Chronic Immune Disease Research Articles

Identification of PLAC8 as a Potential Biomarker for the Diagnosis of Interstitial Cystitis.

Interstitial cystitis is a diagnosis of exclusion due to the complexity of its etiology and pathology, which is a chronic disease with an unknown etiology. To our knowledge, few studies were performed to identify predictive biomarkers for interstitial cystitis. This study aimed to identify and validate potential biomarkers for Interstitial Cystitis (IC). The interstitial cystitis datasets were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using the R package and were subjected to functional and pathway enrichment analysis. Key biomarkers of interstitial cystitis were identified by using Lasso regression analysis and the SVM-RFE algorithm. The diagnostic value of key biomarkers was validated in internal and external datasets, and pathways that relate to biomarkers of interstitial cystitis were screened. The ssGSEA was employed to identify the immune cells closely related to biomarkers. The expression of PLAC8 in patients with interstitial cystitis was detected by Immune-Histochemistry (IHC). Sixteen differentially expressed genes associated with interstitial cystitis were identified, which were primarily linked to the biological process of the chemokine signaling pathway. PLAC8, identified as a biomarker for interstitial cystitis, was validated to express a significantly different between IC and normal bladder tissues. PLAC8-related pathways were analyzed, with a focus on NF-κB, TNF, Toll-like receptor, chemokine, IL-17, and JAK-STAT signaling pathways. PLAC8 was proved to be closely related to immune activations, which is similar to the pathogenesis of IC, which is a chronic dysregulated immune disease. Meanwhile, we also observed a higher level of PLAC8 in IC tissues. PLAC8 has promising application prospects as a biomarker for interstitial cystitis diagnosis. These findings could aid in the diagnosis and treatment of interstitial cystitis.

Responsive Multi-Arm PEG-Modified COF Nanocomposites: Dynamic Photothermal, pH/ROS Dual-Responsive, Targeted Carriers for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic immune disease characterized by the infiltration of immune cells and the proliferation of fibroblast-like synoviocytes (FLS) at the joint site, leading to inflammation and joint destruction. However, the available treatment options targeting both inflammatory and proliferative FLS are limited. Herein, this work presents three covalent organic frameworks (COFs) photothermal composite systems modified with multi-armed polyethylene glycols (PEG) for the treatment of RA. These systems exhibit a dual response under low pH and high reactive oxygen species (ROS) conditions at the site of inflammation, with a specific focus on delivering the protein drug ribonuclease A (RNase A). Notably, molecular docking studies reveal the interaction between RNase A and NF-κB p65 protein, and Western blotting confirm its inhibitory effect on NF-κB activity. In vitro and in vivo experiments verify the significant reduction in joint swelling and deformities in adjuvant-induced arthritis (AIA) rats after treatment with RNase A delivered by multi-armed PEG-modified COF ligands, restoring joint morphology to normal. These findings underscore the promising therapeutic potential of COFs for the treatment of RA, highlighting their unique capabilities in addressing both inflammatory and proliferative aspects of the disease and expanding the scope of biomedical applications for COFs.

Upregulated miR-146b-3p predicted rheumatoid arthritis development and regulated TNF-α-induced excessive proliferation, motility, and inflammation in MH7A cells

BackgroundRheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.ObjectivesThis study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.Materials and methodsA total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.ResultsSignificant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.ConclusionsIncreased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.

Intermittent fasting alleviates IMQ-induced psoriasis-like dermatitis via reduced γδT17 and monocytes in mice.

Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.

Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

New Classification of Rheumatoid Arthritis Based on Immune Cells and Clinical Characteristics.

