Review
Pharmacology & Pharmacy
Yu Miao, Li Peng, Zhaolin Chen, Ying Hu, Liangsong Tao, Yan Yao, Yincui Wu, Dashuai Yang, Tao Xu
Summary: This article summarizes the function and mechanism of phosphodiesterase 4B (PDE4B) in cancer and highlights the potential clinical applications of PDE4B inhibitors. Research has shown that PDE4B inhibition can effectively increase cell apoptosis and inhibit cell proliferation, transformation, and migration, thereby effectively inhibiting the development of cancer.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Biochemistry & Molecular Biology
Viviana Villa, Giulia Montalto, Francesca Caudano, Ernesto Fedele, Roberta Ricciarelli
Summary: Tau protein can form hyperphosphorylated aggregates in neurodegenerative diseases like Alzheimer's, and phosphorylation of tau by cAMP-dependent protein kinase A (PKA) at Ser214 reduces its pathological assembly. The activation of adenylyl cyclase increases pTAU-S214 levels in N2a cells and rat hippocampal slices, and this effect is mimicked by GEBR-7b, a phosphodiesterase 4D inhibitor.
Article
Rheumatology
Alexis Ogdie, Mei Liu, Meghan Glynn, Kelechi Emeanuru, Leslie R. Harrold, Sven Richter, Benoit Guerette, Philip J. Mease
Summary: The study found that apremilast monotherapy is an effective option for patients with oligoarticular PsA. Apremilast initiators experienced greater disease activity improvements at follow-up compared to MTX initiators.
JOURNAL OF RHEUMATOLOGY
(2021)
Article
Rheumatology
Irina Gessl, Claudia A. Hana, Thomas Deimel, Martina Durechova, Miriam Hucke, Victoria Konzett, Mihaela Popescu, Paul Studenic, Gabriela Supp, Michael Zauner, Josef S. Smolen, Daniel Aletaha, Peter Mandl
Summary: The study aimed to assess the predictive value of tenderness in non-swollen joints for subsequent radiographic progression in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), taking into consideration other potential risk factors. Clinical and sonographic examination of hand joints were performed on patients with RA and PsA. The results showed that tenderness in non-swollen joints was associated with radiographic progression in RA, while the impact was weaker in PsA. Other risk factors such as sonographic signs for synovitis and baseline radiographic damage also had an effect on subsequent structural damage in both diseases.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Medicine, Research & Experimental
Rita Hanna, Wared Nour-Eldine, Youakim Saliba, Carole Dagher-Hamalian, Pia Hachem, Pamela Abou-Khalil, Delphine Mika, Audrey Varin, Magali Samia El Hayek, Laetitia Pereira, Nassim Fares, Gregoire Vandecasteele, Aniella Abi-Gerges
Summary: This study found that T1D-induced DCM is associated with cardiac remodeling, steatosis, and fibrosis. Diabetes hearts showed an upregulation of β(1)-AR receptor transcripts at 4 weeks, along with an increase in cAMP levels and improvements in ejection fraction and fraction shortening. However, the expression of β(2)-AR receptors remained unchanged throughout the disease progression.
