Article
Immunology
Asmaa Badr, Mostafa Eltobgy, Kathrin Krause, Kaitlin Hamilton, Shady Estfanous, Kylene P. Daily, Arwa Abu Khweek, Ahmad Hegazi, Midhun N. K. Anne, Cierra Carafice, Frank Robledo-Avila, Youssra Saqr, Xiaoli Zhang, Tracey L. Bonfield, Mikhail A. Gavrilin, Santiago Partida-Sanchez, Stephanie Seveau, Estelle Cormet-Boyaka, Amal O. Amer
Summary: Cystic fibrosis (CF) macrophages show defects in clearing bacteria and autophagy process. CFTR is recruited to autophagosomes and improves autophagy flux, lysosomal acidification, function, and bacterial clearance. These findings clarify the role of CFTR in maintaining cellular acidification and autophagy process.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Gastroenterology & Hepatology
David A. Rudnick, Jiansheng Huang, Tunda Hidvegi, Andrew S. Chu, Pamela Hale, Admire Munanairi, Dennis J. Dietzen, Paul F. Cliften, Eric Tycksen, Andrew J. Lutkewitte, Brian N. Finck, Stephen C. Pak, Gary A. Silverman, David H. Perlmutter
Summary: Insulin signaling exacerbates hepatic proteotoxicity in PiZ mice with alpha 1-antitrypsin deficiency, and PGC1 alpha is identified as a novel therapeutic target.
Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Article
Cell Biology
Xing Guo, Zhenyu Zhang, Chaohui Lin, Huiling Ren, Yijing Li, Yuan Zhang, Yuxing Qu, Hongxin Li, Saiwen Ma, Huijuan Xia, Rongkuan Sun, Haoyu Zu, Yuezhi Lin, Xiaojun Wang
Summary: This study found that H1N1 pdm09 virus promotes its replication through autophagy, leading to faster spread. The results provide theoretical basis for analyzing the epidemiological characteristics of H1N1 pdm09 influenza and the development of anti-influenza drugs and vaccines.
Review
Biochemistry & Molecular Biology
Caitlyn Harvey, Sinead Weldon, Stuart Elborn, Damian G. Downey, Clifford Taggart
Summary: The advent of CFTR modulators in cystic fibrosis treatment has transformed the management of the disease, shifting it from being a life-limiting condition to one that can be effectively managed. These genotype-specific therapies have shown significant improvements in various clinical endpoints, but their effects on pathogenic burden and airway infection need further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Yuting Zhao, Zhongju Zou, Daxiao Sun, Yue Li, Sangita C. Sinha, Li Yu, Lynda Bennett, Beth Levine
Summary: GLIPR2 is a negative regulator of PtdIns3K-C1 activity and basal autophagy. Its depletion leads to increased autophagic flux and phosphatidylinositol 3-phosphate generation, with less compact Golgi structures observed.
Article
Pharmacology & Pharmacy
Jia Liu, Allison P. Berg, Yiting Wang, Walailak Jantarajit, Katy J. Sutcliffe, Edward B. Stevens, Lishuang Cao, Marko J. Pregel, David N. Sheppard
Summary: This study investigates the action of a new CFTR potentiator, CP-628006, and compares it with the marketed CFTR potentiator ivacaftor. CP-628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Hannah Farley, Sarah Poole, Stephen Chapman, William Flight
Summary: A retrospective single-center cohort study identified 19 adult patients diagnosed with CF, all of whom had a history of chronic respiratory symptoms and the majority of whom had a CFTR genotype considered eligible for CFTR modulator therapy.
POSTGRADUATE MEDICAL JOURNAL
(2022)
Article
Cell Biology
Honglei Jin, Jiugao Ma, Jiheng Xu, Hongyan Li, Yuanyuan Chang, Nan Zang, Zhongxian Tian, Xin Wang, Nannan Zhao, Lu Liu, Caiyi Chen, Qipeng Xie, Yongyong Lu, Zhouxi Fang, Xing Huang, Chuanshu Huang, Haishan Huang
Summary: In this study, it was found that MIR516A is upregulated in human bladder cancer, acting as an oncogene by regulating PHLPP2 and inhibiting autophagy, thus promoting tumor growth. This novel oncogenic function of MIR516A in bladder cancer differs from its known tumor suppressor role in other cancers.
