Chronic Immune-mediated Inflammatory Disease Research Articles

Effectiveness of secukinumab in patients with psoriasis and psoriatic arthritis in a Saudi real-world setting.

Psoriasis (PsO) is an immune-mediated chronic inflammatory disease that results in severe outcomes that impact the patient's quality of life and work productivity. We investigated the effectiveness of secukinumab in patients with chronic plaque psoriasis and psoriatic arthritis (PsA) over a 12-month period. This was a longitudinal, retrospective study of the medical records of 81 patients with psoriasis and/or psoriatic arthritis who had been treated with secukinumab for at least 12 weeks. The Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) percentage, and Dermatology Quality of Life Index (DLQI) among patients with PsO and PsO-PsA showed a statistically significant decrease from baseline over 12 months by approximately 9.86, 19.3%, and 9.7, respectively (p values < 0.001 for each). Moreover, there was a statistically significant decrease in the overall Disease Activity in Psoriatic Arthritis score (DAPSA) by approximately 22.35 from baseline over 12 months of treatment (p < 0.001). Considering the patients who started secukinumab 12 months or more prior to the study cutoff date, the 12-month retention rate was 85%. In a Saudi real-world setting, secukinumab proved to be an efficient medication with high efficacy and retention rates.

Epidemiology of autoimmune liver disease in Korea: evidence from a nationwide real-world database

BackgroundAutoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are all immune-mediated chronic inflammatory liver diseases. Autoimmune liver diseases are rare, making identification and treatment difficult. To improve clinical outcomes and enhance patient quality of life, we performed an epidemiological study of autoimmune liver diseases based on real-world comprehensive data.ResultsWe used National Health Insurance Service claims data in Korea from 2005 to 2019. Patients were identified using the International Classification of Disease 10th Revision code, and rare intractable disease codes assigned according to the strict diagnostic criteria. In the AIH cohort, 8,572 (83.9%) were females and the mean age at diagnosis was 56.3 ± 14.3 years. PBC also showed female dominance (83.3%) and the mean age was 57.8 ± 12.6 years. Patients with PSC showed no sex predominance and had a mean age of 57.8 ± 21.5 years. During the study period, there were 10,212, 6,784, and 888 AIH, PBC, and PSC patients, respectively. The prevalence of AIH, PBC, and PSC in 2019 were 18.4, 11.8, and 1.5 per 100,000 population, while the corresponding incidences were 2.3, 1.4, and 0.3 per 100,000 population, respectively. Analysis of sex-age-standardized data showed that the annual prevalence of these diseases is increasing. The 10-year survival rates were 89.8%, 74.9%, and 73.4% for AIH, PBC, and PSC, respectively.ConclusionsThe number of patients with autoimmune liver disease in South Korea is increasing over time. Further research on autoimmune liver disease is needed to fulfill unmet clinical needs.

Colon Targeting pH-Responsive Coacervate Microdroplets for Treatment of Ulcerative Colitis.

Ulcerative colitis (UC), an immune-mediated chronic inflammatory disease, drastically impacts patients' quality of life and increases their risk of colorectal cancer worldwide. However, effective oral targeted delivery and retention of drugs in colonic lesions are still great challenges in the treatment of UC. Coacervate microdroplets, formed by liquid-liquid phase separation, are recently explored in drug delivery as the simplicity in fabrication, spontaneous enrichment on small molecules and biological macromolecules, and high drug loading capacity. Herein, in this study, a biocompatible diethylaminoethyl-dextran hydrochloride/sodium polyphenylene sulfonate coacervates, coated with eudragit S100 to improve the stability and colon targeting ability, named EU-Coac, is developed. Emodin, an active ingredient in traditional Chinese herbs proven to alleviate UC symptoms, is loaded in EU-Coac (EMO@EU-Coac) showing good stability in gastric acid and pepsin and pH-responsive release behavior. After oral administration, EMO@EU-Coac can effectively target and retain in the colon, displaying good therapeutic effects on UC treatment through attenuating inflammation and oxidative stress response, repairing colonic epithelia, as well as regulating intestinal flora balance. In short, this study provides a novel and facile coacervate microdroplet delivery system for UC treatment.

