Disease Activity Index Score Research Articles

Qing Hua Chang Yin alleviates chronic colitis of mice by protecting intestinal barrier function and improving colonic microflora.

Background: Qing Hua Chang Yin (QHCY) is a famous formula of traditional Chinese medicine (TCM) and has been proven to have protective effect on ulcerative colitis. However, its protective effect and potential therapeutic mechanisms in chronic colitis remain unclear. The purpose of this study is to explore the effects and underlying mechanisms of QHCY on dextran sulfate sodium (DSS)-induced chronic colitis mice model. Methods: The chronic colitis model was established by administration of 2% DSS for three consecutive cycles of 7 days with two intervals of 14 days for recovery by drinking water. The experiment lasted 49 days. The DSS + QHCY group received QHCY administration by oral gavage at doses of 1.6g/kg/d, DSS + Mesalazine group was administrated Mesalazine by oral gavage at doses of 0.2g/kg/d. The control and DSS group were given equal volume of distilled water. The body weight, stool consistency and blood in stool were monitored every 2days. The disease activity index (DAI) was calculated. The colon length was measured after the mice were sacrificed. The histomorphology of colonic tissues was checked by the HE and PAS staining. Immunohistochemistry was performed to detect the expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), tight junction proteins (ZO-1, occludin) and Mucin2 (MUC2). 16S rRNA sequencing analysis was conducted to study the diversity and abundance of gut microbiota changes. Results: QHCY treatment not only significantly attenuated DSS-induced the weight loss, DAI score increase, colon shortening and histological damage in mice, but also decreased the expression of pro-inflammatory cytokines in colonic tissues and increased the expression of ZO-1, occludin, and MUC2. Furthermore, QHCY enhanced the diversity of gut microbes and regulated the structure and composition of intestinal microflora in mice with chronic colitis. Conclusion: QHCY has a therapeutic effect on a murine model of chronic colitis. It can effectively reduce the clinical and pathological manifestations of colitis and prevent alterations in the gut microbiota.

Meta-analysis of effectiveness and safety of glucocorticoid combined with hydroxychloroquine in the treatment of systemic lupus erythematosus rash.

Many studies have found that glucocorticoid (GC) combined with hydroxychloroquine (HCQ) has a good clinical effect in the treatment of systemic lupus erythematosus (SLE) rash, but there is no relevant systematic evaluation at present. The purpose of this study was to systematically evaluate and analyze the effectiveness and safety of GC combined with HCQ in the treatment of SLE rash. Randomized controlled trials of GC combined with HCQ in the treatment of SLE rash were collected through computer retrieval of Cochrane Library, PubMed, Embase, CNKI, China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform (Wanfang), and China Biology Medicine disc (CBM) since the establishment of the database. The main outcome indicators included clinical total effective rate, adverse reactions, SLE disease activity index (SLEDAI) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complement 3 (C3). A meta-analysis was conducted using Review Manager 5.3 software. A total of 11 studies involving 809 patients (406 in the test group and 403 in the control group) were included in this article. The meta-analysis results showed that compared with the single use of GC, GC combined with HCQ could improve the clinical total effective rate in the treatment of SLE rash (odds ratio [OR] = 4.27, 95% confidence interval [CI] 2.50-7.30, p < .00001), and reduce the occurrence of adverse reactions (OR = 0.26, 95% CI 0.15-0.44, p < .00001); effectively reduce SLEDAI score (mean difference [MD] = 1.88, 95% CI 1.66-2.10, p < .00001) and ESR level (MD = 7.92, 95% CI 5.66-10.19, p < .00001); increase C3 level after treatment (MD = 0.36, 95% CI 0.32-0.41, p < .00001); and reduce CRP level (MD = 3.22, 95% CI 2.87-3.58, p < .00001), with statistically significant differences. Compared with the use of GC alone, GC combined with HCQ can improve the clinical effectiveness of SLE rash treatment, with a low incidence of adverse reactions and good clinical safety. However, the number and quality of studies included in this article were not high, so the findings need to be further verified by high-quality, multicenter randomized controlled trials.

