Chronic Inflammatory Disease Research Articles

Identification of ubiquitination-related key biomarkers and immune infiltration in Crohn’s disease by bioinformatics analysis and machine learning

Crohn’s disease (CD) is a chronic inflammatory bowel disease with an unknown etiology. Ubiquitination plays a significant role in the pathogenesis of CD. This study aimed to explore the functional roles of ubiquitination-related genes in CD. Differentially expressed ubiquitination-related genes were identified by intersecting differentially expressed genes (DEGs) from the GSE95095 dataset in the Gene Expression Omnibus (GEO) database with a set of ubiquitination-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Key genes were selected by combining hub genes from the protein-protein interaction (PPI) network with feature genes identified by Lasso and Random Forest (RF) algorithms. Additionally, the correlation between key genes and immune infiltration was assessed, and Gene Set Enrichment Analysis (GSEA) of key genes was conducted. The efficacy of key genes was validated using ROC curves in an external dataset, and their expression was confirmed in LPS-induced Caco-2 cells through RT-qPCR. A total of 32 ubiquitination-related DEGs were identified, and two key genes (UBE2R2, NEDD4L) were selected. The infiltration of M2 macrophages was reduced in CD patients, with UBE2R2 expression negatively correlated and NEDD4L expression positively correlated with M2 macrophage infiltration. GSEA indicated that UBE2R2 was enriched in terpenoid backbone biosynthesis, regulation of autophagy, and limonene and pinene degradation, while NEDD4L was enriched in lysosome, Wnt signaling, and calcium signaling pathways. ROC curves demonstrated superior efficacy for NEDD4L. In LPS-induced Caco-2 cells, UBE2R2 expression increased, while NEDD4L expression decreased. A comprehensive analysis of the functional relationship between ubiquitination-related genes and CD can enhance understanding of CD pathogenesis and suggest potential therapeutic targets.

Fast, Present and Future of the Concept of Spondyloarthritis.

Axial spondyloarthritis (axSpA) is a rather prevalent chronic inflammatory rheumatic disease that affects already relatively young patients. It has been known better since the end of the nineteenth century but quite a lot has been learned since the early 60ies when the first classification (diagnostic) criteria for ankylosing spondylitis (AS) were agreed on. I have been part of many developments in the last 30years, and I'm happy to have been able to contribute to the scientific progress in terms of diagnosis, imaging, pathophysiology and therapy. When I was asked to write a manuscript about the SpA concept I felt honored. Thus, the purpose of this extensive review was, on the one hand, to describe the history of AS and axSpA, and on the other hand, to reason about the concept and the gestalt of axSpA, and finally to deliver some ideas what future researchers could possibly do to further study the disease. The last 3 decades were full of innovations for both, classification and treatment of axSpA which also helped us to learn about the pathophysiology. Thus, TNFa, IL-17, IL-23 and Janus kinase are established targets to reduce inflammation. IL-17 and IL-23 are very special in that regard because they both work for psoriasis but only anti-IL-17 agents which don't work in IBD are approved for axSpA, while IL 23 inhibitors are approved for both, psoriasis and IBD, but they don't work in axSpA. New imaging techniques such as low dose CT and synthetic MRI are likely to improve the detection of both active and structural lesions of axSpA. This manuscript tries to describe the most important findings about axSpA. The main aim of research remains to discover the pathophysiology and to further improve treatment options in order to reduce and abolish inflammation and prevent new bone formation to increase the quality of life of our patients. The differences between male and female disease and the role of the immune system in axSpA are now the main challenges, and the role of special T-cell receptors seem to deserve special interest.

Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistulae at intertriginous sites. Pain, pruritus, malodor, and suppuration have a significant impact on quality of life for HS patients. Prevalence figures vary greatly in the literature from 0.05% to 4.1%, and HS is more common in females. The current understanding of the etiology and pathogenesis of HS is incomplete; numerous hypotheses concern the interplay of lifestyle factors, skin microbiota, genetics, and a dysregulated immune system. Due to its phenotypic heterogeneity and multifactorial pathogenesis, HS is a complex disease that can prove challenging to manage. Two approved biologic therapies for the management of HS have led to clinical response in approximately 50% of treated patients. New therapies targeting the interleukin (IL)-1, IL-17, IL-36, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are in ongoing clinical trials, and preliminary data offer hope for greater clinical efficacy in HS in the future.