Rheumatoid arthritis (RA) is a chronic systemic immune disease characterized by joint synovitis, but there are differences in clinical manifestations and serum test results among different patients. This is a bioinformatics study. We first obtained the gene expression profile of RA and normal synovium from the database, and screened the differentially expressed immune related genes for enrichment analysis. Subsequently, we classified RA into three subtypes by unsupervised clustering of serum gene expression profiles based on immune enrichment scores. Then, the enrichment and clinical characteristics of different subtypes were analyzed. Finally, according to the infiltration of different subtypes of immune cells, diagnostic markers were screened and verified by qRT-PCR. C1 subtype is related to the increase of neutrophils, C-reactive protein and erythrocyte sedimentation rate, and joint pain is more significant in patients. C2 subtype is related to the expression of CD8+T cells and Tregs, and patients have mild joint pain symptoms. The RF value of C3 subtype is higher, and the expression of various immune cells is increased. CD4 T cells, NK cells activated, macrophages M1 and neutrophils are immune cells significantly infiltrated in synovium and serum of RA patients. IFNGR1, TRAC, IFITM1 can be used as diagnostic markers of different subtypes. In this study, RA patients were divided into different immune molecular subtypes based on gene expression profile, and immune diagnostic markers were screened, which provided a new idea for the diagnosis and treatment of RA.

Pathogenesis of gout: Exploring more therapeutic target.

Gout is a chronic metabolic and immune disease, and its specific pathogenesis is still unclear. When the serum uric acid exceeds its saturation in the blood or tissue fluid, it is converted to monosodium urate crystals, which lead to acute arthritis of varying degrees, urinary stones, or irreversible peripheral joint damage, and in severe cases, impairment of vital organ function. Gout flare is a clinically significant state of acute inflammation in gout. The current treatment is mostly anti-inflammatory analgesics, which have numerous side effects with limited treatment methods. Gout pathogenesis involves many aspects. Therefore, exploring gout pathogenesis from multiple perspectives is conducive to identifying more therapeutic targets and providing safer and more effective alternative treatment options for patients with gout flare. Thus, this article is of great significance for further exploring the pathogenesis of gout. The author summarizes the pathogenesis of gout from four aspects: signaling pathways, inflammatory factors, intestinal flora, and programmed cell death, focusing on exploring more new therapeutic targets.

Building a ML-based QSAR model for predicting the bioactivity of therapeutically active drug class with imidazole scaffold

Human immunodeficiency virus, a retrovirus, causes AIDS, a chronic immune system disease. HIV interferes with the ability of our body to combat disease and infection by weakening our immune system. An essential enzyme necessary for HIV replication is reverse transcriptase (RT). RT inhibitors (RTIs) are a class of antiretroviral drugs that target HIV's RT enzyme, blocking its ability to convert viral RNA into DNA. The RT-1 enzyme has been found to be inhibited by imidazole. It attaches to the RT-1 enzyme's active site and prevents it from performing its usual activity. As a result, viral replication is inhibited, which can eventually aid in slowing the course of HIV and other retroviral diseases. A computational tool allows researchers to simulate and analyze the drug's behaviour in a virtual environment, providing valuable insights into its pharmacological properties, efficacy, and safety. QSAR modelling uses machine learning methods to create predictive models from datasets of chemical substances and the accompanying biological activity. Here, a comparative analysis of the model performances by four different algorithms for the Imidazole scaffold are reported. The algorithms of Support Vector Regression (SVR), Random Forest Regression (RFR), Decision Tree Regression (DTR) and Hist Gradient Boosting Regression (HGBR) have given promising results with the R2 value of 0.905, 0.993, 0.688 and 0.921 respectively for the train sets and for the test set 0.843, 0.977, 0.567 and 0.880. The best performed RFR model have been validated using developed RFR codes for randomly selected compounds and it shows the error percentage of about 0.151% only. From the R2 values, it is observed that the RFR and HGBR models show a better fit with the variables compared to the other models thereby making them the potential models for predicting the activity of novel anti-viral compounds.

Pediococcus pentosaceus KF159 alleviates house dust mite-induced atopic dermatitis by promoting IL10 production and regulatory T cell induction.

