Exploration of the anti-inflammatory potential of Polygonum bistorta L.: protection against LPS-induced acute lung injury in rats via NF-ĸβ pathway inhibition

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 5, 2025

Traditional medicine uses the roots and rhizomes of Polygonum bistorta L. (Polygonaceae) to treat cough, bronchitis, other respiratory infections. Our goal was gain insights into lung protective effects P. against lipopolysaccharide-induced acute injury in rats, along with possible mechanism(s). The outcomes revealed deliberate quantities total phenolic flavonoid contents 156.2 ± 5.13 GAE/g 179.45 2.08 mg QE/g, respectively. Crude extract possesses a maximum inhibitory potential 81.77% 0.62% for acetylcholinesterase eserine. Acute oral toxicity study LD 50 beyond 7 g/kg. Plant markedly restored LPS-induced hypoxemia, pulmonary edema, histopathological alterations, leukocyte infiltration lung. ELISA testing on BALF found that plant efficiently reinstated superoxide dismutase, anti-oxidant capacity, malondialdehyde, oxidative stress. qRT-PCR indicated decline endotoxin-induced overproduction pro-inflammatory markers, stress, transcription factor, downregulated antioxidant extract-treated groups. Furthermore, 24 metabolites were identified quantified via GC-MS. A molecular docking procedure implemented bioactive evaluate their inhibiting AChE. In conclusion, mitigate inflammation stress by improving redox signaling NF-ĸβ (p65) pathways can thus play role strategies overcoming therapeutic challenges.

Language: Английский

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Do Ultrasound Lung Abnormalities Correlate to Biomarkers and Male Gender in Rheumatoid Arthritis Patients? A Monocentric Cross-Sectional Study

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(12), P. 3534 - 3534

Published: June 17, 2024

Background: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. Objective: We aimed evaluate (i) the prevalence pleural (PLUS) and parenchymal (PAUS) abnormalities LUS RA population their possible correlation biomarkers; (ii) predictivity gender, smoking habits, previous infections (past COVID-19 tuberculosis), treatments; (iii) differences between sexes. Methods: collected data 155 (15 early 140 late) patients with mild respiratory symptoms, evaluating PLUS PAUS, fourteen lung areas also summing scores (LUS-T). Results: Only 13/155 (8.4%) were completely negative; correlated age (all parameters p 0.0001), rheumatoid factor IgM (PLUS 0.0006, PAUS 0.02, LUS-T 0.001) ACPA (p 0.001, 0.006, respectively), IL6 0.02). The male gender was predictive all evaluations 0.05, which higher than women 0.01, respectively). Other potential risk factors independent, except biological treatments, showed low < 0.05). Conclusions: can conclude that useful technique symptoms correlates age, most important biomarkers, sex.

Language: Английский

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Individual Genomic Loci, Transcript Level and Serum Profile of Immune, Antioxidant and Hormonal Markers Associated with Sheep Arthritis

Veterinary Sciences, Journal Year: 2025, Volume and Issue: 12(2), P. 122 - 122

Published: Feb. 3, 2025

Arthritis is a leading cause of economic loss in livestock farming including sheep. This study examined the changes gene expression, antioxidants, pro-inflammatory cytokines, acute-phase proteins (APPs), hormonal assays and iron profiles linked to sheep arthritis, as well diagnostic utility these markers. Blood samples were obtained from 30 apparently healthy rams with arthritis for expression biochemical analyses. Gene intensities much higher arthritis-affected than ones genes IL-1α, IL-1β, IL-6, IL-10, TNFα, NCF4, NFKB, TMED, FCAMR, iNOS COX18. The SOD3, CAT, GPX ATOX1 expressed at substantially lower levels rams. Disparities nucleotide sequence variants amplified DNA bases studied found PCR-DNA verdicts affected Immunological, protein (APP), antioxidant, estimated both groups statistically analyzed. arthritic group relation one showed significant (p < 0.05) increase APPs, free radicals, immunoglobulins, cortisol, GH, TSH, ferritin, TIBC UIBC ˂ decrease anti-inflammatory complements, insulin, T3, T4, SI, Tf sat.% serum levels. cytokines APPs achieved high values sensitivity specificity, positive predictive (PPVs), negative (NPVs), accuracy rate moderate likelihood ratio (LR). concluded that ovine stimulates innate humeral immunity, resulting prominent alterations APP antioxidant profiles, which could be valuable indicators arthritis.