Improving Function and Mobility in Ankylosing Spondylitis through Physiotherapy: A Comprehensive Review

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints, often leading to pain, stiffness, and decreased mobility. Physiotherapy is widely recommended for AS management, aiming to alleviate symptoms, maintain mobility, and improve overall quality of life. Purpose: This review explores the role of physiotherapy in enhancing the quality of life for patients with ankylosing spondylitis, examining its effectiveness in reducing pain, improving physical function, and promoting daily activity engagement. Materials and Methods: A narrative review was conducted by analyzing recent studies on physiotherapy interventions for ankylosing spondylitis. Research articles, systematic reviews, and clinical trials published in the last decade were selected from medical databases. Key physiotherapy modalities, including exercise therapy, stretching, hydrotherapy, and posture training, were evaluated for their outcomes on pain relief, spinal flexibility, and patient-reported quality of life. Results: Evidence suggests that regular physiotherapy can significantly benefit AS patients. Exercise programs, particularly those focused on stretching, aerobic conditioning, and postural training, effectively reduce pain, increase spinal mobility, and prevent postural deformities. Hydrotherapy and supervised group exercises were particularly impactful, promoting social interaction and adherence. Patients reported notable improvements in functional capacity, mental health, and overall life satisfaction. Conclusion: Physiotherapy is a valuable, non-pharmacological intervention for ankylosing spondylitis, offering improvements in pain management, mobility, and quality of life. Regular, individualized physiotherapy programs tailored to patient needs can be instrumental in managing AS symptoms and enabling patients to lead more active, fulfilling lives. Further research is needed to standardize physiotherapy protocols and maximize their therapeutic potential in AS management. Keywords: Ankylosing Spondylitis, Physiotherapy, Pain management, Spinal mobility, Exercise therapy, Quality of life, Hydrotherapy, Functional capacity, Posture training.

Lactobacillus fermentum 016 Alleviates Mice Colitis by Modulating Oxidative Stress, Gut Microbiota, and Microbial Metabolism

Ulcerative colitis (UC) is a chronic and progressive inflammatory gastrointestinal disease closely associated with gut microbiota dysbiosis and metabolic homeostasis disruption. Although targeted microbial therapies are an emerging intervention strategy for inflammatory bowel disease (IBD), the mechanisms by which specific probiotics, such as Lactobacillus fermentum 016 (LF), alleviate UC remain unclear. The current study evaluated the effects of LF supplementation on gut health in a basal model using C57BL/6 mice. Subsequently, the preventive effects and mechanisms of LF supplementation on DSS-induced UC were systematically investigated. According to our findings, LF supplementation revealed immunoregulatory capabilities with significantly altered gut the composition of microbiota and metabolic activities, particularly enhancing tryptophan metabolism. In the UC model, LF supplementation effectively mitigated weight loss, increased the disease activity index (DAI), and alleviated diarrhea, rectal bleeding, and colon shortening. Moreover, it reduced colonic pathological damage and histological injury scores. LF intervention improved antioxidant markers and intestinal mucosal barrier function with the activation of the Nrf2–Keap1 signaling pathway and regulation of systemic inflammatory markers, i.e., IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-10. Importantly, LF supplementation reversed metabolic disturbances by significantly increasing the abundance of beneficial genera (e.g., g_Dubosiella, g_Faecalibaculum, g_Odoribacter, g_Candidatus_saccharimonas, g_Roseburia, and g_Eubacterium_xylanophilum_group) and elevating tryptophan metabolites (e.g., melatonin, kynurenic acid, 3-indoleacetic acid, 5-methoxytryptophan, and 5-hydroxyindoleacetic acid). In conclusion, Lactobacillus fermentum 016 exhibits potential for regulating gut microbiota homeostasis, enhancing tryptophan metabolism, and alleviating UC, providing critical insights for developing probiotic-based precision therapeutic strategies for IBD.

