Article
Biochemistry & Molecular Biology
Bashayer R. Al-Mubarak, Karen F. S. Bell, Sudhir Chowdhry, Paul J. Meakin, Paul S. Baxter, Sean McKay, Owen Dando, Michael L. J. Ashford, Irina Gazaryan, John D. Hayes, Giles E. Hardingham
Summary: Nrf2 is a transcription factor that plays a crucial role in protecting neurons and alleviating the pathology of neurological disorders associated with oxidative stress in astrocytes. The activation of Nrf2 in astrocytes through oxidative stress involves Keap1-independent non-canonical signaling pathways, which suggests that further activation of Nrf2 by Keap1-inhibiting drugs may be a potential therapeutic strategy.
Review
Biochemistry & Molecular Biology
Pelin Telkoparan-Akillilar, Emiliano Panieri, Dilek Cevik, Sibel Suzen, Luciano Saso
Summary: Cancer is a fatal disease with increasing mortality worldwide, and dysregulation of the NRF2/KEAP1 signaling pathway promotes tumor cell survival and metastasis in various cancers.
Article
Biochemistry & Molecular Biology
Vy Ngo, Nadun C. Karunatilleke, Anne Brickenden, Wing-Yiu Choy, Martin L. Duennwald
Summary: Cells respond to oxidative stress by inducing antioxidant proteins through the activation of Nrf2. Both Nrf2 and Keap1 are susceptible to protein misfolding under oxidative stress, potentially due to their intrinsic characteristics. This study provides new insights into the regulation of Nrf2 and Keap1 by oxidation-induced protein misfolding.
Article
Biochemistry & Molecular Biology
Shengnan Liu, Jingbo Pi, Qiang Zhang
Summary: This review article focuses on the quantitative signaling perspective of the KEAP1-NRF2-ARE pathway and highlights the importance of signal amplification for robust induction of antioxidant genes. The study demonstrates that redox-regulated protein events in this pathway can generate highly ultrasensitive NRF2 activation and antioxidant gene induction. Understanding the signal amplification in this pathway can help identify potential targets for preventing and treating oxidative stress-related diseases and facilitate health risk assessment of oxidative chemicals.
Article
Biochemistry & Molecular Biology
Liam Baird, Masayuki Yamamoto
Summary: In human cancer, abnormal activation of the NRF2 pathway can allow cancer cells to evade immune surveillance and develop into malignant tumors by reducing antigen presentation and activating signals for NK cells, which inhibits the involvement of immune effector cells.
Article
Biochemistry & Molecular Biology
Sharadha Dayalan Naidu, Plamena R. Angelova, Elena V. Knatko, Chiara Leonardi, Miroslav Novak, Laureano de la Vega, Ian G. Ganley, Andrey Y. Abramov, Albena T. Dinkova-Kostova
Summary: Transcription factor Nrf2 plays a crucial role in maintaining cellular redox homeostasis and mitochondrial health in lung cancer cells with loss-of-function Keap1 mutations.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Review
Physiology
Wenlong Hao, Minghao Li, Qingmin Cai, Shiying Wu, Xiangyao Li, Quanyu He, Yongbin Hu
Summary: This review discusses the KEAP1/NRF2 signaling mechanisms and recent advances in understanding the role of NRF2 in primary fibrotic lesions. It also explores the therapeutic potential of antioxidant substances and drugs and summarizes the prospects of NRF2 in fibrosis treatment.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Somayyeh Ghareghomi, Mehran Habibi-Rezaei, Marzia Arese, Luciano Saso, Ali Akbar Moosavi-Movahedi
Summary: ROS play a crucial role in cellular processes, with Keap1-Nrf2 pathway acting as a master antioxidant mechanism. While activation of Nrf2 benefits cells in early stages by reducing ROS levels, hyperactivation can support the survival of healthy and cancer cells against oxidative stress and treatments. Understanding the dual role of Nrf2 in cancer cells can be important in cancer treatment strategies.
Article
Biochemistry & Molecular Biology
Juntao Yuan, Zhuoran Yu, Junling Gao, Kai Luo, Xiyue Shen, Bingqing Cui, Zhongbing Lu
Summary: The development of nonalcoholic fatty liver disease (NAFLD) is associated with the regulation of NRF2 by GCN2, which can attenuate hepatic steatosis and oxidative stress.
Article
Plant Sciences
Chuanjing Cheng, Jinling Zhang, Kaixin Liu, Yanyan Xu, Fukui Shen, Yanqi Han, Yuanyuan Hou, Tiejun Zhang, Gang Bai
Summary: The study aims to determine the potential therapeutic targets and molecular mechanisms of Ginsenoside CK in improving oxidative stress injury. It was found that CK improves oxidative damage by regulating the KEAP1-NRF2/ARE pathway, and its target protein is KEAP1. CK binds to KEAP1, disrupting the binding between NRF2 and KEAP1, thereby inhibiting oxidative damage induced by LPS or physical mechanical stress.
