Article
Multidisciplinary Sciences
Sangsang Zhu, Chao Quan, Ruizhen Wang, Derong Liang, Shu Su, Ping Rong, Kun Zhou, Xinyu Yang, Qiaoli Chen, Min Li, Qian Du, Jingzi Zhang, Lei Fang, Hong-Yu Wang, Shuai Chen
Summary: RalGAP alpha 1-RalA signal nexus plays a key role in regulating calcium homeostasis in cardiomyocytes through the calcium pump SERCA2a, which helps maintain cardiac function under pressure overload conditions.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rui Shao, Jinlong Suo, Zhong Zhang, Mingxiang Kong, Yiyang Ma, Yang Wen, Mengxue Liu, Lenan Zhuang, Kai Ge, Qing Bi, Changqing Zhang, Weiguo Zou
Summary: This study found that H3K36 methylation is decreased in senescent chondrocytes and osteoarthritic cartilage. Nsd1 plays an important role in articular cartilage homeostasis and OA, with OSR2 possibly being a key factor regulated by Nsd1. Targeting H3K36 methylation and OSR2 could be a novel strategy for OA treatment.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Medicine, Research & Experimental
Pingping Xiao, Mingxuan Li, Mengsi Zhou, Xuejun Zhao, Cheng Wang, Jinglin Qiu, Qian Fang, Hong Jiang, Huifen Dong, Rui Zhou
Summary: This study reveals a potentially novel mechanism by which TTP modulates mRNA stabilities of CCL2 and CCL5 through m6A RNA methylation in acute liver failure, suggesting its crucial role in the pathogenesis of liver diseases.
Article
Horticulture
Marziyeh Jafari, Ali Reza Shahsavar, Majid Talebi, Mohsen Hesami
Summary: Melatonin treatment can protect lime plants from damage caused by drought stress by reducing electrolyte leakage and oxidative stress, increasing antioxidant enzyme activity and proline content.
Article
Agriculture, Multidisciplinary
Xiangyang Zhu, Fan Si, Rili Hao, Jingjie Zheng, Chen Zhang
Summary: This study investigated the protective effects of nuciferine on kidney damage caused by high-fat diets and its underlying mechanisms. The results showed that nuciferine could alleviate chronic renal dysfunction, delay renal fibrosis progression, and prevent podocyte apoptosis. It achieved these effects by reducing renal lipid accumulation, suppressing inflammation and oxidative stress, and regulating key protein factors.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biology
Fernando Rodrigo Rosas Bringas, Sonia Stinus, Pien de Zoeten, Marita Cohn, Michael Chang
Summary: This study reveals that disruption of Rap1 at telomeres leads to defects in telomere length regulation and capping, while tlc1-tm cells grow similarly to wild-type cells. Rif2 and the Ku complex work in parallel to prevent tlc1-tm telomere degradation, highlighting the redundant mechanisms that may explain the rapid evolution of telomere components in budding yeast species.
Article
Multidisciplinary Sciences
Can Lu, Yuan Cai, Wei Liu, Bi Peng, Qiuju Liang, Yuanliang Yan, Desheng Liang, Zhijie Xu
Summary: This study identified the upregulation of lysine-specific demethylase 1 (LSD1/KDM1A) in lung cancer cells, which is associated with resistance to ferroptosis. Knockdown of KDM1A in human lung cancer cells resulted in increased levels of c-Myc and concentrations of malondialdehyde (MDA) and iron, facilitating ferroptosis. The study elucidates the role of the KDM1A/c-Myc regulatory axis in ferroptosis resistance of lung cancer cells.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Yanna Liu, Mengke Li, Chaopeng Mei, Huning Cui, Qiaofang Wang, Dejian Li, Yaodong Song, Mengwei Cui, Qianqian He, Sanyang Chen, Changju Zhu
Summary: This study investigated the role of TXNIP in arginine-induced acute pancreatitis. The results showed that pancreatic damage and the inflammatory response were restrained in TXNIP knock-out mice, while they were enhanced in mice overexpressing TXNIP. The study also found that TXNIP regulates inflammatory responses and oxidative stress via the ASK1-dependent activation of the JNK/p38 pathways. Targeting TXNIP may represent a promising approach to protect against severe acute pancreatitis.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Chao Wang, Jonathan Leavenworth, Chao Zhang, Zhichao Liu, Katherine Y. Yuan, Yicun Wang, Guangxin Zhang, Shuaibin Wang, Xuelian Cui, Yue Zhang, Sejong Bae, Jiangbing Zhou, Lizhong Wang, Runhua Liu
Summary: In prostate cancer, high expression of eIF4A1 is regulated by DNA methylation and it plays an oncogenic role through the BRD2 signaling pathway.
