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Rheumatology International Jun 2024To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013-2021, total and dependent on gender, age, region and serological...
To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013-2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients' gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55 years of age.
Topics: Humans; Poland; Arthritis, Rheumatoid; Male; Female; Incidence; Middle Aged; Adult; Aged; Prevalence; Adolescent; Young Adult; Antirheumatic Agents; Age Distribution; Sex Distribution; Child; Child, Preschool; Aged, 80 and over; Infant
PubMed: 38678142
DOI: 10.1007/s00296-024-05591-8 -
Current Pharmaceutical Design Apr 2024Bear Bile Powder (BBP) is a traditional Chinese medicine. It has been widely used in clinical practices and has shown a good anti-inflammatory effect. However, its...
BACKGROUND
Bear Bile Powder (BBP) is a traditional Chinese medicine. It has been widely used in clinical practices and has shown a good anti-inflammatory effect. However, its effectiveness in treating Ulcerative Colitis (UC) has not yet been studied.
OBJECTIVE
To explore the therapeutic effect of BBP on ulcerative colitis and its potential mechanism by combining acute ulcerative colitis mouse models and comprehensively observing various physiological and biochemical indexes of mice.
METHODS
The acute ulcerative colitis model was induced by drinking water containing dextran sulfate sodium salt (DSS) for 7 days. Studies were divided into Control, DSS, DSS+ Sulfasalazine (SASP, 450 mg/kg), and DSS + bear bile powder group (BBP, 320 mg/kg). The Disease Activity Index (DAI) and colonic tissue damage of mice were evaluated. Tissue immunofluorescence and western blot were used to determine related tight Junction Proteins (TJs), and 16S V34 amplicon was used to analyze intestinal microorganisms. The therapeutic effect of BBP on ulcerative colitis model mice was studied comprehensively.
RESULTS
After treatment, BBP can significantly improve the physiological condition of acute UC mice and reduce DAI fraction. Compared with the DSS group, the BBP group significantly increased the colon length and significantly decreased the injury fraction of acute UC mice. Regarding the intestinal mechanical barrier, BBP significantly increased the expression of ZO-1, Occludin, and Claudin 1 protein in colon tissue. In terms of microbial community, the intestinal microbial diversity of mice decreased after the administration of BBP, but there was no significant difference in structural composition between the BBP group and the Control group. By comparing the four groups of species with significant differences, it was found that the BBP group significantly reduced the abundance of specific harmful microorganisms at the order, family, genus, and species levels.
CONCLUSION
Oral administration of a certain dose of BBP can significantly improve the symptoms of ulcerative colitis in mice. Part of the reason may be that it increases the expression of tight junction proteins, regulates specific flora in the intestine of mice, and maintains intestinal barrier homeostasis. In the future, the clinical application value of BBP will be explored, and BBP will be developed as a drug with the potential to treat UC and alleviate the pain of UC patients.
PubMed: 38676524
DOI: 10.2174/0113816128294893240403074953 -
Toxics Apr 2024Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight...
Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. L. (), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.
PubMed: 38668491
DOI: 10.3390/toxics12040268 -
Animal Models and Experimental Medicine Apr 2024Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation. Intestinal...
New insights into the interactions between the gut microbiota and the inflammatory response to ulcerative colitis in a mouse model of dextran sodium sulfate and possible mechanisms of action for treatment with PE&AFWE.
BACKGROUND
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation. Intestinal innate immunity, including innate immune cells, defends against pathogens and excessive entry of gut microbiota, while preserving immune tolerance to resident intestinal microbiota, and may be characterized by its capacity to produce a rapid and nonspecific reaction. The association between microbiota dysbiosis and the pathogenesis of IBD is complex and dynamic. When the intestinal ecosystem is in dysbiosis, the reduced abundance and diversity of intestinal gut microbiota make the host more vulnerable to the attack of exogenous and endogenous pathogenic gut microbiota. The aim of our study was to comprehensively assess the relationship between microbial populations within UC, the signaling pathways of pathogenic gut microbe therein and the inflammatory response, as well as to understand the effects of using PE&AFWE (poppy extract [Papaver nudicaule L.] and Artemisia frigida Willd. extract) on UC modulation.
METHODS
A UC mouse model was established by inducing SPF-grade C57BL/6 mice using dextrose sodium sulfate (DSS). Based on metagenomic sequencing to characterize the gut microbiome, the relationship between gut microbiota dysbiosis and gut microbiota was further studied using random forest and Bayesian network analysis methods, as well as histopathological analysis.