Anti-psoriasis effect of 18β-glycyrrhetinic acid by breaking CCL20/CCR6 axis through its vital active group targeting GUSB/ATF2 signaling

BackgroundPsoriasis is an immune-mediated chronic inflammatory skin disease. Current research suggests that the long-term persistence and recurrence of psoriasis are closely related to the feedback loop formed between keratinocytes and immune cells, especially in Th 17 or DC cells expressing CCR6. CCL20 is the ligand of CCR6. Therefore, drugs that block the expression of CCL20 or CCR6 may have a certain therapeutic effect on psoriasis. Glycyrrhetinic acid (GA) is the main active ingredient of the plant drug licorice and is often used to treat autoimmune diseases, including psoriasis. However, its mechanism of action is still unclear. MethodsPsoriasis like skin lesion model was established by continuously applying imiquimod on the back skin of normal mice and CCR6-/- mice for 7 days. The therapeutic and preventive effects of glycyrrhetinic acid (GA) on the model were observed and compared. The severity of skin injury is estimated through clinical PASI scores and histopathological examination. qRT-PCR and multiple cytoline assay were explored to detect the expression levels of cytokines in animal dorsal skin lesions and keratinocyte line HaCaT cells, respectively. The dermis and epidermis of the mouse back were separated for the detection of CCL20 expression. Transcription factor assay was applied to screen, and luciferase activity assay to validate transcription factors regulated by GA. Technology of surface plasmon laser resonance with LC-MS (SPR-MS), molecular docking, and enzyme activity assay were used to identified the target proteins for GA. Finally, we synthesized different derivatives of 18beta-GA and compared their effects, as well as glycyrrhetinic acid (GL), on the skin lesion of imiquimod-induced mice to evaluate the active groups of 18beta-GA. Results18β-glycyrrhetinic acid (GA) improved IMQ-induced psoriatic lesions, and could specifically reduce the chemokine CCL20 level of the epidermis in lesion area, especially in therapeutic administration manner. The process was mainly regulated by transcription factor ATF2 in the keratinocytes. In addition, GUSB was identified as the primary target of 18βGA. Our findings indicated that the subject on molecular target research of glycyrrhizin should be glycyrrhetinic acid (GA) instead of glycyrrhizic acid (GL), because GL showed little activity in vitro or in vivo. Apart from that, α, β, -unsaturated carbonyl in C11/12 positions was crucial or unchangeable to its activity of 18βGA, while proper modification of C3 or C30 position of 18βGA may vastly increase its activity. ConclusionOur research indicates that 18βGA exerted its anti-psoriasis effect mainly by suppressing ATF2 and downstream molecule CCL20 predominately through α, β, -unsaturated carbonyl at C11/12 position binding to GUSB in the keratinocytes, and then broke the feedback loop between keratinocytes and CCR6-expressing immune cells. GA has more advantages than GL in the external treatment of psoriasis. A highlight of this study is to investigate the influence of special active groups on the pharmacological action of a natural product, inspired by the molecular docking result.

Ze-Qi-Tang formula inhibits MDSCs glycolysis through the down-regulation of p21/Hif1α/Glut1 signal in psoriatic-like mice

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease that affects the quality of life and mental health of approximately 150 million people worldwide. Ze-Qi-Tang (ZQT) is a classic compound used in China for lung disease; however, its mechanism of action in psoriasis remains unclear. This study aimed to investigate the therapeutic effect of the ZQT formula on psoriasis and explore the underlying molecular mechanisms. MethodsPeripheral blood samples were collected from patients with psoriasis and healthy individuals. Flow cytometry was used to detect changes in the proportions of myeloid-derived suppressor cells (MDSCs) and other immune cells. Psoriasis was induced in mice by the daily application of imiquimod. ZQT was administered separately or in combination with anti-Gr1 antibody to deplete MDSC. The glycolysis levels of the MDSCs were detected using a Seahorse analyzer. The p21/Hif1α/Glut1 pathway was identified and validated by mRNA sequence, RT-qPCR, WB, IF, and the application of p21 inhibitor UC2288. ResultsThe number of MDSCs was significantly increased in patients with psoriasis, with the increased expression of p21, Hif1α, and Glut1 in MDSCs. ZQT significantly alleviated psoriasis-like skin lesions in mice. ZQT formula significantly reduced the number of MDSCs in psoriatic-like mice and enhanced their suppressive capacity for T cells. The efficacy of ZQT in alleviating psoriatic dermatitis is compromised by MDSC depletion. ZQT decreased the expressions of p21, Hif1α, and Glut1-induced glycolysis in MDSCs, thereby inhibiting Th17 cell differentiation. ConclusionThese suggest that ZQT alleviates IMQ-induced psoriatic dermatitis, by inhibiting p21/Hif1α/Glut1-induced glycolysis in MDSCs.