Nursing Knowledge and Skills in Hidradenitis Suppurativa: A Multi-Centre Exploratory Study

Background/Objectives: Hidradenitis suppurativa (HS) is an under-treated chronic inflammatory disease that affects approximately 0.40–2% of the population. Despite the competences nurses have in wound care, little is known about their management of HS lesions. The objectives of this study were to determine the knowledge and skills of primary care nurses regarding HS as well as to analyse the aspects in which these nurses need to strengthen their competences. Methods: A multicentre exploratory cross-sectional study was carried out in all seven healthcare areas of the Galician Health Service (N-W Spain) during 2021–2022. A questionnaire was developed for the project and subsequently piloted; from it, four dimensions were established. Additionally, sociodemographic data were collected. A total of 211 primary care nurses participated. Results: Both total and dimension scores were lower than 5 out of 10 points. The participants showed more knowledge in the Diagnosis and Clinical Course dimension (M = 4.59 out of 10). An older age correlated with greater knowledge regarding Diagnosis and Clinical Course (rho = 0.196; p = 0.006). Conclusions: These findings highlight the importance of developing evidence-based continuous training in the management and detection of the disease, while reducing the consequences of HS on patients’ quality of life.

Effectiveness of Tralokinumab in Different Phenotypes of Atopic Dermatitis: A Real-World Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and a relapsing course, affecting approximately 25% of children and 4-7% of adults. This study evaluated the efficacy, safety, and quality-of-life impact of tralokinumab, a humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD in a real-world setting, with a focus on different AD phenotypes. An observational cohort of 30 adults treated with tralokinumab for ≥ 16weeks was analyzed. Clinical and demographic data were collected, and outcomes were assessed using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and numeric rating scales (NRS) for pruritus and sleep disturbances. By week16, 60% achieved a 75% improvement inEASI (EASI75)and 31% reached a 90% improvement inEASI (EASI90), reflecting substantial clinical improvements. A ≥ 4-point reduction in pruritus NRS was observed in 63% of patients by week16, increasing to 70% by week32. Similarly, 75% achieved significant improvements in sleep disturbance NRS by week16, with sustained effects through week32. Subgroup analysis revealed superior clinical responses in patients with early-onset AD and atopic comorbidities. Lower total immunoglobulinE (IgE) levels at week16 correlated with better outcomes, suggesting total IgE as a potential biomarker. By week32, 70% of patients had a DLQI ≤ 5, indicating minimal quality-of-life impact. Additionally, 88% reached at least one therapeutic target, and 81% met composite endpoints combining clinician-assessed and patient-reported outcomes. The safety profile was consistent with clinical trials, with mild conjunctivitis and injection site reactions as the most common adverse events. These findings support tralokinumab as an effective and well-tolerated treatment, emphasizing the importance of phenotype-specific approaches in AD management.

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway. Depletion of TAZ in tumor-associated macrophages promoted tumor growth by suppressing the recruitment of tumor-infiltrating lymphocytes. Moreover, in a diet-induced metabolic dysfunction-associated steatohepatitis model, macrophage-specific deletion of TAZ ameliorated liver inflammation and hepatic fibrosis. Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases.

Rate and Timing of Progression to Total Knee Arthroplasty After Anterior Cruciate Ligament Reconstruction in Patients With Systemic Inflammatory Disease: A Long-term Propensity-Matched Cohort Study.

Anterior cruciate ligament reconstruction (ACLR) is one of the most common orthopaedic procedures and one of the most well studied. Despite extensive research dedicated to ACLR, there is limited understanding of how chronic inflammatory systemic diseases (CIDs) such as rheumatoid arthritis and systemic lupus erythematosus affect outcomes. To compare the outcomes of ACLR in cohorts of patients with and without CID. Cohort study; Level of evidence, 3. A retrospective query of a regional data set was conducted for all patients who underwent ACLR from 1990 to 2021 for traumatic ACL rupture. All patients with CID were identified and propensity matched to non-CID controls. Baseline characteristics and clinical outcomes were identified through retrospective chart review, and patients were contacted for subjective outcomes. A total of 30 patients with ACLR and a diagnosis of CID were identified. These patients were propensity matched to 120 non-CID controls. Baseline demographic and surgical characteristics demonstrated no statistical differences. Follow-up duration was similar between the CID and non-CID groups (mean, 14.6 vs 14.2 years; P = .868). The CID cohort had a higher arthrofibrosis rate (16.7% vs 4.3%; P = .031), higher osteoarthritis rate (33.3% vs 16.7%; P = .041), higher total knee arthroplasty (TKA) rate (16.7% vs 3.3%; P = .016), and earlier time to TKA (14.7 vs 23.5 years; P = .032). Knee range of motion, infection rate, retear rate, time to retear, and time to osteoarthritis were not statistically different between the cohorts. The CID cohort had higher visual analog scale pain scores (mean, 2.00 vs 1.20; P = .043) but slightly higher satisfaction (mean, 3.92 vs 3.39; P = .043). There were no differences in preinjury Tegner, postoperative Tegner, change in Tegner, or IKDC score. In a univariate Cox regression model, the CID cohort had a retear hazard ratio of 1.43 (95% CI, 0.46-4.51; P = .537). Kaplan-Meier survival revealed no significant differences in retear-free survival between the CID and non-CID cohorts at 25 years (85.7% vs 87.3%; P = .53). The CID cohort had a TKA hazard ratio of 3.94 (95% CI, 1.05-14.8; P = .042). Kaplan-Meier survival demonstrated significantly decreased TKA-free survival at 25 years in the CID cohort (64.9% vs 91.2%; P = .029). CID increases the incidence of arthrofibrosis, osteoarthritis, and TKA in those undergoing ACLR. Patients with CID also undergo TKA significantly sooner than non-CID counterparts. Notably, the majority of patient-reported outcome measures are no worse in patients who have a CID diagnosis. Thus, ACLR constructs themselves may not necessarily fare worse in patients with CID. Nonetheless, these patients need to be cautiously counseled on the clinical outlook after their ACLR.