Article
Multidisciplinary Sciences
Satoshi Watanabe, Nikolay S. Markov, Ziyan Lu, Raul Piseaux Aillon, Saul Soberanes, Constance E. Runyan, Ziyou Ren, Rogan A. Grant, Mariana Maciel, Hiam Abdala-Valencia, Yuliya Politanska, Kiwon Nam, Lango Sichizya, Hermon G. Kihshen, Nikita Joshi, Alexandra C. McQuattie-Pimentel, Katherine A. Gruner, Manu Jain, Jacob I. Sznajder, Richard I. Morimoto, Paul A. Reyfman, Cara J. Gottardi, G. R. Scott Budinger, Alexander V. Misharin
Summary: This study revealed that promoting the differentiation of AT2 cells into AT1 cells with ISRIB can accelerate epithelial repair, reduce the recruitment of profibrotic alveolar macrophages, and ameliorate lung fibrosis in the pathogenesis of pulmonary fibrosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Oscar Fonseca, Maria Salome Gomes, Maria Adelina Amorim, Ana Cordeiro Gomes
Summary: Cystic fibrosis, a monogenic disease, has a diverse clinical presentation involving chronic lung infection, inflammation, and reduced bone mass. The underlying mechanisms of reduced bone mass in cystic fibrosis patients are still unclear. This review explores the relationship between CFTR dysfunction and intrinsic bone defects, as well as the impact of the proinflammatory environment and chronic infection on bone mass maintenance in CF patients.
Article
Biochemistry & Molecular Biology
Kavisha Arora, Pramodha Liyanage, Qing Zhong, Anjaparavanda P. Naren
Summary: The study reveals that under nutritional stress and bacterial infection, the autophagic SNARE protein syntaxin17 (Stx17) interacts with CFTR to facilitate efficient lysosomal clearance, playing a critical role in preventing defective autophagy.
Editorial Material
Cell Biology
Yuchen Lei, Daniel J. Klionsky
Summary: VCP, a conserved ATPase, regulates autophagy initiation by stabilizing BECN1 and enhancing phosphati-dylinositol 3-kinase (PtdIns3K) complex assembly, in addition to its roles in autophagosome maturation.
Article
Biochemistry & Molecular Biology
Cuneyd Parlayan, Yunus Sahin, Zekiye Altan, Kaifee Arman, Masa-Aki Ikeda, Khandakar A. S. M. Saadat
Summary: The study focused on the role of ARID3A in osteosarcoma progression, revealing its impact on BECN1 expression and cell proliferation. Findings suggest that ARID3A may act as a tumor suppressor and influence the expression level of BECN1 in U-2 OS cells, shedding light on potential treatment strategies for osteosarcoma.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
L. Clara Mok, Antonio Garcia-Uceda, Matthew N. Cooper, Mariette Kemner Van De Corput, Marleen De Bruijne, Nathalie Feyaerts, Tim Rosenow, Kris De Boeck, Stephen Stick, Harm A. W. M. Tiddens
Summary: Newly developed quantitative CT outcomes designed for CF lung disease can assess structural abnormalities. CFTR modulators have the potential to reduce these abnormalities. This study aimed to investigate the effect of CFTR modulators on the progression of structural lung disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Amir Ajoolabady, Daolin Tang, Guido Kroemer, Jun Ren
Summary: Hepatocellular carcinoma is a prevalent form of liver cancer, with genetic, environmental, and behavioral factors influencing its development. Ferroptosis, a form of nonapoptotic cell death, has potential for suppressing hepatocellular carcinoma. However, malignant cells can develop mechanisms to resist ferroptosis.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Qian Xue, Ding Yan, Xi Chen, Xiaofen Li, Rui Kang, Daniel J. J. Klionsky, Guido Kroemer, Xin Chen, Daolin Tang, Jinbao Liu
Summary: Ferroptosis is an iron-dependent regulated cell death characterized by lipid peroxidation and membrane damage. Copper promotes ferroptotic cell death by inducing autophagic degradation of GPX4. These findings provide new insights into the connection between metal stress and autophagy-dependent cell death.
