Chronic Inflammatory Disorder Research Articles

Evaluation of ventricular repolarization in dermatomyositis and relationship with inflammation and autoimmunity.

Dermatomyositis (DM) is a chronic multi-systemic inflammatory disorder of autoimmune origin, which has been associated with cardiovascular complications, including ventricular arrhythmias and sudden cardiac death. The Tp-e interval and Tp-e/QT ratio have been accepted as new markers for the assessment of myocardial repolarization and ventricular arrhythmogenesis. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with DM, and to assess the relation with inflammation and autoimmunity. This study included 281 DM patients (180 females, 101 males; mean age 52.73 ± 15.80years) and 281 control subjects (180 females, 101 males; mean age 53.38 ± 15.72years). QTc, Tp-e interval and Tp-e/QT ratio were measured from the 12-lead ECG. The plasma level of blood routine test, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) was measured. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QTc, Tp-e interval and Tp-e/QT ratio were significantly increased in DM patients compared to the control group (441.44 ± 26.62ms vs 422.72 ± 11.7ms, 104.16 ± 24.34ms vs 77.23 ± 16.25ms and 0.27 ± 0.06ms vs 0.20 ± 0.04ms, all P value < 0.01). QTc, Tp-e interval and Tp-e/QT were positively correlated with NLR, CRP, and ESR (all P values < 0.01), and were increased in anti-Ro/SSA-52kD positive patients compared to those negative (452.33 ± 24.89ms vs 438.55 ± 26.37ms, 114.05 ± 22.68ms vs 101.53 ± 24.13ms, and 0.29 ± 0.06ms vs 0.27 ± 0.05ms, all P value < 0.01). Our study demonstrated that QTc, Tp-e interval, and Tp-e/QT ratio were increased in DM patients and were associated with inflammatory markers and anti-Ro/SSA-52kD positivity.

A Pilot Real-World Study of Ultrasonography Findings of Hidradenitis Suppurativa in Indian Patients and Its Diagnostic and Therapeutic Implications

Abstract Introduction Hidradenitis suppurativa (HS) is a multifactorial chronic inflammatory follicular disorder affecting apocrine gland-bearing areas of the body. We conducted an observational study to assess the ultrasonography (USG) findings in suspected HS patients at a tertiary care center in North India over 6 months. Aim The aim of this article was to study the USG findings in HS and correlate clinical and USG findings and scoring systems in HS with stage wise treatments. Materials and Methods All patients with a clinical suspicion of HS underwent an USG examination after clinical examination with a probe of 18 Hz frequency. Hurley's staging of patients was used to stage clinically, and the HS-SOS scoring and Doppler changes were assessed on USG. The treatment was revised in case of a change in the USG grading of severity. Results A total of 23 patients suspected of HS underwent USG evaluation, of which 12 (52%) were male and 9 (48%) were females, with the mean age being 25.3 years (range: 14–40 years). Based on the HS clinical grading, eleven patients (47.8%) were Hurley's stage I, six patients (26%) were stage II, and six patients (26%) were stage III. USG demonstrated that three patients had been misdiagnosed and had folliculitis (8.6%) and Crohn's disease (4.3%). Out of the remaining twenty patients with USG features of HS, based on HS SOS grading, three patients (15%) were grade I, seven (35%) were grade II, and ten (50%) were grade III. Of these, nineteen patients (95%) had axillary involvement, which was bilateral in 84% of cases. The other region affected was the groin in five patients (26.3%), while two had inframammary involvement (10.5%). On further characterization of the type of lesion, nodules (41; 40.6%) were the most common type of lesion by sinuses and thickened hair follicles in 31 (30.6%) patients. Based on USG findings, the management of 26% of patients was changed from medical to surgical intervention. Conclusion USG and Doppler are noninvasive bedside tools for the examination of HS, which helps to rule out differentials and delineate the extent and depth of the disease better by picking up subclinical lesions and help in determining disease activity by Doppler, which in turn helps in planning appropriate medical and surgical management of patients. It also identifies radiological parameters that help identify patients who could fail medical management.

Lipid mediators in neutrophil biology: inflammation, resolution and beyond.