Article
Microbiology
Chao Lei, Rui Sun, Guangzhong Xu, Yi Tan, Wenke Feng, Craig J. McClain, Zhongbin Deng
Summary: Interactions between the enteric nervous system and intestinal epithelium are crucial for intestinal homeostasis, particularly in monitoring the contact between commensal and pathogenic microbes. This study reveals that enteric neurons regulate the fucosylation of intestinal epithelial cells through the neuropeptide VIP. Perturbation of enteric neurons leads to gut dysbiosis and increased susceptibility to alcohol-associated liver disease.
CELL HOST & MICROBE
(2022)
Article
Chemistry, Multidisciplinary
Huapan Fang, Yicheng Wu, Linfu Chen, Zhiqin Cao, Zheng Deng, Rui Zhao, Lin Zhang, Yang Yang, Zhuang Liu, Qian Chen
Summary: Obesity can worsen the immunosuppressive tumor microenvironment and impair CD8(+) T cell-mediated tumor cell killing. Gene therapy using a modified polyethylenimine with p-methylbenzenesulfonyl and hyaluronic acid can effectively upregulate the expression of PHD3 in tumor tissues, improving the infiltration of CD8(+) T cells and enhancing the responsiveness of immune checkpoint antibody-mediated immunotherapy.
Article
Medicine, Research & Experimental
Shanu Jain, Sai P. Pydi, Young-Hwan Jung, Mirko Scortichini, Efrat L. Kesner, Tadeusz P. Karcz, Donald N. Cook, Oksana Gavrilova, Jurgen Wess, Kenneth A. Jacobson
Summary: Obesity is a major factor in the global epidemic of type 2 diabetes, with elevated plasma free fatty acids contributing to insulin resistance; adipocyte P2Y(14)Rs play a crucial role in regulating lipid and glucose homeostasis, with their absence enhancing lipolysis, reducing body weight, and improving glucose tolerance; P2Y(14)R antagonists may hold therapeutic potential for obesity and T2D by inhibiting lipolysis.
Article
Cell Biology
Yingdong Zhu, Shuwei Hu, Xiaoli Pan, Raja Gopoju, Fathima Cassim N. Bawa, Liya Yin, Yanyong Xu, Yanqiao Zhang
Summary: SIRT6, a histone deacetylase, regulates various biological processes. It has been found that hepatic SIRT6 can inhibit the development of NAFLD, atherosclerosis, and obesity. Mechanistically, hepatocyte SIRT6 likely inhibits NAFLD by regulating lipogenesis, lipid droplet formation, and p53 signaling, and inhibits atherosclerosis by regulating intestinal lipid absorption and hepatic VLDL secretion.
Article
Cardiac & Cardiovascular Systems
Zijie Cheng, Hao Zhang, Li Zhang, Xuejun Wang, Qijun Zhang, Mengwen Feng, Deliang Hu, Hua Li, Lingmei Qian
Summary: Recent studies have shown that proper exercise can reduce the risk of chronic disease, and a novel exercise-induced peptide, TAG-23, may inhibit PKG degradation, serving as a potential therapeutic approach for reperfusion injury.
