scholarly journals Serum-derived extracellular vesicles inhibit osteoclastogenesis in active-phase patients with SAPHO syndrome

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110069
Author(s):  
Yanpan Gao ◽  
Yanyu Chen ◽  
Lun Wang ◽  
Chen Li ◽  
Wei Ge

Objective: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disorder and the underlying pathogenesis is unclear. In this study, 88 SAPHO patients and 118 healthy controls were recruited to investigate the role of serum-derived extracellular vesicles (SEVs) in SAPHO syndrome. Methods: Quantitative proteomics was applied for SEVs proteome identification, and ELISA and Western blotting was performed to verify the results of mass spectrum data. In vitro osteoclastogenesis and osteogenesis assay was used to confirm the effects of SEVs on bone metabolism. Results: Tandem mass tagging-based quantitative proteomic analysis of SAPHO SEVs revealed differential expressed proteins involved in bone metabolism. Of these, serum amyloid A-1 (SAA1) and C-reactive protein (CRP) were upregulated. Higher SAA1 levels in SAPHO patients were confirmed by ELISA. In addition, SAA1 levels were positively correlated with CRP, an inflammatory marker related to the condition of patients. In vitro celluler studies confirmed that SAPHO SEVs inhibited osteoclastogenesis in patients mainly in the active phase of the disease. Further analysis demonstrated that Nucleolin was upregulated in osteoclasts of active-phase patients under SAPHO SEVs stimulation. Conclusion: In this study, we identified SAA1 as an additional inflammation marker that can potentially assist the diagnosis of SAPHO syndrome, and speculated that Nucleolin is a key regulator of osteoclastogenesis in active-phase patients.

2020 ◽  
Vol 2020 ◽  
pp. 1-35 ◽  
Author(s):  
Lucas Amaral-Machado ◽  
Wógenes N. Oliveira ◽  
Susiane S. Moreira-Oliveira ◽  
Daniel T. Pereira ◽  
Éverton N. Alencar ◽  
...  

Asthma, a disease classified as a chronic inflammatory disorder induced by airway inflammation, is triggered by a genetic predisposition or antigen sensitization. Drugs currently used as therapies present disadvantages such as high cost and side effects, which compromise the treatment compliance. Alternatively, traditional medicine has reported the use of natural products as alternative or complementary treatment. The aim of this review was to summarize the knowledge reported in the literature about the use of natural products for asthma treatment. The search strategy included scientific studies published between January 2006 and December 2017, using the keywords “asthma,” “treatment,” and “natural products.” The inclusion criteria were as follows: (i) studies that aimed at elucidating the antiasthmatic activity of natural-based compounds or extracts using laboratory experiments (in vitro and/or in vivo); and (ii) studies that suggested the use of natural products in asthma treatment by elucidation of its chemical composition. Studies that (i) did not report experimental data and (ii) manuscripts in languages other than English were excluded. Based on the findings from the literature search, aspects related to asthma physiopathology, epidemiology, and conventional treatment were discussed. Then, several studies reporting the effectiveness of natural products in the asthma treatment were presented, highlighting plants as the main source. Moreover, natural products from animals and microorganisms were also discussed and their high potential in the antiasthmatic therapy was emphasized. This review highlighted the importance of natural products as an alternative and/or complementary treatment source for asthma treatment, since they present reduced side effects and comparable effectiveness as the drugs currently used on treatment protocols.