The Impact of α-Lipoic Acid Treatment on Multiple Sclerosis Disability: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). Despite the availability of interventions for disease exacerbations and symptomatic management, EM remained without a cure. Oxidative stress has been implicated in the MS demyelination mechanism. Adjuvant therapies like α-lipoic acid (ALA) have garnered interest for their potential to mitigate oxidative damage and control MS symptoms. ALA is found naturally in vegetables and red meat and can also be synthesized in mitochondria through enzymatic reactions involving octanoic acid and cysteine. However, its bioavailability from dietary sources is limited, prompting an investigation into supplemental forms. We conducted a systematic review and meta-analysis to assess the effect of ALA on disability in randomized clinical trials (RCTs) for MS. Methods: Records were searched until June 2023 (CRD42023397760). Five RCTs evaluated ALA’s effect on MS progression using the Expanded Disability Status Scale (EDSS). The quality of evidence was assessed using GRADE, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Following the selection process, five studies were included involving 179 patients (87 placebo and 92 ALA). Oral administration of racemic ALA (R/S-ALA) at 600 mg twice daily reduced EDSS, indicating a potential for ALA supplementation to mitigate MS disability. The North American trials (SPMS patients) did not show heterogeneity, while Asian studies (RRMS patients) were moderated. The quality of evidence was high without publication bias. Conclusions: ALA treatment reduce EDSS scores. However, further studies are warranted to establish the role of ALA as an adjuvant in clinical practice in long-term follow-up (>2 years) RCTs.

Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A.

In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination-proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Topographic corneal changes in children with moderate to severe blepharokeratoconjunctivitis.

Purpose To determine the corneal topographic characteristics of children with blepharokeratoconjunctivitis (BKC), a chronic inflammatory ocular surface disease involving the lid margin, conjunctiva, and cornea. Methods The corneal topography of 21 children diagnosed with BKC between March 2008 and June 2019 at a single institution were reviewed retrospectively. Pachymetry and asymmetry indices were also analyzed. Results Mean flat keratometry (K1), steep keratometry (K2), maximum keratometry (Kmax), and topographic astigmatism (TA) were 42.61 ± 2.63 D, 46.00 ± 3.17 D, 51.00 ± 5.29 D, and 3.39 ± 2.60 D, respectively. Mean central corneal thickness (CCT) was 528.8 ± 72.2 μm; mean thinnest point (TP) was 487.00 ± 88.28 μm; 47% of eyes had a TP of <500 μm. Compared with previously published pediatric normative values, K2, Kmax, and TA were significantly higher (46.00 ± 3.17 vs 45.16 ± 0.27, 51.00 ± 5.29 vs 45.76 ± 0.28, and 3.38 ± 2.48 vs 2.81 ± 0.19 [P < 0.0001]), whereas mean CCT and TP were significantly lower in the BKC group. 72.2% of cases fulfilled the Rabinowitz diagnostic criteria for ectasia: 67% had a Kmax >47.2 D and 31% had an inferior-superior asymmetry value >1.2 D. Using topography-derived indices comparing the superior and inferior corneal characteristics, the index of height decentration, index of surface variance, and index of vertical asymmetry were found to be abnormal in 83%, 69%, and 64% of cases, respectively. Conclusions Children with moderate-to-severe BKC may present with significant topographic corneal changes that can mimic corneal ectasia. Corneal topography could be an important tool in evaluating corneal involvement and explaining reduced visual function due to refractive changes.

P0008 A multi-omics approach across multiple chronic inflammatory diseases identifies a distinct type-1-interferon endotype of Inflammatory Bowel Disease

Abstract Background IBD shares many clinical and immunological features with other chronic inflammatory diseases (CIDs) like rheumatoid arthritis (RA) and psoriasis (Pso). Extraintestinal manifestations, particularly in the joints and skin, often overlap with these CIDs. We hypothesize that a systems medicine approach involving omics-driven phenotyping of multiple CIDs can yield a novel, therapy-relevant molecular taxonomy of disease. In this study, we aim to identify IBD-specific molecular signatures and those shared with other CIDs, as well as novel endotypes of IBD. Methods We recruited a cross-sectional cohort of 650 patients with CIDs (CD, UC, RA, Pso, psoriatic arthritis [PsA], and systemic lupus erythematosus [SLE]) along with 202 healthy controls (HC) at the University Hospital Kiel. Active or inactive disease was defined by clinical activity scores (i.e., CD: CDAI &amp;lt;150; UC: partial Mayo ≤2). Blood samples were collected and subjected to RNA sequencing and methylation profiling. Detailed clinical phenotypes and 5 years-follow-up data were obtained by chart review. We conducted differential gene expression and methylation analyses comparing each CID with HCs to identify shared molecular signatures. Core (activity-independent) signatures were defined by the overlap of differential expression in both active vs. HC and inactive disease vs. HC. Biclustering methods (UnPaSt) were used to uncover distinct patient endotypes based on expression profiles. Results IBD shared the most differential signatures with RA, indicating common pathways in their pathogenesis. Core signatures upregulated across all CIDs correlated with DNA methylation changes, reflecting the molecular mechanism of chronicity, and were enriched in pathways related to cytokine signaling, neutrophil chemotaxis, and humoral immune response. While methylation signatures in enhancer regions were shared among most CIDs, disease-specific methylation was mainly located in CpG islands. One disease-overarching subgroup of 71 patients with active disease, identified by biclustering, exhibited upregulation of interleukin-27 and type-1 interferon signaling, including 16 out of 121 active IBD patients with a skewed sex ratio toward females and higher rates of therapy escalations within 5 years (Log-rank test: p=0.0089). Conclusion Our study highlights shared and disease-specific immune dysregulation pathways contributing to the pathogenesis of IBD and other CIDs. We show the clear presence of core signatures of disease regardless of disease activity, which could represent insights into actionable targets for causative treatments and better disease control of CIDs. With our approach, we identified a distinct molecular endotype of IBD with worse prognosis, warranting further validation studies. References This project has received funding from the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation", the BMBF (e:Med Network iTREAT 01ZX2202A), the European Union/Horizon2020 (SYSCID, No 733100) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434 (3TR) and No 853995 (ImmUniverse).The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The content provided in this publication reflects the author's views only. Neither the Innovative Medicines Initiative (IMI JU) nor the European Commission are responsible for any use that may be made of the information it contains.

Lipid metabolism in myeloid cell function and chronic inflammatory diseases

Immune cells adapt their metabolism in response to their differentiation and activation status to meet the energy demands for an appropriate immune response. Recent studies have elucidated that during immune cell metabolic reprogramming, lipid metabolism, including lipid uptake, de novo lipid synthesis and fatty acid oxidation, undergoes significant alteration, resulting in dynamic changes in the quantity and quality of intracellular lipids. Given that lipids serve as an energy source and structural components of cellular membranes, they have important implications for physiological function. Myeloid cells, which are essential in bridging innate and adaptive immunity, are sensitive to these changes. Dysregulation of lipid metabolism in myeloid cells can result in immune dysfunction, chronic inflammation and impaired resolution of inflammation. Understanding the mechanism by which lipids regulate immune cell function might provide novel therapeutic insights into chronic inflammatory diseases, including metabolic diseases, autoimmune diseases and cancer. (143 words)

P0490 Diagnosis and treatement of latent tuberculosis infection in patients with chronic Inflammatory Bowel Disease candidates for anti-TNFα therapy in a tuberculosis endemic country