RESULTS
(1) We found that the 5 gut microbiota with the highest relative abundance of inflammatory bowel disease UC model gut microbiota were consistent with the top 5 ranked natural bacteria. There were three types of abundance changes in the model groups: increases (Chlamydiae/Proteobacteria and Deferribacteres), decreases (Firmicutes), and no significant changes (Bacteroidetes). The UC model group was significantly different from the control group, with 1308 differentially expressed species with abundance changes greater than or equal to 2-fold. (2) The proportion of the fecal flora in the UC group decreased by 37.5% in the Firmicutes and increased by 14.29% in the proportion of Proteobacteria compared to the control group before treatment. (3) The significantly enriched and increased signaling pathways screened were the 'arachidonic acid metabolic pathway' and the 'phagosomal pathway', which both showed a decreasing trend after drug administration. (4) Based on the causal relationship between different OTUs and the UC model/PE&AFWE administration, screening for directly relevant OTU networks, the UC group was found to directly affect OTU69, followed by a cascade of effects on OTU12, OTU121, OTU93, and OTU7, which may be the pathway of action that initiated the pathological changes in normal mice. (5) We identified a causal relationship between common differentially expressed OTUs and PE&AFWE and UC in the pre- and post-PE&AFWE-treated groups. Thereby, we learned that PE&AFWE can directly affect OTU90, after which it inhibits UC, inhibiting the activity of arachidonic acid metabolic pathway by affecting OTU118, which in turn inhibits the colonization of gut microbiota by OTU93 and OTU7. (6) Histopathological observation and scoring (HS) of the colon showed that there was a significant difference between the model group and the control group (p < 0.001), and that there was a significant recovery in both the sulfasalazine (SASP)and the PE&AFWE groups after the administration of the drug (p < 0.0001).
CONCLUSION
We demonstrated causal effects and inflammatory metabolic pathways in gut microbiota dysbiosis and IBD, with five opportunistic pathogens directly contributing to IBD. PE&AFWE reduced the abundance of proteobacteria in the gut microbiota, and histopathology showed significant improvement.
Topics: Animals; Gastrointestinal Microbiome; Colitis, Ulcerative; Disease Models, Animal; Dextran Sulfate; Mice, Inbred C57BL; Mice; Dysbiosis; Male; Inflammation
PubMed: 38664929
DOI: 10.1002/ame2.12405 -
Medicinal Chemistry (Shariqah (United... Apr 2024Inflammatory Bowel Disease (IBD) encompasses a group of chronic disorders distinguished by inflammation of the gastrointestinal tract. Among these, Crohn's Disease (CD)...
INTRODUCTION
Inflammatory Bowel Disease (IBD) encompasses a group of chronic disorders distinguished by inflammation of the gastrointestinal tract. Among these, Crohn's Disease (CD) stands out as a complex and impactful condition due to challenges for both diagnosis and management, making it a cynosure of research.
METHOD
In CD, there is the predominance of proinflammatory bacteria, including the Adherentinvasive Escherichia coli (AIEC) with virulence-associated metabolic enzyme Propanediol Dehydratase (pduC), which has been identified as a therapeutic target for the management of CD. Herein, molecular modeling techniques, including molecular docking, Molecular Mechanics with Generalized Born and Surface Area (MMGBSA), drug-likeness, and pharmacokinetics profiling, were utilized to probe the potentials of eighty antibacterial compounds to serve as inhibitors of pduC.
RESULT
The results of this study led to the identification of five compounds with promising potentials; the results of the molecular docking simulation revealed the compounds as possessing better binding affinities for the target compared to the standard drug (sulfasalazine), while Lipinski's rule of five-based assessment of their drug-likeness properties revealed them as potential oral drugs. MMGBSA free energy calculation and Molecular Dynamics (MD) simulation of the complexes formed a sequel to molecular docking, revealing the compounds as stable binders in the active site of the protein.
CONCLUSION
Ultimately, the results of this study have revealed five compounds to possess the potential to serve as inhibitors of pduC of AIEC. However, experimental studies are still needed to validate the findings of this study.
PubMed: 38659270
DOI: 10.2174/0115734064295521240227052730 -
Rheumatology (Oxford, England) Apr 2024Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would...
OBJECTIVES
Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would associate with changes in arterial inflammation in an interventional trial.
METHODS
In the TARGET Trial, RA patients with active disease despite methotrexate were randomly assigned to the addition of either a TNF inhibitor or sulfasalazine+hydroxychloroquine (triple therapy). Baseline and 24-week follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans were assessed for change in arterial inflammation measured as the maximal arterial target-to-blood background ratio of FDG uptake in the most diseased segment of the carotid arteries or aorta (MDS-TBRmax). The MBDA test, measured at baseline and weeks 6, 18, and 24, was assessed for its association with the change in MDS-TBRmax.
