Review
Oncology
Barbara Di Francesco, Daniela Verzella, Daria Capece, Davide Vecchiotti, Mauro Di Vito Nolfi, Irene Flati, Jessica Cornice, Monica Di Padova, Adriano Angelucci, Edoardo Alesse, Francesca Zazzeroni
Summary: Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with a high need for new therapeutic options. Constitutive NF-kappa B activation has been reported in around 40% of AML patients, making targeting the NF-kappa B pathway an attractive strategy to treat AML.
Article
Biochemistry & Molecular Biology
Eileen Dahlke, Toni Engmann, Yaman Anan, Robert Haesler, Giovanni Solinas, Franziska Theilig
Summary: Acute kidney injury (AKI) is a common renal injury with significant morbidity and mortality worldwide. This study investigated the role of NF-kappa B in AKI and found that its deletion improved renal function, reduced tissue damage and fibrosis, and enhanced vascularization, metabolism, reactive species disposal, and fine-tuned cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Satoko Oka, Kazuo Ono
Summary: Elevated NF-kB levels in primitive bone marrow cells of MDS/AML patients suggest NF-kB as a potential therapeutic target. In a case study, an MDS patient ineligible for SCT achieved complete remission after monotherapy with ixazomib following transformation to leukemia from treatment with azacitidine and bortezomib.
CLINICAL CASE REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Zhu-Qi Huang, Wu Luo, Wei-Xin Li, Pan Chen, Zhe Wang, Rui-Jie Chen, Yi Wang, Wei-Jian Huang, Guang Liang
Summary: Costunolide (CTD) has anti-atherosclerotic effects by reducing inflammatory responses and oxLDL uptake, and its mechanism involves the inhibition of NF-kappa B signaling pathway through covalent binding to IKKβ.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Genetics & Heredity
Miao Chen, Yi Qu, Pengjie Yue, Xiaojing Yan
Summary: HOXB5, a member of the HOX family, is significantly elevated in AML patients and serves as an important prognostic marker in AML. It shows differential expression in various subgroups of AML patients, particularly those with NPM1, FLT3, or DNMT3A mutations, and the NPM1-FLT3-DNMT3A triple-mutant AML patients exhibit the highest expression level for HOXB5.
FRONTIERS IN GENETICS
(2021)
Letter
Biochemistry & Molecular Biology
Adnan Erol
Summary: Oxidative stress plays a significant role in the development of obesity-related nephropathy (ORN). A causal relationship between IKK and ORN via CYLD-mediated inhibition of NRF2 has been identified. However, contradictory explanations regarding the mechanisms involved need clarification.
MOLECULAR MEDICINE
(2022)
Article
Plant Sciences
Lengqiu Guo, Yun Yang, Jie Yuan, Huiling Ren, Xiaolei Huang, Meng Li, Long Xia, Xiaogang Jiang, Daofeng Chen, Jian Zhang
Summary: This study investigates the therapeutic effects of Da-Yuan-Yin on acute lung injury (ALI) and reveals its potential targets through network pharmacology combined with animal experiments.
PHARMACEUTICAL BIOLOGY
(2023)
Article
Oncology
Shuaibing Hou, Xiaomin Wang, Tengxiao Guo, Yanjie Lan, Shengnan Yuan, Shuang Yang, Fei Zhao, Aizhong Fang, Na Liu, Wanzhu Yang, Yajing Chu, Erlie Jiang, Tao Cheng, Xiaojian Sun, Weiping Yuan
Summary: This study reveals that PHF6 plays a significant role in myeloid leukemia by inhibiting NF-κB signaling pathway to suppress cell proliferation and induce apoptosis. The authors also discovered that PHF6 acts as a tumor suppressor gene in lymphocytic leukemia but as an oncogene in myeloid leukemia.