Language: Английский

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Lung disease in relation to unique monocyte-macrophage subpopulations induced by combined inhalant endotoxin and collagen-induced arthritis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Lung disease is the most overrepresented cause of death in rheumatoid arthritis (RA). Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung with a combination airborne exposures collagen-induced (CIA), model that recapitulates features RA-associated interstitial (RA-ILD). As patients RA-ILD demonstrate unique circulating monocyte subpopulations, this study aims to characterize infiltrating monocytes/macrophages mouse determine whether reducing these cells mitigates development disease. Autoimmune-prone DBA/1J mice received intranasal inhalation lipopolysaccharide (LPS) daily for up 5 weeks CIA induction. Experimental groups included Sham (saline injection/saline inhalation), (CIA/saline), LPS (saline/LPS), CIA+LPS (CIA/LPS). was assessed by longitudinal imaging, function measurements, bronchoalveolar lavage fluid, tissues, histopathology. Cell subpopulations were analyzed single cell RNA-sequencing flow cytometry. Intravenous clodronate liposome administration employed reduce monocytes. Longitudinal imaging increased volume tissue density mice. assessment showed reduced compliance airway resistance dual exposure. Unsupervised clustering revealed 16 discrete clusters among experimental robust overlapping characteristics both CIA. By cytometry, exposure induced activated CD11c+CD206+CD11b+MHC Class IIhiCD80+ alveolar macrophages, CD11cmidCD206-CD11b+Ly6Chi(and Ly6Clo)MHC IIhiCD80+CD86+ CD11c-CD11b+Ly6ChiMHC monocytic-like cells. MHC IIhi-expressing across monocyte/macrophage treated more aligned than alone. CIA+LPS-induced CD11c+CD11b+ CD11cmidCD11b+ neutrophils, lymphocytes, inflammatory/pro-fibrotic mediators, expression vimentin citrullinated malondialdehyde acetaldehyde (MAA)-modified proteins/lung autoantigens. The interaction inhalation-induced inflammation autoimmune results associated uniquely inflammatory macrophages. Moreover, depletion monocytes attenuated Whereas macrophage immunophenotype endotoxin exposure, co-exposure modeling renders potentially inform pathogenesis treatment RA-ILD.

Language: Английский

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Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12823 - 12823

Published: Nov. 28, 2024

Originally discovered in the 1890s, complement system has traditionally been viewed as a "compliment" to body's innate and adaptive immune response. However, emerging data have shown that is much more complex mechanism within body involved regulating inflammation, gene transcription, attraction of macrophages, many processes. Sustained activation contributes autoimmunity chronic inflammation. Pulmonary hypertension disease with poor prognosis an average life expectancy 2-3 years leads vascular remodeling pulmonary arteries; arteries are essential host homeostasis, they divert deoxygenated blood from right ventricle heart lungs for gas exchange. This review focuses on direct links between system's involvement hypertension, along autoimmune conditions, reliance processes artery. Furthermore, circadian rhythmicity highlighted disrupted homeostatic inflammatory consequences arteries, which could potentially open new therapeutic cues. The current treatment options discussed clinical trials using inhibitors potential targets impact cell functions activation, alleviate symptoms block progression disease. Further research complement's interstitial lung diseases prove beneficial our understanding these various prevent arteries.

Language: Английский

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The future of complement therapeutics

Exploration of Immunology, Journal Year: 2024, Volume and Issue: unknown, P. 577 - 615

Published: Oct. 18, 2024

Complement is both evolutionary and scientifically old. It predates the adaptive immunity by some 600 million years was first described in 1905 Jules Bordet Paul Ehrlich. For most of its, existence complement system has been ignored scientists clinicians due to perception it being complicated its relevance for pathogenesis human disease unclear. With recent US Food Drug Administration (FDA) approvals pegcetacoplan paroxysmal nocturnal haemoglobinuria (PNH) geographic atrophy (GA), avacincaptad pegol GA iptacopan danicopan PNH, we are at a crucial juncture complement-targeting therapies. A number companies academic institutions developing next-generation therapies, which resulting an increasingly competitive landscape. If one looks serum cascade, all 3 pathways now have biotechnology or pharmaceutical industry players with 1 multiple clinical-stage inhibitors that expected be FDA approved within next few years. Furthermore, limited clinically validated targets complement-mediated disease, competition this space set further intensify coming In review, will discuss timeline discoveries led development current crop FDA-approved therapeutics. We follow discussion crowded therapy scientific advances emerged two decades underpinning future innovation, including our understanding biology, such as local intracellular complement, emerging targets, combinational approaches non-complement therapeutics unlock new indications technologies gene therapy. also give comprehensive overview landscape how can utilized target dysregulation.

