Article
Immunology
Ruby J. Siegel, Anil K. Singh, Paul M. Panipinto, Farheen S. Shaikh, Judy Vinh, Sang U. Han, H. Mark Kenney, Edward M. Schwarz, Cynthia S. Crowson, Sadik A. Khuder, Basil S. Khuder, David A. Fox, Salahuddin Ahmed
Summary: This study identified a potential role of Sulf-2 in the inflammatory response of rheumatoid arthritis (RA). The study found that overexpression of Sulf-2, which is positively correlated with TNF receptor 1 expression, can be reduced to attenuate TNF-alpha-induced synovial inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Maria Jose Alcaraz
Summary: Synovial cells, especially activated synovial fibroblasts, are key players in joint destruction in rheumatoid arthritis. Identifying SF phenotypes, controlling epigenetic changes, and modulating cellular functions are promising approaches to develop novel therapeutic targets for preserving joint architecture and function in RA. Further research is needed to determine the most relevant targets for drug development.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Rheumatology
Raphael Micheroli, Muriel Elhai, Sam Edalat, Mojca Frank-Bertoncelj, Kristina Buerki, Adrian Ciurea, Lucy MacDonald, Mariola Kurowska-Stolarska, Myles J. Lewis, Katriona Goldmann, Cankut Cubuk, Tadeja Kuret, Oliver Distler, Costantino Pitzalis, Caroline Ospelt
Summary: This study integrated single-cell RNA sequencing data to assess the contribution of synovial fibroblast subsets to synovial pathotypes and clinical characteristics in treatment-naive early arthritis. The findings revealed a previously unexplored association between specific synovial pathologies and subtypes of synovial fibroblasts.
Review
Rheumatology
Tamas Nemeth, Gyorgy Nagy, Thomas Pap
Summary: Fibroblast-like synoviocytes (FLS) are crucial cellular components in the synovial membrane of joints, contributing to normal joint function. However, under inflammatory conditions like rheumatoid arthritis (RA), FLS can become overactive and promote inflammation. Therefore, understanding the role of FLS in RA is essential for disease treatment.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Haruka Tsuchiya, Mineto Ota, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Toyonori Sakata, Yumi Tsuchida, Hiroshi Inui, Jun Hirose, Yuta Kochi, Yuho Kadono, Katsuhiko Shirahige, Sakae Tanaka, Kazuhiko Yamamoto, Keishi Fujio
Summary: Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the synovium, where synovial fibroblasts (SFs) play a major role. This study aimed to understand the genetic contribution to molecular regulatory networks in SFs under inflammatory conditions. Methods: SFs from RA and osteoarthritis (OA) patients were stimulated with various cytokines and immune cell subsets were analyzed. Integrative analyses including mRNA expression, histone modifications, 3D genome architecture, and genetic variations were performed. Results: Unstimulated SFs from RA patients showed differences in transcriptome and epigenome compared to OA SFs. Most responses to stimulations were shared between the diseases. SFs expressed pathogenic genes and chromatin remodeling in activated SFs revealed enrichment of RA risk loci in clusters of enhancers induced by proinflammatory cytokines. A RA risk SNP formed 3D contact with the promoter of a gene related to arthritis, and inhibition of this gene suppressed cytokine and chemokine production in SFs. Conclusions: This study identified potential therapeutic targets associated with genetic risk of RA and established a dynamic landscape of activated SFs.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Immunology
Eva M. L. Philippon, Lisanne J. E. van Rooijen, Fatemeh Khodadust, Jan Piet van Hamburg, Conny J. van der Laken, Sander W. Tas
Summary: A spheroid-based model of RA synovial tissue was developed to mimic the 3D interactions between cells and pro-inflammatory mediators. It can be used to study the pathogenesis of rheumatoid arthritis, examine the effects of specific cell types and signaling pathways, and evaluate the efficacy of novel diagnostic and therapeutic compounds.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Rheumatology
Maximilian Kugler, Mirjam Dellinger, Felix Kartnig, Lena Mueller, Teresa Preglej, Leonhard X. Heinz, Elisabeth Simader, Lisa Goeschl, Stephan E. Puchner, Sebastian Weiss, Lisa E. Shaw, Matthias Farlik, Wolfgang Weninger, Giulio Superti-Furga, Josef S. Smolen, Guenter Steiner, Daniel Aletaha, Hans P. Kiener, Myles J. Lewis, Costantino Pitzalis, Anela Tosevska, Thomas Karonitsch, Michael Bonelli
Summary: Activated FLS play a critical role in synovial tissue remodeling and interaction with immune cells in rheumatoid arthritis (RA). Co-culture experiments demonstrated that cytokine-activated FLS enhance T cell activation, proliferation, and differentiation. Transcriptomic analysis revealed a correlation between FLS cytokine signatures and infiltrating CD4(+) T cells in RA synovial tissue. ICAM1 was identified as an important mediator in TNF-mediated FLS-T cell interaction.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Anil K. Singh, Mahamudul Haque, Bhanupriya Madarampalli, Yuanyuan Shi, Benjamin J. Wildman, Abdul Basit, Sadik A. Khuder, Bhagwat Prasad, Quamarul Hassan, Salahuddin Ahmed, Madhu M. Ouseph
Summary: IL-6 trans-signaling induces molecular reprogramming of RASFs to osteoclast-like cells through the activation of transcription factor Ets2, leading to increased expression of osteoclast-specific proteins and markers of invasive phenotype.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Yi Qin, Ming-Long Cai, Hui-Zhi Jin, Wei Huang, Chen Zhu, Aline Bozec, Jingang Huang, Zhu Chen
Summary: This study found that ABCs contribute to the pathogenesis of RA by inducing the activation of FLS via TNF-alpha-mediated signaling pathways.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Li Zheng, Fanlei Hu, Wenjie Bian, Yingni Li, Linqi Zhang, Lianjie Shi, Xiaoxu Ma, Yanying Liu, Xuewu Zhang, Zhanguo Li
Summary: Dkk-1 exacerbates inflammation, cartilage erosion, and angiogenesis mediated by synovial fibroblasts in RA. Modulation of DKK-1 expression may facilitate the development of novel strategies to control RA.
