Article
Biochemistry & Molecular Biology
Emily A. Hull-Ryde, John T. Minges, Mary E. B. Martino, Takafumi Kato, Jacqueline L. Norris-Drouin, Carla M. P. Ribeiro
Summary: Studies have shown that the endoplasmic reticulum stress transducer IRE1 alpha plays a role in mediating cytokine production in CF airway inflammation, and inhibition of IRE1 alpha kinase and RNase may reduce cytokine production. This finding suggests that small molecule IRE1 alpha kinase inhibitors could be a novel therapeutic approach for CF airway inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sonia Zacarias, Marta S. P. Batista, Sofia S. Ramalho, Bruno L. Victor, Carlos M. Farinha
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. The approval of modulators that act on mutant CFTR protein, correcting its molecular defect and thus alleviating the burden of the disease, revolutionized the field of CF. However, these drugs do not apply to all patients with CF, especially those with rare mutations. In this study, the impact of rare mutations on CFTR expression, processing, and response to modulators was evaluated, and it was found that mutations in different locations have different effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Dan Qiao, Ziwei Zhang, Yali Zhang, Qian Chen, Yujun Chen, Yingjue Tang, Xiong Sun, Zhipeng Tang, Yancheng Dai
Summary: Ulcerative colitis is a chronic inflammatory disease, and endoplasmic reticular stress-induced autophagy plays a crucial role in its pathogenesis. Dysregulated autophagy can lead to inflammation and disruption of the intestinal barrier, increasing the risk of colonic diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Renata Esposito, Davida Mirra, Giuseppe Spaziano, Francesca Panico, Luca Gallelli, Bruno D'Agostino
Summary: Cystic fibrosis (CF) is a prevalent disease with significant lung remodeling and high morbidity and mortality worldwide. Imbalance of proteases and antiproteases, particularly matrix metalloproteases (MMPs), plays a role in CF pathogenesis. While CFTR modulator therapy has shown efficacy in most CF patients, alternative experimental drugs and targeting MMPs are being explored for non-responder patients.
Review
Cell Biology
Pascal Trouve, Claude Ferec, Emmanuelle Genin
Summary: The most common mutation in cystic fibrosis is p.Phe508del in the CFTR gene, leading to retention and rapid degradation of CFTR protein in the endoplasmic reticulum, triggering an atypical Unfolded Protein Response (UPR). There is still debate on the role of UPR in CF, whether it is triggered by accumulation of misfolded CFTR proteins or as a result of inflammation and infection in the disease.
Article
Cell Biology
Asmahan Abu-Arish, Elvis Pandzic, Yishan Luo, Yukiko Sato, Mark J. Turner, Paul W. Wiseman, John W. Hanrahan
Summary: This study found that the clustering of cystic fibrosis transmembrane conductance regulator (CFTR) in the cell membrane does not involve specific protein interactions, but critically depends on membrane lipid order and can be rescued by CFTR modulators.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Melissa Iazzi, Audrey Astori, Jonathan St-Germain, Brian Raught, Gagan D. Gupta
Summary: Deletion of phenylalanine 508 (increment F508) of the CFTR protein is the main cause of CF. This study analyzed the CFTR and increment F508-CFTR interactomes using BioID, and identified known and novel protein interactions. The increment F508 interactome showed significant differences compared to the wild type, with alterations in membrane trafficking and cellular stress functions. Drug therapy also affected the interactome, and depletion of specific interactors impacted CFTR functionality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Isabelle Fajac, Isabelle Sermet
Summary: Cystic fibrosis is a severe genetic disorder caused by mutations in the CFTR gene. New drugs called CFTR modulators aim to restore the function of the CFTR protein, but some patients with rare mutations are not yet eligible for this treatment. Various approaches are being pursued to expand the range of mutations eligible for CFTR modulators and develop new therapies for mutations that do not produce CFTR protein.