Atopic dermatitis (AD) is a chronic immune disease that requires long-term management owing to its relative ease of recurrence. However, steroid treatment is limited owing to the side effects. Therefore, research on therapeutics with proven safety is required. Here, we evaluated the anti-allergic activity of the probiotic strain Pediococcus pentosaceus KF159 (PPKF159) with an ex vivo mouse model sensitized with ovalbumin (OVA) and a mouse model of AD induced by house dust mites. Changes in pathological symptoms were confirmed based on the clinical status of the AD-induced lesion site and the levels of T helper type 2 (Th2)-derived cytokines and immunoglobulin E (IgE). In addition, cell-mediated responses and related mechanisms were elucidated using various kinds of primary cells including splenocytes, mesenteric lymph nodes, Peyer's patch, and bone marrow-derived dendritic cells (BMDCs) in vitro and ex vivo. Oral administration of PPKF159 alleviated AD-like clinical symptoms such as erythema, edema, hemorrhage, and increased tissue thickness, and suppressed the production of Th2-associated cytokines and serum IgE while increasing T helper type 1 (Th1)-mediated cytokine production. PPKF159 induced tolerogenic dendritic cells (tol-DCs) by increasing the expression of ICOS-L, PD-L1, and IDO which were closely related to Treg induction in PPKF159-treated BMDCs. In addition, BMDCs and naive T cells co-cultured in the presence of PPKF159 had elevated IL10 production and increased proportions of CD4+CD25+Foxp3+ Tregs compared to the absence of PPKF159. This study showed that PPKF159 relieved AD-like clinical symptoms, modulated the Th1/Th2 immune balance, and inhibited IgE production in a mouse AD model. PPKF159 induced the transformation of dendritic cells into tolerogenic versions. These induced tol-DCs directly enhanced the production of IL10 or improved the secretion of IL10 through the induction of CD4+CD25+Foxp3+ Treg cells, thereby improving AD. These results suggest that PPKF159 can be applied as a functional food material for the treatment and prevention of AD.

Preventive and therapeutic effects of low-dose whole-body irradiation on collagen-induced rheumatoid arthritis in mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation, resulting in cartilage destruction and bone erosion. It was reported that low-dose radiation modulates immune disease. Here, we investigated whether low-dose whole-body irradiation has preventive and therapeutic effects in collagen-induced RA (CIA) mouse models. Fractionated low-dose irradiation (0.05Gy/fraction, total doses of 0.1, 0.5 or 0.8Gy) was administered either concurrently with CIA induction by Type II collagen immunization (preventive) or after CIA development (therapeutic). The severity of CIA was monitored using two clinical parameters, paw swelling and redness. We also measured total Immunoglobulin G (IgG) and inflammatory cytokines (interleukine (IL)-6, IL-1β and tumor necrosis factor-alpha (TNF-α)) in the serum by enzyme-linked immunosorbent assay, and we evaluated histological changes in the ankle joints by immunohistochemistry and hematoxylin and eosin staining. Low-dose irradiation reduced CIA clinical scores by up to 41% in the preventive model and by 28% in the therapeutic model, while irradiation in the preventive model reduced the typical CIA incidence rate from 82 to 56%. In addition, low-dose irradiation in the preventive model decreased total IgG by up to 23% and decreased IL-1β and TNF-α by 69 and 67%, and in the therapeutic model, decreased total IgG by up to 35% and decreased IL-1β and IL-6 by 59 and 42% with statistical significance (P < 0.01, 0.05 and 0.001). Our findings demonstrate that low-dose radiation has preventive and therapeutic anti-inflammatory effects against CIA by controlling the immune response, suggesting that low-dose radiation may represent an alternative therapy for RA, a chronic degenerative immune disease.

Gas Chromatography-Mass Spectrometry Reveals Stage-Specific Metabolic Signatures of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a type of chronic rheumatic immune disease, and the crucial point of AS treatment is identifying the correct stage of the disease. However, there is a lack of effective diagnostic methods for AS staging. The primary objective of this study was to perform an untargeted metabolomic approach in AS patients in an effort to reveal metabolic differences between patients in remission and acute stages. Serum samples from 40 controls and 57 AS patients were analyzed via gas chromatography-mass spectrometry (GC-MS). Twenty-four kinds of differential metabolites were identified between the healthy controls and AS patients, mainly involving valine/leucine/isoleucine biosynthesis and degradation, phenylalanine/tyrosine/tryptophan biosynthesis, glutathione metabolism, etc. Furthermore, the levels of fatty acids (linoleate, dodecanoate, hexadecanoate, and octadecanoate), amino acids (serine and pyroglutamate), 2-hydroxybutanoate, glucose, etc., were lower in patients in the acute stage than those in the remission stage, which may be associated with the aggravated inflammatory response and elevated oxidative stress in the acute stage. Multiple stage-specific metabolites were significantly correlated with inflammatory indicators (CRP and ESR). In addition, the combination of serum 2-hydroxybutanoate and hexadecanoate plays a significant role in the diagnosis of AS stages. These metabolomics-based findings provide new perspectives for AS staging, treatment, and pathogenesis studies.