CLINICAL RHEUMATOLOGY
(2021)
Article
Rheumatology
Tadashi Hosoya, Tetsuya Saito, Hiroyuki Baba, Nao Tanaka, Seiji Noda, Youji Komiya, Yasuhiro Tagawa, Akio Yamamoto, Fumitaka Mizoguchi, Kimito Kawahata, Nobuyuki Miyasaka, Hitoshi Kohsaka, Shinsuke Yasuda
Summary: This study reveals that inhibiting CDK4/6 activity can attenuate cartilage destruction and MMP-3 production, providing chondroprotective effects. These effects were achieved by impairing AP-1 transcriptional activity and destabilizing JUN.
Article
Agriculture, Multidisciplinary
Guliang Yang, Jie Sun, Kun Lu, Sijie Shan, Shiming Li, Chenglin Sun
Summary: The study showed that Pterostilbene combined with physical exercise has a significant preventive effect on rheumatoid arthritis, increasing the MaR1 content, reversing the abnormal expression of inflammatory signal pathways, and inhibiting the proliferation and apoptosis of synovial cells through promoting cell autophagy.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Immunology
Chun-Han Hou, Po-Chun Chen, Ju-Fang Liu
Summary: This study provides novel insights into the role of CXCL1 in the pathogenesis of rheumatoid arthritis by promoting COX-II expression to regulate disease progression.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Samuel Kemble, Adam P. Croft
Summary: This review focuses on discussing the disease persistence pathways of rheumatoid arthritis and treating the disease through regulating specific cellular behaviors. The article reveals the heterogeneity of tissue resident synovial cells and how they function in joint inflammation. Finally, specific targeted therapeutic strategies against pathogenic subsets of fibroblasts in RA are proposed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Katharina Knab, David Chambers, Gerhard Kroenke
Summary: This review summarizes the phenotypic and molecular characteristics of immune-regulatory macrophages and fibroblasts in the synovial tissue, and highlights their crosstalk during joint homeostasis and joint inflammation, which is vital to understand the molecular basis of prevalent inflammatory joint diseases such as rheumatoid arthritis.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Anil K. Singh, Mahamudul Haque, Kayla O'Sullivan, Mukesh Chourasia, Madhu M. Ouseph, Salahuddin Ahmed
Summary: The study uncovers a novel post-translational mechanism of TAK1 activation by MSU crystals, suggesting the therapeutic potential of targeting TAK1 in regulating MSU-induced inflammation. MSU-induced proinflammatory cytokine production was completely inhibited by a TAK1 inhibitor in an in vivo mouse model, demonstrating the effectiveness of targeting this pathway in treating gout-related inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Rheumatology
Mahamudul Haque, Anil K. Singh, Madhu M. Ouseph, Salahuddin Ahmed
Summary: The study found that GBP-5 is up-regulated in RA synovial tissue and joints of rats with AIA, and is induced by IL-1 beta, TNF, and/or IFN gamma in human RASFs. GBP-5 has the potential to restore cellular homeostasis and blunt inflammation and tissue destruction in RA by regulating cytokine signaling pathways.
ARTHRITIS & RHEUMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mukesh Chourasia, Purushotham Reddy Koppula, Aruna Battu, Madhu M. Ouseph, Anil K. Singh
Summary: COVID-19, caused by SARS-CoV-2, is a global threat with vaccination efficacy still uncertain. Repurposing existing drugs targeting inflammation is gaining attention. Drugs for rheumatoid arthritis may lower COVID-19 morbidity. Study on catechins binding to viral proteins shows potential therapeutic effect.