Article
Oncology
Julia Maier, Andre Lechel, Ralf Marienfeld, Thomas F. E. Barth, Peter Moeller, Kevin Mellert
Summary: This study reports high levels of mRNA and protein expression of CARD9 in the RS cell line U-RT1. Co-immunoprecipitation revealed the assembly of a CBM complex using CARD9 instead of CARD11. Western blot analyses showed phosphorylation of IκB and IKK in U-RT1, indicating a constitutively active canonical NF-kB pathway. Knockdown of CARD9 resulted in a significant reduction in cell viability and CYLD cleavage products. Immunostaining for CARD9 was also observed in 53% of RS tissue specimen cases analyzed. This is the first report on the ectopic expression and function of CARD9 in an aggressive B-cell lymphoma, suggesting that CARD9 may contribute to the pathogenesis of RS.
Article
Multidisciplinary Sciences
John Victor Napoleon, Satish Sagar, Sydney P. Kubica, Lidia Boghean, Smit Kour, Hannah M. King, Yogesh A. Sonawane, Ayrianne J. Crawford, Nagsen Gautam, Smitha Kizhake, Pawel A. Bialk, Eric Kmiec, Jayapal Reddy Mallareddy, Prathamesh P. Patil, Sandeep Rana, Sarbjit Singh, Janani Prahlad, Paul M. Grandgenett, Gloria E. O. Borgstahl, Gargi Ghosal, Yazen Alnouti, Michael A. Hollingsworth, Prakash Radhakrishnan, Amarnath Natarajan
Summary: Activation of IKK beta, characterized by phosphorylation of serine residues 177 and 181, has been implicated in the early onset of cancer. This study used various models to assess the role of IKK beta and its activation in cancer, and identified 39-100 as a potent inhibitor of MAP3K1. It was found that IKK beta activation is critical for tumor growth in Kras mutant pancreatic cancer, and the compound 39-100 inhibits MAP3K1-mediated IKK beta phosphorylation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ni Li, Qiuli Liu, Ying Han, Siyu Pei, Bisheng Cheng, Junyu Xu, Xiang Miao, Qiang Pan, Hanling Wang, Jiacheng Guo, Xuege Wang, Guoying Zhang, Yannan Lian, Wei Zhang, Yi Zang, Minjia Tan, Qintong Li, Xiaoming Wang, Yichuan Xiao, Guohong Hu, Jun Jiang, Hai Huang, Jun Qin
Summary: Loss of ARID1A promotes prostate cancer progression and immunosuppression by promoting the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Inflammatory cues activate IKK beta to phosphorylate ARID1A and degrade it, leading to CXCR2 ligand-mediated PMN-MDSC chemotaxis. Neutralization of PMN-MDSCs restricts the progression of ARID1A-deficient tumors.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yong-Mei Wu, Qing Shi, Peng-Fei Zhu, Hai-Jian Ma, Shi-Chao Cui, Jia Li, Ai-Jun Hou, Jing-Ya Li
Summary: In this study, Rhodomeroterpene (RMT) showed anti-inflammatory effects in LPS-induced sepsis and AKI models by inhibiting inflammation and immune cell infiltration. The mechanism of action for RMT's anti-inflammatory effects involves inactivation of IKK/NF-kappa B and PI3K/PDK1/Akt signaling pathways in macrophages. Overall, RMT may be a potential agent for the treatment of AKI by ameliorating renal injury and alleviating inflammation.
Article
Medicine, General & Internal
Yumei Cao, Su'an Tang, Xiaoyu Nie, Zuoqing Zhou, Guangfeng Ruan, Weiyu Han, Zhaohua Zhu, Changhai Ding
Summary: The study identified miR-214-3p as a key regulator in osteoarthritis, impacting ECM metabolism and cell apoptosis in cartilage by modulating the NF-kappa B signaling pathway. Targeting IKKP, decreased miR-214-3p exacerbates OA development, suggesting it as a potential novel therapeutic target for OA.
Review
Oncology
Sargam Kapoor, Grace Champion, Aparna Basu, Anu Mariampillai, Matthew J. Olnes
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow with poor prognosis. Recent advancements in immune therapies, including immune suppressive therapy and novel treatments like monoclonal antibodies and cellular therapeutics, have shown promise in treating these diseases.