Abstract Background The increasing use of anti-TNFα agents in the management of IBD raises concerns about the increased risk of latent TB reactivation, justifying the need for effective screening recommendations. Our study focuses on IBD patients candidates for anti-TNF therapy aiming to determine the prevalence of latent TB infection, examine factors influencing QantiFERON® outcomes, and describe therapeutic modalities for latent TB in this population. Methods This was a descriptive retrospective study of 87 patients followed up in the gastroenterology department of the Mohammed V Military Training Hospital in Rabat for IBD who were candidates for anti-TNF alpha biotherapy between 2021 and 2024. Results The prevalence of latent tuberculosis TBL identified in patients with chronic inflammatory bowel disease candidates for anti-TNFα therapy in our study was 24.1%, detected by the Quantiferon Gold IT® test. Factors influencing the results of the test found mainly include the various risk factors for tuberculosis in our context of intermediate endemicity, and the use of immunosuppressants, which is associated with a negative test. As the intradermal tuberculin test could not be carried out in Morocco due to a stock shortage, the comparison of the performance of the two tests was not possible. Despite an initially negative Quantiferon Gold IT® test, 4 cases of active tuberculosis were recorded after initiation of anti-TNF treatment. Conclusion The IGRA Quantiferon Gold IT® test is considered a valuable tool for detecting latent tuberculosis in IBD patients who are candidates for anti-TNF treatment. However, its use and interpretation in an endemic country and in vaccinated subjects should be the subject of larger-scale studies aimed at proposing appropriate recommendations based on the risk of latent tuberculosis.

Oxidative balance score and its association with chronic inflammatory airway diseases and mortality: a population-based study

ObjectiveThe aim of this research was to explore the possible connection between combined Oxidative Balance Score (OBS) and the prevalence of chronic inflammatory airway diseases (CIAD), including asthma, chronic obstructive pulmonary disease (COPD), and chronic bronchitis, along with the mortality rate among individuals with CIAD.MethodsData were gathered from the National Health and Nutrition Examination Survey (NHANES) 2013–2018 cycles. The Oxidative Balance Score (OBS) was calculated using 16 different nutrients and 4 different lifestyles, which was then categorized into four groups. The CIAD included individuals with self-reported asthma, chronic bronchitis, or COPD. Mortality data up to December 31, 2019, was obtained from the National Death Index. In cross-sectional studies, the association between OBS and the prevalence of total and specific CIAD was examined using multiple logistic regressions. Dose–response relationships were analyzed through restricted cubic spline regression (RCS). In prospective cohort studies, cumulative survival rates were determined using the Kaplan–Meier method and compared with log-rank tests. Multiple COX regressions were conducted to evaluate the relationship between OBS and all-cause as well as respiratory diseases mortality among participants with CIAD.ResultsA total of 12,458 adults were enrolled in this study. The demographic characteristics of the study population revealed a mean age of 52.25 ± 15.8 years, 47.73% being male, and the majority identified as Non-Hispanic White (66.87%). We found that 20.26% of the participants were suffered from CIAD, followed by asthma (15.41%), chronic bronchitis (6.10%) and COPD (3.80%), respectively. The median OBS levels were 20.98 with a standard deviation of 0.17. After adjusting for all confounders, we found that the highest quartile of OBS was significantly associated with lower prevalence of total CIAD (OR = 0.71, 95% CI 0.64–0.81), asthma (OR = 0.62, 95% CI 0.52–0.73), chronic bronchitis (OR = 0.64, 95% CI 0.44–0.92), and COPD (OR = 0.48, 95% CI 0.31–0.77) compared to the lowest quartile. Additionally, a linear and inverse relationship was found between OBS and the incidence of various respiratory disorders. Kaplan–Meier survival analysis showed that individuals in the highest quartile of OBS had the lowest risk of both all-cause mortality (log-rank test p = 0.017) and respiratory diseases mortality (log-rank test p &amp;lt; 0.001). Furthermore, after adjusting for multiple factors, individuals in the fourth quartile continued to show a significantly reduced risk of all-cause mortality (HR = 0.71, 95% CI 0.55–0.93) and respiratory diseases mortality (HR = 0.53, 95% CI 0.43–0.74) in comparison to those in the lowest quartile of OBS levels.ConclusionThe findings revealed that a higher OBS was significantly linked to a decreased prevalence of total and specific CIAD, including asthma, chronic bronchitis, and COPD. Higher OBS levels were also associated with reduced mortality from both all causes and respiratory diseases among CIAD patients. These findings offer valuable information on the role of diet and lifestyle in preventing CIAD.