Article
Biochemistry & Molecular Biology
Paul M. Panipinto, Anil K. Singh, Farheen S. Shaikh, Ruby J. Siegel, Mukesh Chourasia, Salahuddin Ahmed
Summary: TGF beta-activated kinase 1 (TAK1) is a key player in inflammatory diseases such as rheumatoid arthritis (RA) and gouty arthritis. The role of takinib in inhibiting inflammation involves targeting multiple signaling pathways, particularly the JAK/STAT pathway in human RASFs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Reem Smoum, Christeene Haj, Shira Hirsch, Alina Nemirovski, Zhannah Yekhtin, Benny Bogoslavsky, Gaganjyot Kaur Bakshi, Mukesh Chourasia, Ruth Gallily, Joseph Tam, Raphael Mechoulam
Summary: A series of novel cannabinoid derivatives were synthesized and found to have high affinity and selectivity for the CB2 receptor. One of the synthesized derivatives showed high affinity and selectivity for the human CB2 receptor.
Article
Immunology
Anil K. Singh, Mahamudul Haque, Bhanupriya Madarampalli, Yuanyuan Shi, Benjamin J. Wildman, Abdul Basit, Sadik A. Khuder, Bhagwat Prasad, Quamarul Hassan, Salahuddin Ahmed, Madhu M. Ouseph
Summary: IL-6 trans-signaling induces molecular reprogramming of RASFs to osteoclast-like cells through the activation of transcription factor Ets2, leading to increased expression of osteoclast-specific proteins and markers of invasive phenotype.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Bitya Raphael-Mizrahi, Malka Attar-Namdar, Mukesh Chourasia, Maria G. Cascio, Avital Shurki, Joseph Tam, Moshe Neuman, Neta Rimmerman, Zvi Vogel, Arie Shteyer, Roger G. Pertwee, Andreas Zimmer, Natalya M. Kogan, Itai Bab, Yankel Gabet, Mone Zaidi
Summary: The endocannabinoid system, consisting of OGP and CB2, plays an important role in maintaining bone health and preventing age-related bone loss. OGP acts as an agonist and positive allosteric modulator of CB2, and its decrease in circulation with age is associated with bone loss in premenopausal women and adult mice.
Article
Immunology
Sadiq Umar, Anil K. Singh, Mukesh Chourasia, Stephanie M. Rasmussen, Jeffrey H. Ruth, Salahuddin Ahmed
Summary: This study investigates the role of O-GlcNAcylation in rheumatoid arthritis (RA) and its regulation using human RA patient-derived synovial fibroblasts (RASFs). The results suggest that O-GlcNAcylation could be a potential therapeutic target and PGG has the potential to inhibit inflammatory processes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Surendra Rajit Prasad, Prakash Kumar, Saptarshi Mandal, Anu Mohan, Radhika Chaurasia, Ashish Shrivastava, Pallaprolu Nikhil, Dande Aishwarya, P. Ramalingam, Rahul Gajbhiye, Shriya Singh, Arunava Dasgupta, Mukesh Chourasia, V. Ravichandiran, Prolay Das, Debabrata Mandal
Summary: In this study, we evaluated the effectiveness of different types of saturated medium-chain fatty acids against Leishmania. We found that caprylic acid (CA) showed the most potent anti-leishmanial effect. Further investigation revealed that CA mediates cell death by depleting ergosterol through inhibiting the enzyme mevalonate kinase (MevK) in the ergosterol biosynthesis pathway. This study provides insights into the mechanism of CA against visceral leishmaniasis.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Physical
Mukesh Chourasia, Todd Cowen, Aviva Friedman-Ezra, Eden Rubanovich, Avital Shurki
Summary: The ability to design catalysis depends on understanding the electrostatic effect of the surrounding on the participating chemical bonds. A simplistic model of point charges (PCs) was used to determine a set of rules for constructing PC-bond arrangements that can strengthen or weaken different chemical bonds. The strongest bond strengthening and weakening effects occur when the PC is placed along the bond axis, close to the more and less polarizable atom/fragment, respectively. Overall, bond strengthening is easier to achieve compared to bond weakening.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Immunology
Ruby J. Siegel, Anil K. Singh, Paul M. Panipinto, Farheen S. Shaikh, Judy Vinh, Sang U. Han, H. Mark Kenney, Edward M. Schwarz, Cynthia S. Crowson, Sadik A. Khuder, Basil S. Khuder, David A. Fox, Salahuddin Ahmed
Summary: This study identified a potential role of Sulf-2 in the inflammatory response of rheumatoid arthritis (RA). The study found that overexpression of Sulf-2, which is positively correlated with TNF receptor 1 expression, can be reduced to attenuate TNF-alpha-induced synovial inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Meeting Abstract
Rheumatology
Anil Singh, Paul Panipinto, Ruby Siegel, Farheen Shaikh, Mukesh Chourasia, Salah-Uddin Ahmed
ARTHRITIS & RHEUMATOLOGY
(2021)