Review
Biochemistry & Molecular Biology
Jia-Huang Chen, Chia-Hsien Wu, Chih-Kang Chiang
Summary: ER stress is a trigger for the development of many kidney diseases, and unfolded protein responses (UPRs) play a role in restoring protein homeostasis under this stress. Modulating UPRs and ER proteostasis may have therapeutic potential for kidney diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sofia S. Ramalho, Iris A. L. Silva, Margarida D. Amaral, Carlos M. Farinha
Summary: This study characterized the defects associated with four rare CFTR variants and assessed their response to approved corrector drugs. The results showed that these variants belonged to Class II mutations and had different responses to the corrector drugs, highlighting the need for personalized drug discovery initiatives.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Review
Biochemistry & Molecular Biology
Ilaria Cela, Beatrice Dufrusine, Claudia Rossi, Alberto Luini, Vincenzo De Laurenzi, Luca Federici, Michele Sallese
Summary: KDELRs are ubiquitous receptors involved in cell quality control and stress responses. Mutations in KDELRs are associated with various diseases, making them potential therapeutic targets.
Article
Gastroenterology & Hepatology
Murali K. Yanda, Vartika Tomar, Liudmila Cebotaru
Summary: ARPKD is caused by mutations in the PKHD1 gene, leading to severe complications in neonates. Research shows that FPC malfunction induces cyst formation, and CFTR correctors may be a potential treatment for ARPKD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Giulia Gorrieri, Federico Zara, Paolo Scudieri
Summary: SLC26A9, a member of the solute carrier family 26 (SLC26), is involved in ion transport mechanisms. It has emerged as one of the interesting alternative targets for cystic fibrosis (CF) treatment, although there are still controversies regarding its contribution and potential. This review summarizes various studies related to SLC26A9, aiming to reconcile them and highlight the current understanding and knowledge gap regarding its role in human lung physiology and CF treatment.
Article
Multidisciplinary Sciences
Loes M. Stevers, Madita Wolter, Graeme W. Carlile, Dwight Macdonald, Luc Richard, Frank Gielkens, John W. Hanrahan, David Y. Thomas, Sai Kumar Chakka, Mark L. Peterson, Helmut Thomas, Luc Brunsveld, Christian Ottmann
Summary: This study identified a macrocycle compound that stabilizes the interaction between mutant CFTR and the chaperone-like protein 14-3-3, rescuing its biological function.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Sofia B. Carvalho, Ricardo A. Gomes, Anja Pfenninger, Martina Fischer, Michaela Strotbek, Ines A. Isidro, Nihal Tugcu, Patricia Gomes-Alves
Summary: As the requirements of regulatory agencies for the quality of biopharmaceuticals increase, the use of mass spectrometry-based methods such as the multi-attribute method (MAM) has become a valuable tool for quality control. MAM allows for the direct and simultaneous monitoring of critical product quality attributes using high-quality mass spectrometry data, replacing traditional orthogonal methods and reducing time and costs. This article describes the implementation of MAM using a QTOF high-resolution platform and discusses sample preparation and LC-MS parameters troubleshooting for batch analysis and high-throughput applications.
Review
Biochemical Research Methods
Jose M. Escandell, Daniel Am Pais, Sofia B. Carvalho, Karen Vincent, Patricia Gomes-Alves, Paula M. Alves
Summary: This article discusses the R&D needs and Chemistry, Manufacturing and Control (CMC) efforts required for the growing demand of recombinant adeno-associated (rAAV) vector-based gene therapy. The key aspects mentioned include scalability and productivity improvement, enhanced safety, and increased process understanding along with the development of orthogonal bioanalytics for identifying, monitoring, and controlling Critical Quality Attributes (CQAs) during bioprocessing.
CURRENT OPINION IN BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Ana F. Louro, Marta A. Paiva, Marta R. Oliveira, Katharina A. Kasper, Paula M. Alves, Patricia Gomes-Alves, Margarida Serra
Summary: This study isolated extracellular vesicles (EV) from key stages of human induced pluripotent stem cell-cardiomyocyte differentiation and identified hiPSC as a promising cell biofactory for EV production. The findings demonstrate that hiPSC-EV have pro-angiogenic and pro-proliferative properties, suggesting their potential in cardiac regenerative applications.