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.
Review
Cell Biology
Carlos Lopez-Otin, Federico Pietrocola, David Roiz-Valle, Lorenzo Galluzzi, Guido Kroemer
Summary: Both aging and cancer share similar characteristics, known as hallmarks, some of which are common metahallmarks. While some aging hallmarks suppress cancer development, others have context-dependent effects. The relationship between aging-associated nutrient-sensing and cancer-related cellular metabolism alterations is complex. Understanding the interplay between aging and cancer has significant implications for cancer morbidity and mortality in the elderly and for therapeutic strategies.
Article
Cell Biology
Maria Castedo, Antoine Lafarge, Guido Kroemer
Summary: Deletion or inhibition of the PARP1 gene protects mice against cerebral ischemia and Parkinson's disease, while PARP1 inhibitors are used to eradicate vulnerable cancer cells. Excessive activation of PARP1 is involved in a specific cell death pathway called parthanatos, and inhibition of PARP1 in cancer cells amplifies DNA damage to a lethal level. Therefore, PARP1 plays a context-dependent role in cell fate decisions. Additionally, PARP1 appears to have an ambiguous role in organismal aging.
Article
Multidisciplinary Sciences
Stephanie Solier, Sebastian Mueller, Tatiana Caneque, Antoine Versini, Arnaud Mansart, Fabien Sindikubwabo, Leeroy Baron, Laila Emam, Pierre Gestraud, G. Dan Pantos, Vincent Gandon, Christine Gaillet, Ting-Di Wu, Florent Dingli, Damarys Loew, Sylvain Baulande, Sylvere Durand, Valentin Sencio, Cyril Robil, Francois Trottein, David Pericat, Emmanuelle Naeser, Celine Cougoule, Etienne Meunier, Anne-Laure Begue, Helene Salmon, Nicolas Manel, Alain Puisieux, Sarah Watson, Mark A. Dawson, Nicolas Servant, Guido Kroemer, Djillali Annane, Raphael Rodriguez
Summary: Inflammation is a complex physiological process that involves immune cells clearing sources of injury. Excessive inflammation is associated with infection and several diseases. The cell surface glycoprotein CD44 mediates the uptake of metals, including copper, and affects the metabolic and epigenetic states involved in inflammation.
Review
Cardiac & Cardiovascular Systems
Mahmoud Abdellatif, Peter P. Rainer, Simon Sedej, Guido Kroemer
Summary: In this Review, Kroemer and colleagues summarize eight molecular hallmarks of cardiovascular ageing, including disabled macroautophagy, loss of proteostasis, genomic instability, epigenetic alterations, mitochondrial dysfunction, cell senescence, dysregulated neurohormonal signalling and inflammation. Targeting these hallmarks therapeutically can attenuate residual cardiovascular risk in older individuals.
NATURE REVIEWS CARDIOLOGY
(2023)
Review
Oncology
Jenny Sprooten, Raquel S. Laureano, Isaure Vanmeerbeek, Jannes Govaerts, Stefan Naulaerts, Daniel M. Borras, Lisa Kinget, Jitka Fucikova, Radek Spisek, Lenka Palova Jelinkova, Oliver Kepp, Guido Kroemer, Dmitri V. Krysko, An Coosemans, Rianne D. W. Vaes, Dirk De Ruysscher, Steven De Vleeschouwer, Els Wauters, Evelien Smits, Sabine Tejpar, Benoit Beuselinck, Sigrid Hatse, Hans Wildiers, Paul M. Clement, Peter Vandenabeele, Laurence Zitvogel, Abhishek D. Garg
Summary: Immunogenic cell death (ICD) is a unique process of regulated cell death that activates the immune system. The effectiveness of ICD relies on the antigenicity of dying cells and their ability to expose immunostimulatory molecules. Certain chemotherapies, such as anthracyclines, paclitaxels, and oxaliplatin, have been validated as potent ICD inducers and can be used in combination with immunotherapies against resistant tumors. This article discusses the integration of ICD-inducing chemotherapy in immuno-oncological paradigms.
