Dataset Information

The Role and Potential Mechanism of Complement Factor D in Fibromyalgia Development.

ABSTRACT:

Purpose

Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients.

Methods

In this study, we screened genes and secreted factors that play key roles in FM through bioinformatics and big data analysis. Furthermore, we performed CCK-8, qRT-PCR, glucose, ATP and lactate content testing, dual luciferase reporter gene assay to investigate the potential mechanism of complement factor D in fibromyalgia development.

Results

In bioinformatics and big data analysis, we identified CFD was negatively correlated with the pro-inflammatory factor IL-6 and positively correlated with the anti-inflammatory factor IL-4, which suggested that CFD may be an anti-inflammatory factor. Through cellular assays, we verified that CFD reversed the decrease in IL-4 expression and the increase in IL-6 expression in BV2 cells caused by ATP.

Conclusion

In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain. These findings provide a new theoretical basis for the clinical translation of CFD.

SUBMITTER: Lei X

PROVIDER: S-EPMC10748666 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Role and Potential Mechanism of Complement Factor D in Fibromyalgia Development.

Lei Xinhuan X Song Xiaoting X Fan Yongyong Y Chen Zhen Z Zhang Liwei L

Journal of pain research 20231219

<h4>Purpose</h4>Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients.<h4>Methods</h4>In this study, we screened ge ...[more]

PMID: 38145036

Similar Datasets

Project description:BackgroundComplement factor H (CFH) has been found to be associated with insulin resistance. This study assessed the correlation between CFH and other clinical parameters, and determined whether CFH played a role in gestational diabetes mellitus (GDM) and adverse pregnancy outcomes.MethodsA total of 397 pregnant women were included for analysis in this nested case-control study. Clinical parameters and serum were collected within the 11-17th gestational age at the first prenatal visit. At 24-28 weeks of gestation, a 75 g oral glucose tolerance test was performed and subjects were divided into a GDM (n = 80) and a non-GDM control group (n = 317). The delivery data were also followed. The serum CFH level was assayed by ELISA.ResultsCFH was higher in GDM than in non-GDM controls (280.02 [58.60] vs. 264.20 [68.77]; P = 0.014). CFH level was moderately associated with pre-pregnancy body mass index (BMI), BMI and total triglycerides (TG), and slightly associated with gestational age, low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) in GDM and non-GDM (all P < 0.05). Moreover, CFH level was moderately correlated with alkaline phosphatase (ALP) and slightly correlated with age, uric acid (UA) and total bilirubin (TB) in non-GDM (all P < 0.05). After adjustment for clinical confounding factors, BMI, TG, gestational age, ALP, TB, age and UA were independent risk factors for log10 CFH levels (all P < 0.05) in all subjects. In addition, overweight or obese pregnant women, women with hypertriglyceridemia and women in the second trimester had significantly higher CFH levels than normal weight and underweight group (P < 0.001), the non-hypertriglyceridemia group (P < 0.001) and women in the first trimester group (P < 0.05) in all pregnant women respectively. Following binary logistic regression, CFH was not independently associated with GDM and related pregnant outcomes.ConclusionsThe CFH in 11-17th weeks of gestation might be affected by many factors, including BMI, TG, gestational age, ALP, TB, age and UA. CFH was not an independent risk factor for GDM and avderse pregnancy outcomes.

Project description:BACKGROUND AND OBJECTIVE:Complement activation as an early and important inflammatory process contributes to multiple organ dysfunction after trauma. We have recently shown that complement inhibition by decay-accelerating factor (DAF) protects brain from blast-overpressure (BOP)-induced damage. This study was conducted to determine the effect of DAF on acute lung injury induced by BOP exposure and to elucidate its possible mechanisms of action. METHODS:Anesthetized adult male Sprague-Daley rats were exposed to BOP (120 kPa) from a compressed air-driven shock tube. Rats were randomly assigned to three experimental groups: 1) Control (no BOP and no DAF treatment), 2) BOP (120 kPa BOP exposure), and 3) BOP followed by treatment with rhDAF (500μg/kg, i.v) at 30 minutes after blast. After a recovery period of 3, 24, or 48 hours, animals were euthanized followed by the collection of blood and tissues at each time point. Samples were subjected to the assessment of cytokines and histopathology as well as for the interaction of high-mobility-group box 1 (HMGB1) protein, NF-κB, receptor for advanced glycation end products (RAGE), C3a, and C3aR. RESULTS:BOP exposure significantly increased in the production of systemic pro- and anti-inflammatory cytokines, and obvious pathological changes as characterized by pulmonary edema, inflammation, endothelial damage and hemorrhage in the lungs. These alterations were ameliorated by early administration of rhDAF. The rhDAF treatment not only significantly reduced the expression levels of HMGB1, RAGE, NF-κB, C3a, and C3aR, but also reversed the interaction of C3a-C3aR and nuclear translocation of HMGB1 in the lungs. CONCLUSIONS:Our findings indicate that early administration of DAF efficiently inhibits systemic and local inflammation, and mitigates blast-induced lung injury. The underlying mechanism might be attributed to its potential modulation of C3a-C3aR-HMGB1-transcriptional factor axis. Therefore, complement and/or HMGB1 may be potential therapeutic targets in amelioration of acute lung injury after blast injury.

Dataset Information

The Role and Potential Mechanism of Complement Factor D in Fibromyalgia Development.

Purpose

Methods

Results

Conclusion

Publications

The Role and Potential Mechanism of Complement Factor D in Fibromyalgia Development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets