Article
Biology
Angelo Ferreira Chora, Dora Pedroso, Eleni Kyriakou, Nadja Pejanovic, Henrique Colaco, Raffaella Gozzelino, Andre Barros, Katharina Willmann, Tiago Velho, Catarina F. Moita, Isa Santos, Pedro Pereira, Silvia Carvalho, Filipa Batalha Martins, Joao A. Ferreira, Sergio Fernandes de Almeida, Vladimir Benes, Josef Anrather, Sebastian Weis, Miguel P. Soares, Arie Geerlof, Jacques Neefjes, Michael Sattler, Ana C. Messias, Ana Neves-Costa, Luis Ferreira Moita, Yousef Abu-Amer
Summary: Anthracyclines, a class of commonly used and effective anticancer drugs, were found to decrease the transcription of NF-kappa B-dependent gene targets and disturb the complexes formed between NF-kappa B subunit RelA and its DNA-binding sites. The anthracycline variants without inducing DNA damage also suppressed inflammation, which has implications for cancer therapy and the development of anti-inflammatory drugs with limited side effects.
Article
Biochemistry & Molecular Biology
Sidneia Sousa Santos, Milena Karina Colo Brunialti, Larissa de Oliveira Cavalcanti Peres Rodrigues, Ana Maria Alvim Liberatore, Ivan Hong Jun Koh, Vanessa Martins, Francisco Garcia Soriano, Csaba Szabo, Reinaldo Salomao
Summary: This study evaluated the effects of the PARP1 inhibitor olaparib on white blood cells from healthy volunteers in response to various challenges, showing that olaparib has cytoprotective effects, reduces inflammatory cytokine production, and does not inhibit the cells' ability to phagocytose or eradicate pathogens.
Article
Biochemistry & Molecular Biology
Andrea Holickova, Jan Roska, Eveline Orasova, Vladimira Bruderova, Patrik Palacka, Dana Jurkovicova, Miroslav Chovanec
Summary: Cisplatin-based chemotherapy is commonly used for muscle-invasive bladder cancer, but many cases develop resistance or do not respond. This study found that the response to cisplatin in urothelial carcinoma cells is dependent on DNA damage repair and tolerance factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Lin Wu, James R. Sowers, Yingmei Zhang, Jun Ren
Summary: Cardiovascular diseases (CVDs) are caused by abnormalities in the genomic, proteomic, and metabolomic aspects. Recent evidence has confirmed the presence of DNA damage in various CVDs. DNA damage triggers a cellular response called DNA damage response (DDR), which can be beneficial for cardiovascular function temporarily, but persistent activation of DDR promotes the onset and development of CVDs. Therefore, targeting DNA damage and DDR could potentially improve cardiovascular dysfunction and disease outcome.
CARDIOVASCULAR RESEARCH
(2023)
Article
Multidisciplinary Sciences
Tengfei Wang, Shuxiang Shi, Yuanyuan Shi, Peipei Jiang, Ganlu Hu, Qinying Ye, Zhan Shi, Kexin Yu, Chenguang Wang, Guoping Fan, Suwen Zhao, Hanhui Ma, Alex C. Y. Chang, Zhi Li, Qian Bian, Chao-Po Lin
Summary: Chemotherapeutic drug adriamycin induces visible local condensation and global conformational change of chromatin, leading to weakened chromatin interaction, lower chromatin accessibility, and transcriptomic changes. Mechanistically, adriamycin complexes with histone H1 and induces phase transition of H1. This study reveals a phase separation-driven mechanism for the chemotherapeutic drug.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Thomas A. Guilliam, Joseph T. P. Yeeles
Summary: The study shows that a yeast replisome is inherently tolerant to the oxidative lesion Tg, efficiently bypassing leading-strand Tg even in the absence of TLS machinery. A switch from Pol epsilon to Pol delta after helicase-polymerase uncoupling promotes rapid, efficient, and error-free lesion bypass at physiological nucleotide levels. Replicase switching may facilitate continued leading-strand synthesis when Pol delta is more effective at bypassing damage than Pol epsilon.
Article
Obstetrics & Gynecology
Kashmira Bane, Junita Desouza, Diksha Shetty, Prakash Choudhary, Shalaka Kadam, R. R. Katkam, Gwendolyn Fernandes, Raj Sawant, Uddhavraj Dudhedia, Neeta Warty, Anahita Chauhan, Uddhav Chaudhari, Rahul Gajbhiye, Geetanjali Sachdeva
Summary: The study indicates that the DNA damage response is dysregulated in the eutopic endometrium of women with endometriosis, with higher expression of DDR genes compared to those without the disease. Additionally, DNA repair genes are also up-regulated in the eutopic endometrium of women with endometriosis.
