scholarly journals In Vivo Studies on the Influence of Bacteriophage Preparations on the Autoimmune Inflammatory Process

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ryszard Międzybrodzki ◽  
Jan Borysowski ◽  
Marlena Kłak ◽  
Ewa Jończyk-Matysiak ◽  
Bożena Obmińska-Mrukowicz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Phage Therapy ◽  
Joint Disease ◽  
In Vivo Studies ◽  
Immune Disorders ◽  
Collagen Induced Arthritis ◽  
E Coli ◽  
Negative Bacillus ◽  
T4 Phage

Phage preparations used for phage therapy may have not only direct antibacterial action but also immunomodulating effects mediated by phages themselves as well as by bacterial antigens. Therefore phage application in patients with immune disorders, and especially with autoimmune diseases, requires special attention. The aim of this study was to investigate the effect of phage lysates (staphylococcal phages A3/R, phi200, and MS-1 cocktail, enterococcal phage 15/P, Pseudomonas phage 119x, and E. coli T4 phage) as well as purified T4 phage on the course of murine collagen-induced arthritis (CIA), commonly used as an animal model of rheumatoid arthritis. Intraperitoneal application of phage lysates or purified T4 phage did not aggravate the course of autoimmune joint disease. Moreover, although endotoxins are known to potentiate CIA, the systemic administration of phage lysate of Pseudomonas aeruginosa, which contains debris of this Gram-negative bacillus, did not significantly influence CIA although the sonicate of the corresponding bacterial strain did. Interestingly, a purified T4 phage revealed some anti-inflammatory activity when applied under the therapeutic scheme. Our preliminary results do not suggest that phages may aggravate the symptoms of rheumatoid arthritis. In contrast T4 phage may even exert an immunosuppressive effect.

scholarly journals DNA origami as a nanomedicine for targeted rheumatoid arthritis therapy through reactive oxygen species and nitric oxide scavenging

2022 ◽  
Author(s):  
Yuxuan Ma ◽  
Zhangwei Lu ◽  
Ye Shi ◽  
Zhe Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Dna Origami ◽  
In Vivo Studies ◽  
Oxygen Species ◽  
Collagen Induced Arthritis ◽  
M1 Macrophages

High levels of reactive oxygen species (ROS) and nitric oxide (NO) generated by M1 macrophages induce inflammation in the development of rheumatoid arthritis (RA). The eliminating of ROS and NO therefore represents an alternative strategy for RA treatment. Because DNA molecules possess ROS- and endogenous NO-scavenging capability, herein, we develop a nanomedicine based on triangular DNA origami nanostructures for targeted RA treatment. We showed that folic acid-modified triangular DNA origami nanostructures (FA-tDONs) could reduce ROS and NO simultaneously inside proinflammatory M1 macrophages, leading to their polarization into anti-inflammatory M2 subtype. Further in vivo studies confirmed that FA-tDONs could actively target inflamed joints in collagen-induced arthritis (CIA) mice, attenuate inflammatory cytokines and alleviate disease progression. This work demonstrated that DNA origami itself could act as a potential nanomedicine for targeted RA treatment.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2223
Author(s):  
Manon Dominique ◽  
Nicolas Lucas ◽  
Romain Legrand ◽  
Illona-Marie Bouleté ◽  
Christine Bôle-Feysot ◽  
...  
Keyword(s):  
Food Intake ◽  
Peptide Yy ◽  
Molecular Mimicry ◽  
Potential Effect ◽  
In Vivo Studies ◽  
Sprague Dawley ◽  
E Coli ◽  
In Vivo Effects

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague–Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

In-silico Molecular Docking of Coumarin and Naphthalene Derivatives from Pyrenacantha volubilis with the Pathological Mediators of Rheumatoid Arthritis