2020 ◽  
Author(s):  
Jing Wang ◽  
Yuan Yuan ◽  
Xiaxia Jin ◽  
Guoguang Lu

Abstract Background: Ankylosing spondylitis (AS)is a chronic inflammatory disorder involving the sacroiliac joints, lumbar spine, thoracic spine and even cervical spine, and could leading to disability due to the failure of timely treatment. Therefore, early diagnosis is essential to for AS treatment. The lymphocyte-monocyte ratio (LMR) is a systemic inflammatory and immunological indicator for prediction of disease development and progression. However, its role in AS remains unclear. The aim of this study was to investigate the role of LMR in AS diagnosis, disease activity classification and sacroiliac arthritis staging. Methods: Seventy-eight AS patients and 78 sex-age-matched healthy controls (HCs) were enrolled in this study. The diagnosis of AS was performed according to the New York criteria, whereas the staging of sacroiliac arthritis of AS patients was determined by X-ray examination.Comparison of between AS patients and HCs and between patients with high and low stages on LMR levels and other laboratory indicators were carried out. Results: A higher level of NLR, RDW, PLR, MPV, ESR, CRP and lower level of RBC, Hb, Hct, LMR, ALT, AST, TBIL and A/G were noted in the AS patients compared to HCs. A positive correlation was observed between LMR and RBC, Hb, Hct and A/G, while negative correlation was found between LMR and NLR, PLR, AST, TBIL (P< 0.05). The ROC curve showed that the area under the curve of LMR was 0.803(95%CI =0.734-0.872), with a sensitivity and specificity of 62.8% and 87.2%,and the AUC (95%CI) for ESR, CRP and LMR in the combined diagnosis of ankylosing spondylitis were 0.975(0.948-1.000),with the sensitivity and specificity of 94.9% and 97.4% .Levels of WBC and NLR were higher in high X-ray stage patients, whereas levels of LMR was lower (P<0.05) and statistical differences were observed of LMR values among different stages (P<0.05). Conclusions: Our study suggested that LMR is an important inflammatory marker that can be used to diagnosis AS and identify disease activity and X-ray stage of sacroiliac arthritis in AS patients.


2014 ◽  
Vol 112 (7) ◽  
pp. 1129-1136 ◽  
Author(s):  
Nida Nadeem ◽  
Jayne V. Woodside ◽  
Charlotte E. Neville ◽  
Damian O. McCall ◽  
David McCance ◽  
...  

The present study assessed whether increased fruit and vegetable (F&V) intake reduced the concentrations of the inflammatory marker serum amyloid A (SAA) in serum, HDL2 and HDL3 and whether the latter reduction influenced any of the functional properties of these HDL subfractions. The present study utilised samples from two previous studies: (1) the FAVRIT (Fruit and Vegetable Randomised Intervention Trial) study – hypertensive subjects (systolic blood pressure (BP) range 140–190 mmHg; diastolic BP range 90–110 mmHg) were randomised to receive a 1-, 3- or 6-portion F&V/d intervention for 8 weeks, and (2) the ADIT (Ageing and Dietary Intervention Trial) study – older subjects (65–85 years) were randomised to receive a 2- or 5-portion F&V/d intervention for 16 weeks. HDL2 and HDL3 were isolated by rapid ultracentrifugation. Measurements included the following: serum high-sensitive C-reactive protein (hsCRP) by an immunoturbidimetric assay; serum IL-6 and E-selectin and serum-, HDL2- and HDL3-SAA by ELISA procedures; serum-, HDL2- and HDL3-cholesterol ester transfer protein (CETP) activity by a fluorometric assay. Although the concentrations of hsCRP, IL-6 and E-selectin were unaffected by increasing F&V intake in both studies (P>0·05 for all comparisons), those of SAA in HDL3 decreased in the FAVRIT cohort (P= 0·049) and those in HDL2 and HDL3 decreased in the ADIT cohort (P= 0·035 and 0·032), which was accompanied by a decrease in the activity of CETP in HDL3 in the FAVRIT cohort (P= 0·010) and in HDL2 in the ADIT cohort (P= 0·030). These results indicate that SAA responds to increased F&V intake, while other inflammatory markers remain unresponsive, and this leads to changes in HDL2 and HDL3, which may influence their antiatherogenic potential. Overall, the present study provides tangible evidence of the effectiveness of increased F&V intake, which may be of use to health policy makers and the general public.


Author(s):  
Isabel Maria Oliveira ◽  
Diogo Castro Fernandes ◽  
Ibrahim Fatih Cengiz ◽  
Rui Luís Reis ◽  
Joaquim Miguel Oliveira

AbstractRheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disorder that mostly affects the synovial joints and can promote both cartilage and bone tissue destruction. Several conservative treatments are available to relieve pain and control the inflammation; however, traditional drugs administration are not fully effective and present severe undesired side effects. Hydrogels are a very attractive platform as a drug delivery system to guarantee these handicaps are reduced, and the therapeutic effect from the drugs is maximized. Furthermore, hydrogels can mimic the physiological microenvironment and have the mechanical behavior needed for use as cartilage in vitro model. The testing of these advanced delivery systems is still bound to animal disease models that have shown low predictability. Alternatively, hydrogel-based human dynamic in vitro systems can be used to model diseases, bypassing some of the animal testing problems. RA dynamic disease models are still in an embryonary stage since advances regarding healthy and inflamed cartilage models are currently giving the first steps regarding complexity increase. Herein, recent studies using hydrogels in the treatment of RA, featuring different hydrogel formulations are discussed. Besides, their use as artificial extracellular matrices in dynamic in vitro articular cartilage is also reviewed.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Birgit Fendl ◽  
René Weiss ◽  
Tanja Eichhorn ◽  
Ingrid Linsberger ◽  
Taras Afonyushkin ◽  
...  

AbstractThere is increasing evidence that C-reactive protein (CRP) can mediate inflammatory reactions following the transformation of functionally inert pentameric CRP (pCRP) into its structural isoform pCRP* and into monomeric CRP (mCRP). This conversion can occur on the membranes of apoptotic or activated cells or on extracellular vesicles (EVs) shed from the cell surface. Here, we characterized the association of CRP with EVs in plasma from sepsis patients using flow cytometry, and found highly elevated levels of total EV counts and CRP+ EVs as compared to healthy individuals. We further assessed the ability of PentraSorb CRP, an extracorporeal device for the adsorption of CRP, to deplete free CRP and CRP+ EVs. Treatment of septic plasma with the adsorbent in vitro resulted in almost complete removal of both, free CRP and CRP+ EVs, while total EV counts remained largely unaffected, indicating the detachment of CRP from the EV surface. EVs from septic plasma elicited a release of interleukin-8 from cultured human monocytes, which was significantly reduced by adsorbent treatment prior to EV isolation. Our findings provide evidence that CRP+ EVs exhibit pro-inflammatory characteristics and can contribute to the spreading of inflammation throughout the circulation on top of their pro-coagulant activity.


2020 ◽  
Vol 10 ◽  
Author(s):  
Dan Liu ◽  
Yonghe Chen ◽  
Yunxiu Wang ◽  
Mangjuan Lei ◽  
Lin Chen ◽  
...  

The role of angiogenesis in tumor progression has been recognized as one of the hallmarks of cancer, but the mechanism of its action remains unclear. Inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) are proposed to play causal roles in the development of various disorders, including malignancies. Previously, we identified the complex of CRP and SAA (CRP-SAA) with diagnostic and prognostic value better than either one of them in the serum of lung cancer patients. In this study, we further explored the stimulation function of CRP-SAA on angiogenesis and inflammation. To explore possible mechanisms, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and multi-bioinformatics analysis revealed that THP-1 and human umbilical vein endothelial cells (HUVECs) responded to SAA stimulation with upregulation of two pro-angiogenic cytokines in common, i.e., C-X-C motif ligand 6 (CXCL6) and CXCL8, which were validated by subsequent experiments in vitro. CRP had weak effects as a single stimulus, but it can efficiently potentiate the SAA induction of cytokines, which was stronger than the sum of the both (P &lt; 0.001). The synergistical effect of the combination of CRP and SAA enhanced HUVECs transwell and constricted morphology by upregulating the pro-angiogenic genes. These results indicated that the binding of CRP and SAA acted synergistically in pro-angiogenesis by increasing inflammation and inducing vascular network.


Author(s):  
Leong Tung Ong

Asthma is a chronic inflammatory condition, and the main features include airway hyper-responsiveness and inflammation of the airway with the accumulation of inflammatory cells. Increased level of plasma fibrinogen and serum amyloid A suggests the involvement of systemic inflammation in asthma. C-reactive protein (CRP) is an acute-phase protein that produced mainly by hepatocytes and is an inflammatory marker. CRP levels monitoring is useful in the evaluation of early inflammation and efficacy of treatment in acute-phase illnesses. Several studies show that asthma alone can cause an increase in high-sensitivity CRP (hs-CRP) when compared with the healthy controls. Besides that, steroid-naïve patients have a higher mean value of hs-CRP levels compared with those on inhaled corticosteroid. Furthermore, studies have shown that an elevated hs-CRP level has a positive correlation with non-atopic asthma but not atopic asthma. Additionally, an increase in serum hs-CRP levels correlates with the severity of asthma. Therefore, serum hs-CRP is a useful surrogate marker to predict the severity of inflammation of the bronchus in asthma and assess the asthma status.


