Mucic Acid Loaded Polyethylenimine@Gold Nanoparticles for the Treatment of Rheumatoid Arthritis

2021 ◽  
Author(s):  
Yixia Cui ◽  
Junwei Zhang ◽  
Yanwu Liu ◽  
Guolin Meng ◽  
Changwei Lv
Keyword(s):  
Rheumatoid Arthritis ◽  
Gold Nanoparticles ◽  
Inflammatory Disease ◽  
Average Diameter ◽  
Collagen Induced Arthritis ◽  
Transmission Microscopy ◽  
Mucic Acid ◽  
Joint Deformation ◽  
Area Unit ◽  
Pro Inflammatory Cytokines

Abstract Rheumatoid arthritis (RA) could be a common autoimmune disease that involves severe Joint deformation. The main off-target medicines unable to cure RA, that permits associate in nursing infection with the unwellness. The nanomaterials-based RA medical aid is a good strategy to enhance the treatment efficaciousness within the inflammatory region. Specifically, metal-based nanomaterials are a wonderful choice for a possible delivery vehicle for inflammatory disease agents, attributable to their novel properties. Herein, we have got developed a small-sized Polyethylenimine (PEI) coated gold nanoparticles (AuNPs) with an average diameter of 80 nm, that area unit used for top loading of carboxylic acid (MA). Various microscopic and qualitative analysis tools like high-resolution transmission microscopy (HR-TEM), Field-emission scanning microscope (FE-SEM), and Fourier-transform infrared (FTIR) spectroscopic analysis studies were accustomed to make sure as-made PEI-AuNPs. The invented PEI-coated AuNPs (PEI-AuNPs) exhibited higher contrast with an extended expanse that's promising to store giant amounts of MA medicine. MA is attributed to deduce the inflammatory response by inhibiting the pro-inflammatory cytokines and averting undesirable ancient drug aspect effects in Collagen-induced inflammatory disease (CIA). Numerous organic chemistry parameters like weight, hind paw volume, protein estimation, anti-serum protein analysis, and microscopic anatomy examination were conducted in Collagen-induced arthritis mice treated at a dose (10 µg) of MA packed PEI-AuNPs. The obtained results showed the MA-PEI-AuNPs were used with success within the treatment of Collagen-induced arthritis, relative to PEI-AuNPs and MA. Therefore, MA loaded PEI-AuNPs as a stimulating candidate in future RA applications.

scholarly journals Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α

2021 ◽  
Vol 22 (8) ◽  
pp. 3898
Author(s):  
Kenta Kaihara ◽  
Shuji Nakagawa ◽  
Yuji Arai ◽  
Hiroaki Inoue ◽  
Shinji Tsuchida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Joint Destruction ◽  
Hypoxia Inducible Factor ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Risk Patients ◽  
Sustained Hypoxia ◽  
Pro Inflammatory Cytokines

Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.

scholarly journals What Have We Learned about the Pathogenesis of Rheumatoid Arthritis from TNF-Targeted Therapy?

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Richard O. Williams
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Susceptibility ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Inflammatory Bowel ◽  
Genetic And Environmental Factors ◽  
The Impact ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Studies of cytokine regulation in rheumatoid arthritis led to the development of TNFα inhibitors which are now used for a number of indications, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, and ankylosing spondylitis. The widespread use of biologics in the clinic offers unique opportunities for probing disease pathogenesis and this paper provides an overview of rheumatoid arthritis, with a particular emphasis on the impact of anti-TNFα therapy on pathogenetic mechanisms. An overview is also provided on the most commonly used animal models that mimic RA, including adjuvant-induced arthritis, collagen-induced arthritis, TNFα-transgenic mice, and the K/BxN and SKG models. These models have led to significant discoveries relating to the importance of pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis, resulting from disregulation of the normally finely tuned balance of pro- and anti-inflammatory cytokine signalling. In addition, experimental evidence is discussed suggesting how genetic and environmental factors can contribute to disease susceptibility. The role of effector and regulatory T cells is discussed in the light of the relatively disappointing therapeutic effects of T cell modifying agents such as anti-CD4 antibody and cyclosporin. It is concluded that comprehensive analyses of mechanisms of action of biologics and other drugs entering the clinic will be essential to optimise therapy, with the ultimate aim of providing a cure.

scholarly journals Hyaluronic acid Hydrogels Hybridized with Au-Triptolide Nanoparticle for Intra-articular targeted multi-therapy of Rheumatoid Arthritis

