Article
Oncology
Junjun Li, Tingting Liao, Hongya Liu, Hongliang Yuan, Taohui Ouyang, Jiajing Wang, Songshan Chai, Jinsong Li, Jingchao Chen, Xiang Li, Hongyang Zhao, Nanxiang Xiong
Summary: The study elucidated the mechanisms by which hypoxic lncRNA derived from glioma stem cells (GSC) drive glioma progression, involving the Linc01060 gene, exosomes containing it, and proteins regulating the gene. Transfer of exosomes from GSCs to glioma cells increased Linc01060 levels and activated prooncogenic signaling pathways. Inhibition of Linc01060-containing exosomes or targeting the Linc01060/MZEI/c-Myc/HIF1 alpha axis could be an effective therapeutic strategy in glioma.
Article
Cell Biology
Rajeshwary Ghosh, Jennifer Jason Gillaspie, Kenneth S. Campbell, J. David Symons, Sihem Boudina, James Scott Pattison
Summary: This study establishes a protective role for chaperone-mediated autophagy (CMA) in hypoxia-induced cardiomyocyte loss and suggests that CMA activation may offer a novel treatment for ischemic heart disease.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kazutomo Baba, Andrey Mikhailov, Yoshiyuki Sankai
Summary: A three-layered tissue structure similar to physiological can be assembled by seeding different cell types in succession; training the formed tissue with increasing flow in a bioreactor is effective for promoting cell survival, improving pressure resistance, and cell layer formation of desired properties.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Zigui Chen, Xin Yan, Changfeng Miao, Longyang Liu, Su Liu, Ying Xia, Weiyi Fang, Dandan Zheng, Qisheng Luo
Summary: This study provides evidence that MYH9 plays an important role in glioma by promoting cell proliferation and temozolomide resistance. Mechanistically, MYH9 inhibits the ubiquitination and degradation of NAP1L1, leading to activation of c-Myc and increased expression of CCND1/CDK4, which contributes to temozolomide resistance and proliferation in glioma cells. Additionally, upregulation of MYH9 is associated with poor prognosis in glioma patients. Targeting MYH9 could be a potential therapeutic strategy for glioma treatment in the future.
CANCER CELL INTERNATIONAL
(2023)
Article
Oncology
Tian-Jun Chen, Qi Zheng, Fei Gao, Tian Yang, Hui Ren, Yang Li, Ming-Wei Chen
Summary: miR-665 is upregulated in LUSC tissues and cell lines, promoting cell proliferation and G1-S transition while suppressing apoptosis. Its target gene TRIM8 is negatively correlated with miR-665 expression in LUSC, and TRIM8 affects cell growth and apoptosis through Wnt5a/beta-catenin and Caspase-3 signaling pathways. MiR-665 may be a potential therapeutic target for LUSC.
CANCER CELL INTERNATIONAL
(2021)
Article
Oncology
Pan Wang, Sheng Gong, Bin Liao, Jinyu Pan, Junwei Wang, Dewei Zou, Lu Zhao, Shuanglong Xiong, Yangmin Deng, Qian Yan, Nan Wu
Summary: The study demonstrated that in a hypoxic microenvironment, the HIF1 alpha/HIF2 alpha-Sox2 network induced the formation of glioma stem cells through the dedifferentiation of differentiated glioma cells, thus promoting glioma cell chemoresistance. Both HIF1 alpha and HIF2 alpha, as genes upstream of Sox2, regulate the malignant progression of glioma through dedifferentiation. The knockout of HIF1 alpha, HIF2 alpha, and Sox2 in glioma cells under hypoxic conditions led to decreased CD133 and CD15 expression and inhibited sphere formation.
Article
Cell Biology
Zhirui Zeng, Shan Lei, Zhiwei He, Tengxiang Chen, Jianxin Jiang
Summary: Hypoxia is involved in the development of pancreatic cancer, where the key hypoxia-associated gene YEATS2 is upregulated and promotes proliferation and metastasis of PC cells. HIF1α regulates the expression of YEATS2 by binding to its HRE, and both are coexpressed in PC tissues.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ewelina Jozefczuk, Piotr Szczepaniak, Tomasz Jan Guzik, Mateusz Siedlinski
Summary: The silencing of Sphk1 in neonatal mouse CMs was shown to enhance their postnatal maturation in both physiological and stress conditions, as evidenced by accelerated cell maturation, inhibition of proliferation, and induction of developmental pathways. This effect was further supported by the upregulation of the Akt signaling pathway and downregulation of Gsk3β, indicating physiological hypertrophy in the absence of Sphk1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Patrick G. Burgon, Jonathan J. Weldrick, Omar Mohamed Sayed Ahmed Talab, Muhammad Nadeer, Michail Nomikos, Lynn A. Megeney
Summary: This review surveys recent discoveries regarding the developmental transition of proliferative fetal cardiomyocytes into hypertrophic postnatal cardiomyocytes, providing a detailed perspective for future research directions.