Transcriptome sequencing reveals novel molecular features of SLE severity.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of autoantibodies, immune complex deposition, and tissue/organ damage. In this study, we aimed to identify molecular features and signaling pathways associated with SLE severity using RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and clinical parameters. Methods: We analyzed transcriptome profiles of 45 SLE patients, grouped into mild (mSLE, SLEDAI ≤ 9) and severe (sSLE, SLEDAI > 9) based on SLE Disease Activity Index (SLEDAI) scores. We also collected clinical data on anti-dsDNA, ANA, ESR, CRP, snRNP, AHA, and anti-Smith antibody status for each patient. Results: By comparing gene expression across groups, we identified 12 differentially expressed genes (DEGs), including 7 upregulated (CEACAM6, UCHL1, ARFGEF3, AMPH, SERPINB10, TACSTD2, and OTX1) and 5 downregulated (SORBS2, TRIM64B, SORCS3, DRAXIN, and PCDHGA10) DEGs in sSLE compared to mSLE. Furthermore, using the CIBERSORT algorithm, we found that Treg cells were significantly decreased in sSLE and negatively correlated with AMPH expression, which was mainly expressed in Treg cells from SLE patients according to public scRNA-seq data (GSE135779). Discussion: Overall, our findings shed light on the molecular mechanisms underlying SLE severity and provide insight into potential therapeutic targets.

Anti-C1q antibodies in lupus nephritis children with glomerular microthrombosis.

Glomerular microthrombosis (GMT) was a common vascular lesion in patients with lupus nephritis (LN). The objective of this study was to investigate the relationship between serum anti-beta2-glycoprotein I antibodies (a-β2GP1) and anti-complement 1q antibodies (a-C1q) antibodies and to investigate the possible mechanism of GMT in children with LN. The subjects were 191 children with LN diagnosed by renal biopsy in our hospital from January 2017 to January 2020. The patients were divided into GMT group and non-GMT group. The clinical manifestations, laboratory tests, renal pathology, prognosis of the two groups and the relationship between a-β2GP1 and a-C1q antibodies were observed. In 191 children with LN, 52 cases (27.23%) presented with GMT. The value of C3, haemoglobin (Hb), estimate glomerular filtration rate (eGFR) and anticardiolipin antibody (ACA) in GMT group were lower than that of non-GMT group (p < .05, p < .01). The value of serum creatinine (Scr), 24 h proteinuria (PRO), urine red blood cells (RBC), N-acetyl-β-d-glucosidase (NAG) and retinol-binding protein (RBP), a-C1q, a-β2GP1, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal histopathological activity index (AI) score in GMT group were higher than that of non-GMT group (p < .05, p < .01). The positive proportions of serum a-C1q and a-β2GP1 in GMT group were higher than those in non-GMT group (p < .05). According to Spearman correlation analysis, a-C1q was positively correlated with AI score, SLEDAI, a-β2GP1, GMT, LN-III and LN-IV. Hb, eGFR and a-C1q Ab were associated with the formation of GMT in children with LN. The complete proteinuria remission and renal survival in GMT group were significantly lower than those in non-GMT group (p < .05, p < .01). LN children with GMT had more severe clinical manifestations and renal pathologic damages, and poor outcome. Serum a-C1q level was positively correlated with a-β2GP1, and a-β2GP1 may be involved in the formation of GMT in children with LN, which might involve in the activation of complement classical pathway.

Epidemiology and clinical characteristics of interstitial lung disease in patients with rheumatoid arthritis from the JointMan database

Interstitial lung disease (ILD) is a progressive fibrotic disease associated with rheumatoid arthritis (RA); real-world data for evaluating RA–associated ILD (RA–ILD) are limited. We evaluated prevalence, time to onset, clinical characteristics and prognostic factors in patients diagnosed with RA (n = 8963) in the Discus Analytics JointMan database (2009–2019) with and without ILD. ILD prevalence was 4.1% (95% confidence interval 3.7–4.5); > 90% had an ILD diagnosis after RA diagnosis (mean time to onset 3.3 years). At baseline, a higher proportion of patients with RA–ILD were older (> 65 years), male, with history of chronic obstructive pulmonary disease (COPD) compared with patients in the RA cohort. Patients in the RA–ILD cohort were likely to have more severe RA characteristics and joint evaluation compared with patients without ILD, at baseline and before/after ILD diagnosis. In this large, real-world database patients with (vs without) ILD had a higher burden of RA characteristics. Previously established risk factors for RA–ILD were confirmed (age, baseline COPD, anti-cyclic citrullinated peptide positivity, C-reactive protein, Clinical Disease Activity Index score); thus, recognition of these factors and tracking routine disease activity metrics may help identify patients at higher risk of RA complications and lead to improved diagnosis and earlier treatment.