Language: Английский

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Unveiling Actin Cytoskeleton Role in Mediating Chikungunya-Associated Arthritis: An Integrative Proteome–Metabolome Study

Vector-Borne and Zoonotic Diseases, Journal Year: 2024, Volume and Issue: 24(11), P. 753 - 762

Published: May 8, 2024

Chikungunya is a zoonotic disease caused by the virus (CHIKV), primarily transmitted to humans through infected Aedes mosquitoes. The infection characterized symptoms such as high fever, musculoskeletal pain, polyarthritis, and rash, which can lead severe complications encephalitis, meningitis, even fatalities. While many manifestations resemble those of other viral infections, chronic arthritis CHIKV unique, its molecular mechanisms remain ill-defined.

Language: Английский

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Plasma proteome profiling in giant cell arteritis

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(12), P. 1762 - 1772

Published: Aug. 17, 2024

This study aimed to identify plasma proteomic signatures that differentiate active and inactive giant cell arteritis (GCA) from non-disease controls. By comprehensively profiling the proteome of both patients with GCA controls, we proteins (1) distinguish controls (2) associate disease activity in GCA.

Language: Английский

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Proteomics analysis of lung tissue reveals protein makers for the lung injury of adjuvant arthritis rats

Molecular Medicine Reports, Journal Year: 2023, Volume and Issue: 28(3)

Published: July 11, 2023

Lung injury is one of the common extra‑articular lesions in rheumatoid arthritis (RA). Due to its insidious onset and no obvious clinical symptoms, it can be easily dismissed early stage diagnosis, which reasons that leads a decline quality life subsequent death patients with RA. However, pathogenesis still unclear there lack effective therapeutic targets. In present study, tandem mass tag‑labeled proteomics was used research lung tissue proteins RA model (adjuvant arthritis, AA) rats had secondary injury. The aim study identify differentially expressed related RA‑lung injury, determine their potential role provide targets for treatment. samples were collected from AA‑lung normal rats. (DEPs) identified by spectrometry. Bioinformatic analysis assess biological processes signaling pathways associated these DEPs. A total 310 DEPs found, 244 upregulated 66 downregulated. KEGG anlysis showed 'fatty acid degradation', metabolism', elongation', 'complement coagulation cascades', 'peroxisome proliferator‑activated receptor pathway' 'hypoxia‑inducible factor significantly tissues Immunofluorescence staining confirmed increased expression clusterin, serine protease inhibitors complement 1qc AA results revealed significance certain (for example, C9, C1qc Clu) occurrence development provided support through experiments biomarkers diagnosis prevention

Language: Английский

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Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study

International Journal of General Medicine, Journal Year: 2023, Volume and Issue: Volume 16, P. 3583 - 3592

Published: Aug. 1, 2023

Objective: The purpose of the research was to explore possible risk factors for development hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features. Methods: This retrospective contained 501 RA patients, divided into with HC (n=78) without (n=423). Demographic characteristics test results were collected analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) erythrocyte sedimentation rate (ESR), etc. Spearman correlation served assessing correlations levels C3 C4 each index. Receiver operating characteristic (ROC) curves diagnostic efficacy index HC. Furthermore, occurrence analyzed employing binary logistic regression single multiple factors. Results: Compared HC, former older had a longer disease duration increased Anti-MCV, IgM DAS28 lower Hb, PLT ESR; analysis verified level Anti-MCV negative (r=− 0.156); area under ROC curve (AUC) diagnosing largest at 0.65 (95% CI: 0.60– 0.69); indicated that advanced age (> 66 years), long 62 months), high value 6.13), Anti-MCV> 107.68IU/mL, IgM> 1.54g/L, ESR≤ 69.00mm/h, Hb≤ 99.00g/L PLT≤ 305.00× 10 9 /L probable patients. Conclusion: Age duration, DAS28, IgM, ESR, are closely related Timely monitoring these indicators can help evaluate activity further improve prognosis. Keywords: arthritis, hypocomplementemia, factors,

Language: Английский

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