Construction and validation of m6A-related diagnostic model for psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively. M6A-related genes were obtained from the literature and their expression levels in GSE30999 samples were measured to identify M6A-related DEGs between psoriasis lesions (LS) and non-lesional lesions (NL). We identified m6A-related DEGs using differential expression analysis and assessed their interactions through correlation analysis and network construction. A logistic regression analysis followed by LASSO optimization was employed to select m6A-related DEGs for the construction of a diagnostic model. The performance of the model was validated using support vector machine (SVM) methodology with sigmoid kernel function and extensive cross-validation. Additionally, the correlation between m6A-related DEGs and immune cell infiltration was analyzed, as well as the association of these DEGs with psoriasis subtypes. Functional analysis of the m6A-related DEGs included the construction of regulatory networks involving miRNAs, transcription factors (TFs), and small-molecule drugs. The m6A modification patterns were also explored by examining the gene expression differences between psoriasis subtypes and their enriched biological pathways. Finally, the expression of significant m6A regulators involved in the diagnostic model was examined by RT-qPCR. In this study, ten optimal m6A-related DEGs were identified, including FTO, IGF2BP2, METTL3, YTHDC1, ZC3H13, HNRNPC, IGF2BP3, LRPPRC, YTHDC2, and HNRNPA2B1. A diagnostic model based on these m6A-related DEGs was constructed, demonstrating high diagnostic accuracy with an area under the curve (AUC) in GSE30999 and GSE13355 of 0.974 and 0.730, respectively. Meanwhile, the expression level of m6A regulators verified by RT-qPCR was consistent with the results in GSE30999. The infiltration of activated mast cells and NK cells was significantly associated with all ten m6A-related DEGs in psoriasis. Among them, YTHDC1, HNRNPC, and FTO were targeted by most miRNAs and were regulated by nine related TFs. Therefore, patients may benefit from dorsomorphin and cyclosporine therapy. Between the two subgroups, 1,592 DEGs were identified, including LRPPRC and METTL3. These DEGs were predicted to be involved in neutrophil activation, cytokine-cytokine receptor interactions, and chemokine signaling pathways. A diagnostic model based on ten m6A-related DEGs in patients with psoriasis was constructed, which may provide early diagnostic biomarkers and therapeutic targets for psoriasis.

Pszichodermatológiai faktorok szerepe a psoriasis hátterében

Psoriasis is a chronic immune-mediated inflammatory disease that can often be associated with psychiatric problems such as depression and anxiety. Although psychiatric disorders were initially considered secondary, their high prevalence suggests that common pathophysiological mechanisms may be involved in the development of psoriasis and certain psychiatric disorders. Moreover, certain psychological and psychiatric treatments may not only improve quality of life, but also alleviate psoriasis symptoms. This article highlights the psychodermatological aspects of psoriasis, summarizes the most common psychiatric problems in its background and describes the potential of psychotherapeutic and psychotropic treatments to reduce the severity of psoriasis.

Interleukins and Psoriasis.

Psoriasis is an immune-mediated chronic inflammatory skin disease that affects 2% to 3% of the world's population. It is widely assumed that immune cells and cytokines acting together play a crucial part in the pathophysiology of psoriasis by promoting the excessive proliferation of skin keratinocytes and inflammatory infiltration. Interleukins (ILs), as a critical component of cytokines, have been closely associated with the pathogenesis and progression of psoriasis. This review summarizes the current contribution of ILs to psoriasis and describes the role each IL performs in psoriasis. Furthermore, the paper presents the therapeutic effects and application prospects of biologics developed for ILs in clinical treatment and experiments. The study aims to further the research on ILs in the treatment of psoriasis.

Neuroimaging characterization of multiple sclerosis lesions in pediatric patients: an exploratory radiomics approach.