Acute inflammation is the body's first defense in response to pathogens or injury. Failure to efficiently resolve the inflammatory insult can severely affect tissue homeostasis, leading to chronic inflammation. Neutrophils play a pivotal role in eradicating infectious pathogens, orchestrating the initiation and resolution of acute inflammation, and maintaining physiological functions. The resolution of inflammation is a highly orchestrated biochemical process, partially modulated by a novel class of endogenous lipid mediators known as specialized pro-resolving mediators (SPMs). SPMs mediate their potent bioactions via activating specific cell-surface G protein-coupled receptors (GPCR). This review focuses on recent advances in understanding the multifaceted functions of SPMs, detailing their roles in expediting neutrophil apoptosis, promoting clearance by macrophages, regulating their excessive infiltration at inflammation sites, orchestrating bone marrow deployment, also enhances neutrophil phagocytosis and tissue repair mechanisms under both physiological and pathological conditions. We also focus on the novel role of SPMs in regulating bone marrow neutrophil functions, differentiation, and highlight open questions about SPMs' functions in neutrophil heterogeneity. SPMs play a pivotal role in mitigating excessive neutrophil infiltration and hyperactivity within pathological milieus, notably in conditions such as sepsis, cardiovascular disease, ischemic events, and cancer. This significant function highlights SPMs as promising therapeutic agents in the management of both acute and chronic inflammatory disorders.

Research progress of ferroptosis and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disorder of the gastrointestinal tract, imposing significant burdens on both society and individuals. As a new type of regulated cell death (RCD), ferroptosis is different from classic RCDs such as apoptosis and necrosis in cell morphology, biochemistry and genetics. The main molecular mechanisms of ferroptosis include dysregulation of iron metabolism, impaired antioxidant capacity, mitochondrial dysfunction, accumulation of lipid-associated super-oxides, and membrane disruption. In recent years, increasing evidence has shown that ferroptosis is involved in the pathophysiology of inflammatory bowel disease. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This article reviews the mechanism of ferroptosis in the occurrence and development of inflammatory bowel disease, in order to provide new ideas for the pathophysiological research of inflammatory bowel disease. Additionally, we discuss potential strategies for the prevention and treatment of inflammatory bowel disease by targeting ferroptosis.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

Serum levels of tumour necrosis factor (TNF-α) and interleukin-17 (IL-17) in patients with nail psoriasis: A cross-sectional study

Background Psoriasis is a common chronic inflammatory disorder affecting all aspects of a patient’s life. Nail involvement is frequent, but little is known about its associated inflammatory biomarker profile, including similarities or differences from cutaneous disease. Aims We conducted this cross-sectional study to evaluate serum levels of inflammatory cytokines [tumour necrosis factor-alpha (TNF-α) and interleukin -17 (IL-17)] in patients with nail psoriasis and compared these to psoriasis patients without nail involvement, as well as in non-psoriatic healthy controls. Methods Adult psoriasis patients with (Group I, n = 30) and without nail involvement (Group-II, n = 30) were sequentially recruited. In addition, non-psoriatic healthy controls (Group-III, n = 20) were recruited. The nail disease severity by NAPSI score was determined for patients in Group I. Cutaneous disease severity (by PASI score) and presence of psoriatic arthritis (through CASPAR criteria) were evaluated for patients in Groups I and II. Serum levels of TNF-α, IL-17, erythrocyte sedimentation rate (ESR), rheumatoid factor (RA factor), and anti-cyclic citrullinated peptide antibody (Anti-CCP) were evaluated for all three groups. Results The median age was significantly higher for Group I as compared to Group II patients (41 ± 12.6 years vs 30 ± 12.4 years, p = 0.017). Group I patients also had higher median PASI score than Group II patients, although the difference was not statistically significant (10 ± 11.41 vs 6.50 ± 5.46, p = 0.275). The mean serum IL-17 levels were significantly higher for Group-I (113.39 ± 251.30 pg/mL) than Group II (27.91 ± 18.22 pg/mL, p = 0.002) and Group III (25.67 ± 12.08 pg/mL, p = 0.005). A weak positive correlation was found between NAPSI and serum IL-17 levels (Spearman’s Rho = 0.355) though not statistically significant (p = 0.054). Correlation between serum IL-17 and PASI was poor for Group-I patients (Spearman’s Rho = 0.13, p = 0.944) and strongly negative for Group-II patients (Spearman’s Rho = −0.368, statistically significant with p = 0.045). The mean serum levels of TNF-α were below the detection threshold of the assay kit, hence no meaningful comparison could be made. Limitations A small sample size and low sensitivity of TNF-α assay kit. Conclusion Our study showed that nail psoriasis could be independently associated with an elevation of IL-17. This can help choose appropriate drugs and estimate drug response in patients with nail psoriasis.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4+ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