HUMAN REPRODUCTION
(2021)
Review
Biochemistry & Molecular Biology
Dana Jurkovicova, Christiana M. Neophytou, Ana Cipak Gasparovic, Ana Cristina Goncalves
Summary: Resistance to chemo- and radiotherapy is a common occurrence in cancer patients, necessitating the continuous investigation and development of new cancer therapies. The DNA damage response (DDR) plays a crucial role in maintaining genomic stability, but defects in DDR machinery are associated with different types of cancers. Current developments include the use of poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) as DDR inhibitors (DDRi) for various cancers. However, resistance to DDRi, including PARP inhibitors, is becoming a growing concern in clinical settings. This review highlights the importance of DDR pathways in cancer therapy, its role in treatment resistance, and its potential for anticancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Chenyao Wang, Jing Nan, Elise Holvey-Bates, Xing Chen, Samantha Wightman, Muhammad-Bilal Latif, Junjie Zhao, Xiaoxia Li, Ganes C. Sen, George R. Stark, Yuxin Wang
Summary: In cancer cells, the abnormal presence of DNA in the cytoplasm activates cGAS and STING. STAT2 inhibits the expression of IRF3-dependent genes induced by cGAMP by binding to STING and blocking its intracellular trafficking. STAT2 reshapes STING signaling by inhibiting IRF3-dependent gene induction, but not NF-xB-dependent gene induction. This noncanonical activity of STAT2 depends on the phosphorylation of threonine 404, which promotes the formation of a STAT2:STING complex that keeps STING bound to the endoplasmic reticulum (ER) and increases resistance to DNA damage.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Genetics & Heredity
Yongxin Li, Yan Tong, Jiaqi Liu, Jianlin Lou
Summary: DNA is crucial for organism development and function. MiRNA, a type of non-coding RNA, may play an important role in the DNA damage response by influencing processes like cell cycle, DNA repair, and apoptosis, thereby impacting genomic stability and tumorigenesis.
FRONTIERS IN GENETICS
(2022)
Article
Plant Sciences
Ivanthi Kumasaruge, Rui Wen, Lipu Wang, Peng Gao, Gary Peng, Wei Xiao
Summary: This study reports the identification and functional characterization of 12 Brassica napus UBC13 genes. These genes can physically interact with the Arabidopsis UEV AtUev1D to form stable complexes that can catalyze K63-linked polyubiquitination in vitro. In addition, BnUBC13 genes can complement the yeast ubc13 null mutant defects, suggesting their role in mediating K63-linked polyubiquitination and error-free DNA-damage tolerance.
Review
Biochemistry & Molecular Biology
Xiaobing Qing, Guangyu Zhang, Zhao-Qi Wang
Summary: The central nervous system is highly susceptible to DNA repair deficiency, leading to various neurodevelopmental and neurodegenerative disorders. While there are gaps in our understanding of the mechanisms and specificity of DNA damage and repair in neural development and homeostasis, recent studies have identified significant findings in this field.
Article
Multidisciplinary Sciences
Olimpia Alessandra Buoninfante, Bas Pilzecker, Aldo Spanjaard, Daniel de Groot, Stefan Prekovic, Ji-Ying Song, Cor Lieftink, Matilda Ayidah, Colin E. J. Pritchard, Judith Vivie, Kathleen E. Mcgrath, Ivo J. Huijbers, Sjaak Philipsen, Marieke von Lindern, Wilbert Zwart, Roderick L. Beijersbergen, James Palish, Paul C. M. van den Berk, Heinz Jacobs
Summary: DNA damage poses a threat to genomic integrity and leads to stem cell failure. Cells use DNA damage tolerance (DDT), regulated by PCNA ubiquitination and REV1, to bypass genotoxic lesions during replication. While DDT is conserved in all domains of life, its relevance in mammals has been unclear. Our study demonstrates that inactivation of both PCNA ubiquitination and REV1 results in embryonic and adult lethality, as well as accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) which ultimately leads to their depletion. This highlights the crucial importance of DDT in the maintenance of stem cell compartments and mammalian life under unperturbed conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Linke Tang, Weifeng Yuan, Shitao Li, Xiuyan Ding, Liqian Zhu
Summary: In this study, the interaction between UV-primed global DDR and BoHV-1 productive infection was demonstrated. UV-primed global DDR differentially modulated the transcription of virus genes and stabilization of virus protein. Vice versa, the virus infection may affect UV-primed DDR signaling.
Review
Oncology
Caroline Molinaro, Alain Martoriati, Katia Cailliau
Summary: Cells respond to genotoxic stress through complex protein pathways called DNA damage response (DDR), ensuring genomic integrity and activating processes like DNA repair, cell cycle regulation, and programmed cell death. Alterations in DDR network proteins can lead to various diseases, including cancer. Recent technological advancements have allowed for the exploitation of DDR vulnerabilities to improve cancer treatments through DNA damage strategies and combination therapies.
