Article
Immunology
Wenting Jian, Huigai Ma, Dingming Wang, Peng Yang, Mengbi Jiang, Yu Zhong, Xiang Long, Jingjing Jiang, Yuan Gong
Summary: This study demonstrates that omaveloxolone exerts significant cardioprotective effects in treating sepsis-induced cardiomyopathy by activating the Nrf2 signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Daniela Maria Tanase, Alina Georgiana Apostol, Claudia Florida Costea, Claudia Cristina Tarniceriu, Ionut Tudorancea, Minela Aida Maranduca, Mariana Floria, Ionela Lacramioara Serban
Summary: Arterial hypertension is a prevalent disease characterized by increased incidence and heterogeneous pathophysiology. Oxidative stress plays an important role in its development, with excessive levels causing vascular cell damage and promoting hypertension. Transcription factors such as Nrf2 mediate antioxidant response pathways and provide protection.
Article
Biotechnology & Applied Microbiology
Huiyan Deng, Miaojian Wan, Huaping Li, Quan Chen, Runxiang Li, Bihua Liang, Huilan Zhu
Summary: The study demonstrates that curcumin can protect the skin from UV damage by regulating the Nrf2 pathway. UV irradiation leads to cell apoptosis and oxidative stress, which can be reversed by adding curcumin. Additionally, curcumin induces Nrf2 nuclear accumulation in Hacat cells to provide protection against UV exposure-induced photodamage.
Review
Gastroenterology & Hepatology
Dan-Dan Zhu, Xue-Mei Tan, Li-Qing Lu, Si-Jia Yu, Ru-Li Jian, Xin-Fang Liang, Yi-Xuan Liao, Wei Fan, Luciia Barbier-Torres, Austin Yang, He-Ping Yang, Ting Liu
Summary: COVID-19 caused by SARS-CoV-2 is a global pandemic that not only affects respiratory system but also leads to systemic inflammation and liver damage. NRF2 plays a crucial role in regulating antioxidant proteins in the context of COVID-19-induced inflammation and liver injury.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Cell Biology
David Rysanek, Pavla Vasicova, Jayaprakash Narayana Kolla, David Sedlak, Ladislav Andera, Jiri Bartek, Zdenek Hodny
Summary: The accumulation of senescent cells in aging tissues contributes to age-associated diseases. Inhibiting the anti-apoptotic machinery of senescent cells through BCL-2 protein family inhibitors can eliminate these cells. Combination therapy with BCL-2 inhibitors shows synergistic effects in eliminating senescent cells and overcoming resistance to monotherapy.
Article
Oncology
Yanqiong Liu, Qiulian Wu, Fuyong Zhang, Xue Qin
Summary: This study provides evidence for the first time that the NRF2 gene rs6721961 variation is a potential genetic marker for susceptibility to hepatocellular carcinoma (HCC).
CANCER CELL INTERNATIONAL
(2023)
Review
Gastroenterology & Hepatology
Vidyasagar Naik Bukke, Archana Moola, Gaetano Serviddio, Gianluigi Vendemiale, Francesco Bellanti
Summary: Oxidative stress is a key driver in the development and progression of various diseases, including MAFLD. NRF2, a master regulator of redox homeostasis, plays a crucial role in every step of MAFLD development. NRF2 activators regulate lipid metabolism and oxidative stress, alleviating fatty liver disease by inducing the expression of cytoprotective genes.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Omayma A. Eldahshan, Yasmine M. Abdelkhalek, Magdy El Dahshan, Eman A. Ahmed, Jean-Marc Sabatier, Gaber E. -S. Batiha
Summary: COVID-19 is caused by SARS-CoV-2 and results in pulmonary and extra-pulmonary manifestations due to oxidative stress and hyperinflammation. The Nrf2 pathway plays a crucial role in mitigating viral toxicity and inflammation in COVID-19, and Nrf2 activators could be a potential therapeutic strategy for managing the disease.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Sichen Zhang, Chunguo Qian, Hailing Li, Zhimin Zhao, Jianchun Xian, Depo Yang
Summary: The antioxidant peptide DR12 from housefly pupae showed neuroprotective effects by reducing oxidative stress, upregulating endogenous antioxidants, and activating specific signaling pathways. DR12 may have potential therapeutic applications for neurodegenerative diseases.