Depletion of hepatic glutathione and adenosine by glucocorticoid exposure in Wistar rats is pregnancy-independent

Liver diseases have gained increasing attention due to their substantial impact on health, independently as well as in association with cardio-metabolic disorders. Studies have suggested that glutathione and adenosine assist in providing protection against oxidative stress and inflammation while glucocorticoid (GC) therapy has been associated with chronic inflammatory disorders, even in pregnancy. The implications of Glucocorticoid exposure on maternal health and fetal growth is a concern, however, the possible role of glutathione and adenosine has not been thoroughly investigated. The study therefore hypothesize that exposure to glucocorticoids leads to depletion of hepatic glutathione and adenosine levels, contributing to oxidative stress and tissue injury. Additionally, we aim to investigate whether the effects of glucocorticoids on hepatic health are pregnancy dependent in female rats. Twelve Pregnant and twelve age-matched non-pregnant rats were used for this study; an exogenous administration of glucocorticoid (Dex: 0.2 mg/kg) or vehicle (po) was administered to six pregnant and six non-pregnant rats from gestational day 14 to 19 or for a period of 6 days respectively. Data obtained showed that GC exposure led to a decrease in hepatic glucose-6-phosphate dehydrogenase, glutathione peroxidase, GSH/GSSG ratio and adenosine content in both pregnant and non-pregnant rats. In addition, increased activities of adenosine deaminase and xanthine oxidase, along with increased production of uric acid and increased levels of lactate dehydrogenase, aspartate aminotransferase, alanine transferase, alkaline phosphatase and gamma-glutamyl transferase were observed. In summary, the study indicates that GC-induced liver damage is underlined by depleted hepatic adenosine and glutathione levels as well as elevated markers of tissue inflammation and/or injury. Furthermore, the findings suggest that the effects of GC exposure on hepatic health are pregnancy independent.

Association of periodontal disease with gestational diabetes mellitus among postpartum women at a private tertiary care hospital of Karachi, Pakistan: a cross-sectional study

Due to the overlapping aetiology of Gestational Diabetes Mellitus (GDM) and Periodontal disease (PD), which are prevalent metabolic disorder and chronic inflammatory disorder in pregnant women respectively, they are often at risk of developing both diseases simultaneously. This study aims to evaluate the association of periodontal disease and gestational diabetes mellitus among post-partum women who delivered within 24 h at private tertiary care hospital, Karachi, Pakistan. Analytical cross sectional study with sample size of 178 by non- probability purposive sampling, a total of 101 postpartum women (57%) were diagnosed with periodontal disease and 50 (28%) were GDM positive. Of those who had PD, 35% (n = 35/101) were GDM positive. An insignificant association of the prevalence ratio of GDM in women with periodontal disease was found. [PR = 1.7; 95% CI: 0.2–3.2; p-value 0.07] A statistically significant association was found between the prevalence ratio of GDM in women with obesity. It was 2.6 times compared to women who were not obese (p value < 0.01, 95% CI: 1.3–5.1). There is insignificant association found between the prevalence ratio of GDM in women with periodontal disease in our setting. Women who are overweight or tend to gain weight should be closely monitored and guided to take dietary measures.

Synbiotic Bacillus megaterium DSM 32963 and n-3 PUFA Salt Composition Elevates Pro-Resolving Lipid Mediator Levels in Healthy Subjects: A Randomized Controlled Study.