Inula japonica Thunb. and its active compounds ameliorate airway inflammation by suppressing JAK-STAT signaling.

Asthma, a chronic inflammatory disease, remains a global health challenge due to its complex pathophysiology and the limited treatment efficacy. This study explored the effect of Inula japonica Thunb. water extract (IJW) on asthma and its protective mechanisms. To assess the effects of IJW, we established an experimental asthma model in BALB/c mice using ovalbumin (OVA). Airway hyper-responsiveness (AHR) in response to methacholine was measured. We quantified inflammatory cell infiltration and cytokine and chemokine levels in bronchoalveolar lavage fluid (BALF), as well as total IgE levels in serum. Staining with hematoxylin and eosin and periodic acid-Schiff was used to examine the impact of IJW on lung pathology. We performed RNA sequencing to identify differentially expressed genes, which were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We used interleukin (IL)-4/IL-13-treated human bronchial epithelial (HBE) cells to explore the associated mechanisms. IJW showed therapeutic effects against OVA-induced asthma by alleviating AHR, peribronchial inflammation, mucus hypersecretion, and collagen fiber deposition. It reduced total IgE levels in the serum and IL-4, IL-5, IL-13, eotaxin, macrophage-derived chemokines, and periostin levels in BALF. In IL-4/IL-13-treated HBE cells, IJW and its components suppressed the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) signaling. These findings support IJW's potential as a pharmacological agent for allergic airway inflammation and asthma.

P0703 Risk factors and nomogram for massive postoperative gastrointestinal bleeding in patients with Crohn’s disease: a multicenter retrospective study

Abstract Background Crohn’s disease (CD) is a chronic inflammatory disease that is prone to complications such as intestinal obstruction and perforation, which often require surgical treatments. Massive postoperative gastrointestinal bleeding (MPGB) is a severe complication with a high mortality rate, deteriorating postoperative recovery and disease prognosis. However, there are few related studies and it lacks effective prevention measures. Therefore, we conducted a multicenter study to explore the risk factors for MPGB in CD patients. Methods This study was a multicenter retrospective case-control study. Inclusion criteria included: patients diagnosed with CD; aged over 16 years old; underwent gastrointestinal surgery. Exclusion criteria included: patients with massive gastrointestinal bleeding before surgery. Massive gastrointestinal bleeding is defined as: hemodynamic impairment, requiring active fluid resuscitation; decreased hemoglobin concentration, requiring blood transfusion or surgical treatment; with symptoms of gastrointestinal bleeding. The included patients were divided into a case group and a control group. By comparing medical information between two groups, risk factors for MPGB were identified through logistic regression analysis, and a nomogram was constructed. Results From January 2018 to February 2024, a total of 170 CD patients were included, including 34 patients with MPGB and 136 matched controls. Univariate logistic regression analysis showed that for albumin (P=0.001, OR=0.89), nutrition risk screening (NRS2002) scale (P=0.003, OR=1.61), predictive nutritional index (PNI) (P=0.005, OR=0.92), number of previous surgeries (P&amp;lt;0.001, OR=2.39), history of gastrointestinal bleeding (P&amp;lt;0.001, OR=8.75), international normalized ratio (INR) (P=0.004, OR=1.60), and abnormal liver function (P=0.049, OR=6.29) (P＜0.05), the difference between two groups was statistically significant. Multivariate logistic regression analysis further revealed that NRS2002 (P=0.022, OR=1.53), history of gastrointestinal bleeding (P=0.005, OR=5.71), number of previous surgeries (P&amp;lt;0.001, OR=2.43), and INR (P=0.011, OR=1.61) were associated with an increased risk of MPGB. Based on these results, a nomogram was constructed. The training and validation group achieved an area under the curve (AUC) value of 0.87 and 0.73 respectively with well-fitted Hosmer-Lemeshow calibration curves. Conclusion The risk of MPGB in CD patients will be increased with a history of gastrointestinal bleeding, more previous surgeries, a higher NRS2002 score, and a higher INR value. Strengthening the perioperative nutritional status management of CD patients may prevent the MPGB. Besides, we conduct a nomogram model, which can effectively predict the risk of MPGB in CD patients.