BASIC RESEARCH IN CARDIOLOGY
(2021)
Review
Cell Biology
Jiaqi Li, Lifang Li, Xiaoxiao Sun, Tuo Deng, Gan Huang, Xia Li, Zhiguo Xie, Zhiguang Zhou
Summary: Epigenetic modifications, particularly DNA methylation regulated by TET enzymes, play crucial roles in regulating gene expression and have been implicated in the development of autoimmune and autoinflammatory diseases. The TET family proteins, especially Tet2, function as gene regulators and have potential as antitumor drug targets due to their ability to oxidize methylcytosine to hydroxymethylcytosine. Further research on Tet2 in immune response regulation and its effects on inflammatory gene expression may provide new therapeutic targets for related diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Giuseppe Bosso, Pablo Lanuza-Gracia, Sergio Pineiro-Hermida, Merve Yilmaz, Rosa Serrano, Maria A. Blasco
Summary: BRAF(V600E) mutation is common in cancer and its expression leads to DNA damage response, inflammation, and differential changes in cell cycle and senescence-associated proteins in lung epithelia.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Miriam Ayora, David Fraguas, Renzo Abregu-Crespo, Sandra Recio, Maria A. Blasco, Ana Moises, Aksinya Derevyanko, Celso Arango, Covadonga M. Diaz-Caneja
Summary: The meta-analysis found that leukocyte telomere length was significantly shorter in patients with schizophrenia and related disorders compared to healthy controls, with no significant effects of age or illness duration on this difference. The results support the hypothesis of accelerated cellular aging in schizophrenia and related disorders, highlighting the need for large longitudinal studies with repeated telomere length measurements and appropriate assessments of associated factors.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Alberto Martin, Carolina Epifano, Borja Vilaplana-Marti, Ivan Hernandez, Rocio I. R. Macias, Angel Martinez-Ramirez, Ana Cerezo, Pablo Cabezas-Sainz, Maria Garranzo-Asensio, Sandra Amarilla-Quintana, Deborah Gomez-Dominguez, Eduardo Caleiras, Jordi Camps, Gonzalo Gomez-Lopez, Marta Gomez de Cedron, Ana Ramirez de Molina, Rodrigo Barderas, Laura Sanchez, Susana Velasco-Miguel, Ignacio Perez de Castro
Summary: Despite being frequently observed in cancer cells, chromosomal instability (CIN) and aneuploidy have adverse effects on cellular homeostasis. Epitranscriptomic marks catalyzed by RNA-modifying enzymes change under stress, but their association with aneuploidy is still unknown. TRMT61B, a mitochondrial RNA methyltransferase enzyme, is found to be associated with high levels of aneuploidy in cancer cells. Depletion of TRMT61B induces senescence in cells with low aneuploidy, and apoptosis in cells with high aneuploidy. These findings suggest TRMT61B as a potential biomarker for targeting highly aneuploid tumors.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Genetics & Heredity
Paula Martinez, Raul Sanchez-Vazquez, Iole Ferrara-Romeo, Rosa Serrano, Juana M. Flores, Maria A. Blasco
Summary: By generating a mouse model for the human POT1(R117C) mutation, this study found that the mutation leads to longer telomeres and exerts dominant-negative effects at telomeres. Heterozygous mice with this mutation also develop angiosarcomas, including cardiac angiosarcomas. This research provides important insights into human cancers initiated by POT1 mutations.
Article
Cell Biology
Miguel Rovira, Rebecca Sereda, David Pladevall-Morera, Valentina Ramponi, Ines Marin, Mate Maus, Julio Madrigal-Matute, Antonio Diaz, Fernando Garcia, Javier Munoz, Ana Maria Cuervo, Manuel Serrano
Summary: The lysosomal proteome of senescent cells undergoes significant changes, and some senescent cells can be highly active in lysosomal exocytosis.
Article
Medicine, Research & Experimental
Therese Seidlitz, Tim Schmaeche, Fernando Garcia, Joon Ho Lee, Nan Qin, Susan Kochall, Juliane Fohgrub, David Pauck, Alexander Rothe, Bon-Kyoung Koo, Juergen Weitz, Marc Remke, Javier Munoz, Daniel E. Stange
Summary: This study generated three murine organoid models to investigate the impact of different pathway alterations on gastric cancer. It identified a potential treatment approach for gastric cancer patients with RTK/MAPK pathway alterations, suggesting their susceptibility to HDAC inhibition.
EMBO MOLECULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Summary: Aging is driven by hallmarks that manifest with age, accelerate aging when accentuated experimentally, and can be decelerated, stopped, or reversed with therapeutic interventions. The twelve proposed hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected with each other and with the recently proposed hallmarks of health.