Beneficial health effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n-3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels. Healthy participants (n = 72) received either SynΩ3 (250 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) lysine salts; two billion CFU Bacillus megaterium; n = 23), placebo (n = 24), or fish oil (300 mg EPA plus DHA; N = 25) capsules daily for 28 days in a randomized, double-blind placebo-controlled parallel 3-group design. Biomarkers were assessed at baseline and after 2 and 28 days of intervention. The primary analysis involved the comparison between SynΩ3 and placebo. In addition, SynΩ3 was compared to fish oil. The synbiotic SynΩ3 comprising Bacillus megaterium DSM 32963 and n-3 PUFA salts significantly increased circulating SPM precursor levels, including 18-hydroxy-eicosapentaenoic acid (18-HEPE) plus 5-HEPE, which was not achieved to this extent by fish oil with a similar n-3 PUFA content. Omega-3 indices were increased slightly by both SynΩ3 and fish oil. These findings suggest reconsidering conventional n-3 PUFA supplementation and testing the effectiveness of SynΩ3 particularly in conditions related to inflammation.

Ruscogenin Attenuates Ulcerative Colitis in Mice by Inhibiting Caspase-1-Dependent Pyroptosis via the TLR4/NF-κB Signaling Pathway

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders affecting the digestive tract, including ulcerative colitis and Crohn’s disease. Ruscogenin, a prominent steroidal sapogenin present in radix ophiopogon japonicus, has shown a protective effect on attenuating the inflammatory response associated with inflammatory diseases, but the efficacy of ruscogenin in IBD remains unclear. The aim of this study is to explore the effect of ruscogenin on intestinal barrier dysfunction and inflammatory responses as well as the underlying mechanism in ulcerative colitis. A dextran sulfate sodium salt (DSS)-induced C57BL/6 mouse colitis model was employed for the in vivo studies, while in vitro experiments were performed in THP-1 cells and human intestinal epithelial cells involved in inducing inflammatory responses and pyroptosis using LPS/nigericin. The results indicated that ruscogenin treatment attenuated the symptoms of ulcerative colitis, reduced the release of inflammatory cytokines and the expression of pyroptosis-associated proteins, and restored the integrity of the intestinal epithelial barrier in colon tissue in mice. Moreover, ruscogenin inhibited LPS/nigericin-induced pyroptosis in THP-1 cells. Mechanically, ruscogenin inhibited NLRP3 inflammasome activation and canonical pyroptosis, at least in part, through the suppression of the TLR4/NF-κB signaling pathway. These findings might provide new insights and a solid foundation for further exploration into the therapeutic potential of ruscogenin in the treatment of IBD.

Lactococcus lactis D4 Has Potential Effect to Alleviate Inflammation and Reverse Dysbiosis in Colitis Rat Model

BACKGROUND: Inflammatory bowel disease (IBD) is a prevalent chronic inflammatory disorder of the gastrointestinal tract that may lead to colorectal cancer if untreated. Several medications for IBD have adverse side effects. Thus, there are high interest for searching alternative treatment to treat IBD. Lactococcus lactis D4 isolated from dadih, a traditional fermented buffalo milk product, was investigated for the effect on gut inflammation and microbial composition in the colitis rat model.METHODS: Eighteen male Sprague-Dawley rats were divided into three groups; control rats, colitis-induced rats, and colitis-induced rats treated with L. lactis D4 isolate. The control group received water, while the colitis-induced rats were given azoxymethane (AOM) and dextran sodium sulphate (DSS). Rats’ feces were collected for the analysis of gut microbiota diversity by next-generation sequencing and for the measurement of transforming growth factor (TGF)-β, nuclear factor kappa-B (NF-κB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α colonic expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).RESULTS: L. lactis D4 administration was able to reduce inflammation in colitis by decreasing IL-6 expression (0.87 vs. 0.73), while expression of TGF-β, NF-κB, and TNF-α were increased compared to the model group, suggesting a complex immunomodulatory effect. Gut microbiota sequencing revealed a similarity between the control and treatment groups, suggesting L. lactis D4 has great potential to ameliorate gut microbiota dysbiosis in colitis rats.CONCLUSION: L. lactis D4 has a beneficial effect in decreasing pro-inflammatory cytokines and is able to reserve dysbiosis in colitis rat model. Thus, L. lactis D4 might be used as a therapeutic agent for IBD.KEYWORDS: colitis, gut microbiota, inflammation, inflammatory bowel disease, Lactococcus lactis D4, probiotic, proinflammatory cytokines