Mesalazine: a novel therapeutic agent for periodontitis via regulation of periodontal microbiota and inhibiting Porphyromonas gingivalis

IntroductionPeriodontitis and inflammatory bowel disease are chronic inflammatory diseases with shared epidemiological, biological, and therapeutic associations. Given the similarities in their pathogenic factors, this study hypothesized that mesalazine, a key treatment agent for inflammatory bowel disease, could also be effective in managing periodontitis.MethodsThe antimicrobial effect of mesalazine on Porphyromonas gingivalis was investigated in vitro, including observations of morphological changes on the surface of P. gingivalis. Additionally, the impact of mesalazine on both the formation and established plaque biofilms was examined. The antimicrobial mechanism was elucidated by assessing the expression of P. gingivalis virulence genes and by determining the disruptive effect on P. gingivalis cell membranes. An in vivo rat model of periodontitis was constructed to evaluate mesalazine’s efficacy and its influence on the periodontal bacterial flora in the context of periodontitis.Results and discussionOur results demonstrated that mesalazine concentrations ranging from 0.5 to 2 mg/mL significantly inhibited P. gingivalis proliferation over 72 h. Flow cytometry revealed a marked reduction in the number of viable cells following mesalazine treatment. At the nanometer scale, mesalazine induced crumpling and rupture of the P. gingivalis surface, compromising cell membrane integrity. Mesalazine not only suppressed the formation of plaque biofilms by P. gingivalis and polymicrobial communities but also disrupted pre-existing biofilms. The data also suggested that mesalazine could disrupt the integrity of the P. gingivalis cell membrane and inhibit the expression of virulence factors. An animal model of periodontitis in rats was successfully constructed in vivo. Mesalazine treatment inhibited alveolar bone resorption, alleviated inflammation of periodontal tissues, and improved the composition of the periodontal flora to a healthier state. This study establishes that mesalazine can treat periodontitis through modulation of the periodontal flora and its anti-inflammatory properties, thus broadening its classical therapeutic applications.

Preclinical Evaluation of the Anti-inflammatory Properties of Plants Extracts of Ficus exasperata (Moraceae) on Wistar Rat Models

Introduction: In view of the rising global death rate associated with inflammatory diseases, a cost friendly, more effective and, safer drug with lesser side effects is needed. Inflammation is a part of the complex biological response of vascular tissue to harmful stimuli, such as pathogens, damaged cells, or irritants. It is characterized by redness, swollen joints, joint pain, heat, and loss of joint functions. Chronic inflammatory diseases have been recognized as the most significant cause of death in the world today, with more than 50% of all deaths being attributable to inflammation-related diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) and Steroidal anti-inflammatory (SAIDs) are used throughout the world for the treatment and management of inflammation, pain, and fever. Since many NSAIDs are associated with, side effects such as gastrointestinal bleeding and suppressed function of the immune system, medicinal herbs are new alternatives to search out new chemical substances that would have better therapeutic results with low toxic profile. Recent studies on Ficus exasperata suggest that it might be as effective as some NSAIDs in the treatment of inflammation and related pain. Objectives: To evaluate the anti-inflammatory properties of the different plants extracts of Ficus exasperata in rats of Wistar train. Methods: The powdered material of leaves of Ficus exasperata was extracted by decoction, infusion, aqueous maceration, and hydroethanolic maceration. Phytochemical screening was carried out on the four different extracts: aqueous extract, hydroethanolic extracts, decoction and Infusion. The anti-inflammatory properties of Ficus exasperata were evaluated in vitro by egg albumin and bovine albumin using the heat induced Protein denaturation assay. Results: The leaves of Ficus exasperata was effective in inhibiting albumin denaturation. Varying concentrations of the plant extract significantly, (p &lt; 0.05) inhibited the denaturation of albumin when compared to the control group. Aspirin and Indomethacin showed a similar trend. The inhibition by the extract is concentration-dependent with 32.25 µg/ml having an inhibition of 8.89 for infusion, 9.66% for hydroethanolic, 10.29% for aqueous maceration, and 12.6% for decoction compared to indomethacin and aspirin with inhibition 36.94% and 40.36%, respectively. The highest percentage inhibition was seen at 1000 µg/mL with inhibition of 34.22% for aqueous maceration, 40.77% for infusion, 41.61 % for hydroethanolic and 42.34% for decoction compared to indomethacin and aspirin with 67.06% and 58.45%, respectively. The plants extracts showed anti-inflammatory activity by decreasing the rate of denaturation of protein. Conclusion: The studied extract justifies anti-inflammatory properties, which were confirmed by protecting against protein denaturation.