Article
Multidisciplinary Sciences
Laura Sole, Teresa Lobo-Jarne, Daniel Alvarez-Villanueva, Josune Alonso-Maranon, Yolanda Guillen, Marta Guix, Irene Sangrador, Catalina Rozalen, Anna Vert, Antonio Barbachano, Joan Lop, Marta Salido, Beatriz Bellosillo, Raquel Garcia-Romero, Marta Garrido, Jessica Gonzalez, Maria Martinez-Iniesta, Erika Lopez-Arribillaga, Ramon Salazar, Clara Montagut, Ferran Torres, Mar Iglesias, Toni Celia-Terrassa, Alberto Munoz, Alberto Villanueva, Anna Bigas, Lluis Espinosa
Summary: This study reveals that sub-lethal dose of chemotherapy induces a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state in wild-type p53 colorectal cancers, which is associated with higher metastatic activity and poor prognosis in patients.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Natthakan Thongon, Feiyang Ma, Andrea Santoni, Matteo Marchesini, Elena Fiorini, Ashley Rose, Vera Adema, Irene Ganan-Gomez, Emma M. Groarke, Fernanda Gutierrez-Rodrigues, Shuaitong Chen, Pamela Lockyer, Sarah Schneider, Carlos Bueso-Ramos, Guillermo Montalban-Bravo, Caleb A. Class, Kelly A. Soltysiak, Matteo Pellegrini, Ergun Sahin, Alison A. Bertuch, Courtney D. DiNardo, Guillermo Garcia-Manero, Neal S. Young, Karen Dwyer, Simona Colla
Summary: The study reveals that telomere attrition leads hematopoietic stem cells towards differentiation into megakaryocytic lineage through upregulated innate immune signaling response, ultimately compromising their self-renewal capabilities and leading to depletion. Targeting the IFI16 signaling axis could potentially prevent functional decline of hematopoietic stem cells under conditions affecting telomere maintenance.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Pianpian Huang, Lijuan Bai, Lihua Liu, Jun Fu, Kefei Wu, Hongxia Liu, Yun Liu, Benming Qi, Benling Qi
Summary: Redd1 plays a crucial role in senescence of cardiomyocytes, with its high expression associated with increased cellular senescence markers and pro-inflammatory cytokine expression. It promotes cardiomyocyte senescence through the p38 MAPK/NF-kB signaling pathway.
Article
Multidisciplinary Sciences
Joe Nassour, Lucia Gutierrez Aguiar, Adriana Correia, Tobias T. T. Schmidt, Laura Mainz, Sara Przetocka, Candy Haggblom, Nimesha Tadepalle, April Williams, Maxim N. N. Shokhirev, Semih C. C. Akincilar, Vinay Tergaonkar, Gerald S. S. Shadel, Jan Karlseder
Summary: Cancers arise through genetic and epigenetic alterations that enable cells to evade proliferative barriers. Little is known about the molecular events that regulate the onset of replicative crisis, a tumour-suppressive barrier. In this study, Z-DNA binding protein 1 (ZBP1) was identified as a regulator of the crisis program. It was found that a crisis-associated isoform of ZBP1 is induced by the cGAS-STING DNA-sensing pathway, but reaches full activation only when associated with telomeric-repeat-containing RNA (TERRA) transcripts. TERRA-bound ZBP1 activates the innate immune adapter protein MAVS, leading to the elimination of cells destined for neoplastic transformation.
Article
Immunology
Yu Zhang, Dan Zhang, Tingting Meng, Peng Tian, Jianlin Chen, Anbang Liu, Yan Zheng, Guohai Su
Summary: Breast cancer is a common cancer among women worldwide, and the chemotherapy drug DOX has the potential to prolong survival but can cause cardiovascular toxicity. The study found that SGK1 plays an important role in DOX-induced cardiotoxicity, with upregulated expression accompanied by increased levels of inflammatory factors. Inhibition of SGK1 can suppress the production of inflammatory factors and apoptosis of cardiomyocytes, providing cardioprotective effects. In addition, targeting SGK1 can inhibit the proliferation of breast cancer cells. The study suggests that inhibiting SGK1 may be an effective treatment strategy for breast cancer that has both tumor-killing and cardioprotective functions.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Lichao Wang, Binsheng Wang, Nathan S. Gasek, Yueying Zhou, Rachel L. Cohn, Dominique E. Martin, Wulin Zuo, William F. Flynn, Chun Guo, Evan R. Jellison, Taewan Kim, Larissa G. P. Langhi Prata, Allyson K. Palmer, Ming Li, Christina L. Inman, Lauren S. Barber, Iman M. A. Al-Naggar, Yanjiao Zhou, Wenqiang Du, Kshitiz, George A. Kuchel, Alexander Meves, Tamar Tchkonia, James L. Kirkland, Paul Robson, Ming Xu
Summary: This study identifies a small population of p21 high-expressing cells that accumulate in adipose tissue with obesity and shows that intermittent clearance of these cells can prevent and alleviate insulin resistance. Inactivation of the NF-kB pathway within these cells attenuates insulin resistance. Additionally, a drug combination of dasatinib and quercetin can eliminate p21 high-expressing cells in human fat and mitigate insulin resistance.