Article
Pharmacology & Pharmacy
Barbara Fernandes, Rute Castro, Farien Bhoelan, Denzel Bemelman, Ricardo A. Gomes, Julia Costa, Patricia Gomes-Alves, Toon Stegmann, Mario Amacker, Paula M. Alves, Sylvain Fleury, Antonio Roldao
Summary: This study developed a scalable bioprocess using the insect cells-baculovirus expression vector system (IC-BEVS) to produce high-quality S protein. The insect cell-derived S protein exhibited glycan processing similar to mammalian cells and mid-term stability upon storage. The results demonstrate the potential of using IC-BEVS to produce the highly glycosylated S protein for a virosome-based COVID-19 vaccine candidate.
Article
Neurosciences
Ana Chegao, Mariana Guarda, Bruno M. Alexandre, Liana Shvachiy, Mariana Temido-Ferreira, Ines Marques-Morgado, Barbara Fernandes Gomes, Rune Matthiesen, Luisa V. Lopes, Pedro R. Florindo, Ricardo A. Gomes, Patricia Gomes-Alves, Joana E. Coelho, Tiago Fleming Outeiro, Hugo Vicente Miranda
Summary: This study found that MGO-induced glycation accelerates PD-like sensorimotor and cognitive alterations and increases the accumulation of α-synuclein in the brain. In addition, the study also found that MGO mainly affects glutamatergic signaling in the midbrain, which may be associated with PD and dopaminergic pathways.
NPJ PARKINSONS DISEASE
(2022)
Article
Physiology
Ana F. Louro, Nikolaus Virgolini, Marta A. Paiva, Ines A. Isidro, Paula M. Alves, Patricia Gomes-Alves, Margarida Serra
Summary: Extracellular Vesicles (EV) play a critical role in regulating regenerative processes in wounded tissues through cell-to-cell communication. This study investigated the piRNA profiles of EV derived from different stages of differentiation and maturation, and found significant differences between piRNA and miRNA expression. Only a small number of piRNA were found to be deregulated in EV. These results provide valuable information for further studying the role of piRNA in the bioactivity and therapeutic potential of EV.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Microbiology
Luis Gafeira Goncalves, Susana Santos, Laidson Paes Gomes, Jean Armengaud, Maria Miragaia, Ana Varela Coelho
Summary: Staphylococcus epidermidis is a common bacterium found on human skin, which can act both as a commensal and an opportunistic pathogen. It is associated with 80% of medical devices related infections and is difficult to treat due to its ability to form biofilms and develop resistance to antimicrobials. Understanding the metabolic and cellular processes of S. epidermidis in different pH conditions could provide insights into colonization and disease processes. The study found that at skin pH, the bacteria were more active metabolically and promoted adhesion, while at blood pH, metabolism was reduced and a more virulent profile was observed. Targeting S. epidermidis proteins induced by pH 7.4 and promoting acidification could be strategies to treat and prevent S. epidermidis infections.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Oncology
Rita Mendes, Goncalo Graca, Fernanda Silva, Ana C. L. Guerreiro, Patricia Gomes-Alves, Jacinta Serpa, Erwin R. Boghaert, Paula M. Alves, Ana Felix, Catarina Brito, Ines A. Isidro
Summary: This study explores metabolic signatures of chemosensitivity and resistance in ovarian cancer by exposing patient-derived tumor tissue to chemotherapy drugs. The study identifies potential metabolic biomarkers of drug response and establishes a platform to explore metabolic features of the tumor microenvironment. Predicting patient response to treatment and chemoresistance remains a major challenge in oncology.