2019 ◽  
Vol 89 (5-6) ◽  
pp. 357-370 ◽  
Author(s):  
Ahmad Nazrun Shuid ◽  
Srijit Das ◽  
Isa Naina Mohamed

Abstract. The present review explored the anti-inflammatory and immunomodulatory properties of vitamin E, which has protective action against osteoporosis. A systematic review of the literature was conducted to identify the published bone studies on vitamin E. The studies included inflammatory or immunology-related parameters. Medline and Scopus databases were searched for relevant studies published from 2005 till 2015. Research articles published in English and confined to the effect of vitamin E on bone were included. It is pertinent to mention that these studies took into consideration inflammatory or immunology parameters including interleukin (IL)-1, IL-6, receptor activator of nuclear factor kappa-B ligand (RANKL), inducible nitric oxide synthases (iNOS), serum amyloid A (SAA), e-selection and high-sensitivity C-reactive protein (hs-CRP). An extended literature search yielded 127 potentially relevant articles with seven articles meeting the inclusion and exclusion criteria. Another recent article was added with the total number accounting to eight. All these included literature comprised five animal studies, one in-vitro study and two human studies. These studies demonstrated that vitamin E, especially tocotrienol, was able to alleviate IL-1, IL-6, RANKL, iNOS and hs-CRP levels in relation to bone metabolism. In conclusion, vitamin E exerts its anti-osteoporotic actions via its anti-inflammatory and immunomodulatory effects.


2019 ◽  
Vol 32 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Ramona F. Stroescu ◽  
Otilia Mărginean ◽  
Teofana Bizerea ◽  
Mihai Gafencu ◽  
Adrian Voicu ◽  
...  

Abstract Background Obesity is a chronic inflammatory disorder in which leptin, adiponectin and C-reactive protein (CRP) play an important role. This study aimed to investigate the relationship between markers of adiposity such as leptin, adiponectin and high sensitivity C-reactive protein (hs-CRP) in obese children, and to determine whether these adipokines are significant markers in defining metabolic syndrome (MetS) in pediatric population. Methods A cross-sectional study was conducted over a period of 1 year, between July 2013 and June 2014, on 122 cases of obesity in children diagnosed at the Louis Ţurcanu Emergency Hospital for Children Timişoara, in the departments of Diabetes and Nutritional Diseases, Endocrinology and Cardiology. The patients were divided into two groups, according to the presence of MetS. Results MetS was present in 27% of obese children. The groups were homogenous with respect to age, sex and body mass index (BMI). Adiponectin, leptin and hs-CRP were significantly modified in the group with MetS (p=0.04, p=0.04, p=0.01, respectively). Conclusions hs-CRP, leptin and adiponectin can be used as predictors of cardiovascular risk in pediatric population.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao Liang ◽  
Jie Li ◽  
Cheng Lu ◽  
Duoli Xie ◽  
Jin Liu ◽  
...  

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide is originally developed to suppress inflammation via its metabolite A77 1726 to attenuate bone erosion. However, distinctive responsiveness to Leflunomide is observed among RA individuals. Here we show that Leflunomide exerts immunosuppression but limited efficacy in RA individuals distinguished by higher serum C-reactive protein (CRPHigher, CRPH), whereas the others with satisfactory responsiveness to Leflunomide show lower CRP (CRPLower, CRPL). CRP inhibition decreases bone erosion in arthritic rats. Besides the immunomodulation via A77 1726, Leflunomide itself induces AHR-ARNT interaction to inhibit hepatic CRP production and attenuate bone erosion in CRPL arthritic rats. Nevertheless, high CRP in CRPH rats upregulates HIF1α, which competes with AHR for ARNT association and interferes Leflunomide-AHR-CRP signaling. Hepatocyte-specific HIF1α deletion or a HIF1α inhibitor Acriflavine re-activates Leflunomide-AHR-CRP signaling to inhibit bone erosion. This study presents a precision medicine-based therapeutic strategy for RA.


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