Article
Immunology
Waqar M. Ahmed, Dominic Fenn, Iain R. White, Breanna Dixon, Tamara M. E. Nijsen, Hugo H. Knobel, Paul Brinkman, Pouline M. P. Van Oort, Marcus J. Schultz, Paul Dark, Royston Goodacre, Timothy Felton, Lieuwe D. J. Bos, Stephen J. Fowler
Summary: Microbial volatiles were detected in the exhaled breath of mechanically ventilated patients with bacterial lung infection. Concentration of isovaleric acid and isovaleraldehyde were higher in patients with Staphylococcus aureus. Indole was higher in patients with bacteria known to metabolize tryptophan.
CLINICAL INFECTIOUS DISEASES
(2023)
Editorial Material
Obstetrics & Gynecology
Joana Seabra, Andre Silva, Isa Santos, Joana Almeida, Lucia Correia, Margarida Correia
Summary: Retroperitoneal recurrence after excision of a juvenile granulosa cell tumor is rare and can mimic other conditions with nonspecific symptoms.
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
(2023)
Article
Critical Care Medicine
Tai Pham, Leo Heunks, Giacomo Bellani, Fabiana Madotto, Irene Aragao, Gaetan Beduneau, Ewan C. Goligher, Giacomo Grasselli, Jon Henrik Laake, Jordi Mancebo, Oscar Penuelas, Lise Piquilloud, Antonio Pesenti, Hannah Wunsch, Frank van Haren, Laurent Brochard, John G. Laffey
Summary: This study investigated the management and outcomes of weaning from invasive mechanical ventilation in patients requiring at least 2 days of ventilation. The results showed that only 65% of patients were successfully weaned at 90 days. Factors such as delayed initiation of weaning and excessive sedation levels were associated with weaning failure. Understanding these factors could improve the success rate of weaning.
LANCET RESPIRATORY MEDICINE
(2023)
Article
Engineering, Biomedical
Neel Shah, Bing Xue, Ziqi Xu, Hanqing Yang, Eva Marwali, Heidi Dalton, Philip P. R. Payne, Chenyang S. Lu, Ahmed Said
Summary: In this study, several ECMO mortality prediction and severity of illness scores were validated for a large COVID-19 V-V ECMO cohort. The results showed inconsistent discrimination and calibration of these scores, highlighting the need for better clinically applicable decision support tools.
Letter
Critical Care Medicine
Ignacio Martin-Loeches, Pedro Povoa, Saad Nseir
INTENSIVE CARE MEDICINE
(2023)
Article
Critical Care Medicine
Alexis Tabah, Niccolo Buetti, Quentin Staiquly, Stephane Ruckly, Murat Akova, Abdullah Tarik Aslan, Marc Leone, Andrew Conway Morris, Matteo Bassetti, Kostoula Arvaniti, Jeffrey Lipman, Ricard Ferrer, Haibo Qiu, Jose-Artur Paiva, Pedro Povoa, Liesbet De Bus, Jan De Waele, Farid Zand, Mohan Gurjar, Adel Alsisi, Khalid Abidi, Hendrik Bracht, Yoshiro Hayashi, Kyeongman Jeon, Muhammed Elhadi, Francois Barbier, Jean-Francois Timsit
Summary: This study investigated hospital-acquired bloodstream infections (HA-BSI) in 2600 adult patients from 333 ICUs in 52 countries. HA-BSI were frequently caused by Gram-negative, carbapenem-resistant, and difficult-to-treat pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy, resulting in high mortality rates.