Multiple sclerosis (MS), a chronic inflammatory immune-mediated disease of the central nervous system (CNS), is a common condition in young adults, but it can also affect children. The aim of this study was to construct radiomic models of lesions based on magnetic resonance imaging (MRI, T2-weighted-Fluid-Attenuated Inversion Recovery), to understand the correlation between extracted radiomic features, brain and lesion volumetry, demographic, clinical and laboratorial data. The neuroimaging data extracted from eleven scans of pediatric MS patients were analyzed. A total of 60 radiomic features based on MR T2-FLAIR images were extracted and used to calculate gray level co-occurrence matrix (GLCM). The principal component analysis and ROC analysis were performed to select the radiomic features, respectively. The realized classification task by the logistic regression models was performed according to these radiomic features. Ten most relevant features were selected from data extracted. The logistic regression applied to T2-FLAIR radiomic features revealed significant predictor for multiple sclerosis (MS) lesion detection. Only the variable "contrast" was statistically significant, indicating that only this variable played a significant role in the model. This approach enhances the classification of lesions from normal tissue. Our exploratory results suggest that the radiomic models based on MR imaging (T2-FLAIR) may have a potential contribution to characterization of brain tissues and classification of lesions in pediatric MS.

HMGB1 regulates Th17 cell differentiation and function in patients with psoriasis.

Psoriasis is an immune-mediated chronic inflammatory skin disease, in which T helper 17 (Th17) cells and its effective cytokine interleukin (IL)-17A play a pivotal pathogenic role. High mobility group box 1 (HMGB1) is an important proinflammatory cytokine, which has been confirmed to be highly expressed in the peripheral circulation and epidermis tissues of psoriasis patients. The regulatory effect of HMGB1 on IL-17A expression and function has been reported in some inflammatory and autoimmune diseases by theHMGB1-Toll-like receptor 4 (TLR4)-interleukin (IL)-23-IL-17A pathway. While, in the pathological environment of psoriasis, whether HMGB1 can exert the regulatory effect on IL-17A is not clear. We aimed to evaluate the role of HMGB1-TLR4-IL-23-IL-17A pathway in the pathogenesis of psoriasis and explore the possible regulatory mechanism of HMGB1 on Th17 cell differentiation. Serum levels of HMGB1, TLR4, IL-23, and IL-17A were quantified in 50 patients with moderate-to-severe plaque psoriasis and 30 healthy controls. Peripheral blood mononuclear cells were acquired from 10 severe psoriasis patients and administrated by different concentrations of recombinant-HMGB1 (rHMGB1) to detect the Th17 cell percentage, mRNA and protein levels of TLR4, IL-23, IL-17A and retinoid-related orphan receptor γt (RORγt). The serum levels of HMGB1, TLR4, IL-23, and IL-17A in psoriasis patients were significantly higher than healthy controls, especially in severe patients, and positively correlated with the severity index. There were also positive correlations between every two detected indicators of HMGB1, TLR4, IL-23, and IL-17A. In vitro study, rHMGB1 can promote the elevated expression of Th17 cell percentage as well as TLR4, IL-23, IL-17A, and RORγt in a dose-dependent manner. HMGB1 can contribute to the pathogenesis of psoriasis by regulating Th17 cell differentiation through HMGB1-TLR4-IL-23-RORγt pathway, then promotesIL-17A production and aggravates inflammation process. Targeting HMGB1 may be a possible potential candidate for the immunotherapy of psoriasis.

P502 Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4 T cells as predictors for response to integrin alpha4 beta7-blocking therapy in patients with Inflammatory Bowel Disease

Abstract Background Despite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors. Methods Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response. Results Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4+ memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients. Conclusion Our study provides a comprehensive framework for assessing therapy response and understanding the mechanisms underlying resistance in chronic immune-mediated inflammatory diseases such as IBD. Identifying personalized treatment strategies based on individual patient characteristics, as exemplified by our "stratify to target" approach, can significantly improve IBD management.

A Novel Multi-Strain E3 Probiotic Formula Improved the Gastrointestinal Symptoms and Quality of Life in Chinese Psoriasis Patients.

Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin and other systems. Gastrointestinal disease was found to be correlated with psoriasis in previous studies and it can significantly affect the quality of life of psoriasis patients. Despite the importance of the gut microbiome in gut and skin health having already been demonstrated in many research studies, the potential effect of probiotics on GI comorbidities in psoriasis patients is unclear. To investigate the effects of probiotics on functional GI comorbidities including irritable bowel syndrome, functional constipation, and functional diarrhea in psoriasis patients, we conducted a targeted 16S rRNA sequencing and comprehensive bioinformatic analysis among southern Chinese patients to compare the gut microbiome profiles of 45 psoriasis patients over an 8-week course of novel oral probiotics. All the participants were stratified into responders and non-responders according to their improvement in GI comorbidities, which were based on their Bristol Stool Form Scale (BSFS) scores after intervention. The Dermatological Life Quality Index (DLQI) score revealed a significant improvement in quality of life within the responder group (DLQI: mean 10.4 at week 0 vs. mean 15.9 at week 8, p = 0.0366). The proportion of psoriasis patients without GI comorbidity manifestation at week 8 was significantly higher than that at week 0 (week 0: Normal 53.33%, Constipation/Diarrhea 46.67%; week 8: Normal 75.56%, Constipation/Diarrhea 24.44%, p = 0.0467). In addition, a significant difference in the gut microbiome composition between the responders and non-responders was observed according to alpha and beta diversities. Differential abundance analysis revealed that the psoriasis patients exhibited (1) an elevated relative abundance of Lactobacillus acidophilus, Parabacteroides distasonis, and Ruminococcus bromii and (2) a reduced relative abundance of Oscillibacter, Bacteroides vulgatus, Escherichia sp., and Biophila wadsworthia after the 8-week intervention. The responders also exhibited a higher relative abundance of Fusicatenibacter saccharivorans when compared to the non-responders. In summary, our study discovers the potential clinical improvement effects of the novel probiotic formula in improving GI comorbidities and quality of life in psoriasis patients. We also revealed the different gut microbiome composition as well as the gut microbial signatures in the patients who responded to probiotics. These findings could provide insight into the use of probiotics in the management of psoriasis symptoms.

Lipid mediators obtained from docosahexaenoic acid by soybean lipoxygenase attenuate RANKL-induced osteoclast differentiation and rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by persistent inflammation and joint destruction. A lipid mediator (LM, namely, 17S-monohydroxy docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50) produced by soybean lipoxygenase from DHA, exhibits anti-inflammatory activity. In this study, we determined the effect of LM on collagen antibody-induced arthritis (CAIA) in mice and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in RAW264.7 cells. LM effectively downregulated the expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K, inhibited osteoclast formation, and suppressed the NF-κB signaling pathway in vitro. In vivo, LM at 10 μg/kg/day significantly decreased paw swelling and inhibited progression of arthritis in CAIA mice. Moreover, proinflammatory cytokine (tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-17, and interferon-γ) levels in serum were decreased, whereas IL-10 levels were increased following LM treatment. Furthermore, LM alleviated joint inflammation, cartilage erosion, and bone destruction in the ankles, which may be related to matrix metalloproteinase and Janus kinase (JAK)–signal transducer and activators of transcription (STAT) signaling pathway. Our findings suggest that LM attenuates arthritis severity, restores serum imbalances, and modifies joint damage. Thus, LM represents a promising therapy for relieving RA symptoms.

Inter-relationships of galectin-3 and NLR family pyrin domain containing 3 inflammasomes with oral lichen planus: a preliminary cross-sectional in vitro study

BackgroundThe nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome has been reported to be highly expressed in oral lesions with the potential for malignant development such as oral lichen planus (OLP). And the NLRP3 inflammasome can be activated by galectin-3 (Gal-3) in immune-mediated chronic inflammatory diseases. This study aimed to explore the inter-relationships among Gal-3, NLRP3 inflammasome, and OLP.MethodsA cross-sectional analysis of oral biopsy specimens from 30 patients with Erosive OLP and 30 healthy controls was performed. Immunohistochemical staining was used to evaluate the expression of Gal-3 and NLRP3 inflammasome. Two-sample t-test and Pearson correlation test were applied to analyze the data.Results Erosive OLP patients had significantly higher Gal-3 levels compared with controls (p < 0.0001). A similar pattern emerged for NLRP3 inflammasome. In the overall sample, a positive correlation was observed between Gal-3 and NLRP3 (r = 0.92, p < 0.01).ConclusionsPatients with Erosive OLP lesions showed increased protein expression levels of Gal-3. A positive correlation was observed between Gal-3 and NLRP3 inflammasome.

Interprofessional cooperation with a dermatovenerologist - specifics of hidradenitis suppurativa management in gynaecological practice.