JOURNAL OF NATURAL MEDICINES
(2023)
Review
Cell Biology
Rabab S. Hamad, Hayder M. Al-kuraishy, Athanasios Alexiou, Marios Papadakis, Eman A. Ahmed, Hebatallah M. Saad, Gaber El-Saber Batiha
Summary: COVID-19 is a recent pandemic caused by SARS-CoV-2, leading to pulmonary and extra-pulmonary manifestations. Inhibition of Nrf2 may contribute to oxidative stress and hyperinflammation in COVID-19. Nrf2 pathway suppresses pro-inflammatory cytokines, reducing pulmonary symptoms. Nrf2 activators can improve endothelial dysfunction, RAS dysregulation, immune thrombosis, and coagulopathy.
CELL STRESS & CHAPERONES
(2023)
Review
Biochemistry & Molecular Biology
Zihang Liu, Panpan Deng, Shengnan Liu, Yiying Bian, Yuanyuan Xu, Qiang Zhang, Huihui Wang, Jingbo Pi
Summary: Cytokine storm refers to a state of the immune system characterized by excessive release of cytokines, leading to inflammation, organ failure, and disease outcomes. NRF2, a transcription factor involved in cellular redox homeostasis, has emerged as a potential therapeutic target in preventing and treating cytokine storms. This review summarizes the causes of cytokine storms and the rationale for targeting NRF2 as a therapeutic intervention.
Article
Integrative & Complementary Medicine
Xiaoting Lu, Xue Liu, Ershun Liang, Ruixue Yang, Yan Liu, Xiaoqiong Liu, Fangfang Yan, Yifan Xing
Summary: This study found that Panax quinquefolius saponin (PQS) can effectively inhibit vascular smooth muscle cell calcification by ameliorating oxidative stress and regulating osteogenic genes through promoting the expression of Nrf2.
BMC COMPLEMENTARY MEDICINE AND THERAPIES
(2023)
Article
Integrative & Complementary Medicine
Zhipeng Chen, Heqian Liu, Xiaoqi Zhao, Subinur Mamateli, Cheng Liu, Lei Wang, Jing Yu, Yutong Liu, Jing Cai, Tong Qiao
Summary: This study found that oridonin can protect endothelial cells from shear stress and reduce the impact of oxidative stress, thus alleviating the occurrence and development of AS. This research provides new ideas and directions for finding therapeutic drugs for AS.
BMC COMPLEMENTARY MEDICINE AND THERAPIES
(2022)
Article
Surgery
Jake J. Wen, Keyan Mobli, Victoria G. Rontoyanni, Claire B. Cummins, Geetha L. Radhakrishnan, Andrew Murton, Ravi S. Radhakrishnan
Summary: Burn injury can cause cardiac dysfunction by interrupting the antioxidant-response element pathway in cardiac mitochondria. This study showed that Nrf2 deficiency worsens burn-induced cardiac dysfunction, while Nrf2 activation with Olti improves cardiac function and offers a promising therapeutic strategy.
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2022)
Article
Nutrition & Dietetics
Hai Jia, Yunchang Zhang, Xuemeng Si, Yuhang Jin, Da Jiang, Zhaolai Dai, Zhenlong Wu
Summary: This study demonstrates that quercetin can alleviate diquat-induced cell injury in enterocytes by upregulating the protein abundance of Nrf2 and regulating GSH-related redox homeostasis.
Article
Pharmacology & Pharmacy
Camila Juliana Dominguez, Guillermo Nicolas Tocchetti, Juan Pablo Rigalli, Aldo Domingo Mottino
Summary: The ABC transporters on the intestinal surface play a crucial role in regulating the absorption and efficacy of therapeutic agents, and the rapid modulation of their activity is of increasing interest to pharmacologists. Controlled regulation of these transporters could provide a basis for optimizing bioavailability of drugs and preventing potential drug interactions.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Eric R. Barros, Juan Pablo Rigalli, Alejandra Tapia-Castillo, Andrea Vecchiola, Morag J. Young, Joost G. J. Hoenderop, Rene J. M. Bindels, Carlos E. Fardella, Cristian A. Carvajal
Summary: This study evaluated the proteome of urinary extracellular vesicles (uEVs) from patients with primary aldosteronism (PA) and identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, suggesting AGP1 as a potential biomarker for PA. Additionally, the concentration of uEVs was positively correlated with urinary creatinine, and the size of uEVs in PA patients was smaller compared to the control group, indicating differences in uEV characteristics between the two groups.