Fruit of Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils Attenuates DSS-induced Ulcerative Colitis by Adjusting Nrf2/NF-κB Signaling Pathway

Background Rosa odorata Sweet var. gigantean (Coll. et Hemsl.) Rehd. et Wils (FOE), a sort of ethnodrug from the Yi nationality called “GU-GONG-GUO,” the root of which has been shown to have the effect of relieving diarrhea with astringents. Whether fruit extract (FOE) has therapeutic properties for related intestinal diseases is unclear. Objectives The study dedicates to expounding the results and mechanisms of FOE for treating ulcerative colitis (UC). Materials and Methods we used dextran sulfate sodium to induce UC in vivo and lipopolysaccharide to stimulate macrophage in vitro for the purpose of exploring and determining the effectiveness and potential mechanism of action of FOE. Results The weight loss ratio and Disease activity index score of FOE administration groups were obviously lower and the colon tissue morphology was significantly relieved. The levels of various proinflammatory cytokines in colon tissue were evaluated to be decreased. Meanwhile, the FOE administration group also alters oxidative stress factor levels. The levels of Nrf2 and HO-1 protein were once distinctly up-regulated, whereas the levels of NF-κB p65, p-IKK α/β, and Keap1 were dose-independently and prominently suppressed by FOE administration. In vitro, FOE significantly reduced the secretion of proinflammatory cytokines and inhibited the oxidant stress injury in macrophage cells induced by macrophage. The relative expressions of NF-κB p65, p-IKK α/β, and Keap1 proteins in FOE groups were memorably down-regulated, while the Nrf2 and HO-1 levels presented as a contrary tendency. Conclusion These results indicated that FOE has shown potential therapeutic efficacy on UC and might be considered an effective anti-inflammatory agent from natural sources.

Prevalence and Risk Factors of Anemia in Inflammatory Bowel Diseases: A Case-Control Study.

Introduction Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis may induce anemia, ranging from 25% to 75% depending on the study population and diagnostic criteria. It might negatively impact their health and quality of life. Objectives The aim of this work is to study the effectiveness and safety of treatments for anemia in patients with IBD. Methodology This case-control study compared patients with IBD who have anemia (cases; n=60) with patients who have IBD but do not have anemia (controls; n=60) from June 2019 to August 2021 in Hayatabad Medical Complex, Peshawar, Pakistan. Data were collected through interviews, from patients` medical records, and from lab test reports. Statistical analysis was performed using SPSS, Version 23.0 (IBM Corp., Armonk, NY). Results Cases had a greater mean age (45.2 years) than controls (42.8 years). Cases included 60% females and controls 45%. Also, cases earned less (p = 0.019). Anemic patients (group 1) had lower mean hemoglobin (10.2 g/dL) and iron than non-anemic controls (group 2) (p = 0.042 and 0.009, respectively). Anemia increased Crohn's Disease Activity Index and Mayo Score. Group 1 has iron deficiency anemia, whereas group 2 has chronic disease. Group 1 reacts rapidly, but gastrointestinal side effects, allergies, and iron overload are more prevalent. Conclusion IBD patients exhibited low hemoglobin and iron, suggesting anemia. Anemia increased disease activity, but not statistically. IBD patients need iron and anemia treatment. Comparing groups demonstrates differences in anemia types, iron replacement history, treatment response, and bad effects, proposing targeted iron supplementation for deficiency anemia and managing chronic illness factors for chronic disease anemia. IBD anemia treatment involves individualization.

An inulin-type fructan isolated from Serratula chinensis alleviated the dextran sulfate sodium-induced colitis in mice through regulation of intestinal barrier and gut microbiota