AEE alleviates ox-LDL-induced lipid accumulation and inflammation in macrophages

Atherosclerosis is a chronic immune inflammatory disease. Aspirin eugenol ester (AEE) is a novel safe and non-toxic compound with many pharmacological effects such as anti-inflammatory, anti-hyperlipidemic and anti-thrombotic action. In order to investigate the effect of AEE on the inhibition of aortic lipid plaque formation and macrophage-derived foam cell formation induced by oxidized low density lipoprotein (ox-LDL), in vivo atherosclerosis model by feeding ApoE-/- mice with a high-fat diet and foam cells formation in vitro model by ox-LDL-induced RAW264.7 macrophages were established. It was found that AEE decreased the levels of TC and LDL-C in serum, and the plaque formation area and lipid accumulation in the aortic intima of ApoE-/- mice. In vitro studies showed that AEE could prevent the uptake of ox-LDL and reduce the contents of TC and FC in cells. AEE enhanced the cholesterol efflux by increasing the expression of ABCA1, ABCG1 and PPARγ, which effectively alleviated excess cholesterol accumulated in the cells. Meanwhile, AEE also reduced the secretion and expression of inflammatory factors in the cells. In addition, AEE could reverse the action of PPARγ inhibitor T0070907 and/or ox-LDL. Therefore, AEE may become an effective candidate drug for the prevention of atherosclerosis.

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.

Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease. The purpose of this study was to: (1) investigate the role of systemic IL-4 in patients with intermediate AMD (iAMD) and in geographic atrophy (GA), an advanced form of AMD, compared to controls without AMD, and (2) determine if IL-4 levels are moderated by sex. We examined plasma levels of IL-4 in patients with iAMD, GA, and controls without AMD included in the University of Colorado AMD registry (August 2014 to June 2021). Cases and controls were defined by multimodal imaging. IL-4 was measured by multiplex immunoassay. Data were analyzed using a nonparametric rank based linear regression model fit to IL-4. There were 199 patients with iAMD, 97 patients with GA, and 139 controls, with a percentage of female patients 61%, 55%, and 66%, respectively. We demonstrated significantly higher median IL-4 levels in GA (35.3; interquartile range [IQR] = 22.8-50.5) compared to iAMD (6.1; IQR = 2.2-11.3, P < 0.01) and controls (10.7; IQR = 5.0-16.8, P < 0.01). There were no significant differences in levels of IL-4 for cases and controls when stratified by sex. These findings demonstrate a systemic immunological difference between iAMD and GA, indicating IL-4 may be a systemic biomarker for GA development. The plasma biomarker IL-4 is significantly elevated in patients with GA.

Role of F-box WD Repeat Domain Containing 7 in Type 1 Diabetes

Type I diabetes (T1DM) is a chronic immune system disease characterized by the devastation or injury of ß-cells in the Langerhans Island, resulting in insulin deficiency and hyperglycemia. This study determines the new marker F-box and WD repeat domain containing 7 (FBXW7). One hundred twenty type 1 diabetic patients from three different places (central child hospital, Alkindi center for diabetes and endocrinology, Children’s Education Hospital) in Iraq during the period from (20 December 2021 to 25 March 2022) an age ranges of (4-17) years. The patient group consisted of being derived to three groups: group one healthy patient group (33) was included as healthy patient, group two (20) newly diagnosed T1DM and (67) type 1 diabetic with insulin treatment. The quantitative enzyme-linked immunosorbent assay (ELISA) biochemical parameters were used to quantify the protein FBXW-7 levels. FBG, Cholesterol, Triglyceride, HDL, LDL, VLDL, HbA1c, GOT, GPT, Total Oxidant status, and Total Antioxidant status were measured through spectrophotometry. Serum FBXW-7 protein levels were considerably elevated noticeably (p-value = 0.00). In terms of FBXW7 protein, there was a significant variation between the new and therapy groups. There was no significant variation in protein levels between the new compared to healthy groups. Serum FBXW-7 protein was positively correlated with FBG, TG, cholesterol, GOT, GPT, LDL, and VLDL, and was negatively correlated with HDL in the patient group. According to ROC analysis, the cutoff value for FBXW-7 protein was (1.9) in the newly group and (2.1) in the treatment group. Levels of FBXW-7 protein are elevated in DM patients. FBXW-7 protein was significantly different in the treatment group but not different in the newly group when compared with the healthy group.