Article
Biochemistry & Molecular Biology
Eric R. Barros Lamus, Valentina Carotti, Christine R. S. de Vries, Femke Witsel, Onno J. Arntz, Fons A. J. van de Loo, Cristian A. Carvajal, Rene J. M. Bindels, Joost G. J. Hoenderop, Juan P. Rigalli
Summary: This study investigates the regulatory effect of EVs from renal proximal tubule and collecting duct cells on extracellular ATP levels and the expression of the alpha subunit of the epithelial sodium channel. The findings reveal that EVs can modulate purinergic signaling through mechanisms such as miRNA regulation and ATPase activity, impacting renal physiological and pathophysiological processes. Further research on EV release and cargo content may shed light on the role of EVs in renal purinergic signaling.
Article
Urology & Nephrology
Charles J. Blijdorp, Omar A. Z. Tutakhel, Thomas A. Hartjes, Thierry P. P. van den Bosch, Martijn H. van Heugten, Juan Pablo Rigalli, Rob Willemsen, Usha M. Musterd-Bhaggoe, Eric R. Barros, Roger Carles-Fontana, Cristian A. Carvajal, Onno J. Arntz, Fons A. J. van de Loo, Guido Jenster, Marian C. Clahsen-van Groningen, Cathy A. Cuevas, David Severs, Robert A. Fenton, Martin E. van Royen, Joost G. J. Hoenderop, Rene J. M. Bindels, Ewout J. Hoorn
Summary: This study investigated the quantification and characterization of urinary extracellular vesicles (uEVs) in spot urines from healthy individuals and patients with kidney disease. The research found a strong correlation between urine particle and creatinine concentrations, as well as effects of water loading on uEV size and protein detection. Additionally, using detergent improved intracellular-epitope recognition in uEVs and suggested specific binding of exosome markers CD9 and CD63 with distal nephron markers.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Medicine, Research & Experimental
Lucila Cere, Maria G. Sedlmeier, Mariana Semeniuk, Marcelo G. Luquita, Daniel Frances, Maria T. Ronco, Juan Pablo Rigalli, Maria L. Ruiz, Viviana A. Catania
Summary: This study investigates the modulation of hepatic P-gp by PRL in hyperprolactinemic states, demonstrating increased expression and activity of P-gp in lactating post-partum rats and ovariectomized rats treated with PRL. The research also shows a transcriptional up-regulation of P-gp by PRL in primary hepatocyte cultures, suggesting a potential impact on the pharmacokinetics of xenobiotics substrates of P-gp in hyperprolactinemic situations.
Editorial Material
Medicine, General & Internal
Oscar Escribano, Daniel E. Frances, Yolanda F. Otero, Javier Egea, Agueda Gonzalez-Rodriguez
FRONTIERS IN MEDICINE
(2021)
Article
Chemistry, Medicinal
Alejandro Pezza, Luis E. Tavernelli, Victoria L. Alonso, Virginia Perdomo, Raquel Gabarro, Rab Prinjha, Elvio Rodriguez Araya, Inmaculada Rioja, Roberto Docampo, Felix Calderon, Julio Martin, Esteban Serra
Summary: TcBDF2 is an important bromodomain protein in T. cruzi, playing a crucial role in infection, replication, and differentiation of the parasite, as well as pathogenesis.
ACS INFECTIOUS DISEASES
(2022)
Article
Immunology
Laura Fraccaroli, Maria Daniela Ruiz, Virginia Gabriela Perdomo, Agustina Nicole Clausi, Dario Emmanuel Balcazar, Luciana Larocca, Carolina Carrillo
Summary: "Chagas disease is an endemic American parasitosis caused by Trypanosoma cruzi. Current therapies have limited efficacy and side effects, leading to the need for new trypanocidal strategies. Ivermectin shows potential as a repurposed drug for Chagas disease, with dose-dependent effects on T. cruzi and other trypanosomatids, and potential novel molecular targets identified in this study."