Article
Biochemistry & Molecular Biology
Ana Filipa Fernandes, Luis Gafeira Goncalves, Maria Bento, Sandra Anjo, Bruno Manadas, Clara Barroso, Miguel Villar, Rita Macedo, Maria Joao Simoes, Ana Varela Coelho
Summary: This study aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Proteomics and metabolomics analyses were performed, and a combination of protein and metabolite markers was found to accurately identify tuberculosis patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Jose Escandell, Filipa Moura, Sofia B. Carvalho, Ricardo J. S. Silva, Ricardo Correia, Antonio Roldao, Patricia Gomes-Alves, Paula M. Alves
Summary: The majority of rAAVs for clinical use are produced using the HEK293 cell line, but this platform has manufacturing bottlenecks such as low product quality and high cost. The HeLa-based stable cell line rAAV production system offers a scalable alternative, but has barriers due to time and complexity. This study developed a more streamlined and efficient process using the HeLaS3-based cell line, achieving high yield and purity of rAAV2.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemical Research Methods
Muhammad Asif, Hugo F. M. C. Martiniano, Andre Lamurias, Samina Kausar, Francisco M. Couto
Summary: DGH-GO is a user-friendly application that helps biologists study the multi-etiological nature of complex diseases by dissecting their genetic heterogeneity. It can stratify disease-causing genes into clusters that may contribute to distinct disease outcomes, and study the shared etiology of complex diseases. By creating a semantic similarity matrix using Gene Ontology (GO) and visualizing it through dimension reduction and clustering methods, DGH-GO identifies functionally similar gene clusters. It has been applied to study the multi-etiology of Autism Spectrum Disorder (ASD) and the shared etiology of different Neurodevelopmental Disorders (NDDs).
BMC BIOINFORMATICS
(2023)
Article
Cell Biology
Filipe Magalhaes, Claudia Andrade, Beatriz Simoes, Fredi Brigham, Ruben Valente, Pedro Martinez, Jose Rino, Michela Sugni, Ana Varela Coelho
Summary: The regenerative potential varies among animals, with starfish showing outstanding abilities in this aspect. In contrast, humans have limited abilities to restore organ systems. Therefore, studying the regeneration process in starfish could provide insights for the development of new therapeutic approaches in humans. This study examined the anatomical and behavioral traits, coelomocyte populations, and neuronal tissue architecture during starfish central nervous system regeneration, revealing several anatomic anomalies and induced behavioral modifications. A new coelomocyte population was also discovered, suggesting its potential involvement in radial nerve cord regeneration.
CELL AND TISSUE RESEARCH
(2023)
Article
Biochemical Research Methods
Diana F. Sousa, Francisco M. Couto
Summary: This study developed a novel biomedical relation extraction system called K-RET, which improves performance by injecting knowledge about different types of associations, multiple sources, and multi-token entities. Testing on three independent open-access corpora showed that K-RET achieved an average improvement of 2.68%. The most significant boost in performance was observed in the DDI Corpus, with a F-measure increase from 79.30% to 87.19%.
Meeting Abstract
Cell & Tissue Engineering
Ana Filipa Louro, Marta Oliveira, Patricia Gomes-Alves, Paula Alves, Margarida Serra
TISSUE ENGINEERING PART A
(2022)
Article
Rheumatology
A. Neto, R. Pinheiro Torres, S. Ramiro, A. Sardoo, S. Rodrigues-Manica, J. Lagoas-Gomes, L. Domingues, C. Lage Crespo, D. Teixeira, A. Sepriano, A. T. Masi, K. Nair, P. Gomes-Alves, J. Costa, J. C. Branco, F. M. Pimentel-Santos
Summary: This study aimed to compare muscle physical properties, strength, mass, physical performance, and the prevalence of sarcopenia between patients with axial spondylarthritis (axSpA) and healthy controls (HC). The results showed that there was no significant difference in muscle physical properties between axSpA patients and HC, despite slightly higher lumbar stiffness. There was also no sarcopenia observed in either group. However, axSpA patients had lower strength and physical performance compared to HC, suggesting possible muscle dysfunction.
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)