Article
Biology
Xiaowei Zheng, Sampath Narayanan, Cheng Xu, Sofie Eliasson Angelstig, Jacob Grunler, Allan Zhao, Alessandro Di Toro, Luciano Bernardi, Massimiliano Mazzone, Peter Carmeliet, Marianna Del Sole, Giancarlo Solaini, Elisabete A. Forsberg, Ao Zhang, Kerstin Brismar, Tomas A. Schiffer, Neda Rajamand Ekberg, Ileana Ruxandra Botusan, Fredrik Palm, Sergiu-Bogdan Catrina
Summary: Excessive production of mitochondrial reactive oxygen species (ROS) in diabetes complications is mainly caused by impaired responses to hypoxia due to the inhibition of hypoxia-inducible factor-1 (HIF-1) by hyperglycemia. Restoring HIF-1 function can attenuate ROS overproduction, protect cells against apoptosis and renal injury in diabetes. These findings suggest that targeting HIF-1 repression could be a potential therapeutic strategy for diabetic complications.
Article
Gastroenterology & Hepatology
Pan Cao, Qian Chen, Chun-Xia Shi, Lu-Wen Wang, Zuo-Jiong Gong
Summary: This study suggests that Sirt1 may protect against acute liver failure by inducing the deacetylation of HIF-1 alpha to reduce ROS.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Urology & Nephrology
Szu-Yu Pan, Pei-Zhen Tsai, Yu-Hsiang Chou, Yu-Ting Chang, Fan-Chi Chang, Yen-Ling Chiu, Wen-Chih Chiang, Tien Hsu, Yung-Ming Chen, Tzong-Shinn Chu, Shuei-Liong Lin
Summary: PHD inhibitors are effective in treating CKD-associated anemia by stabilizing HIF and increasing erythropoiesis. However, their impact on kidney fibrosis is inconsistent due to the context-dependent effects of HIF. Studies on pericytes suggest that HIF stabilization in these cells may not negatively affect kidney fibrosis despite increased erythropoietin production.
KIDNEY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Naoko Kida, Yoshiyuki Matsuo, Yoshiko Hashimoto, Kenichiro Nishi, Tomoko Tsuzuki-Nakao, Hidemasa Bono, Tetsuo Maruyama, Kiichi Hirota, Hidetaka Okada
Summary: Cigarette smoking is a major risk factor for various fatal diseases, including cancers. The study found that smoking induced HIF-1 alpha activation in human endometrial cells, leading to cellular stress, inflammation, and endometrial remodeling. These findings suggest a potential mechanism underlying the detrimental effects of smoking on endometrial health.
Article
Cell Biology
Petr Fojtik, Deborah Beckerova, Katerina Holomkova, Martin Senfluk, Vladimir Rotrekl
Summary: Mild hypoxia attenuates the pluripotency-promoting PI3K/AKT signaling pathway in human pluripotent stem cells compared to normoxic conditions, due to the downregulation of ROS. In addition, the MAPK pathway also downregulates ROS and attenuates the PI3K/AKT signaling via a novel interaction between these pathways. This ROS-mediated regulatory circuit may have implications for enhancing cultivation and differentiation protocols for hPSCs, as well as providing insights into cancer stem cell signaling regulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Engineering, Biomedical
Kelsey G. DeFrates, Daniela Franco, Ellen Heber-Katz, Phillip B. Messersmith
Summary: Traditional approaches in regenerative medicine face limitations in translation and commercialization, prompting the development of therapies that stimulate endogenous processes for regeneration. Recent studies highlight the potential of oxygen-sensing pathways, with upregulation of HIF-1α showing promise in modulating cell metabolism and plasticity for tissue regeneration.
Article
Chemistry, Applied
Cheng Chen, Zhaobin Guo, Xixiong Shi, Yuxuan Guo, Guoyuan Ma, Jibing Ma, Qunli Yu
Summary: ROS accelerates postmortem glycolysis and tenderization of bovine muscle by activating the PI3K/AKT signaling pathway, leading to the accumulation of HIF-1α.