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Valentina Carotti, Juan P. Rigalli, Jenny van Asbeck-van der Wijst, Joost G. J. Hoenderop
Summary: Purinergic signalling is a process mediated by purinergic receptors, where extracellular nucleotides and nucleosides bind to the receptors, resulting in changes in cell physiology. This signalling is involved in important physiological processes and pathophysiological situations such as cancer and inflammation. Extracellular vesicles (EVs) play a crucial role in modulating purinergic signalling and can affect target cells and tissues located at distant locations. The regulation of extracellular ATP levels and adenosine by EVs has significant impact on processes like inflammation, immune response, and cancer pathogenesis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Valentina Carotti, Jenny van der Wijst, Eric H. J. Verschuren, Luco Rutten, Nico Sommerdijk, Charlotte Kaffa, Vera Sommers, Juan P. Rigalli, Joost G. J. Hoenderop
Summary: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development of renal cysts. Recent studies have suggested the involvement of extracellular vesicles (EVs) in the progression of ADPKD, but the underlying mechanisms are still unclear. This study used cell models of the distal convoluted tubule and inner medullary collecting duct to demonstrate that Pkd1 deficiency significantly increases EV release. Further investigations revealed an exacerbated signaling of the extracellular ATP/P2X7 pathway and an upregulation of ceramide biosynthesis enzymes as potential molecular mechanisms for the changes in EV release.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Valentina Carotti, Wouter H. van Megen, Juan P. Rigalli, Eric R. Barros, Vera Sommers, Luco Rutten, Nico Sommerdijk, Dorien J. M. Peters, Jenny van Asbeck-van der Wijst, Joost G. J. Hoenderop
Summary: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of fluid-filled cysts within the kidney due to mutations in PKD1 or PKD2. EVs released from PKD1 knockout cells can stimulate cyst growth through effects on recipient cells, indicating their potential role in intersegmental communication and cyst growth.
Article
Infectious Diseases
Maria Veronica Humpola, Roque Spinelli, Melina Erben, Virginia Perdomo, Georgina Guadalupe Tonarelli, Fernando Albericio, Alvaro Sebastian Siano
Summary: In this study, analogs of two antimicrobial peptides, C10:0-A2 and TA4, were designed and synthesized, and non-proteinogenic amino acids were used to improve their therapeutic properties. The physicochemical properties and antimicrobial activity of these analogs were analyzed. The results showed that substitution with D- and N-methyl amino acids could enhance stability against enzymatic degradation and modulate the therapeutic properties of antimicrobial peptides and lipopeptides. The study provides insights into the design and optimization of antimicrobial peptides for improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies.
Article
Nutrition & Dietetics
Maria Manuela Barranco, Virginia Gabriela Perdomo, Felipe Zecchinati, Romina Manarin, Greta Massuh, Nicolas Sigal, Silvana Vignaduzzo, Aldo Domingo Mottino, Silvina Stella Maris Villanueva, Fabiana Garcia
Summary: This study found that a high-fat diet leads to a decrease in the expression and transport activity of multidrug resistance transporter 1 (Mdr-1) in the intestines of C57BL/6 male mice, thus affecting the bioavailability of drugs. Meanwhile, the intestinal Mdr-1 mRNA and protein expression in tumor necrosis factor a receptor 1 knockout mice (R1KO) did not show significant changes. Therefore, a high-fat diet may affect the Mdr-1 function in the intestines by inhibiting the expression of Mdr-1 gene homologues.
Review
Biology
Anna Gagliardi, Gzona Bajraktari-Sylejmani, Elisabetta Barocelli, Johanna Weiss, Juan Pablo Rigalli
Summary: Drug-metabolizing enzymes (DMEs) and transporters are crucial for drug efficacy and safety. This article explores the use of extracellular vesicles (EVs) as a less invasive way to estimate the expression and activity of DMEs and transporters in the liver, intestine, and kidney. Preliminary evidence suggests a correlation between EVs and tissue expression, indicating that EVs could potentially be used for precision therapy based on individual biotransformation and excretion capacities.
Review
Biology
Maria Bucci-Munoz, Aldana Magali Gola, Juan Pablo Rigalli, Maria Paula Ceballos, Maria Laura Ruiz
Summary: Cancer multidrug resistance (MDR) is a major cause of therapy failure and mortality, often caused by the overexpression of drug transporters. Extracellular vesicles (EVs) play a role in cell-cell communication and can transfer various biomolecules, including transporter molecules and noncoding RNAs, leading to MDR or drug-sensitive phenotype. This article reviews the regulation of ABC transporters by EV-mediated cell-cell communication and discusses the potential for novel therapeutic strategies.