Herein, we aimed to explore the polysaccharide material basis of Serratula chinensis and establish its beneficial effects against colitis. A neutral polysaccharide (SCP) was extracted from S. chinensis in high yield using hot water. The molecular weights were calculated by HPSEC as Mw = 2928 Da, Mn = 2634 Da, and Mw/Mn = 1.11. FT-IR and 1D/2D-NMR spectroscopic analyses confirmed that SCP was an inulin-type fructan with α-D-Glcp-(1 → [1)-β-D-Fruf-(2]17) linkages. Treatment with SCP (200 or 400 mg/kg) alleviated dextran sulfate sodium (DSS)-induced mouse colitis symptoms, including the loss of body weight, increase of disease activity index score, and shortening of colon length. Histopathological and immunofluorescence assessments revealed that SCP could reduce pathological damage to the colon, restore the number of goblet cells, increase the content of glycoproteins in goblet cells and mucins in crypts, and enhance the expression of tight junction proteins ZO-1 and occludin. In addition, metagenomic sequencing revealed that SCP could improve the dysbiosis of gut microbiomes and act on multiple microbial functions. Moreover, SCP treatment increased the content of colonic acetic acid and butanoic acid. Collectively, these results indicated that SCP could alleviate the DSS-induced colitis in mice through regulation of intestinal barrier and gut microbiota.

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice

Context Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. Objective This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. Materials and methods Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. Results Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1β and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1β, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. Discussion and conclusion Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1β, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

Mesenchymal stem cell transplantation as a potential therapy for refractory lupus nephritis: A systematic review

AbstractBackgroundLupus nephritis (LN) results in high morbidity and mortality in patients with systemic lupus erythematosus. Refractory cases of standard immunosuppressive therapy have been recorded. Mesenchymal stem cell transplantation (MSCT) shows potential use in autoimmune diseases. We aim to review MSCT in the treatment of refractory LN.MethodsPublished articles were systematically extracted from the databases in May 2022. The quality of the studies was assessed using the Oxford Centre for Evidence‐Based Medicine critical appraisal checklist.ResultsFour studies were included. All studies recruit severe or refractory LN patients and show significant improvement in post‐MSCT 24‐h proteinuria. However, the improvement of renal function after MSCT is inconsistent between studies after a 1‐month follow‐up, with one study showing deterioration of the estimated glomerular filtration rate after 3 months and one study showing an increase in serum creatinine at 6 and 9 months. Moreover, all studies show improvement in Systemic Lupus Erythematosus Disease Activity Index scores after MSCT, while two studies show that a decrease in anti‐double‐stranded DNA (anti‐dsDNA) levels after MSCT is only evident for up to 1‐month period.ConclusionsMSCT can be effective, especially in severe or refractory LN. More randomized‐controlled trials are needed to support this evidence.

A study of the association between Galectin-9 gene (LGALS9) polymorphisms and rheumatoid arthritis in Egyptian patients

BackgroundRheumatoid arthritis (RA) is an incessant synovial inflammation of an autoimmune origin, destroying articular cartilages and bones. Galectins are an evolutionarily conserved family of immune-modulatory animal lectins detected in a number of immune cells like T cells, fibroblasts and macrophages. Galectin 9 (Gal-9) has been the subject of many studies for being linked to regulation of both innate and adaptive immune reactions. The objective of the study was to evaluate the link between the Galectin-9 gene (LGALS9) polymorphisms and the susceptibility of RA in Egyptian patients, as well as, detection of the serum level of Gal-9 in RA and its association with LGALS9 polymorphisms, the activity of RA and radiological damage.MethodsA study of 85 participants; group (I): 60 RA cases and group (II): 25 apparently healthy subjects. RA Disease activity index (DAS-28) and Larsen index score were assessed. LGALS9 gene and serum Gal-9 were investigated.Resultsrs4239242 TT genotype and T allele occurred more frequently in RA cases than controls with a significant difference (P = 0.006; P < 0.001 respectively). Gal-9 level was significantly higher among RA cases than control group (P = 0.017). The Gal-9 level showed negative significant correlations with DAS-28 and Larsen score (P < 0.001).ConclusionRA is strongly linked to genetic alterations in the LGALS9 gene and the single nucleotide polymorphism (SNP) rs4239242 TT genotype in the Egyptian population. RA cases in remission or those with low disease activity had higher levels of serum Gal-9 in comparison to cases with moderate and high disease activity and this would be promising in the future of RA treatment.