Article
Cell Biology
Yusuke Kametani, Shota Tanaka, Yuriko Wada, Shota Suzuki, Ayaka Umeda, Kosuke Nishinaka, Yoshiaki Okada, Makiko Maeda, Shigeru Miyagawa, Yoshiki Sawa, Masanori Obana, Yasushi Fujio
Summary: Mammalian cardiomyocytes largely cease to proliferate immediately after birth, limiting the regenerative activity of the heart. Inhibition of GSK-3 promotes cardiomyocyte proliferation, and YAP is endogenously activated. This study addresses the importance of YAP activity in GSK-3 inhibitor-induced cardiomyocyte proliferation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Libang Yang, Adam Gilbertsen, Hong Xia, Alexey Benyumov, Karen Smith, Jeremy Herrera, Emil Racila, Peter B. Bitterman, Craig A. Henke
Summary: Hypoxia promotes self-renewal and fibrogenicity of idiopathic pulmonary fibrosis mesenchymal progenitor cells (MPCs) through lactate/GPR81/HIF1 alpha pathway. Hypoxia enhances lactate production and release by increasing LDHA function in IPF MPCs. The expression of GPR81 is upregulated by hypoxia, and exogenous lactate through GPR81 promotes IPF MPC self-renewal. Knockdown of GPR81 inhibits hypoxia-induced IPF MPC self-renewal in vitro and attenuates hypoxia-induced IPF MPC fibrogenicity in vivo.
Article
Genetics & Heredity
Kun Wu, Yiming Tang, Qiaoqiao Zhang, Zhangpeng Zhuo, Xiao Sheng, Jingping Huang, Jie'er Ye, Xiaorong Li, Zhiming Liu, Haiyang Chen
Summary: This study found that the differentiation efficiency of adult stem cells declines in aged Drosophila, with the caudal (cad) gene playing a key role in regulating this process. Depletion of cad promotes activation of quiescent intestinal stem cells (ISCs) to produce enterocytes in the midguts, while overexpression of cad leads to failure of ISC differentiation. Cad prevents ISC differentiation by modulating specific signaling pathways and reducing its expression restrains age-associated gut hyperplasia in Drosophila.
Article
Agriculture, Dairy & Animal Science
Yixin Chu, Ying Yao, Youbo Zhu, Xin'E Shi, Shiduo Sun, Xiao Li
Summary: The study found that miR-370 is highly conserved across domestic animals and relatively enriched in adipose tissues and skeletal muscles. Overexpression of miR-370 promotes porcine preadipocyte proliferation, but inhibits adipogenic differentiation.
ANIMAL BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shanshan Wu, Yafen Wei, Jingxin Li, Yan Bai, Ping Yin, Shun Wang
Summary: The study revealed that SIRT5 plays a crucial role in the treatment of Alzheimer's disease (AD), as its overexpression can ameliorate AD progression by activating autophagy, reducing oxidative stress, and protecting neurons by inhibiting activated microglia and astrocytes. This therapeutic approach shows promise for AD treatment.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biotechnology & Applied Microbiology
Shen Zheng, Ran Wu, Yunlong Deng, Qiang Zhang
Summary: Dysregulation of mitochondrial calcium uniporter (MCU) plays a carcinogenic role in several cancers, including oral squamous cell carcinoma (OSCC). The study aimed to investigate the role of MCU in OSCC and its regulatory relationship with dihydroartemisinin (DHA). The results showed that MCU and its complex members were overexpressed in OSCC and DHA treatment suppressed MCU expression. MCU overexpression reversed the inhibitory effects of DHA on other proteins. Knockdown of MCU or DHA treatment suppressed proliferation and migration of OSCC cells.