Article
Oncology
Julie Le Naour, Guido Kroemer
Summary: Accumulating evidence suggests that TLR agonists have favorable immune-activating effects and can be used as immunological adjuvants for cancer immunosurveillance. Several TLR agonists have been approved for oncological applications and extensively investigated. Clinical trials are ongoing to evaluate the combination of TLR agonists with other cancer treatments. Antibodies targeting tumor-enriched surface proteins conjugated with TLR agonists are also being developed to stimulate anticancer immune response within the tumor microenvironment. This review summarizes recent preclinical and clinical advances in TLR agonists for anticancer immunotherapy.
Article
Oncology
Vincent Carbonnier, Julie Le Naour, Thomas Bachelot, Erika Vacchelli, Fabrice Andre, Suzette Delaloge, Guido Kroemer
Summary: Formyl peptide receptor-1 (FPR1) is involved in pathogen recognition, inflammation control and cancer immunosurveillance. A single nucleotide polymorphism (SNP), rs867228, in FPR1 accelerates age at diagnosis of specific carcinomas, including luminal B breast cancer, by 4.9 years. Genetic analysis of 215 patients with metastatic luminal B breast cancer confirmed that rs867228 accelerates age of diagnosis by 6.3 years. Detection of rs867228 may be useful in breast cancer screening to start examinations at a younger age.
Article
Cell Biology
Mathilde Coulet, Sylvie Lachkar, Marion Leduc, Marc Trombe, Zelia Gouveia, Franck Perez, Oliver Kepp, Guido Kroemer, Stephane Basmaciogullari
Summary: In this study, a selective hook system called RUSH was used to identify cell secretion modulators in U2OS cells. They created a U2OS cell line that expressed a modified antibody bait and a streptavidin hook, which allowed the antibody to be retained in the endoplasmic reticulum (ER). Biotin was used to trigger the release of the antibody from the ER, resulting in its secretion.
Article
Cell Biology
Yaiza Corral Nieto, Sokhna M. S. Yakhine-Diop, Paula Moreno-Cruz, Laura Manrique Garcia, Amanda Gabrielly Pereira, Jose A. Morales-Garcia, Mireia Niso-Santano, Rosa A. Gonzalez-Polo, Elisabet Uribe-Carretero, Sylvere Durand, Maria Chiara Maiuri, Marta Paredes-Barquero, Eva Alegre-Cortes, Saray Canales-Cortes, Adolfo Lopez de Munain, Jordi Perez-Tur, Ana Perez-Castillo, Guido Kroemer, Jose M. Fuentes, Jose M. Bravo-San Pedro
Summary: Using mass spectrometry, this study identified metabolic changes in the liver of mouse models of Parkinson's disease, with the aim of finding new peripheral biomarkers for diagnosis.
Article
Cell Biology
Safae Terrisse, Laurence Zitvogel, Guido Kroemer
Summary: Recent observations show that hormone-receptor breast cancer is influenced by immune and microbial factors. The immune system retards the development of hormone-positive breast cancer and affects the efficacy of hormone therapy. The gut microbiota modulates the anticancer immune response, tumor microenvironment, and estrogen metabolism. Understanding these mechanisms is still in its early stages and requires further analysis.
Article
Oncology
Laurence Zitvogel, Lisa Derosa, Guido Kroemer
Summary: In patients with multiple myeloma, mRNA-based vaccination schemes failed to generate detectable SARS-CoV-2 Omicron-neutralizing antibodies in approximately 60% of the cases and S1-RBD-specific CD8+ T cells in 80% of the cases. Patients who experienced breakthrough infections had very low levels of live-virus neutralizing antibodies and lacked follicular T helper cells.
BLOOD CANCER DISCOVERY
(2023)
Review
Cell Biology
Lea Montegut, Mahmoud Abdellatif, Omar Motino, Frank Madeo, Isabelle Martins, Victor Quesada, Carlos Lopez-Otin, Guido Kroemer
Summary: Acyl coenzyme A binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an ancient protein that plays a role in fatty acid metabolism and has been found to have anti-aging effects. Inhibition of ACBP can extend lifespan and improve healthspan in multiple species.