Article
Medicine, General & Internal
Salvatore D'Angelo, Enrico Tirri, Angela Maria Giardino, Marco Mattucci-Cerinic, Lorenzo Dagna, Leonardo Santo, Francesco Ciccia, Bruno Frediani, Marcello Govoni, Francesca Bobbio Pallavicini, Rosa Daniela Grembiale, Andrea Delle Sedie, Rita Mule, Francesco Paolo Cantatore, Rosario Foti, Elisa Gremese, Paola Conigliaro, Fausto Salaffi, Ombretta Viapiana, Alberto Cauli, Roberto Giacomelli, Luisa Arcarese, Giuliana Guggino, Romualdo Russo, Amy Puenpatom, Domenico Capocotta, Francesca Nacci, Maria Grazia Anelli, Valentina Picerno, Corrado Binetti, Florenzo Iannone
Summary: This prospective observational study collected data from rheumatology clinics in Italy and found that golimumab (GLM) as a second anti-TNF drug is effective in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). GLM improved disease activity and quality of life in these patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Rheumatology
Achilleas Floudas, Conor M. Smith, Orla Tynan, Nuno Neto, Vinod Krishna, Sarah M. Wade, Megan Hanlon, Clare Cunningham, Viviana Marzaioli, Mary Canavan, Jean M. Fletcher, Ronan H. Mullan, Suzanne Cole, Ling-Yang Hao, Michael G. Monaghan, Sunil Nagpal, Douglas J. Veale, Ursula Fearon
Summary: This study provides a global transcriptomic analysis of the synovial joints in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), revealing the immune-stromal cell interactions in synovial inflammation. The findings highlight the differential transcription profiles and interactions between cell subsets in RA and PsA, suggesting potential targets for targeted therapeutic intervention in these diseases.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Avelina Lee, Iryna Lebedyeva, Wenbo Zhi, Vani Senthil, Herjot Cheema, Michael W. Brands, Weston Bush, Nevin A. Lambert, Madeline Snipes, Darren D. Browning
Summary: Phosphodiesterase-5 inhibitors (PDE5i) are being studied for their potential in preventing colon cancer. However, their side-effects and interactions with other drugs have been a concern. By modifying the prototypical PDE5i sildenafil, we developed a new analog called malonyl-sildenafil which exhibited reduced lipophilicity and showed promising effects on colon epithelium. This analog suppressed proliferation in the colon epithelium, providing a novel approach to developing a first-in-class drug for colon cancer chemoprevention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Ewa Zelnio, Mihra Taljanovic, Malgorzata Manczak, Iwona Sudol-Szopinska
Summary: The hand and wrist are frequently involved in rheumatic diseases, and this study aimed to identify the distinguishing radiographic characteristics of psoriatic arthritis (PsA), seropositive rheumatoid arthritis (RA), and seronegative RA, especially in the early stages. The analysis of radiographic hand findings on 180 seropositive RA patients, 154 PsA patients, and 36 seronegative RA patients revealed that symmetric distribution of lesions was more suggestive of seropositive or seronegative RA, while lesions affecting PIP joints, wrist, or styloid process of the radius were more common in patients with seropositive RA. PsA was more likely to be suggested by DIP joints' involvement and proliferative bone changes. Furthermore, there were differences in the types of bone lesions and their distribution between seropositive RA, seronegative RA, and PsA, with ulnar styloid involvement more commonly seen in seronegative RA patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Andrea Becciolini, Simone Parisi, Patrizia Del Medico, Antonella Farina, Elisa Visalli, Aldo Biagio Molica Colella, Federica Lumetti, Rosalba Caccavale, Palma Scolieri, Romina Andracco, Francesco Girelli, Elena Bravi, Matteo Colina, Alessandro Volpe, Aurora Ianniello, Maria Chiara Ditto, Valeria Nucera, Veronica Franchina, Ilaria Plate, Eleonora Di Donato, Giorgio Amato, Carlo Salvarani, Simone Bernardi, Gianluca Lucchini, Francesco De Lucia, Francesco Molica Colella, Daniele Santilli, Natalia Mansueto, Giulio Ferrero, Antonio Marchetta, Eugenio Arrigoni, Rosario Foti, Gilda Sandri, Vincenzo Bruzzese, Marino Paroli, Enrico Fusaro, Alarico Ariani
Summary: This retrospective observational study aimed to report the long-term disease activity index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and analyze the predictors of clinical response. The study found that almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. Baseline DAPSA was the only factor associated with achieving low disease activity or remission at both 6 and 12 months.
Article
Rheumatology
Veerle Stouten, Sofia Pazmino, P. Verschueren, Pavlos Mamouris, Rene Westhovens, Kurt de Vlam, Delphine Bertrand, Kristien van der Elst, Bert Vaes, Diederik De Cock
Summary: This study compared the comorbidity burden and pain medication prescription in patients with chronic inflammatory rheumatic conditions, identifying higher burden in RA and PsA patients. The remarkable finding was the high opioid use in all population groups.