Editorial Material
Physiology
Milos Gojkovic, Pedro Velica, Helene Rundqvist, Randall S. Johnson
Article
Multidisciplinary Sciences
Irene Salamon, Simone Serio, Simona Bianco, Christina Pagiatakis, Silvia Crasto, Andrea M. Chiariello, Mattia Conte, Paola Cattaneo, Luca Fiorillo, Arianna Felicetta, Elisa di Pasquale, Paolo Kunderfranco, Mario Nicodemi, Roberto Papait, Gianluigi Condorelli
Review
Biochemistry & Molecular Biology
Rugile Matuleviciute, Pedro P. Cunha, Randall S. Johnson, Iosifina P. Foskolou
Summary: Hypoxia plays a significant role in physiological and pathological processes, especially in cancer. TET family enzymes are crucial in epigenetic remodelling and cancer development. Inhibiting TETs has shown positive impact in cancer immunotherapy and vaccine studies, highlighting their potential as therapeutic targets.
Article
Pharmacology & Pharmacy
Lindsay M. Henderson, Scarlett E. Hopkins, Bert B. Boyer, Timothy A. Thornton, Allan E. Rettie, Kenneth E. Thummel
Summary: Alaska Native people have unique gene variations that may impact their response to pharmacotherapy. The novel CYP2C9 Met1Leu variant was identified in this population, with potential clinical implications for drug metabolism. The Leu1 variant enzyme exhibited loss of function, indicating a need for further research on genetic variations in understudied populations.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Oncology
Pedro Velica, Pedro P. Cunha, Nikola Vojnovic, Iosifina Petrina Foskolou, David Bargiela, Milos Gojkovic, Helene Rundqvist, Randall S. Johnson
Summary: By ectopically expressing the HIF transcription factor in CD8(+) T cells, this study demonstrated an enhanced antitumor efficacy against tumor targets. A specific mutation in HIF2 alpha showed the most effective antitumor T cell response, suggesting a potential strategy to increase therapeutic efficacy of CD8(+) T cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Critical Care Medicine
Simon Lambden, Andrew S. Cowburn, David Macias, Tessa A. C. Garrud, Bernardo J. Krause, Dino A. Giussani, Charlotte Summers, Randall S. Johnson
Summary: The deficiency of HIF-1 alpha in the systemic or pulmonary endothelium is associated with increased systemic blood pressure and metabolic rate, a pattern that persists in both normoxic conditions and in response to acute stress.
INTENSIVE CARE MEDICINE EXPERIMENTAL
(2021)
Article
Pharmacology & Pharmacy
Lindsay M. Henderson, Claire E. Steinbronn, Jingjing Yu, Catherine K. Yeung, Isabelle Ragueneau-Majlessi
Summary: This study focused on evaluating the consistency in drug-drug interaction labeling language in New Drug Applications, finding differences in DDI result presentation and clinical recommendations. Studies with negative results often lacked mechanistic interpretation, limiting the extrapolation of information.
CLINICAL THERAPEUTICS
(2021)
Article
Medicine, Research & Experimental
Sharon M. Rymut, Siddharth Sukumaran, Gizette Sperinde, Meire Bremer, Joshua Galanter, Kenta Yoshida, Jordan Smith, Prajna Banerjee, Viyia Sverkos, Fang Cai, Verena Steffen, Lindsay M. Henderson, Horace Rhee, Paula N. Belloni, Joseph H. Lin, Tracy L. Staton
Summary: Tryptase is an important protein in asthma pathogenesis, and MTPS9579A is a novel monoclonal antibody that selectively inhibits its activity. The study showed that MTPS9579A has good safety and tolerability in healthy participants, with significant inhibition of active tryptase.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Immunology
David Bargiela, Pedro P. Cunha, Pedro Velica, Iosifina P. Foskolou, Laura Barbieri, Helene Rundqvist, Randall S. Johnson
Summary: Targeting T cell metabolism, specifically vitamin B6 metabolism, can improve anti-tumor immunotherapy by affecting CD8+ T cell proliferation and effector differentiation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Elisa Lenti, Luca Genovese, Silvia Bianchessi, Aurora Maurizio, Simona Baghai Sain, Alessia di Lillo, Greta Mattavelli, Itamar Harel, Francesca Bernassola, Thomas Hehlgans, Klaus Pfeffer, Mariacristina Crosti, Sergio Abrignani, Sylvia M. Evans, Giovanni Sitia, Nuno Guimaraes-Camboa, Vincenzo Russo, Serge A. van de Pavert, Jose Manuel Garcia-Manteiga, Andrea Brendolan
Summary: This study identifies the origin and composition of lymph node stromal and endothelial cells through lineage tracing and single-cell transcriptome analysis. The results show that stromal and endothelial cells originate from different cell populations in the embryo. Single-cell RNA sequencing reveals different subsets of stromal cells and suggests the presence of proliferating progenitors in embryonic lymph nodes.