2022 ◽  
Author(s):  
Chenxi Li ◽  
Rui Liu ◽  
Yurong Song ◽  
Dongjie Zhu ◽  
Liuchunyang Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gold Nanoparticles ◽  
Hyaluronic Acid ◽  
Near Infrared ◽  
Mtor Pathway ◽  
Collagen Induced Arthritis ◽  
Hybrid Hydrogels ◽  
Low Dosage

Abstract Triptolide (TP) is a DMARD highly effective in patients with RA. Hyaluronic acid (HA) hydrogels loaded RGD-attached gold nanoparticles containing TP were synthesized to alleviate the toxicity and increase therapeutic specificity. The hydrogels can be applied for targeted photothermal-chemo therapy, and in vivo imaging of RA. Heat was locally generated at the inflammation site after degradation of HA chains due to near-infrared resonance (NIR) irradiation of gold nanoparticles (AuNPs), and TP was released. Administration of the hybrid hydrogels containing low dosage of TP combined with NIR irradiation alleviated arthritic conditions and improved the inflamed joint in collagen-induced arthritis (CIA) mice. In vitro effect of the hydrogel was mediated through decrease of phosphorylation of mTOR and its substrate, p70S6K1, thus inhibiting mTOR pathway.

scholarly journals SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.3-934
Author(s):  
M. Kim ◽  
Y. Choe ◽  
H. Lee ◽  
Y. H. Cheon ◽  
S. I. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Translationally Controlled Tumor Protein ◽  
Biochemical Analyses ◽  
Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

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 Facile Green, Room-Temperature Synthesis of Gold Nanoparticles Using Combretum erythrophyllum Leaf Extract: Antibacterial and Cell Viability Studies against Normal and Cancerous Cells

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 893
Author(s):  
Olufunto T. Fanoro ◽  
Sundararajan Parani ◽  
Rodney Maluleke ◽  
Thabang C. Lebepe ◽  
Jose R. Varghese ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cell Viability ◽  
Leaf Extract ◽  
Room Temperature ◽  
Klebsiella Oxytoca ◽  
Cost Effective ◽  
Average Diameter ◽  
Antibacterial Activities ◽  
Inhibition Concentration ◽  
First Time

We herein report a facile, green, cost-effective, plant-mediated synthesis of gold nanoparticles (AuNPs) for the first time using Combretum erythrophyllum (CE) plant leaves. The synthesis was conducted at room temperature using CE leaf extract serving as a reducing and capping agent. The as-synthesized AuNPs were found to be crystalline, well dispersed, and spherical in shape with an average diameter of 13.20 nm and an excellent stability of over 60 days. The AuNPs showed broad-spectrum antibacterial activities against both pathogenic Gram-positive (Staphylococcus epidermidis (ATCC14990), Staphylococcus aureus (ATCC 25923), Mycobacterium smegmatis (MC 215)) and Gram-negative bacteria (Proteus mirabilis (ATCC 7002), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13822), Klebsiella oxytoca (ATCC 8724)), with a minimum inhibition concentration of 62.5 µg/mL. In addition, the as-synthesized AuNPs were highly stable with exceptional cell viability towards normal cells (BHK- 21) and cancerous cancer cell lines (cervical and lung cancer).

scholarly journals AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Serum ◽  
Inflammatory Cytokines ◽  
Inflammatory Markers ◽  
Healthy People ◽  
Healthy Individuals ◽  
Markers Of Inflammation ◽  
High Level ◽  
Pro Inflammatory Cytokines

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared

scholarly journals Metabolomics study of the therapeutic mechanism of a Chinese herbal formula on collagen-induced arthritis mice

RSC Advances ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 3716-3725 ◽  
Author(s):  
Zhen Jin ◽  
Ji-da Zhang ◽  
Xin Wu ◽  
Gang Cao
Keyword(s):  
Rheumatoid Arthritis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Herbal Formula ◽  
Collagen Induced Arthritis ◽  
Chinese Herbal Formula ◽  
Chinese Herbal ◽  
Therapeutic Mechanism ◽  
Metabolomics Study

Wenjinghuoluo (WJHL) prescription, the typical rheumatoid arthritis (RA) treatment compound in traditional Chinese medicine, shows favorable efficacy.

scholarly journals Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 587
Author(s):  
Fu-Tzu Pai ◽  
Cheng-You Lu ◽  
Chia-Hsin Lin ◽  
John Wang ◽  
Ming-Cheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Suppressor Cells ◽  
Clinical Severity ◽  
Histopathological Analysis ◽  
Human Rheumatoid Arthritis ◽  
Psoralea Corylifolia ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Synovial Tissues ◽  
Orthopedic Diseases

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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