2021 ◽  
pp. 5121-5125
Author(s):  
Anjali P ◽  
Vimalavathini R
Keyword(s):  
Rheumatoid Arthritis ◽  
Symptomatic Relief ◽  
In Vivo Studies ◽  
Gas Chromatography Mass Spectrometry ◽  
Therapeutic Drugs ◽  
Herbal Plants ◽  
In Silico Molecular Docking ◽  
Inflammatory Autoimmune Disease

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which mainly targets synovial membrane during its disease pathogenesis. Available therapeutic drugs for the treatment of RA provide only symptomatic relief and are associated with severe side effects. Herbal plants comprise many active biological compounds that cure the disease with minimal adverse effects. Pyrenacantha volubilis is a climber and member of Icacinaceae family. Gas chromatography- mass spectrometry (GC-MS) analysis of ethanolic extracts of leaves of Pyrenacantha volubilis (EEPV) reveals the presence of 2-isopropyl-5-methylcyclohexyl 3-(1-(4- chlorophenyl)-3-oxobutyl)-coumarin-4-yl carbonate and 1-naphthalenepropanol, alpha-ethyldecahydro-5- (hydroxymethyl)-alpha,5,8A-trimethyl-2-methyl phytoconstitutents. Hence these compounds were docked with various pathological mediators of RA using Autodock 4.2. The docking results unveils that these compounds had better binding energy against inflammatory, oxidative stress and receptor for advanced glycation end products (RAGE) mediators that plays a pivotal role in the progression of RA. However, this study warrants further in- vitro and in-vivo studies to be carried out to establish the anti-inflammatory and anti-arthritic activity of selected phytoconstitutents.

scholarly journals Dysregulation of Innate Lymphoid Cells in Patients with Active Rheumatoid Arthritis and Mice with Collagen-Induced Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fengfan Yang ◽  
Xing Luo ◽  
Wenxiao Zhu ◽  
Jia Li ◽  
Zhaohui Zheng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Immunofluorescence Staining ◽  
Joint Disease ◽  
Collagen Induced Arthritis ◽  
Das28 Score ◽  
Immune Pathways ◽  
Positive Correlations

Innate lymphoid cells (ILCs) have roles in many diseases and immune pathways. To determine the roles of these cells in patients with rheumatoid arthritis (RA) and mice with collagen-induced arthritis (CIA), we measured ILC subsets using flow cytometry and multiplex immunofluorescence staining. Patients with stable RA had greater proportions of ILC2s and decreased proportions of ILC1s and ILC3s (all p < 0.05 ). The 28-joint disease activity (DAS28) score had positive correlations with the proportion of ILC1s and negative correlations with ILC2s (both p < 0.05 ). ILC2s of patients with RA expressed more IL-4 than healthy controls ( p < 0.05 ). The proportions of ILC1s and ILC2s were greater in mice with CIA (both p < 0.05 ), especially the ILC2s in mice without arthritis after immunization and had correlations with multiple inflammatory and anti-inflammatory cytokines. Multiplex immunofluorescence staining described the distribution of ILCs in spleen tissues. Our results indicate that dysregulation of ILCs occurs during the pathogenesis of RA and CIA.

Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systematic Review of In Vivo Studies

2020 ◽  
Vol 16 (2) ◽  
pp. 276-287 ◽  
Author(s):  
Alexia Karamini ◽  
Athina Bakopoulou ◽  
Dimitrios Andreadis ◽  
Konstantinos Gkiouras ◽  
Aristeidis Kritis
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Stem Cells ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Stromal Stem Cells

An effective and safe treatment strategy for rheumatoid arthritis based on human serum albumin and Kolliphor® HS 15

Nanomedicine ◽  
2019 ◽  
Vol 14 (16) ◽  
pp. 2169-2187 ◽  
Author(s):  
Ting Gong ◽  
Pei Zhang ◽  
Caifeng Deng ◽  
Yu Xiao ◽  
Tao Gong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Therapeutic Strategy ◽  
Inflammatory Cell ◽  
In Vivo Studies ◽  
Targeting Ability