Article
Biochemistry & Molecular Biology
Sergio Pineiro-Hermida, Giuseppe Bosso, Raul Sanchez-Vazquez, Paula Martinez, Maria A. Blasco
Summary: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and tumor progression is influenced by the interaction between cancer cells and the tumor microenvironment. Increased copy number and mRNA expression of TERT, a catalytic subunit of telomerase, is associated with decreased survival in NSCLC patients. Targeting telomeres may be an effective therapeutic approach in NSCLC treatment.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Geriatrics & Gerontology
Sara E. Espinoza, Sundeep Khosla, Joseph A. Baur, Rafael de Cabo, Nicolas Musi
Summary: The geroscience hypothesis suggests that targeting key hallmarks of aging can improve healthspan and prevent age-related diseases. Several pharmacological interventions, including senolytics, NAD(+) boosters, and metformin, are being studied for their potential benefits. Preclinical studies show that senolytic drugs improve healthspan in rodents, while increasing NAD(+) through supplementation appears to extend healthspan in model organisms. Metformin, on the other hand, has pleiotropic effects and is being examined for its potential to improve healthspan and prevent frailty in clinical trials. However, further research is needed to determine their efficacy, safety, target populations, and long-term outcomes.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Jose Jimenez-Santos, Alba Nogueira-Rodriguez, Elena Pineiro-Yanez, Hugo Lopez-Fernandez, Santiago Garcia-Martin, Paula Gomez-Plana, Miguel Reboiro-Jato, Gonzalo Gomez-Lopez, Daniel Glez-Pena, Fatima Al-Shahrour
Summary: PanDrugs2 is an upgraded version of PanDrugs that helps researchers interpret tumor molecular alterations and guide personalized treatment selection. It incorporates multi-omics analysis and considers cancer genetic dependencies, providing therapeutic options for genes that are difficult to target. PanDrugs2 generates an intuitive report to support clinical decision-making. The database has been updated, integrating 23 primary sources that support >74K drug-gene associations obtained from 4642 genes and 14 659 unique compounds. It is freely available for use.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Cristina Sayago, Jana Sanchez-Wandelmer, Fernando Garcia, Begona Hurtado, Vanesa Lafarga, Patricia Prieto, Eduardo Zarzuela, Pilar Ximenez-Embun, Sagrario Ortega, Diego Megias, Oscar Fernandez-Capetillo, Marcos Malumbres, Javier Munoz
Summary: Protein methylation is an important modification that is not extensively studied compared to other modifications. The authors developed a method based on thermal stability to explore the molecular and functional events associated with protein methylation. They found that protein methylation regulates processes such as mRNA binding proteins and chromosome compaction. The findings provide valuable insights into the role of protein methylation in pluripotency.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Isidoro Cobo, Sumit Paliwal, Cristina Bodas, Irene Felipe, Julia Melia-Aloma, Ariadna Torres, Jaime Martinez-Villarreal, Marina Malumbres, Fernando Garcia, Irene Millan, Natalia del Pozo, Joo-Cheol Park, Ray J. MacDonald, Javier Munoz, Raul Mendez, Francisco X. Real
Summary: NFIC is a transcription factor that regulates the function of pancreatic acinar cells and suppresses the development of pancreatic ductal adenocarcinoma. It controls the differentiation and physiological functions of pancreatic acinar cells by regulating the expression of acinar genes, including those involved in RNA and protein metabolism, as well as the genes involved in resolving endoplasmic reticulum stress. In pancreatic cancer, NFIC expression is down-regulated, leading to the formation of pre-neoplastic lesions driven by mutant KRAS.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Jayanta Kumar Das, Nirad Banskota, Julian Candia, Michael E. Griswold, Melissa Orenduff, Rafael de Cabo, David L. Corcoran, Sai Krupa Das, Supriyo De, Kim Marie Huffman, Virginia B. Kraus, William E. Kraus, Corby K. Martin, Susan B. Racette, Leanne M. Redman, Birgit Schilling, Daniel W. Belsky, Luigi Ferrucci
Summary: Using high-depth RNA-Seq analysis, this study found that caloric restriction (CR) positively affects skeletal muscle quality in humans and alters the gene expression and splicing profiles of biological pathways affected by CR in model organisms.
Article
Cell Biology
Paula Martinez, Raul Sanchez-Vazquez, Arpita Saha, Maria S. Rodriguez-Duque, Sara Naranjo-Gonzalo, Joy S. Osorio-Chavez, Ana V. Villar-Ramos, Maria A. Blasco
Summary: The severity of COVID-19 increases with age, suggesting that organismal aging contributes to its fatality. Previous studies have shown that COVID-19 severity is correlated with shorter telomeres in patient's leukocytes. Lung injury is a prominent feature of acute SARS-CoV-2 infection, which can progress to lung fibrosis. In this study, we found that post-COVID-19 patients have shorter telomeres and increased lung fibrosis compared to age-matched controls with lung cancer, suggesting a link between short telomeres in ATII cells and long-term lung fibrosis in post-COVID-19 patients.
Article
Cell Biology
Hitoshi Watanabe, Wen Du, Jinsook Son, Lina Sui, Shun-ichiro Asahara, Irwin J. Kurland, Taiyi Kuo, Takumi Kitamoto, Yasutaka Miyachi, Rafael de Cabo, Domenico Accili
Summary: Sulfonylureas are effective and affordable antidiabetic drugs, but chronic use leads to secondary failure. Cytochrome b5 reductase 3 (Cyb5r3) down-regulation is identified as a mechanism of secondary SU failure and can be successfully reversed. Cyb5r3 activators can rescue secondary SU failure and potentially rehabilitate SU use in diabetes.
SCIENCE TRANSLATIONAL MEDICINE
(2023)