Article
Oncology
Yun Zhang, Guo-Xin Zhang, Li-Shuang Che, Shu-Han Shi, Yue-Ting Li
Summary: The expression of miR-212 was significantly increased in patients with renal interstitial fibrosis and UUO mice, and it was found to promote the progression of renal interstitial fibrosis by targeting HIF1AN.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Cell Biology
Hong-Mou Shih, Szu-Yu Pan, Chih-Jen Wu, Yu-Hsiang Chou, Chun-Yuan Chen, Fan-Chi Chang, Yi-Ting Chen, Wen-Chih Chiang, Hsing-Chen Tsai, Yung-Ming Chen, Shuei-Liong Lin
Summary: This study found that C3H10T1/2 cells possess the property of HIF2 alpha-dependent Epo expression, and TGF-beta 1 induces both myofibroblast transition and a repressive effect on the Epas1-Epo axis in these cells. The repressive effect of TGF-beta 1 on the Epas1-Epo axis was also confirmed in REP pericytes in vivo, suggesting that inhibition of TGF-beta 1-ALK5 signaling could be a novel treatment approach to rescue EPO expression in REP pericytes of injured kidneys.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Review
Cell Biology
Yirui Shao, Kexing Wang, Xia Xiong, Hongnan Liu, Jian Zhou, Lijun Zou, Ming Qi, Gang Liu, Ruilin Huang, Zhiliang Tan, Yulong Yin
Summary: The gastrointestinal tract is susceptible to oxidative damage from high levels of reactive oxygen species, which can disrupt essential biomolecules. Hypoxia-inducible factors play a critical role in mediating responses to changes in cellular oxygen tension and are involved in various processes in the gastrointestinal tract. Understanding the interactions between HIF and ROS may lead to the development of new therapies for gastrointestinal diseases associated with oxidative stress and HIF-1 alpha.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Review
Pharmacology & Pharmacy
Baoqi Yu, Xia Wang, Yanting Song, Guomin Xie, Shiyu Jiao, Li Shi, Xuejie Cao, Xinyao Han, Aijuan Qu
Summary: Cardiovascular diseases are the leading cause of death worldwide, and hypoxia-inducible factors (HIFs) play an important role in their pathogenesis. Recent studies have revealed the role of cell-specific HIFs in various cardiovascular diseases, but the potential clinical application of HIF inhibitors in the treatment of cardiovascular diseases is not well understood.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Physiology
Jing Gao, Junfei Zhu, Yuwei Zhao, Xueqi Gan, Haiyang Yu
Summary: Hypoxia induces apoptosis and leptin expression in hPDLCs through ROS and HIF-1 alpha pathways, with leptin showing feedback inhibition on ROS-mediated apoptosis. Leptin may have a new application in protecting against hypoxic damage in periodontal diseases.
EXPERIMENTAL PHYSIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
David Mate Csiki, Haneen Ababneh, Andrea Toth, Greta Lente, Arpad Szoor, Anna Toth, Csaba Filler, Tamas Juhasz, Bela Nagy, Eniko Balogh, Viktoria Jeney
Summary: Valve calcification (VC) is a common complication in chronic kidney disease (CKD) patients. In this study, the role of hypoxia inducible factor (HIF) activation in VC and osteogenic transition of valve interstitial cells (VICs) was examined. HIF activation promotes VC and Pi-induced calcification of VICs through increased ROS production and cell death.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Jinwook Chung, Md Nazmul Huda, Yoonhwa Shin, Sunhee Han, Salima Akter, Insug Kang, Joohun Ha, Wonchae Choe, Tae Gyu Choi, Sung Soo Kim
Summary: The interaction between reactive oxygen species (ROS) and transforming growth factor-beta (TGF-beta) signaling pathway plays a critical role in tumor development and progression. While ROS can influence TGF-beta signaling, the TGF-beta pathway can regulate ROS production, leading to a complex relationship between the two in cancer cells. Understanding this crosstalk may provide new insights and potential approaches in cancer biology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yukino Kobayashi, Ami Oguro, Susumu Imaoka
Summary: This study revealed that prolonged hypoxia increases cellular ROS levels, leading to the induction of HIF-1α regulators PHD2 and FIH-1. Cellular stress response enhances HIF-1α transcriptional activity by scavenging ROS, while Ref-1, regulated by ROS, plays a crucial role in HIF-1α activation and subsequent regulation of PHD2 and FIH-1.
