoxia pathways critical for tumor growth. However, DPY30 was dispensable in vitro. Additionally, DPY30 was shown to regulate the downstream effector PDE4B, with the inhibitor rolipram preferentially targeting DPY30-expressing cells and impairing the growth of patient-derived xenograft tumors in mice.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Zhixin Qiu, Linjie Zhao, Jia Z. Shen, Zhengyu Liang, Qiulian Wu, Kailin Yang, Lihua Min, Ryan C. Gimple, Qiyuan Yang, Shruti Bhargava, Chunyu Jin, Cheryl Kim, Denise Hinz, Deobrat Dixit, Jean A. Bernatchez, Briana C. Prager, Guoxin Zhang, Zhen Dong, Deguan Lv, Xujun Wang, Leo J. Y. Kim, Zhe Zhu, Katherine A. Jones, Ye Zheng, Xiuxing Wang, Jair L. Siqueira-Neto, Lukas Chavez, Xiang-Dong Fu, Charles Spruck, Jeremy N. Rich
Summary: This study identifies the YY1-CDK9 transcription elongation complex as a crucial factor in maintaining glioblastoma stemness and therapeutic resistance. Targeting this complex can activate interferon response, reduce regulatory T-cell infiltration, and enhance the efficacy of immune checkpoint therapy.
Article
Oncology
Daqi Li, Qian Zhang, Lu Li, Kexin Chen, Junlei Yang, Deobrat Dixit, Ryan C. Gimple, Shusheng Ci, Chenfei Lu, Lang Hu, Jiancheng Gao, Danyang Shan, Yangqing Li, Junxia Zhang, Zhumei Shi, Danling Gu, Wei Yuan, Qiulian Wu, Kailin Yang, Linjie Zhao, Zhixin Qiu, Deguang Lv, Wei Gao, Hui Yang, Fan Lin, Qianghu Wang, Jianghong Man, Chaojun Li, Weiwei Tao, Sameer Agnihotri, Xu Qian, Yu Shi, Yongping You, Nu Zhang, Jeremy N. Rich, Xiuxing Wang
Summary: The study reveals the tumor-promoting functions of B2M in glioblastoma and suggests potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment. B2M activation leads to the maintenance of stem-like neoplastic populations and induces an anti-inflammatory state, while promoting the polarization of macrophages towards an M2-like phenotype. Inhibition of B2M could attenuate glioblastoma stem cell survival, self-renewal, and tumor growth.
Article
Cell Biology
Deguan Lv, Ryan C. Gimple, Cuiqing Zhong, Qiulian Wu, Kailin Yang, Briana C. Prager, Bhaskar Godugu, Zhixin Qiu, Linjie Zhao, Guoxin Zhang, Deobrat Dixit, Derrick Lee, Jia Z. Shen, Xiqing Li, Qi Xie, Xiuxing Wang, Sameer Agnihotri, Jeremy N. Rich
Summary: Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. PDGF signaling induces m(6)A accumulation in GBM stem cells to regulate mitophagy. PDGF-METTL3-OPTN signaling is identified as a therapeutic target for GBM treatment.
DEVELOPMENTAL CELL
(2022)
Article
Cell Biology
Kirti Lathoria, Pruthvi Gowda, Sonia B. Umdor, Shruti Patrick, Vaishali Suri, Ellora Sen
Summary: Mutations in the Krebs cycle enzyme IDH1 are associated with better prognosis in gliomas. The study reveals that IDH1 mutant gliomas have diminished expression of the PRMT1-PTX3 axis, leading to dysregulation of autophagy and ferritinophagy. The findings suggest that targeting the PRMT1-PTX3 ferritinophagy regulatory circuit could be a potential therapeutic strategy.
Article
Biochemistry & Molecular Biology
Raffaella Spina, Ian Mills, Fahim Ahmad, Chixiang Chen, Heather M. Ames, Jeffrey A. Winkles, Graeme F. Woodworth, Eli E. Bar
Summary: Glioma stem cells (GSCs) are sensitive to perturbations in de novo pyrimidine synthesis, and EGFR amplification confers resistance. BAY2402234, an inhibitor of DHODH, effectively inhibits GSC proliferation and induces apoptosis and DNA damage. Clinical testing of BAY2402234 in primary glioblastoma patients lacking EGFR amplification is warranted.
Article
Neurosciences
Surajit Chakraborty, Ellora Sen, Anirban Basu
Summary: Infection by Japanese Encephalitis Virus (JEV) can lead to neuronal apoptosis. This study found that JEV infection can regulate the abundance of neuronal pyruvate dehydrogenase kinase 1 (PDK1), and inhibiting the upregulation of PDK1 can improve neuronal apoptosis and reduce the generation of reactive oxygen species.
IBRO NEUROSCIENCE REPORTS
(2022)
Article
Medicine, Research & Experimental
Ryan C. Gimple, Guoxin Zhang, Shuai Wang, Tengfei Huang, Jina Lee, Suchet Taori, Deguan Lv, Deobrat Dixit, Matthew E. Halbert, Andrew R. Morton, Reilly L. Kidwell, Zhen Dong, Briana C. Prager, Leo J. Y. Kim, Zhixin Qiu, Linjie Zhao, Qi Xie, Qiulian Wu, Sameer Agnihotri, Jeremy N. Rich
Summary: In this study, the researchers found that SNX10 was selectively expressed in glioblastoma stem cells (GSCs) compared with non-neoplastic neural stem cells (NSCs). SNX10 was essential for GSC survival and promoted GSC proliferation and stem cell signaling pathways through posttranscriptional regulation of PDGFR tyrosine kinase. Targeting SNX10 expression decreased GSC viability and self-renewal capacity. High expression of SNX10 correlated with poor prognosis in glioblastoma patients.
Article
Oncology
Wei Yuan, Qian Zhang, Danling Gu, Chenfei Lu, Deobrat Dixit, Ryan C. Gimple, Yisu Gao, Jiancheng Gao, Daqi Li, Danyang Shan, Lang Hu, Lu Li, Yangqing Li, Shusheng Ci, Hao You, Linping Yan, Kexin Chen, Ningwei Zhao, Chuanhai Xu, Jianyun Lan, Dong Liu, Junxia Zhang, Zhumei Shi, Qiulian Wu, Kailin Yang, Linjie Zhao, Zhixin Qiu, Deguang Lv, Wei Gao, Hui Yang, Fan Lin, Qianghu Wang, Jianghong Man, Chaojun Li, Weiwei Tao, Sameer Agnihotri, Xu Qian, Stephen C. Mack, Nu Zhang, Yongping You, Jeremy N. Rich, Guan Sun, Xiuxing Wang
Summary: The study reveals the crucial roles of CXCL8 in maintaining the mesenchymal state of GSCs and M2-like TAM polarization in GBM, suggesting that targeting CXCL8 and its downstream effectors could effectively improve GBM treatment.
CLINICAL CANCER RESEARCH
(2023)