Article
Cell Biology
Lei Zhang, Jing Zhao, Xiaodong Mu, Sara J. McGowan, Luise Angelini, Ryan D. O'Kelly, Matthew J. Yousefzadeh, Ayumi Sakamoto, Zaira Aversa, Nathan K. LeBrasseur, Yousin Suh, Johnny Huard, Theodore M. Kamenecka, Laura J. Niedernhofer, Paul D. Robbins
Summary: Inhibiting NF-κ B activation with SR12343 shows promising results in reducing cellular senescence markers, improving muscle fiber size, and extending healthy lifespan. The therapeutic effects of SR12343 were observed in different mouse models, suggesting it as a potential treatment for reducing cellular senescence and aging-related diseases.
Article
Biochemistry & Molecular Biology
Marina Kolesnichenko, Nadine Mikuda, Uta E. Hoepken, Eva Kaergel, Bora Uyar, Ahmet Bugra Tufan, Maja Milanovic, Wei Sun, Inge Krahn, Kolja Schleich, Linda Hoff, Michael Hinz, Michael Willenbrock, Sabine Jungmann, Altuna Akalin, Soyoung Lee, Ruth Schmidt-Ullrich, Clemens A. Schmitt, Claus Scheidereit
Summary: The study reveals that DNA double-strand breaks elicit two subsequent phases of NF-kappa B activation, with the first phase controlling anti-apoptotic gene expression and the second phase driving expression of senescence-associated genes.
Article
Cardiac & Cardiovascular Systems
Bo Lei, Xiaohong Wu, Kexin Xia, Hui Sun, Jinsong Wang
Summary: This study shows that exosomal miR-96 derived from bone marrow mesenchymal stem cells protects myocardium against doxorubicin-induced toxicity by inhibiting the Rac/nuclear factor-kappa B signaling pathway.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Biochemistry & Molecular Biology
Di Jia, Jiahui Han, Jimin Cai, Zhirong Huan, Yan Wang, Xin Ge
Summary: This study found that MSCs overexpressing PBX1 can improve HS-induced kidney damage by inhibiting NF-kappa B pathway-mediated NLRP3 inflammasome activation and the inflammatory response.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Dong Suk Yoon, Kyoung-Mi Lee, Yoorim Choi, Eun Ae Ko, Na-Hyun Lee, Sehee Cho, Kwang Hwan Park, Jung-Hwan Lee, Hae-Won Kim, Jin Woo Lee
Summary: This study found that PUM1 is associated with the self-renewal capacity and aging process of human mesenchymal stem cells (MSC). PUM1 acts by suppressing TLR4-mediated NF-kappa B activity to protect MSCs against cellular senescence and inflammation. Furthermore, the PUM1-TLR4 regulatory axis represents a potential therapeutic target for osteoarthritis.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Haijun Zhao, Weijie Zhu, Wude Mao, Chengkai Shen
Summary: The study demonstrates that PRP can protect chondrocytes from doxorubicin-induced damage, inhibiting apoptosis and inflammation, and improving cartilage destruction. This research provides a new theoretical basis for the clinical treatment of osteoarthritis caused by doxorubicin.
MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Changwei Li, Minglong Qiu, Leilei Chang, Jin Qi, Lianfang Zhang, Bernhard Ryffel, Lianfu Deng
Summary: This study identified USP26 as a regulator of bone homeostasis that coordinates bone formation and resorption. USP26 stabilizes beta-catenin to promote osteogenesis and inhibits osteoclastic differentiation by stabilizing inhibitors of NF-kappa B alpha. These findings highlight the osteoprotective effect of USP26 and suggest it as a potential therapeutic target for osteoporosis.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Giovanna M. Bernal, Longtao Wu, David J. Voce, Ralph R. Weichselbaum, Bakhtiar Yamini
Summary: This study found that the p52 subunit increases in the nucleus of cells during senescence, and factors in the conditioned media play a role in promoting p52 nuclear translocation. Additionally, mature p52 can induce cellular senescence. These findings support the observation of increased p52 in aged tissue and suggest that p52 contributes to organismal aging.
CELL AND BIOSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Qian Li, Yu-Heng Zhao, Cheng Xu, Ye-Lin Liang, Yin Zhao, Qing-Mei He, Jun-Yan Li, Kai-Lin Chen, Han Qiao, Na Liu, Jun Ma, Lei Chen, Ying-Qin Li
Summary: This study reveals that circWDR37 deficiency limits the proliferation, migration, and invasion of senescent NPC cells induced by cisplatin or gemcitabine. Mechanistically, circWDR37 binds and dimerizes PKR, leading to PKR autophosphorylation and activation. Activated PKR phosphorylates IKKβ, releasing RELA from IκBα and activating NF-κB, thus promoting the transcription of CCND1 and senescence-associated secretory phenotype component genes in a circWDR37-dependent manner. Low circWDR37 levels are associated with favorable survival and chemotherapy response in NPC patients treated with gemcitabine or cisplatin induction chemotherapy.