Article
Cell Biology
Qianqian Huang, Sheng Chen, Xiaowei Xiong, Tingting Yin, Yanan Zhang, Guohua Zeng, Qiren Huang
Summary: Vascular endothelium dysfunction caused by endothelium inflammation is a trigger of numerous cardiovascular diseases. This study investigated the effect of Asprosin (ASP) on endothelium inflammation induced by hyperlipidemia. The results showed that ASP may play a pro-inflammation role in obesity-associated endothelium dysfunction, and could be a potential target for the prevention and treatment of obesity-related cardiovascular diseases.
Article
Cell Biology
Xin Chen, Xinxin Song, Jingbo Li, Ruoxi Zhang, Chunhua Yu, Zhuan Zhou, Jiao Liu, Siyan Liao, Daniel J. Klionsky, Guido Kroemer, Jinbao Liu, Daolin Tang, Rui Kang
Summary: This study identifies HPCAL1 as a novel autophagy receptor for the selective degradation of CDH2 during ferroptosis. Depletion of CDH2 increases susceptibility to ferroptotic death. The phosphorylation of HPCAL1 and the non-classical LC3-interacting region motif play key roles in the autophagic degradation of CDH2. A ferroptosis inhibitor is found to suppress HPCAL1 expression. Inhibition of HPCAL1 prevents ferroptosis-induced tumor suppression and pancreatitis in mouse models.
Review
Gastroenterology & Hepatology
Amir Ajoolabady, Neil Kaplowitz, Cynthia Lebeaupin, Guido Kroemer, Randal J. Kaufman, Harmeet Malhi, Jun Ren
Summary: The endoplasmic reticulum stress and unfolded protein response play important roles in the pathophysiology of liver diseases. Understanding this process is crucial for developing interventions for the treatment of nonmalignant liver diseases.
Article
Cell Biology
Lea Montegut, Adrien Joseph, Hui Chen, Mahmoud Abdellatif, Christoph Ruckenstuhl, Omar Motino, Flavia Lambertucci, Gerasimos Anagnostopoulos, Sylvie Lachkar, Silvia Dichtinger, Maria Chiara Maiuri, Francois Goldwasser, Benoit Blanchet, Frederic Fumeron, Isabelle Martins, Frank Madeo, Guido Kroemer
Summary: Autophagy defects accelerate aging, while activation of autophagy slows down aging. Acyl-coenzyme A binding protein (ACBP), encoded by diazepam-binding inhibitor (DBI), acts as an extracellular regulator of autophagy. Knockout of ACBP gene in yeast improves chronological aging, and this effect is reversed by knockout of autophagy genes but less so by knockout of mitophagy gene. In humans, ACBP levels correlate with body mass index (BMI) and age, with high ACBP levels predicting future cardiovascular events independently of BMI and age. ACBP plasma concentrations in mice are associated with cardiovascular risk factors and can be attenuated by a monoclonal antibody, suggesting its prognostic value in cardiovascular disease.
Article
Biochemistry & Molecular Biology
Guido Kroemer, Jennifer L. McQuade, Miriam Merad, Fabrice Andre, Laurence Zitvogel
Summary: Traditionally, cancer research and therapy has focused on malignant cells and their tumor microenvironment. However, the communication between the tumor and the host is established through the vascular, lymphatic, and nervous systems. This intricate relationship is mediated by various factors, such as metabolites, neuroendocrine, pro-inflammatory, and immune circuitries, which influence the development and progression of malignant disease. Understanding this relationship will lead to improved systemic interventions and tumor control in cancer patients.
Review
Biochemistry & Molecular Biology
Yvonne Giannoula, Guido Kroemer, Federico Pietrocola
Summary: Cellular senescence involves cell cycle arrest, the acquisition of senescence-associated secretory phenotype (SASP), and changes in cell surface proteins influencing the recognition of senescent cells by immune effectors. Excessive or insufficient senescent cell generation can contribute to pathological aging. Mechanisms such as immunosuppressive molecule expression and secretion of factors attracting immune cells into the microenvironment allow evasion of immune destruction. Immune interventions can target these mechanisms and stimulate an immune response against senescence-associated antigens.
BIOMEDICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Layale Youssef, Melanie Bourgin, Sylvere Durand, Fanny Aprahamian, Deborah Lefevre, Maria Chiara Maiuri, Vincent Marcangeli, Maude Dulac, Guy Hajj-Boutros, Fanny Buckinx, Eva Peyrusque, Pierrette Gaudreau, Jose A. Morais, Gilles Gouspillou, Guido Kroemer, Mylene Aubertin-Leheudre, Philippe Noirez
Summary: Participating in HIIT and MICT can improve the quality of life for obese older individuals, with significant changes observed in serum metabolites related to muscle strength, glycemic parameters, and lipid profile parameters. Further research is needed to confirm the association between these metabolites and healthy aging.
Editorial Material
Pharmacology & Pharmacy
Mahmoud Abdellatif, Frank Madeo, Simon Sedej, Guido Kroemer
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Review
Biochemistry & Molecular Biology
Daniel Barriuso, Lucia Alvarez-Frutos, Lucia Gonzalez-Gutierrez, Omar Motino, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
Summary: The Bcl-2 family of proteins, known for regulating apoptosis, is also involved in cellular senescence. These proteins play a role in determining the entry into senescence and the expression levels are modulated during senescence, promoting cell survival. Manipulation of Bax and Bcl-2 expression affects the appearance and survival of tetraploid cells. Understanding the role of Bcl-2 family proteins in senescence can lead to new therapeutic strategies for targeting cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Lorenzo Galluzzi, Oliver Kepp, Erik Hett, Guido Kroemer, Francesco M. Marincola
Summary: Mammalian cells can undergo regulated cell death in response to specific disruptions of homeostasis, leading to adaptive immune responses. This immunogenic cell death (ICD) is distinct from immunostimulation or inflammatory responses that do not depend on cellular demise. In this article, we critically discuss the key concepts and mechanisms of ICD and its implications for cancer immunotherapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Vanessa Klapp, Beatriz Alvarez-Abril, Giuseppe Leuzzi, Guido Kroemer, Alberto Ciccia, Lorenzo Galluzzi
Summary: Genomic stability is vital for normal cells to prevent oncogenesis. The DNA damage response (DDR) plays a role as a tumor suppressor protein in preserving genomic stability, inducing the death of cells with unrepairable DNA lesions and engaging cell-extrinsic oncosuppression through immunosurveillance. However, DDR signaling in cancer cells can inhibit tumor-targeting immune responses, favoring tumor progression and therapy resistance. This article discusses the complex interactions between DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy.
Editorial Material
Oncology
Oliver Kepp, Peng Liu, Laurence Zitvogel, Guido Kroemer
Editorial Material
Oncology
Oliver Kepp, Hui Pan, Peng Liu, Guido Kroemer
Review
Immunology
Daolin Tang, Guido Kroemer, Rui Kang
Summary: Ferroptosis is a regulated cell death process that occurs when there is an accumulation of toxic lipid peroxides, particularly in the plasma membrane, due to iron-dependency. While it is crucial for maintaining overall health, it can also lead to tissue damage and pathological conditions. Understanding the immune characteristics of ferroptosis in infection, sterile inflammation, and tumor immunity is important for developing therapeutic strategies.
IMMUNOLOGICAL REVIEWS
(2023)
Editorial Material
Immunology
Laurence Zitvogel, Guido Kroemer
Summary: Dietary fibers, including chitin, have significant effects on gastrointestinal physiology and immunity. Depletion or supplementation of dietary fibers can have negative or positive effects on the immune system of the murine digestive tract, which is relevant to food allergies and systemic metabolism.
TRENDS IN IMMUNOLOGY
(2023)
Review
Immunology
Yuting Ma, Guido Kroemer
Summary: While there is little direct evidence supporting the effect of stress on cancer incidence, it does impact the evolution, dissemination, and therapeutic outcomes of tumors. Neuroendocrine changes and stress-associated immunomodulatory molecules play important roles in the interaction between stress and cancer immunity, with implications for cancer therapy.
NATURE REVIEWS IMMUNOLOGY
(2023)