FREE RADICAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Fabiola Carrara, Piero Ruggenenti, Annalisa Perna, Ilian Petrov Iliev, Flavio Gaspari, Silvia Ferrari, Nadia Stucchi, Antonio Bossi, Roberto Trevisan, Giuseppe Remuzzi, Aneliya Parvanova
Summary: The study aimed to investigate the prediction of glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients by examining changes in glomerular hemodynamic parameters. Results showed that an increased Ra/Re ratio and longer duration of arterial hypertension were independently associated with GFR decline. These findings suggest that glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing play a role in early GFR decline in this patient population.
ACTA DIABETOLOGICA
(2022)
Review
Immunology
Erica Daina, Monica Cortinovis, Giuseppe Remuzzi
Summary: Dysregulation and accelerated activation of the alternative pathway of complement play important roles in kidney diseases, and complement-directed therapies have shown potential for treatment. Although there have been successful cases, incorporating these therapies into clinical practice still faces challenges.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Endocrinology & Metabolism
Aneliya Parvanova, Manuela Abbate, Aina Maria Yanez, Miquel Bennasar-Veny, Angel Arturo Lopez-Gonzalez, Jose Ignacio Ramirez-Manent, Ilian Petrov Iliev, Sergio Fresneda, Maria Arias-Fernandez, Giuseppe Remuzzi, Piero Ruggenenti
Summary: This study investigated the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in prediabetes, visceral obesity, and preserved kidney function, and explored the association between MAFLD and hyperfiltration. It was found that MAFLD was more frequent in hyperfiltering subjects and was independently associated with hyperfiltration, as well as potentiated the age-related decline in estimated glomerular filtration rate (eGFR).
DIABETES RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Piera Trionfini, Elena Romano, Marco Varinelli, Lorena Longaretti, Paola Rizzo, Roberta Giampietro, Annalina Caroli, Sistiana Aiello, Marta Todeschini, Federica Casiraghi, Giuseppe Remuzzi, Ariela Benigni, Susanna Tomasoni
Summary: Induced pluripotent stem cells (iPSC) have the potential for cell therapy due to their self-renewal and differentiation capabilities. However, the high production costs and limited use for acute conditions hinder their applications. An allogeneic iPSC-based strategy may overcome these issues, but immune rejection is a concern. In this study, CRISPR/Cas9 was used to create hypoimmunogenic iPSCs that can differentiate into liver cells, providing a cost-effective and off-the-shelf opportunity for liver disease cell therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Norberto Perico, Giuseppe Remuzzi, Matthew D. Griffin, Paul Cockwell, Alexander P. Maxwell, Federica Casiraghi, Nadia Rubis, Tobia Peracchi, Alessandro Villa, Marta Todeschini, Fabiola Carrara, Bernadette A. Magee, Piero L. Ruggenenti, Stefano Rota, Laura Cappelletti, Veronica Mcinerney, Tomas P. Griffin, Md Nahidul Islam, Martino Introna, Olga Pedrini, Josee Golay, Andrew A. Finnerty, Jon Smythe, Willem E. Fibbe, Stephen J. Elliman, Timothy O'Brien, NEPHSTROM Trial Consortium
Summary: The NEPHSTROM study evaluates the safety, tolerability, and preliminary efficacy of ORBCEL-M cell therapy in adults with type 2 diabetes and progressive diabetic kidney disease. The results show that ORBCEL-M cell therapy is safe and well-tolerated in the lowest dose cohort, and significantly reduces the decline rate of eGFR over 18 months.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
Anna Pezzotta, Luca Perico, Daniela Corna, Marina Morigi, Giuseppe Remuzzi, Ariela Benigni, Barbara Imberti
Summary: SIRT3 plays a crucial regulatory role in the kidney, and its dysregulation may lead to vascular dysfunction and progression of kidney disease. In the presence of nephrotoxic stimulus, Sirt3-deficient mice exhibit aggravated endothelial rarefaction and oxidative stress, resulting in more severe kidney injury.