Therapeutic Implications of Phenolic Acids for Ameliorating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the potential to alleviate colitis due to their powerful antioxidant and anti-inflammatory properties. In this review, we provide an overview of the structures and main dietary sources of phenolic acids, encompassing benzoic acid and cinnamic acid. Additionally, we explore the potential of phenolic acids as a nutritional therapy for preventing and treating IBD. In animal and cell experiments, phenolic acids effectively alleviate IBD induced by drug exposure or genetic defects. The mechanisms include improving intestinal mucosal barrier function, reducing oxidative stress, inhibiting excessive activation of the immune response, and regulating the balance of the intestinal microbiota. Our observation points towards the need for additional basic and clinical investigations on phenolic acids and their derivatives as potential novel therapeutic agents for IBD.

Impaired Fibroblast Growth Factor 21 (FGF21) Associated with Visceral Adiposity Leads to Insulin Resistance: The Core Defect in Diabetes Mellitus.

The Central nervous system (CNS) is the prime regulator of signaling pathways whose function includes regulation of food intake (consumption), energy expenditure, and other metabolic responses like glycolysis, gluconeogenesis, fatty acid oxidation, and thermogenesis that have been implicated in chronic inflammatory disorders. Type 2 diabetes mellitus (T2DM) and obesity are two metabolic disorders that are linked together and have become an epidemic worldwide, thus raising significant public health concerns. Fibroblast growth factor 21 (FGF21) is an endocrine hormone with pleiotropic metabolic effects that increase insulin sensitivity and energy expenditure by elevating thermogenesis in brown or beige adipocytes, thus reducing body weight and sugar intake. In contrast, during starvation conditions, FGF21 induces its expression in the liver to initiate glucose homeostasis. Insulin resistance is one of the main anomalies caused by impaired FGF21 signaling, which also causes abnormal regulation of other signaling pathways. Tumor necrosis factor alpha (TNF-α), the cytokine released by adipocytes and inflammatory cells in response to chronic inflammation, is regarded major factor that reduces the expression of FGF21 and modulates underlying insulin resistance that causes imbalanced glucose homeostasis. This review aims to shed light on the mechanisms underlying the development of insulin resistance in obese individuals as well as the fundamental flaw in type 2 diabetes, which is malfunctioning obese adipose tissue.

Recalcitrant pityriasis rubra pilaris in a Middle Eastern patient and arguments for early anti‐IL‐23 targeting

AbstractPityriasis rubra pilaris (PRP) is a rare, chronic cutaneous inflammatory disorder of keratinization affecting adults, children and patients with HIV. The pathogenesis of PRP is not fully understood with clinical presentations, and severity remains highly variable. Current treatment modalities for PRP result in recalcitrant disease with potentially unfavourable therapeutic side effects and low tolerability. Due to the rarity of this condition, limited data on treatment efficacies and established management guidelines are lacking. The psychological burden of PRP is detrimental to the quality of life of patients affected with PRP and remains a persistent gap of knowledge. Here, we provide a review of the literature, summarizing new developments in the treatment of PRP and a case report of a patient treated successfully with the anti‐interleukin (IL)‐23p19 antibody Risankizumab with sustained clinical improvement. Risankizumab appears to be an effective and safe treatment for PRP in Asian‐Arabic patients. Further studies are required to assess the efficacy, safety and tolerability of newer targeted therapies for severe PRP.

A Novel Recombinant Human Filaggrin Segment (rhFLA-10) Alleviated a Skin Lesion of Atopic Dermatitis

Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients’ quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties (p &lt; 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin (p &lt; 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD.

Research progress on the role of macrophages in acne and regulation by natural plant products.

Acne vulgaris is one of the most common skin diseases. The current understanding of acne primarily revolves around inflammatory responses, sebum metabolism disorders, aberrant hormone and receptor expression, colonization by Cutibacterium acnes, and abnormal keratinization of follicular sebaceous glands. Although the precise mechanism of action remains incompletely understood, it is plausible that macrophages exert an influence on these pathological features. Macrophages, as a constituent of the human innate immune system, typically manifest distinct phenotypes across various diseases. It has been observed that the polarization of macrophages toward the M1 phenotype plays a pivotal role in the pathogenesis of acne. In recent years, extensive research on acne has revealed an increasing number of natural remedies exhibiting therapeutic efficacy through the modulation of macrophage polarization. This review investigates the role of cutaneous macrophages, elucidates their potential significance in the pathogenesis of acne, a prevalent chronic inflammatory skin disorder, and explores the therapeutic mechanisms of natural plant products targeting macrophages. Despite these insights, the precise role of macrophages in the pathogenesis of acne remains poorly elucidated. Subsequent investigations in this domain will further illuminate the pathogenesis of acne and potentially offer guidance for identifying novel therapeutic targets for this condition.

