Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to cartilage destruction and bone erosion. In-depth exploration of the pathogenesis of RA and the development of effective therapeutic drugs are of important clinical and social value. Herein, we explored the medicinal value of Cornus officinalis Sieb. and Paeonia lactiflora Pall. in RA treatment using a rat model of collagen-induced arthritis (CIA). We compared the therapeutic effect of Cornus officinalis and Paeonia lactiflora with that of their main active compounds, ursolic acid and paeoniflorin, respectively. We demonstrated that the combination of Cornus officinalis and Paeonia lactiflora effectively inhibited the release of factors associated with oxidative stress and inflammation during RA, therein ameliorating the symptoms and suppressing the progression of RA. We further showed that the underlying mechanisms may be related to the regulation of apoptosis in synovial tissues, and we investigated the potential involvement of AMPK-mediated mitochondrial dynamics in the therapeutic action of the two drugs and their active components.

Cardiac involvement, displayed as premature cardiovascular disease (CVD), is one of common clinical symptoms of patients with systemic lupus erythematosus (SLE), contributing to mortality of the disease. The precise underlying pathological mechanism(s) for the cardiac involvement in lupus remains poorly understood. Lipids and their metabolites are directly involved in atherosclerosis development, oxidative stress, and inflammation, which are closely related to the development of CVD. In the study, shotgun lipidomics was exploited to quantitatively analyze cellular lipidomes in the cardiac tissue of MRL/lpr mice at two different time points (i.e., pre-lupus and lupus state) with/without treatment with glucocorticoids (GCs). Urine protein, spleen index, and renal histopathological evaluation of the mice were also performed for assessment of SLE onset and/or outcome. Lipidomics analysis revealed that the deposition of cholesterol and the aberrant metabolism of lipids caused by the increased energy metabolism and the enhanced activation of phospholipases, both of which were originally induced by inflammation, were already present in cardiac tissues from lupus-prone mice even at pre-lupus state. These lipid alterations could further induce inflammation and autoimmune responses, accelerating the process of CVD. In addition, the present study also demonstrated that GCs therapy could not only delay the progression of SLE, but also partially corrected these alterations of lipid species in cardiac tissue due to their anti-inflammatory effect. Thus, the medications with better anti-inflammatory effect might be a useful therapeutic method for premature CVD of SLE.

Cornus officinalis Sieb et. Zucc and Paeonia lactiflora Pall. have exhibited favorable therapeutic effects against rheumatoid arthritis (RA), but the specific mechanisms of their active compounds remain unclear. The aim of this study was to comprehensively analyze the therapeutic mechanisms of selected active compounds in Cornus officinalis (loganin, ursolic acid, and morroniside) and Paeonia lactiflora (paeoniflorin and albiflorin) via network pharmacology. The pharmacological properties of the five active compounds were evaluated and their potential target genes were identified by database screening. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analysis were performed to determine the enriched molecular pathways associated with the active compounds. Using network pharmacology tools, eight genes (IL1β, VEGFA, STAT3, TP53, IL6, TNF, FOS, and LGALS3) were identified as common targets between RA and the five active compounds. Molecular docking simulation revealed the compound-target relationship between the five active compounds and three selected targets from the eight common ones (LGALS3, STAT3, and VEGFA). The compound-target relationships were subsequently validated via preliminary in vivo experiments in a rat model of collagen-induced arthritis. Rats subjected to collagen-induced arthritis showed increased protein expression of LGALS3, STAT3, and VEGFA in synovial tissues. However, treatment using Cornus officinalis or/and Paeonia lactiflora, as well as their most drug-like active compounds (ursolic acid or/and paeoniflorin, respectively, identified based on pharmacological properties), attenuated the expression of these three targets, as previously predicted. Collectively, network pharmacology allowed the pharmacological and molecular roles of Cornus officinalis and Paeonia lactiflora to be systematically revealed, further establishing them as important candidate drugs in the treatment and management of RA.

Objective: To analyze the disease burden of anxiety disorders globally, in middle SDI countries, and in China using GBD public database.Methods: Data on anxiety disorders were extracted from the GBD database, and GBDR_V2.36 was used for data visualization and plotting.Results: From 1990 to 2021, global anxiety disorder cases and prevalence rose steadily. In 2021, the 30–34 age group had the highest global cases (male:female≈3:7), while DALY rates peaked in 25–29-year-olds. Medium-SDI countries followed similar trends, with peak DALYs in the 20–24 age group. China saw declining prevalence/incidence but rising DALYs, with highest cases in 50–54-year-olds (male:female≈3:5) and DALY rates in 75–84-year-olds. Globally, medium-SDI countries, and China, incidence peaked in 10–14-year-olds. Projections suggest China’s anxiety disorder burden will surge through 2035.Conclusion: Globally and in middle SDI countries, prevalence, incidence, and DALY rates increased, with the 30–34 age group showing the highest case burden (women outnumbering men) and peak DALY rates in younger adults (25–29 globally, 20–24 in middle SDI). In contrast, China saw a decline in prevalence and incidence, with the burden peaking later (50–54 for cases, 75–84 for DALYs). Projections indicate rising anxiety disorder burden in China by 2035, necessitating region- and age-specific interventions.

Background: Liver injury, such as nonalcoholic fatty liver disease, is a common symptom observed in patients with gout/hyperuricaemia. However, the exact mechanisms are still unclear. There is ongoing controversy about whether representative agents like colchicine and febuxostat, commonly used to manage gout, could also help prevent the liver injury. Liver plays a crucial role in uric acid (UA) production and lipid metabolism. Thus, the study aimed to investigate the aberrant lipid metabolism in the liver during injury and the effects of these drugs. Methods: An advanced multi-dimensional mass spectrometry-based shotgun lipidomics technology was employed for class-targeted lipid analysis of cellular lipidomes in hepatic tissue of a gouty model induced by a combination of monosodium urate crystals and high-fat diet with or without treatment with colchicine and febuxostat. Serum UA, blood urea nitrogen, creatinine, proinflammatory cytokines, expression of AMP-activated protein kinase protein, footpad histopathology, and footpad swelling and pain threshold of these mice were assessed to evaluate the progression of gout. Results: Lipidomics analysis clearly demonstrated that the ectopic fat accumulation as well as changes in fatty acyls composition in TAG pool, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, and reduced 4-hydroxyalkenal bioavailability in liver tissue could contribute to liver damage to the gouty model. Treatment with colchicine or febuxostat not only ameliorated gouty symptoms but also corrected these abnormal hepatic lipid metabolism patterns. Conclusion: This study shed light on underlying mechanism(s) for liver injury in gout/hyperuricaemia and suggested that administration of drugs like colchicine and febuxostat could prevent liver injury.