Bioinformatics identification of ferroptosis-related genes and therapeutic drugs in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic immune disease characterized by synovial inflammation and bone destruction, with a largely unclear etiology. Evidence has indicated that ferroptosis may play an increasingly important role in the onset and development of RA. However, ferroptosis-related genes are still largely unexplored in RA. Therefore, this work focused on identifying and validating the potential ferroptosis-related genes involved in RA through bioinformatics analysis. We screened differentially expressed ferroptosis-related genes (DEFGs) between RA patients and healthy individuals based on GSE55235 dataset. Subsequently, correlation analysis, protein-protein interaction (PPI) network analysis, GO, and KEGG enrichment analyses were performed using these DEFGs. Finally, our results were validated by GSE12021 dataset. We discovered 34 potential DEFGs in RA based on bioinformatics analysis. According to functional enrichment analysis, these genes were mainly enriched in HIF-1 signaling pathway, FoxO signaling pathway, and Ferroptosis pathway. Four genes (GABARPL1, DUSP1, JUN, and MAPK8) were validated to be downregulated by GSE12021 dataset and were diagnostic biomarkers and therapeutic targets for RA via the regulation of ferroptosis. Our results help shed more light on the pathogenesis of RA. Ferroptosis-related genes in RA are valuable diagnostic biomarkers and they will be exploited clinically as therapeutic targets in the future.

Comparative Study on Efficacy of Topical Application of Triamcinolone Acetonide and Curcumin in Management of Oral Lichen Planus

Introduction: Oral lichen planus (OLP) is a chronic inflammatory and immune mediated disease that affects the mucous membranes. OLP is cell-mediated, immune damage to basal keratinocytes that are recognized as being antigenically foreign or altered. Many treatment modalities have been tried since the time immemorial, steroids being the mainstay of the treatment, with more benefits than adversities, but now-a-days alternative/ herbal medicines are used keeping in view the chronicity of disease and long term treatment required to cure it. Curcuminoids, the major constituent of turmeric, has anti-inflammatory, antioxidant and anticancer properties. Natural / herbal product has minimal adversities so this can be more helpful for patients in the upcoming time. Aim: The study was conducted to compare the efficacy of conventional topical corticosteroid, triamcinolone acetonide 0.1% with 1% curcumin gel in OLP patient and to assess reduction in burning sensation, regression of size and ulcero-erosive appearance of lesion. Materials and Methods: An intervention study was conducted on 40 patients diagnosed with OLP which were divided into two groups. Group A was provided with Ointment 0.1% triamcinolone acetonide while Group B was provided with 1% curcuma longa extracts gel for local application on the affected regions The results were analysed using Students t-test,discrete (categorical) data were summarised in number (n) and percentage (%) and compared by chi-square (χ2) test. Groups were also compared by two factor (groups and periods) repeated measure (RM) analysis of variance (ANOVA). Results: Intragroup comparison showed statistically significant reduction in burning sensation, size and extension of lesion (p&lt;0.001) as well as erythema and ulceration (p&lt;0.001) in both the groups. In inter-group comparison, Group A showed reduction in burning sensation (97.3%), size and extension of lesion (100%), reduction in erosive pattern (94.7%) and reduction in ulcerative .......

Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products.