Elucidating the Molecular Pathways and Therapeutic Interventions of Gaseous Mediators in the Context of Fibrosis

Fibrosis, a pathological alteration of the repair response, involves continuous organ damage, scar formation, and eventual functional failure in various chronic inflammatory disorders. Unfortunately, clinical practice offers limited treatment strategies, leading to high mortality rates in chronic diseases. As part of investigations into gaseous mediators, or gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), numerous studies have confirmed their beneficial roles in attenuating fibrosis. Their therapeutic mechanisms, which involve inhibiting oxidative stress, inflammation, apoptosis, and proliferation, have been increasingly elucidated. Additionally, novel gasotransmitters like hydrogen (H2) and sulfur dioxide (SO2) have emerged as promising options for fibrosis treatment. In this review, we primarily demonstrate and summarize the protective and therapeutic effects of gaseous mediators in the process of fibrosis, with a focus on elucidating the underlying molecular mechanisms involved in combating fibrosis.

OA01 Cluster medicine: the role of genetics for identifying shared biological pathways between rheumatoid arthritis and common comorbidities for targeting treatments

Abstract Background/Aims Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with significant pain and disability, as well as increased risk of comorbidities. These comorbidities, such as coronary artery disease, stroke, heart failure and type 2 diabetes, often form predictable clusters highlighting the importance of common disease mechanisms. Identifying these clusters, and the underlying shared mechanisms, is key to the concept of cluster medicine which aims to take a more systemic approach to treating comorbidity. It is hypothesised that inflammatory processes in RA promote the pathogenesis of these comorbid diseases, which typically occur at an earlier stage of life than in the general population. However, few studies have investigated the degree of shared genetic susceptibility implicated across these traits. The present study aimed to identify and characterise pleiotropic loci and shared biological pathways involved in the pathogenesis of RA and cardiometabolic disorders. Methods European-only GWAS summary statistics were collected for RA (seropositive, seronegative, and overall) and seven cardiometabolic traits, including ischemic stroke, any stroke, heart failure, coronary artery disease, hypertension, atrial fibrillation, and type 2 diabetes. Cross-trait linkage disequilibrium score regression was employed to estimate the degree of genetic correlation (rg) between all pairs of traits. Subset-based meta-analysis was performed using the R package ASSET to identify pleiotropic single nucleotide polymorphisms (SNPs). Pleiotropic SNPs were assigned to genes based on positional and eQTL mapping. Prioritised genes were tested for over-representation in functional categories and biological pathways in gene sets obtained from MsigDB and WikiPathways using the hypergeometric test loci. Gene mapping and enrichment analyses were conducted in FUMA. Results RA showed significant positive genetic correlation with all cardiometabolic traits, with the seronegative subtype showing greater correlation than the seropositive subtype. Correlations between RA and cardiometabolic phenotypes ranged from 0.11 - 0.38, the strongest of which was between seronegative RA and heart failure (rg = 0.38, P = 2.6e-07). A total of 67 lead SNPs were identified as potentially pleiotropic. Pleiotropic SNPs were mapped to genes including IL6R, PTPN11, ATXN2, PLCL1 and SOX6. Pathway enrichment analyses revealed that mapped genes were primarily involved in inflammatory signalling pathways, involving interleukins, TNF-α and interferon (gamma and alpha) response. Conclusion This study provides evidence for pleiotropy across RA and cardiometabolic traits, whereby inherited genetic variants predispose to aberrant cytokine signalling, thus conferring risk to multiple diseases where inflammation is a key driver of pathogenesis. Disclosure M. Stoves: None. M. Soomro: None. S. Zhao: None. D. Plant: None. A. Barton: None. J. Bowes: None.