Article
Cell Biology
Lin Zhu, Shulei He, Lu Huang, Dongni Ren, Tiejian Nie, Kai Tao, Li Xia, Fangfang Lu, Zixu Mao, Qian Yang
Summary: Accumulation of oxidative stress is closely associated with aging and aging-related diseases. Understanding the molecular mechanisms that regulate oxidative stress is crucial for uncovering the pathogenesis of these diseases. Chaperone-mediated autophagy (CMA), a selective lysosome-dependent degradation process, has been shown to maintain cellular homeostasis and attenuate oxidative stress. This study reveals that CMA directly degrades Keap1, leading to increased Nrf2 levels, nuclear translocation, and expression of antioxidative genes. Furthermore, a feed-forward loop between CMA and Nrf2 is identified. These findings highlight the role of CMA as a regulator of the Keap1-Nrf2 pathway and emphasize its antioxidative function.
Article
Biochemistry & Molecular Biology
Ronja Brinks, Christoph Jan Wruck, Jutta Schmitz, Nicole Schupp
Summary: Nrf2 expression is decreased in chronic kidney disease (CKD). Activating Nrf2 may be a possible therapy for CKD. However, this study found that Nrf2 activation was unable to prevent oxidative injury induced by Aldo.
Review
Genetics & Heredity
Yingcai Niu, Jing Zhang, Miaoxian Dong
Summary: Parkinson's disease is a complex neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the brain. Current treatments focus on symptom relief rather than modifying the course of the disease. Oxidative stress, caused by genetic and environmental factors, is thought to play a key role in the development of Parkinson's disease. Targeting Nrf2, a key regulator of redox homeostasis, may offer a therapeutic option to alleviate oxidative stress in Parkinson's disease.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Environmental Sciences
Xianlei Jiang, Xupeng Xing, Yingbing Zhang, Chengtu Zhang, Ying Wu, Yongzhong Chen, Ru Meng, Huiqun Jia, Yuyao Cheng, Yong Zhang, Jianmin Su
Summary: This study found that lead exposure has adverse effects on the reproductive system of female mice, inducing oxidative stress, reducing oocyte maturation and fertilization rates, and impacting fertility. Lead activates the Nrf2/Keap1 pathway to protect oocytes against oxidative stress but ultimately impairs their maturation and fertilization.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Plant Sciences
Xiaoju Zhuge, Xiaosheng Jin, Tingting Ji, Rongzhou Li, Liwei Xue, Weilai Yu, Zijiao Quan, Haibin Tong, Fang Xu
Summary: This study aimed to explore the therapeutic effect of geniposide on colitis and uncover the underlying mechanisms of geniposide-mediated antioxidant and anti-inflammatory activities. The study found that geniposide ameliorates colitis by activation of the Nrf2/ARE signaling pathway, preventing colonic redox imbalance and inflammatory damage.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Manuela Malatesta
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Mirco Galie
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Flavia Carton, Manuela Malatesta
Summary: Nanoconstructs developed for biomedical purposes need to overcome biological barriers. In vivo models are complex and limited, so simplified in vitro models are preferred. Various in vitro models have been set up, including 2D cell cultures, cell monolayers, 3D cell cultures, and bioreactors. This review provides an overview of the most representative and performing in vitro models for studying biological barriers in nanomedical research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Manuela Malatesta
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Giovanni Gotte, Elena Butturini, Ilaria Bettin, Irene Noro, Alexander Mahmoud Helmy, Andrea Fagagnini, Barbara Cisterna, Manuela Malatesta
Summary: RNase A can form oligomers through the 3D domain swapping mechanism. These oligomers can evolve into large aggregates called super-aggregates (SAs), which are not derived from native RNase A monomers or oligomers with C-terminus swapping. Two subunits' N-termini swapping is required for SA formation. SAs retain low ribonucleolytic activity and are confirmed to be derived from RNase A. TEM analyses and Thioflavin-T (ThT) interactions indicate that SAs are large and circular, but not amyloid-like derivatives. These findings suggest that the opening of RNase A N-terminus and 3D-DS-mediated oligomerization may be a preliminary step in massive RNase A aggregation. The study provides insights into protein aggregation and its potential applications in combating amyloidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Anatomy & Morphology
Maria Assunta Lacavalla, Chiara Rita Inguscio, Barbara Cisterna, Paolo Bernardi, Manuela Costanzo, Mirco Galie, Ilaria Scambi, Osvaldo Angelini, Gabriele Tabaracci, Manuela Malatesta
Summary: Low-dose ozone (O-3) does not damage activated microglial cells in vitro, but decreases cell motility and pro-inflammatory cytokine secretion.
MICROSCOPY RESEARCH AND TECHNIQUE
(2022)
Article
Cell Biology
Flavia Carton, Manuela Malatesta
Summary: Studying the permeability of biological barriers to nanoparticles in vivo is difficult, so in vitro modeling methods have become more relevant. Microscopy techniques play a crucial role in visualizing and evaluating the behavior of nanoparticles inside biological barriers.