Aim: We aimed to construct human serum albumin-Kolliphor® HS 15 nanoparticles (HSA-HS15 NPs) to overcome the limitations in targeted therapy for rheumatoid arthritis (RA) and enhance the safety of drug-loaded HSA NPs. Methodology: Celastrol (CLT)-loaded HSA-HS15 NPs were prepared and the properties were adequately investigated; the treatment effect were evaluated in RA rats; in vitro and in vivo studies were performed to explain the mechanism. Results: CLT-HSA-HS15 NPs had remarkable treatment ability and enhanced safety in the treatment of RA compared with free CLT and CLT-HSA NPs. Conclusion: HSA-HS15 NPs could be a safe and efficient therapeutic strategy for the treatment of RA, because of the inflammatory targeting ability of albumin, the added HS15 and ELVIS effect (extravasation through leaky vasculature followed by inflammatory cell-mediated sequestration) of nanoparticles.

scholarly journals Role of cell migration in the pathogenesis of rheumatoid arthritis: in vivo studies in SCID mice transplanted with human synovial membrane

Reumatismo ◽  
2011 ◽  
Vol 54 (2) ◽  
Author(s):  
F. Ingegnoli ◽  
M. Blades ◽  
A. Manzo ◽  
S. Wahid ◽  
M. Perretti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Migration ◽  
Synovial Membrane ◽  
Scid Mice ◽  
In Vivo Studies

scholarly journals Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1232
Author(s):  
Stefania D’Adamo ◽  
Silvia Cetrullo ◽  
Veronica Panichi ◽  
Erminia Mariani ◽  
Flavio Flamigni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Antioxidant Activities ◽  
Synergistic Effects ◽  
National Health System ◽  
Bioactive Molecules ◽  
Joint Disease ◽  
In Vivo Studies ◽  
Wide Range

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

scholarly journals The Micro-Immunotherapy Medicine 2LARTH® Reduces Inflammation and Symptoms of Rheumatoid Arthritis In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ilaria Floris ◽  
Víctor García-González ◽  
Belen Palomares ◽  
Kurt Appel ◽  
Beatrice Lejeune
Keyword(s):  
Rheumatoid Arthritis ◽  
Histological Analysis ◽  
Pure Water ◽  
Joint Destruction ◽  
Clinical Signs ◽  
Clinical Score ◽  
Type Ii Collagen ◽  
Joint Disease ◽  
Paw Edema

Background. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damages as well as pain and disability. In order to prevent disease progression, reduce pain, and major symptoms of RA, one good strategy consists in targeting proinflammatory cytokines that have the key role in the vicious circle of synovial inflammation and pain. The micro-immunotherapy medicine (MIM) 2LARTH® targets cytokines involved in inflammation. Aim. The aim of the study is to evaluate the effect of the MIM compared to vehicle in an in vivo model of RA, induced in mice after immunization with articular bovine type II collagen. Methods. Vehicle and MIM were dissolved in pure water (1 capsule in 100 ml) and 100 µl was given by gavage daily for 14 days. To evaluate the severity of arthritis, wrist and ankle thickness was determined, paw edema was measured, and a clinical score from 0 to 4 was established. Furthermore, histological analysis was performed. To evaluate systemic inflammation, circulating levels of IL-1β and TNF-α were measured by ELISA. Results. Ankle thickness was found to be significantly reduced in MIM-treated mice compared to vehicle-treated mice (P<0.05) and compared to untreated me (P<0.01). Paw edema was reduced, as well as clinical score attributed to MIM-treated mice in comparison with vehicle-treated mice and untreated CIA mice (P<0.01). In line with these results, histological analysis confirmed that MIM reduced inflammation and joint destruction in comparison to controls. No significant changes were found in plasmatic IL-1β levels between CIA and controls, while the levels of TNF-α significantly increased in the CIA group, and were lowered in MIM-treated mice (P<0.05 vs. vehicle and vs. CIA). Conclusion. The results indicate that the tested medicine reduces inflammation, histological, and clinical signs of RA in a CIA model.

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