Article
Cardiac & Cardiovascular Systems
Jie Su, Pierre Coleman, Angeliki Ntorla, Rhys Anderson, Michael J. Shattock, Joseph R. Burgoyne
Summary: This study demonstrates that the cytosolic DNA sensor cGAS can activate PKGI directly through the generation of cGAMP, showing a link between inflammation and blood pressure regulation.
Article
Multidisciplinary Sciences
Dao X. Nguyen, Helen M. Baldwin, Amara N. Ezeonyeji, Mohammed Rohan Butt, Michael R. Ehrenstein
Summary: The study revealed that patients with PsA have an increased Th17:Treg ratio, which can be reversed by anti-TNF therapy. Treg from patients treated with different therapies showed contrasting effects on regulating effector T-cell migration, with TNF blockade boosting Treg suppression of migration.
Article
Rheumatology
Emilio Filippucci, Gianluca Smerilli, Andrea Di Matteo, Walter Grassi
Summary: Enthesitis plays a crucial role in the diagnosis and management of patients with spondyloarthritis and psoriatic arthritis, but clinical assessment is often inaccurate due to poor specificity. Ultrasound has the potential to improve the evaluation of enthesitis and enhance patient management in this context. Reviewing the OMERACT definitions for ultrasound enthesitis can help identify current limitations and their potential implications for rheumatology research and clinical practice.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Immunology
Orsolya Tuende Kovacs, Eszter Toth, Oliver Ozohanics, Eszter Soltesz-Katona, Nikolett Marton, Edit Iren Buzas, Laszlo Hunyady, Laszlo Drahos, Gabor Turu, Gyorgy Nagy
Summary: This study investigated the proteomic changes during osteoclast differentiation in healthy donors, RA, and PsA. The results showed increased expression of proteins involved in metabolic activity, secretory function, and cell polarity during differentiation, while immune signaling pathways were downregulated. The expression differences between healthy donors and RA/PsA patients were most noticeable after the final steps of differentiation. The study provides important insights into the pathophysiology of RA and PsA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
M. A. Nielsen, D. Koster, S. Greisen, A. Troldborg, K. Stengaard-Pedersen, P. Junker, K. Horslev-Petersen, M. L. Hetland, M. Ostergaard, M. Hvid, H. Leffler, T. W. Kragstrup, B. Deleuran
Summary: The study found that patients with rheumatoid arthritis (RA) had persistently increased levels of galectin-3 (Gal-3) in their plasma, and changes in Gal-3 levels were associated with long-term disease activity. Gal-3 levels in synovial fluid were also significantly elevated. In vitro experiments showed that a Gal-3 inhibitor could reduce the activity of inflammatory cells.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
E. B. Rasmussen, L. S. Thiele, K. Stengaard-Pedersen, M. L. Hetland, K. Horslev-Petersen, P. Junker, M. Ostergaard, A. S. Hansen, M. Hvid, B. Deleuran, S. R. Greisen
Summary: ACPAs IgA and IgG have weak associations with disease activity in early RA, but are not superior in predicting long-term radiographic progression.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
M. Pfeiffer-Jensen, D. Liao, U. Tarp, B. Deleuran, K. Stengaard-Pedersen, J. Venborg, B. Brock, C. Brock
Summary: This study examines the use of therapeutic drug monitoring (TDM) to personalize the dosing of TNF-alpha inhibitors, finding that it reduces drug prescription and prolongs treatment intervals. Additionally, TDM allows for the identification of patients who would benefit from a drug switch, minimizing treatment failure and unnecessary adverse events.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Dermatology