Hidradenitis suppurativa is a chronic immune-mediated inflammatory disease that is manifested by formation of painful nodules, abscesses and suppurating fistulas, primarily in the intertriginous spaces. This painful, often under-diagnosed disease affects much more women. They are also exposed to certain specific challenges in the management of this disease, especially during menstruation or pregnancy. The treatment requires the interdisciplinary cooperation of a dermatologist, gynaecologist, obstetrician and last but not least an algesiologist and psychotherapist. Above all, early and correct diagnosis, initiation of therapy in the early stages of the disease, is a key, which also plays a fundamental role in controlling inflammatory activity, preventing complications and further prognosis.

A bibliometrics study on the status quo and hot topics of pathogenesis of psoriasis based on Web of Science.

Psoriasis is an immune-mediated chronic inflammatory skin disease. Great progress has been made in the pathogenesis of psoriasis in recent years, but there is no bibliometric study on the pathogenesis of psoriasis. The purpose of this study was to use bibliometrics method to analyze the research overview and hot spots of pathogenesis of psoriasis in recent 10years, so as to further understand the development trend and frontier of this field. The core literatures on the pathogenesis of psoriasis were searched in the Web of Science database, and analyzed by VOSviewer, CiteSpace, and Bibliometrix in terms of the annual publication volume, country, institution, author, journal, keywords, and so on. A total of 3570 literatures were included. China and the United States were the main research countries in this field, and Rockefeller University was the main research institution. Krueger JG, the author, had the highest number of publications and the greatest influence, and Boehncke (2015) was the most cited local literature. J INVEST DERMATOL takes the top spot in terms of the number of Dermatol articles and citation frequency. The main research hotspots in the pathogenesis of psoriasis are as follows: (1) The interaction between innate and adaptive immunity and the related inflammatory loop dominated by Th17 cells and IL-23/IL-17 axis are still the key mechanisms of psoriasis; (2) molecular genetic studies represented by Long Non-Coding RNA (LncRNA); (3) integrated research of multi-omics techniques represented by gut microbiota; and (4) Exploring the comorbidity mechanism of psoriasis represented by Metabolic Syndrome (MetS). This study is a summary of the current research status and hot trend of the pathogenesis of psoriasis, which will provide some reference for the scholars studying the pathogenesis of psoriasis.

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis.

Background: Ulcerative colitis is a chronic immune-mediated inflammatory bowel disease that involves inflammation and ulcers of the colon and rectum. To date, no definite cure for this disease is available. Objective: The objective of the current study was to assess the effect of Calliandra haematocephala on inflammatory mediators and oxidative stress markers for the exploration of its anti-ulcerative colitis activity in rat models of acetic acid-induced ulcerative colitis. Methods: Methanolic and n-hexane extracts of areal parts of the plant were prepared by cold extraction method. Phytochemical analysis of both extracts was performed by qualitative analysis, quantitative methods, and high-performance liquid chromatography (HPLC). Prednisone at 2mg/kg dose and plant extracts at 250, 500, and 750mg/kg doses were given to Wistar rats for 11days, which were given acetic acid on 8th day through the trans-rectal route for the induction of ulcerative colitis. A comparison of treatment groups was done with a normal control group and a colitis control group. To evaluate the anti-ulcerative colitis activity of Calliandra haematocephala, different parameters such as colon macroscopic damage, ulcer index, oxidative stress markers, histopathological examination, and mRNA expression of pro and anti-inflammatory mediators were evaluated. mRNA expression analysis was carried out by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Results: The phytochemical evaluation revealed polyphenols, flavonoids, tannins, alkaloids, and sterols in both extracts of the plant. Results of the present study exhibited that both extracts attenuated the large bowel inflammation and prevented colon ulceration at all tested doses. Macroscopic damage and ulcer scoreswere significantly decreased by both extracts. Malondialdehyde (MDA) levels and nitrite/nitrate concentrations in colon tissues were returned to normal levels while superoxide dismutase (SOD) activity was significantly improved by all doses. Histopathological examination exhibited that both extracts prevented the inflammatory changes, cellular infiltration, and colon thickening. Gene expression analysis by RT-qPCR revealed the downregulation of pro-inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) whereas the anti-inflammatory cytokines including Interleukin-4 (IL-4) and Interleukin-10 (IL-10) were found to be upregulated in treated rats. Conclusion: It was concluded based on study outcomes that methanolic and n-hexane extracts of Calliandra haematocephala exhibited anti-ulcerative colitis activity through modulation of antioxidant defense mechanisms and the immune system. In this context, C. haematocephala can be considered as a potential therapeutic approach for cure of ulcerative colitis after bioassay-directed isolation of bioactive phytochemicals and clinical evaluation.