Oxysophocarpine suppresses TRAF6 level to ameliorate oxidative stress and inflammatory factors secretion in mice with dextran sulphate sodium (DSS) induced-ulcerative colitis

PurposeUlcerative colitis is an inflammation-related disease with a high recurrence risk. Oxysophocarpine (OSC) is a traditional Chinese medicine isolated from legumes and exerts vital functions on many human diseases. However, the OSC's role in ulcerative colitis has not been fully elucidated. This research aimed to investigate the OSC's impact on ulcerative colitis and its mechanisms. MethodsA mouse model of ulcerative colitis was induced by dextran sulphate sodium (DSS). The effect of OSC on ulcerative colitis was examined using Disease Activity Index detection, hematoxylin-eosin (HE) staining, and enzyme-linked immunosorbent assay (ELISA). Meanwhile, the mechanism of OSC in ulcerative colitis was assessed by immunohistochemistry assay, Western blot, HE staining, and ELISA. ResultsFor the OSC's function in ulcerative colitis, OSC increased the mice weight, decreased Disease Activity Index scores, and alleviated colitis cell infiltration and epithelial cell destruction in DSS-induced ulcerative colitis. Also, OSC mitigated oxidative stress (decreased PGE2, MPO levels, and increased SOD levels) and inflammation (decreased IL-6, TNF-α and IL-1β levels) in DSS-induced ulcerative colitis. For the OSC's mechanism in ulcerative colitis, OSC inhibited the level of tumor necrosis factor receptor-associated Factor 6 (TRAF6) and the phosphorylation of nuclear factor-κB (NF-κB). TRAF6 overexpression abolished the effect of OSC on DSS-induced colon injury and its associated oxidative stress and inflammatory properties in ulcerative colitis. ConclusionOSC decreased the TRAF6 level to reduce oxidative stress and inflammatory factors secretion in mice with DSS induced-ulcerative colitis.

Inhibitory effect of Portulaca oleracea L. aqueous extract and juice on NLRP3 inflammasome activation in an ulcerative colitis mouse model.

Portulaca oleracea L. (PO) is an edible and medicinal plant used for treating gastrointestinal diseases. However, the effects of PO on ulcerative colitis (UC) and underlying mechanisms remain unclear. This study investigated the effects of PO aqueous extract (POE) and PO juice (PJ) on dextran sulfate sodium (DSS)-induced UC in a mouse model and attempted to unravel their underlying mechanisms. The results revealed that PJ contains more bioactive compounds and has more overlapping targets with UC than POE. Both POE and PJ effectively reduced Disease Activity Index scores and inflammatory cell infiltration in the UC mouse model, but PJ had a better effect than POE. Furthermore, PJ inhibited pyroptosis by decreasing the expression of the NLRP3 inflammasome, while also repairing the dysfunction of the intestinal barrier by upregulating the expression of tight junction proteins. Therefore, based on the study findings, we concluded that PJ can improve DSS-induced UC and may suppress pyroptosis by interfering with the activation of the NLRP3 inflammasome.

20(S)‐Protopanaxadiol saponins isolated from Panax notoginseng target caveolin‐1 against intestinal barrier dysfunction by alleviating inflammatory injury and oxidative stress in experimental murine colitis

AbstractUlcerative colitis (UC) is a digestive disease with a high incidence and is difficult to be cured due to its complex etiology. It has evidenced that intestinal barrier dysfunction plays a predominant role in UC. 20(S)‐protopanaxadiol saponins (PDS) isolated from Panax notoginseng possess anti‐inflammatory and antioxidative activities, suggesting its potential of treating UC. Herein, the therapeutic effects of PDS against UC and underlying mechanisms in the aspect of intestinal barrier dysfunction were investigated in vivo and in vitro. The results showed PDS had protective effects against dextran sulfate sodium–induced colitis, including attenuating weight loss, disease activity index score elevation, colon length shortening, and histological lesions. Additionally, PDS reduced the colonic activity of myeloperoxidase and the cytokine levels of TNF‐α, IL‐6, and IL‐1β, decreased MDA production, and elevated colonic activities of SOD and GSH‐Px in the colitis mice. The expressions of proteins related to tight junction (TJ), including ZO‐1, claudin‐5, occludin, caveolin‐1 (Cav‐1), and Nrf2 were downregulated, whereas that of Keap1 was upregulated after colitis induction. These changes were reversed by PDS. Cav‐1 expression was downregulated in lipopolysaccharides (LPS)‐ and H2O2‐induced HCT116 cells, and the expressions of ZO‐1, claudin‐5, and occludin were suppressed in HCT116 cells stimulated by LPS and H2O2 combined with Cav‐1 small interfering RNA transfection, which were ameliorated by PDS, suggesting PDS targeted Cav‐1 against intestinal barrier damage. Collectively, PDS alleviates inflammatory injury and oxidative stress by regulating the Nrf2/Keap1 pathway, contributing to targeting Cav‐1 against intestinal epithelial TJ proteins loss. It suggests PDS might be a promising therapeutic natural product for UC treatment.