RESULTS
Interpretable scans were available at baseline and week 24 for n = 112 patients. The MBDA score at week 24 was significantly correlated with the change in MDR-TBRmax (Spearman's rho = 0.239; p= 0.011) and remained significantly associated after adjustment for relevant confounders. Those with low MBDA at week 24 had a statistically significant adjusted reduction in arterial inflammation of 0.35 units vs no significant reduction in those who did not achieve low MBDA. Neither DAS28-CRP nor CRP predicted change in arterial inflammation. The MBDA component with the strongest association with change in arterial inflammation was serum amyloid A (SAA).
CONCLUSIONS
Among treated RA patients, achieved MBDA predicts of changes in arterial inflammation. Achieving low MBDA at 24 weeks was associated with clinically meaningful reductions in arterial inflammation, regardless of treatment.
PubMed: 38652572
DOI: 10.1093/rheumatology/keae242 -
Current Neurovascular Research Apr 2024Ferroptosis is an iron-dependent regulating programmed cell death discovered recently that has been receiving much attention in traumatic brain injury (TBI). xCT, a...
BACKGROUND
Ferroptosis is an iron-dependent regulating programmed cell death discovered recently that has been receiving much attention in traumatic brain injury (TBI). xCT, a major functional subunit of Cystine/glutamic acid reverse transporter (System Xc-), promotes cystine intake and glutathione biosynthesis, thereby protecting against oxidative stress and ferroptosis.
OBJECTIVE
The intention of this research was to verify the hypothesis that electroacupuncture (EA) exerted an anti-ferroptosis effect via an increase in the expression of xCT and activation of the System Xc-/GSH/GPX4 axis in cortical neurons of TBI rats.
METHODS
After the TBI rat model was prepared, animals received EA treatment at GV20, GV26, ST36 and PC6, for 15min. The xCT inhibitor Sulfasalazine (SSZ) was administered 2h prior to model being prepared. The degree of neurological impairment was evaluated by means of TUNEL staining and the modified neurological severity score (mNSS). Specific indicators of ferroptosis (Ultrastructure of mitochondria, Iron and ROS) were detected by transmission electron microscopy (TEM), Prussian blue staining (Perls stain) and flow cytometry (FCM), respectively. GSH synthesis and metabolism-related factors in the content of the cerebral cortex were detected by an assay kit. Real-time quantitative PCR (RT-QPCR), Western blot (WB), and immunofluorescence (IF) were used for detecting the expression of System Xc-/GSH/GPX4 axisrelated proteins in injured cerebral cortex tissues.
RESULTS
EA successfully relieved nerve damage within 7 days after TBI, significantly inhibited neuronal ferroptosis, upregulated the expression of xCT and System Xc-/GSH/GPX4 axis forward protein and promoted glutathione (GSH) synthesis and metabolism in the injured area of the cerebral cortex. However, aggravation of nerve damage and increased ferroptosis effect were found in TBI rats injected with xCT inhibitors.
CONCLUSIONS
EA inhibits neuronal ferroptosis by up-regulated xCT expression and by activating System Xc-/GSH/GPX4 axis after TBI, confirming the relevant theories regarding the EA effect in treating TBI and providing theoretical support for clinical practice.
PubMed: 38629369
DOI: 10.2174/0115672026297775240405073502 -
Rheumatology International Jun 2024Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with... (Comparative Study)
Comparative Study
BACKGROUND/OBJECTIVES
Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US).
METHODS
Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2).
RESULTS
A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period.
CONCLUSIONS
The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.
Topics: Humans; Female; Antirheumatic Agents; Western Australia; Middle Aged; Retrospective Studies; Pharmacovigilance; Aged; Male; Adverse Drug Reaction Reporting Systems; Adult; Drug-Related Side Effects and Adverse Reactions; Databases, Factual; United States; Time Factors; Young Adult
PubMed: 38615313
DOI: 10.1007/s00296-024-05588-3 -
The Journal of Allergy and Clinical... May 2024
Topics: Humans; Alleles; Drug Eruptions; HLA-A Antigens; HLA-B Antigens; Sulfasalazine
PubMed: 38613561
DOI: 10.1016/j.jaip.2024.02.041 -
Journal of Controlled Release :... May 2024Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site....
Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota.
Topics: Mesalamine; Humans; Colon; Gastrointestinal Microbiome; Anti-Inflammatory Agents, Non-Steroidal; Sulfasalazine; Prodrugs; Drug Delivery Systems; Colitis, Ulcerative; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Drug Liberation
PubMed: 38599548
DOI: 10.1016/j.jconrel.2024.04.016