Primary biliary cirrhosis (PBC) is a chronic cholestatic immune liver disease characterized by persistent cholestasis, interlobular bile duct damage, portal inflammation, liver fibrosis, eventual cirrhosis, and death. Existing clinical and animal studies have made a good progress in bile acid metabolism, intestinal flora disorder inflammatory response, bile duct cell damage, and autoimmune response mechanisms. However, the pathogenesis of PBC has not been clearly elucidated. We focus on the pathological mechanism and new drug research and development of PBC in clinical and laboratory in the recent 20 years, to discuss the latest understanding of the pathological mechanism, treatment options, and drug discovery of PBC. Current clinical treatment mode and symptomatic drug support obviously cannot meet the urgent demand of patients with PBC, especially for the patients who do not respond to the current treatment drugs. New treatment methods are urgently needed. Drug candidates targeting reported targets or signals of PBC are emerging, albeit with some success and some failure. Single-target drugs cannot achieve ideal clinical efficacy. Multitarget drugs are the trend of future research and development of PBC drugs.

The Rate of Social Acceptance in Psoriasis Patients: A Cross-Sectional Study in Iran

Background: Psoriasis is recognized as a chronic immune system disease with unknown etiology that affects the skin. It might lead to psychological issues and pose considerable distress. The purpose of this study was to investigate the rate of social acceptance in psoriasis patients. Methods: This was a cross-sectional study which was carried out on all the patients (n=100) referred to specialized skin diseases clinic in Yazd, Iran. 100 psoriasis patients and 100 healthy people as a control group were enlisted. The patients were eliminated from the research in case they had other chronic medical conditions since it could affect social acceptance. The patients completed a social acceptability questionnaire (Marlowe–Crowne Social Desirability Scale) and demographic information was also collected. Data were analyzed by ANOVA and chi square test in the form of descriptive and inferential statistics using SPSS-24 software. Results: The mean of patients’ age was 36.97±13.94 years old and 66% of the patients were female. Mean score of social acceptance was 18.04±4.4. The mean score of social acceptance in psoriasis patients’ group (&gt;40 years old) was estimated higher than in other groups (p&gt;0.05). The results revealed that only the job variable affected the Mean±SD of social acceptance in these patients. The rate of social acceptance in psoriasis patients was higher in those with governmental jobs in comparison to those with self-employment jobs. Overall, the level of social acceptance in people with psoriasis was lower than in the control group. Conclusion: This study showed that psoriasis patients who had governmental jobs received a great deal of acceptance via the people around them and they generally had a better quality of life.

Mechanism underlying the action of Duanteng-Yimu Tang in regulating Treg/Th17 imbalance and anti-rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms. MethodsNetwork pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and RORγt in the serum and synovial tissue and IL-17, IL-1β, TNF-α, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry. ResultsNetwork pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited RORγt expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1β, IL-17, and TNF-α mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells. ConclusionsThese results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.

Artificial Intelligence in Inflammatory Bowel Disease Endoscopy: Advanced Development and New Horizons.

Inflammatory bowel disease (IBD) is a complex chronic immune disease with two subtypes: Crohn's disease and ulcerative colitis. Considering the differences in pathogenesis, etiology, clinical presentation, and response to therapy among patients, gastroenterologists mainly rely on endoscopy to diagnose and treat IBD during clinical practice. However, as exemplified by the increasingly comprehensive ulcerative colitis endoscopic scoring system, the endoscopic diagnosis, evaluation, and treatment of IBD still rely on the subjective manipulation and judgment of endoscopists. In recent years, the use of artificial intelligence (AI) has grown substantially in various medical fields, and an increasing number of studies have investigated the use of this emerging technology in the field of gastroenterology. Clinical applications of AI have focused on IBD pathogenesis, etiology, diagnosis, and patient prognosis. Large-scale datasets offer tremendous utility in the development of novel tools to address the unmet clinical and practice needs for treating patients with IBD. However, significant differences among AI methodologies, datasets, and clinical findings limit the incorporation of AI technology into clinical practice. In this review, we discuss practical AI applications in the diagnosis of IBD via gastroenteroscopy and speculate regarding a future in which AI technology provides value for the diagnosis and treatment of IBD patients.