Article
Medicine, General & Internal
Damiano Baldassarre, Licia Iacoviello, Roberta Baetta, Maria Carla Roncaglioni, Gianluigi Condorelli, Giuseppe Remuzzi, Gianfranco Gensini, Luigi Frati, Walter Ricciardi, Pier Giulio Conaldi, Antonio Uccelli, Fabio Blandini, Silvano Bosari, Giovanni Scambia, Massimo Fini, Antonio Di Malta, Mauro Amato, Fabrizio Veglia, Alice Bonomi, Catherine Klersy, Francesca Colazzo, Martino Pengo, Francesca Gorini, Luciana Auteri, Giuseppe Ferrante, Marta Baviera, Giuseppe Ambrosio, Alberico Catapano, Alessandro Gialluisi, Alexis Elias Malavazos, Serenella Castelvecchio, Massimiliano Marco Corsi-Romanelli, Rosanna Cardani, Maria Teresa La Rovere, Valentina Agnese, Bianca Pane, Daniele Prati, Laura Spinardi, Giovanna Liuzzo, Eloisa Arbustini, Maurizio Volterrani, Marco Visconti, Jose Pablo Werba, Stefano Genovese, Grzegorz Bilo, Cecilia Invitti, Anna Di Blasio, Carolina Lombardi, Andrea Faini, Debora Rosa, Luisa Ojeda-Fernandez, Andreana Foresta, Amalia De Curtis, Augusto Di Castelnuovo, Simonetta Scalvini, Antonia Pierobon, Alessandra Gorini, Luca Valenti, Livio Luzi, Annarosa Racca, Manuela Bandi, Elena Tremoli, Lorenzo Menicanti, Gianfranco Parati, Giulio Pompilio
Summary: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial aiming to compare the effectiveness of an educational and motivational mobile health intervention with usual care in reducing cardiovascular risk. The trial plans to enrol approximately 80,000 subjects without overt cardiovascular diseases and evaluate the short-term endpoints, as well as conduct a long-term follow-up to assess the incidence of major adverse cardiovascular events.
Editorial Material
Surgery
Giuseppe Remuzzi
UPDATES IN SURGERY
(2023)
Article
Multidisciplinary Sciences
Angelo M. Lavecchia, Polyxeni Mantzouratou, Domenico Cerullo, Monica Locatelli, Sara Conti, Matteo Tironi, Fabio Sangalli, Daniela Corna, Carlamaria Zoja, Giuseppe Remuzzi, Christodoulos Xinaris
Summary: Research shows that activation of thyroid hormone (TH) signaling can counteract cellular remodeling and pathological alterations caused by diabetes, providing a potential approach for the treatment of diabetes and its complications.
Article
Radiology, Nuclear Medicine & Medical Imaging
Anna Caroli, Giulia Villa, Paolo Brambilla, Matias Trillini, Kanishka Sharma, Sandro Sironi, Giuseppe Remuzzi, Norberto Perico, Andrea Remuzzi
Summary: This study presents and validates a diffusion MRI (DWI)-based method for quantifying total kidney and cyst volume (TCV) and characterizing non-cystic tissue microstructure in autosomal dominant polycystic kidney disease (ADPKD). DWI shows potential in ADPKD to assess and predict disease progression, evaluate the impact of novel therapies, and identify microcysts and peritubular interstitial fibrosis in non-cystic kidney tissue.
EUROPEAN RADIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Federica Casiraghi, Marta Todeschini, Manuel Alfredo Podesta, Marilena Mister, Barbara Ruggiero, Matias Trillini, Camillo Carrara, Olimpia Diadei, Alessandro Villa, Ariela Benigni, Giuseppe Remuzzi
Summary: Immune dysregulation plays a key role in the pathogenesis of steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS). However, no major B- or T-cell alterations have been described for adults, unlike in pediatric cases. This study found that patients with SDNS/FRNS have expansion of memory B cells and reduced memory Tregs. The levels of CD45RO(+) Tregs at baseline may help predict which patients will achieve sustained remission following rituximab infusion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Monica Locatelli, Daniela Rottoli, Rayan Mahmoud, Mauro Abbate, Daniela Corna, Domenico Cerullo, Susanna Tomasoni, Giuseppe Remuzzi, Carlamaria Zoja, Ariela Benigni, Daniela Macconi
Summary: In BTBR ob/ob mice with type 2 diabetic nephropathy, peritubular capillaries show endothelial cell abnormalities and basement membrane thickening. Remodeling and focal loss of the endothelial glycocalyx were observed in diabetic kidneys, and ACEi treatment preserved the glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Primary Health Care
Livio Garattini, Michela Bozzetto, Giuseppe Remuzzi, Nick Freemantle, Alessandro Nobili