Amanda Kvist-Hansen, Laura Perez-Alos, Rownaq Fares Al-Sofi, Line Dam Heftdal, Sebastian Rask Hamm, Dina Leth Moller, Mia Marie Pries-Heje, Kamille Fogh, Cecilie Bo Hansen, Rasmus Bo Hasselbalch, Johannes Roth Madsen, Jose Juan Almagro Armenteros, Ruth Frikke-Schmidt, Linda Hilsted, Erik Sorensen, Sisse Rye Ostrowski, Henning Bundgaard, Susanne Dam Nielsen, Kasper Iversen, Claus Zachariae, Peter Garred, Lone Skov
Summary: This study examined the long-term immunity after mRNA-based COVID-19 vaccination in psoriasis patients on immunomodulatory therapy. The study found that patients receiving anti-TNF treatment had a faster decline in immunity markers compared to the control group at the 6-month mark.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Immunology
Kathrine Pedersen, Morten Aagaard Nielsen, Kristian Juul-Madsen, Malene Hvid, Bent Deleuran, Stinne Ravn Greisen
Summary: This study focuses on impaired PD-1 signalling and upregulation of Galectin-3 (Gal-3) in rheumatoid arthritis (RA). The results show that Gal-3 binds PD-1 and PD-L1, inhibiting PD-1 signalling when PD-L1 is present. High expression of PD-1 and Gal-3 is observed on mononuclear cells, especially from synovial fluid (SF). Gal-3 also affects osteoclast formation directly and through PD-1:PD-L1 inhibition. The inhibitory role of Gal-3 on the PD-1 signalling axis suggests that targeting Gal-3 could have therapeutic potential in RA.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Rheumatology
Soren Lomholt, Malthe Jessen Pedersen, Mia Glerup, Tue Wenzel Kragstrup
Summary: This scoping review aimed to summarize the current knowledge on synovial fibroblasts and their potential involvement in the pathogenesis of juvenile idiopathic arthritis. The review identified several mechanisms and characteristics of synovial fibroblasts that may contribute to disease traits in juvenile idiopathic arthritis. However, the limited number of studies highlights the need for further research in this area.
SEMINARS IN ARTHRITIS AND RHEUMATISM
(2023)
Article
Cell Biology
Morten A. A. Nielsen, Ditte Koster, Akul Y. Y. Mehta, Kristian Stengaard-Pedersen, Pierre Busson, Peter Junker, Kim Horslev-Petersen, Merete Lund Hetland, Mikkel ostergaard, Malene Hvid, Hakon Leffler, Tue W. W. Kragstrup, Richard D. D. Cummings, Bent Deleuran
Summary: This study evaluated the clinical and pathogenic aspects of Gal-9 in rheumatoid arthritis (RA) and found that it plays a role in modulating synovial FLS activities and maintaining subclinical disease activity.
Article
Rheumatology
Alessia Alunno, Tadej Avcin, Catherine Haines, Sofia Ramiro, Francisca Sivera, Sara Badreh, Xenofon Baraliakos, Johannes W. J. Bijlsma, Frank Buttgereit, Kaushik Chaudhuri, Jose A. P. Da Silva, Jean Dudler, Ricardo J. O. Ferreira, Tania Gudu, Eric Hachulla, Mette Holland-Fischer, Annamaria Iagnocco, Tue Wenzel Kragstrup, Gyoergy Nagy, Vasco C. Romao, Simon R. Stones, Marloes van Onna, Christopher J. Edwards
Summary: This study aimed to define competences and standards for the training of rheumatologists. Through collaboration and analysis of international training documents, an overall framework, 7 domains, 8 core themes, and 28 competences were established. The results suggest that these standards can contribute to harmonizing rheumatology training across European countries.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Hematology
Line Dam Heftdal, Sebastian Rask Hamm, Laura Perez-Alos, Johannes Roth Madsen, Jose Juan Almagro Armenteros, Kamille Fogh, Christoffer Cronwald Kronborg, Anders Pommer Vallentin, Rasmus Bo Hasselbalch, Dina Leth Moller, Cecilie Bo Hansen, Mia Pries-Heje, Anne Ortved Gang, Sisse Rye Ostrowski, Ruth Frikke-Schmidt, Erik Sorensen, Linda Hilsted, Henning Bundgaard, Kasper Iversen, Peter Garred, Susanne Dam Nielsen, Kirsten Gronbaek