INTENSIVE CARE MEDICINE
(2023)
Editorial Material
Critical Care Medicine
Ignacio Martin-Loeches, Pedro Povoa, Saad Nseir
INTENSIVE CARE MEDICINE
(2023)
Editorial Material
Critical Care Medicine
Pedro Povoa, Saad Nseir, Jorge Salluh
INTENSIVE CARE MEDICINE
(2023)
Article
Multidisciplinary Sciences
Luis Coelho, Fatima Falcao, Pedro Povoa, Erica Viegas, Antonio Pais Martins, Eduarda Carmo, Candida Fonseca, Luis Campos, Kamal Mansinho, Ines Carmo, Joana Soares, Mariana Solano, Dina Mendes, Ana Claudia Miranda, Antonio Carvalho, Ana Mirco, Helena Farinha, Isabel Aldir, Jose Correia
Summary: This study aimed to assess the effectiveness of remdesivir with and without corticosteroids in treating COVID-19 patients. The study found that patients treated with remdesivir alone had a shorter time to recovery and a shorter length of hospital stay compared to those treated with remdesivir and corticosteroids. However, the use of corticosteroids as adjunctive therapy did not improve the mortality of COVID-19 patients.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Nursing
Goncalo Guerreiro, Pedro Povoa
INTENSIVE AND CRITICAL CARE NURSING
(2023)
Article
Medicine, General & Internal
Jose Pedro Cidade, Vicente Ces de Souza Dantas, Alessandra de Figueiredo Thompson, Renata Carnevale Carneiro Chermont de Miranda, Rafaela Mamfrim, Henrique Caroli, Gabriela Escudini, Natalia Oliveira, Taiza Castro, Pedro Povoa
Summary: This study conducted a multicenter prospective cohort study in five hospitals in Portugal and Brazil for one year, and identified three distinct clinical phenotypes of severe COVID-19 patients with different characteristics and outcomes. Identifying and differentiating these phenotypes can help physicians develop different treatment strategies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Medicine, General & Internal
Rachael Cusack, Lieuwe D. Bos, Pedro Povoa, Ignacio Martin-Loeches
Summary: Acute respiratory distress syndrome (ARDS) is a severe organ failure mainly occurring in critically ill patients due to various insults such as sepsis, trauma, or aspiration. Sepsis is the leading cause of ARDS, resulting in high mortality and resource consumption. ARDS is characterized by acute respiratory failure with severe and often refractory hypoxemia. Endothelial damage plays a crucial role in the development of ARDS. Understanding the mechanisms of ARDS provides opportunities for novel diagnostic and therapeutic approaches. Biochemical signals can be utilized to identify and classify patients into ARDS phenotypes, enabling earlier personalized treatment.
FRONTIERS IN MEDICINE
(2023)
Article
Critical Care Medicine
Carl Thomas Anthon, Frederic Pene, Anders Perner, Elie Azoulay, Kathryn Puxty, Andry van de Louw, Andreas Barratt-Due, Sanjay Chawla, Pedro Castro, Pedro Povoa, Luis Coelho, Victoria Metaxa, Matthias Kochanek, Tobias Liebregts, Thomas Kander, Johanna Hastbacka, Jo Bonding Andreasen, Edwige Peju, Lene Bjerregaard Nielsen, Christine Lodberg Hvas, Etienne Dufranc, Emmanuel Canet, Linda Lundqvist, Christopher John Wright, Julien Schmidt, Fabrice Uhel, Hafid Ait-Oufella, Mette Krag, Elisabet Cos Badia, Candido Diaz-Lagares, Sophie Menat, Guillaume Voiriot, Niels Erikstrup Clausen, Kristian Lorentzen, Reidar Kvale, Thomas Hildebrandt, Aleksander Rygh Holten, Kristian Strand, Asterios Tzalavras, Morten Heiberg Bestle, Pal Klepstad, Sara Fernandez, Damien Vimpere, Carolina Paulino, Carina Graca, Catherina Lueck, Christian Svendsen Juhl, Carolina Costa, Per Martin Badstolokken, Teresa Miranda, Lia Susana Aires Ledo, Joao Carlos Sousa Torres, Anders Granholm, Morten Hylander Moller, Lene Russell
Summary: Thrombocytopenia is common in ICU patients and is associated with worse outcomes, including increased mortality. In this study, 43.2% of ICU patients had thrombocytopenia, with 23.4% presenting at ICU admission and 19.8% developing it during their ICU stay. Prophylactic platelet transfusions were given to 22.6% of thrombocytopenic patients.
INTENSIVE CARE MEDICINE
(2023)
Review
Medicine, General & Internal
Luis Coelho, Patricia Moniz, Goncalo Guerreiro, Pedro Povoa
Summary: Ventilator-associated pneumonia (VAP) is a common ICU-acquired infection in mechanically ventilated patients. It has various negative impacts such as prolonged duration of mechanical ventilation, increased antibiotic consumption, morbidity, and mortality. Preventing VAP is a priority for the intensive care team, and the use of specialized airways and devices can help reduce its incidence, although their effectiveness is still debated.
MEDICINA-LITHUANIA
(2023)
Article
Medicine, Research & Experimental
Olav Sivertsen Garvik, Pedro Povoa, Pernille Just Vinholt, Stig Lonberg Nielsen, Thoger Gorm Jensen, Henrik Frederiksen, Ming Chen, Ram Benny Dessau, John Eugenio Coia, Jens Kjolseth Moller, Kim Oren Gradel
Summary: The study developed four algorithms for automatic capture of C-reactive protein peaks in patients with acute myeloid leukemia, which detected CRP peaks for BSI episodes and negative blood cultures with high accuracy. The automatic capture of CRP peaks can serve as a tool for monitoring BSI episodes and other infections in these patients.
BIOMARKERS IN MEDICINE
(2023)