Esofagitis eosinofílica

Eosinophilic esophagitis is a chronic immune-mediated inflammatory disease of the esophagus. Its incidence has increased in recent years and it is one of the most prevalent esophageal diseases, with a significant impact on physical health and quality of life. Symptoms are variable and it is an increasingly common cause of dysphagia in both children and adults. The gold standard for diagnosis is upper gastrointestinal endoscopy with biopsies of patches demonstrating inflammatory infiltrate with more than 15 eosinophils per high-power field. Various effective treatments are currently available for both induction and maintenance of disease remission, including proton pump inhibitors, swallowed topical corticosteroids, and exclusion diets.

Upadacitinib: Mechanism of action, clinical, and translational science.

Upadacitinib is a selective Janus kinase (JAK) inhibitor which is approved by the US Food and Drug Administration, the European Medicines Agency, as well as other agencies around the world for the treatment of several chronic inflammatory diseases, including rheumatic, dermatologic, and gastrointestinal diseases. Through inhibition of JAK, upadacitinib inhibits phosphorylation of downstream effector proteins, which consequently inhibits cytokine signaling for key pathways involved in inflammatory diseases. Upadacitinib more potently inhibits JAK1 than other JAK isoforms. The pharmacokinetics, pharmacodynamics, efficacy, and safety of upadacitinib were characterized in many clinical trials, which demonstrated the superiority of upadacitinib treatment over placebo or an active comparator in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis. The safety profile of upadacitinib supported a favorable benefit-risk profile across all the approved indications. In this article, we review the mechanism of action of upadacitinib and describe how the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway is involved in the pathogenesis of several chronic and progressive immune-mediated inflammatory diseases. In addition, this review also provides an overview of key clinical trials that were conducted as well as relevant data which supported the clinical development of upadacitinib and informed the recommended dose(s) in each of the approved indications.

Comparative effectiveness and cost evaluation of Risankizumab and Adalimumab in the management of psoriasis: a real-world study in Saudi Arabia

BackgroundPsoriasis, an immune-mediated chronic inflammatory disease primarily affecting skin and joints, has varying prevalence rates globally. It manifests in five types, with chronic plaque psoriasis being the most common. Treatment, which has no definitive cure, aims for complete resolution of skin symptoms and depends on disease extent, severity, and impact on patients’ lives. Biologics are an emerging treatment for psoriasis, targeting specific inflammatory pathways for potentially safer, more effective outcomes. However, these come with significant costs, necessitating more research to ensure value for money. This study aimed to compare the effectiveness of Risankizumab versus Adalimumab, the most commonly utilized biologic for managing psoriasis in Saudi Arabia.MethodsThis study retrospectively compared the effectiveness and direct medical cost of Risankizumab and Adalimumab in treating chronic plaque psoriasis in adults from two Saudi Arabian healthcare centers. The Psoriasis Area and Severity Index (PASI) and body surface area (BSA) were used to assess treatment effectiveness, with patient data sourced from electronic medical records. Multiple regression analysis was performed to examine various factors affecting treatment outcomes. An economic evaluation was conducted to examine the cost-effectiveness of the two drugs, considering four scenarios with varying dosage patterns and costs. Analysis was performed from the perspective of public healthcare payers and considered all utilized health services.ResultsThe data for 70 patients were analyzed, with comparable baseline characteristics between groups. While Risankizumab led to a greater reduction in PASI scores and BSA affected, these results were not statistically significant. The annual treatment cost for Risankizumab was higher than Adalimumab. Various scenarios were studied, considering real acquisition costs, double dosing for Adalimumab, and the use of biosimilars. A scenario assuming double dosing for Adalimumab and a 40% discount for Risankizumab demonstrated both cost and efficacy advantages in 71.25% of cases.ConclusionsThis study compared the effectiveness and cost of Risankizumab and Adalimumab for treating chronic plaque psoriasis in Saudi Arabian hospitals. Although Risankizumab showed a greater reduction in symptoms, the difference was not statistically significant. However, under certain scenarios, Risankizumab demonstrated cost and efficacy advantages. These findings may influence treatment decisions for psoriasis, but further research is needed.