Summary: The initial responses to COVID-19 vaccination are impaired in patients with blood cancers. This study examined the immune responses of patients with myeloid and lymphoid malignancies who received three or four doses of the BNT162b2 vaccine, compared to controls. Risk factors for humoral and cellular nonresponse one year after vaccination were also identified.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2023)
Letter
Hematology
Emil R. Kyvsgaard, Caroline Riley, Michael Roost Clausen, Mads Harslof, Line Dam Heftdal, Carsten U. Niemann, Kirsten Gronbaek, Martin Hutchings, Simon Husby
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Victor Yang, Tue W. Kragstrup, Christopher McMaster, Pankti Reid, Namrata Singh, Stine R. Haysen, Philip C. Robinson, David F. L. Liew
Summary: Janus kinase inhibitors (JAKi) have shown great potential as immune-modulating therapies for chronic inflammatory diseases. However, concerns about cardiovascular and cancer risks have arisen from recent studies, particularly in patients with rheumatoid arthritis and existing cardiovascular risk. While this risk has not been fully demonstrated in other patient populations, it has led to a re-evaluation of the use of JAKi in various contexts. Clinicians must carefully consider these risks and other factors when considering JAKi as a treatment option for their patients.
Article
Medicine, Research & Experimental
Marie Louise Naestholt Dahl, Jakob Hauge Mikkelsen, Malene Hvid, Trine-Line Korsholm, Kirstine Overgaard Nielsen, Christian Brix Folsted Andersen, Stinne Greisen, Bent Deleuran
Summary: We established an indirect ELISA method to detect autoantibodies against full-length TRIM21 protein and its four domains, and validated the efficacy using plasma from anti-SSA positive patients and healthy controls. Our results showed significantly higher levels of autoantibodies against full-length TRIM21, PRY/SPRY, Coiled-Coil, and RING domains in patients compared to healthy controls. There was no significant difference in autoantibody levels against the B-box domain. Our protocols allow for further study of different autoantibodies in anti-SSA positive patients, enabling stratification of patients based on autoantibody profile and specific phenotypes or endotypes.
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
(2023)
Article
Cell Biology
Aida S. S. Hansen, Lea S. S. Jensen, Kristine R. R. Gammelgaard, Kristoffer G. G. Ryttersgaard, Christian Krapp, Jesper Just, Kasper L. L. Jonsson, Pia B. B. Jensen, Thomas Boesen, Mogens Johansen, Anders Etzerodt, Bent W. W. Deleuran, Martin R. R. Jakobsen
Summary: This article introduces the highly immunosuppressive tumor microenvironment, and explores a novel method to improve immunotherapy effectiveness by activating the STING signaling pathway. The researchers found that extracellular vesicles derived from activated CD4(+) T cells can sensitize macrophages and activate the STING pathway, effectively disrupting the immune suppressive environment in the tumor and priming for a robust immune response towards STING activation.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Rheumatology
Janni Maria Pedersen, Aida Solhoj Hansen, Caecilie Skejo, Kristian Juul-Madsen, Peter Junker, Kim Horslev-Petersen, Merete Lund Hetland, Kristian Stengaard-Pedersen, Mikkel ostergaard, Bjarne Kuno Moller, Lene Dreyer, Ellen-Margrethe Hauge, Malene Hvid, Stinne Greisen, Bent Deleuran
Summary: This study investigated the role of lymphocyte activation gene-3 (LAG-3) as a serological marker and mediator in the pathogenesis of rheumatoid arthritis (RA). The results showed increased levels of LAG-3 in both early and chronic RA patients, particularly in the inflamed joint. LAG-3 plays a biological role in reducing inflammatory cytokine production in chronic RA, and this function is not affected by Gal-3 interference. Our findings suggest that LAG-3 is a multifaceted regulator of inflammation in early and chronic RA.
ARTHRITIS RESEARCH & THERAPY
(2023)