Article
Engineering, Biomedical
Raymond M. Wang, Joshua M. Mesfin, Jervaughn Hunter, Paola Cattaneo, Nuno Guimaraes-Camboa, Rebecca L. Braden, Colin Luo, Ryan C. Hill, Monika Dzieciatkowska, Kirk C. Hansen, Sylvia Evans, Karen L. Christman
Summary: This study demonstrates that myocardial matrix hydrogel exhibits the ability to scavenge reactive oxygen species and protect cells from oxidative stress, as well as enhance cell proliferation. In in vivo experiments using a rat myocardial infarction model, animals treated with matrix injection showed increased thymidine analog uptake in cardiomyocytes, reduced oxidative damage, and improved preservation of tissue free thiol content compared to saline controls. Overall, this study provides evidence that the properties of the myocardial matrix material create a supportive microenvironment for cardiomyocytes undergoing DNA synthesis, potentially facilitating DNA repair or cell cycle activation.
ACTA BIOMATERIALIA
(2022)
Letter
Cardiac & Cardiovascular Systems
Zhe Yu, Lunfeng Zhang, Paola Cattaneo, Nuno Guimaraes-Camboa, Xi Fang, Yusu Gu, Kirk L. Peterson, Julius Bogomolovas, Cecilia Cuitino, Gustavo W. Leone, Ju Chen, Sylvia M. Evans
Article
Multidisciplinary Sciences
Paola Cattaneo, Michael G. B. Hayes, Nina Baumgarten, Dennis Hecker, Sofia Peruzzo, Galip S. Aslan, Paolo Kunderfranco, Veronica Larcher, Lunfeng Zhang, Riccardo Contu, Gregory Fonseca, Simone Spinozzi, Ju Chen, Gianluigi Condorelli, Stefanie Dimmeler, Marcel H. Schulz, Sven Heinz, Nuno Guimaraes-Camboa, Sylvia M. Evans
Summary: This study reveals that H3K79me2, a modification catalyzed by DOT1L, plays a specific role in regulating gene expression during cardiogenesis. It is important for left ventricle-specific genes during embryonic cardiogenesis and is involved in postnatal cardiomyocyte cell cycle withdrawal. Mechanistic analyses show that H3K79me2 in gene bodies and regulatory elements synergistically promote gene expression activated by DOT1L. Additionally, H3K79me2 in specific regulatory elements also contributes to silencing genes not usually expressed in cardiomyocytes.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Sharon M. Rymut, Lindsay M. Henderson, Victor Poon, Tracy L. Staton, Fang Cai, Siddharth Sukumaran, Horace Rhee, Ryan Owen, Saroja Ramanujan, Kenta Yoshida
Summary: The study assessed the relationship between MTPS9579A concentrations and tryptase levels in healthy subjects and patients with moderate-to-severe asthma. A PK/PD model was developed to quantitatively relate MTPS9579A exposure and inhibition of active tryptase in the airway. The model predicted almost complete neutralization of active tryptase with MTPS9579A doses of 900 mg and greater in patients with asthma.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Cell Biology
Iosifina P. Foskolou, Pedro P. Cunha, Elena Sanchez-Lopez, Eleanor A. Minogue, Beno P. Nicolet, Aurelie Guislain, Christian Jorgensen, Sarantos Kostidis, Nordin D. Zandhuis, Laura Barbieri, David Bargiela, Demitris Nathanael, Petros A. Tyrakis, Asis Palazon, Martin Giera, Monika C. Wolkers, Randall S. Johnson
Summary: 2-Hydroxyglutarate (2HG) is a byproduct of the tricarboxylic acid (TCA) cycle, found in two enantiomeric forms. The study investigates the differential roles of these two enantiomers in CD8+ T cell biology and reveals their divergent effects on proliferation, differentiation, and T cell function. Treatment with exogenous S-2HG enhances CD8+ T cell fitness and anti-tumor activity, highlighting the importance of considering S-2HG and R-2HG as distinct regulatory factors in T cell function.