EUROPEAN JOURNAL OF HISTOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ilaria Andreana, Manuela Malatesta, Maria Assunta Lacavalla, Federico Boschi, Paola Milla, Valeria Bincoletto, Carlo Pellicciari, Silvia Arpicco, Barbara Stella
Summary: Muscular dystrophies are rare genetic pathologies with diverse clinical phenotypes and disease mechanisms. This study successfully developed nanocarriers that target muscular pathologies using the high affinity of skeletal muscle cells for carnitine, enabling precise control and targeted drug release.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Elisabetta Esposito, Laura Calderan, Andrea Galvan, Enrica Cappellozza, Markus Drechsler, Paolo Mariani, Alessia Pepe, Maddalena Sguizzato, Enrico Vigato, Edoardo Dalla Pozza, Manuela Malatesta
Summary: This study investigated the transdermal fate of ethosomes and transethosomes on human skin. The results showed that the vesicle penetration capability was influenced by their physical-chemical features, with different vesicles reaching different levels of the skin. This offers potential for tailored transdermal drug delivery based on specific cutaneous pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Nanoscience & Nanotechnology
Mathieu Repellin, Flavia Carton, Federico Boschi, Mirco Galie, Massimiliano Perduca, Laura Calderan, Arnaud Jacquier, Julien Carras, Laurent Schaeffer, Stephanie Briancon, Giovanna Lollo, Manuela Malatesta
Summary: In this study, hyaluronic acid-based nanoparticles were proposed as a novel encapsulation strategy to efficiently deliver pentamidine (PTM) to skeletal muscle cells and mitigate myotonic dystrophy type 1 (DM1) pathology. The nanoparticles demonstrated efficient internalization with minimal toxicity in vitro, and their therapeutic efficacy in reducing nuclear foci was demonstrated in a novel DM1 in vitro model.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Federico Boschi, Manuela Malatesta
Summary: Bladder cancer is a common disease with a significant impact on patients' quality of life. The impermeable urothelial barrier makes the diagnosis and treatment of bladder cancer challenging. Nanotechnology provides opportunities to improve the diagnostic and therapeutic approaches by enabling the crossing of the urothelial barrier, active targeting, therapeutic agent delivery, and visualization using different imaging techniques. This article presents recent experimental applications of nanoparticle-based imaging techniques for the specific detection of bladder cancer cells, showing promising results in vivo and potential translation to clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrea Galvan, Enrica Cappellozza, Yann Pellequer, Anita Conti, Edoardo Dalla Pozza, Enrico Vigato, Manuela Malatesta, Laura Calderan
Summary: Skin is a major administration route for drugs and developing reliable skin models is crucial for preclinical studies. Currently, excised human skin is considered the gold standard for in vitro permeation studies. However, the limited life span of skin explants poses a problem. In this study, an innovative bioreactor was used to preserve the structural and functional integrity of explanted human skin for up to 72 hours, allowing for the simulation of inflammatory events observed in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chiara Rita Inguscio, Elisa Dalla Pozza, Ilaria Dando, Federico Boschi, Gabriele Tabaracci, Osvaldo Angelini, Pietro Maria Picotti, Manuela Malatesta, Barbara Cisterna
Summary: Low doses of gaseous ozone (O-3) induce mild oxidative stress that activates the antioxidant cell response through the Nrf2 pathway, leading to beneficial effects without damaging the cells. Mitochondria, being sensitive to oxidative stress, are a target of O-3. This in vitro study demonstrates that low O-3 doses finely regulate mitochondrial features, with a concentration of 10 μg maintaining normal levels of Nrf2, promoting mitochondrial size and cristae extension, reducing ROS, and preventing cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Chiara Rita Inguscio, Barbara Cisterna, Maria Assunta Lacavalla, Franco Donati, Osvaldo Angelini, Gabriele Tabaracci, Manuela Malatesta
Summary: Platelet-rich plasma (PRP) is an innovative and efficient therapeutic approach in regenerative medicine. In this study, the effects of ozone or procaine, or both, on platelets in PRP were investigated. The results show that ozone and procaine induce morpho-functional modifications in platelets, resulting in increased release of factors.
EUROPEAN JOURNAL OF HISTOCHEMISTRY
(2023)
Correction
Biochemistry & Molecular Biology
Siew Chin Chan, Chih-Wei Tung, Chia-Wei Lin, Yun-Shiuan Tung, Po-Min Wu, Pei-Hsun Cheng, Chuan-Mu Chen, Shang-Hsun Yang
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Suyuan Liu, Meiling Tan, Jiangxue Cai, Chenxuan Li, Miaoxin Yang, Xiaoxiao Sun, Bin He
Summary: This study reveals that the antibiotic doxycycline effectively inhibits NLRP3 inflammasome activation by targeting mitochondrial translation and mtDNA synthesis, offering potential for the treatment of NLRP3-related diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Hao Liu, Nana Li, Ge Kuang, Xia Gong, Ting Wang, Jun Hu, Hui Du, Minxuan Zhong, Jiashi Guo, Yao Xie, Yang Xiang, Shengwang Wu, Yiling Yuan, Xinru Yin, Jingyuan Wan, Ke Li
Summary: Protectin D1 (PTD1) improves hepatic steatosis, inflammation and fibrosis in a NASH mouse model by inhibiting the activation of TLR4 downstream signaling pathway, possibly through upregulation of IRAK-M expression, suggesting a potential new treatment for NASH.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)