Matrix metalloproteinases are key targets of acupuncture in the treatment of ulcerative colitis.

The aim of this study was to elucidate the key targets of acupuncture in the colon of ulcerative colitis (UC) mice model using full-length transcriptome sequencing. 2.5% dextran sodium sulfate (DSS)-induced colitis mice were treated with or without acupuncture. Intestinal pathology was observed, and full transcriptome sequencing and bioinformatic analysis were performed. The results demonstrated that acupuncture treatment reduced the UC symptoms, disease activity index score, and histological colitis score and increased body weight, colon length, and the number of intestinal goblet cells. In addition, acupuncture can also decrease the expression of necrotic biomarker phosphorylates mixed lineage kinase domain-like pseudo kinase (p-MLKL). Full-length transcriptome analysis indicated that acupuncture reversed the expression of 987 of the 1918 upregulated differentially expressed genes (DEGs), and 632 of the 1351 downregulated DEGs induced by DSS. DEGs regulated by acupuncture were mainly involved in inflammatory responses and intestinal barrier pathways. The protein-protein interaction network analysis revealed that matrix metalloproteinases (MMPs) are important genes regulated by acupuncture. Gene set enrichment analysis revealed that extracellular matrix (ECM)-receptor interaction was an important target of acupuncture. In addition, alternative splicing analysis suggested that acupuncture improved signaling pathways related to intestinal permeability, the biological processes of xenobiotics, sulfur compounds, and that monocarboxylic acids are closely associated with MMPs. Overall, our transcriptome analysis results indicate that acupuncture improves intestinal barrier function in UC through negative regulation of MMPs expression.

Eriocalyxin B ameliorated Crohn's disease-like colitis by restricting M1 macrophage polarization through JAK2/STAT1 signalling

Background and aimsM1 polarization of macrophages in the intestine is an important maintenance factor of the inflammatory response in Crohn's disease (CD). Eriocalyxin B (EriB) is a natural medicine that antagonizes inflammation. Our study aimed to determine the effects of EriB on CD-like colitis in mice, as well as the possible mechanism. Methods2,4,6-trinitrobenzene sulfonic acid (TNBS) mice and Il-10−/− mice were used as CD animal models, and the therapeutic effect of EriB on CD-like colitis in mice was addressed by the disease activity index (DAI) score, weight change, histological analysis and flow cytometry assay. To assess the direct role of EriB in regulating macrophage polarization, bone marrow-derived macrophages (BMDMs) were induced to M1 or M2 polarization separately. Molecular docking simulations and blocking experiments were performed to explore the potential mechanisms by which EriB regulates the macrophage polarization. ResultsEriB treatment reduced body weight loss, DAI score and histological score, demonstrating the improvement of colitis symptoms in mice. In vivo and in vitro experiments both showed that EriB decreased the M1 polarization of macrophages, and suppressed the release of proinflammatory cytokines (IL-1β, TNF-α and IL-6) in mouse colons and BMDMs. The activation of Janus kinase 2/signal transducer and activator of transcription 1 (JAK2/STAT1) signals could be inhibited by EriB, which may be related to the regulation of EriB on M1 polarization. ConclusionsEriB inhibits the M1 polarization of macrophages by attenuating the JAK2/STAT1 pathway, which partially explains the potential mechanism by which EriB ameliorates colitis in mice, and provides a new regimen for the clinical treatment of CD.

Novel ginsenoside monomer RT4 promotes colitis repair in mice by regulating miR-144-3p/SLC7A11 signaling pathway.

Ginsenoside RT4 (RT4) is a new biologically active compound extracted from ginseng that possesses numerous medicinal and pharmacological properties. However, its potential therapeutic effect of ginsenoside RT4 on ulcerative colitis remains unknown. In this study, we investigated the anti-inflammatory effects of ginsenoside RT4 and its underlying molecular mechanism in the treatment of ulcerative colitis mice induced with dextran sulfate sodium (DSS). Our results demonstrate that ginsenoside RT4 effectively reduced weight, shortening of colonic tract length, colonic bowel damage, and disease activity index (DAI) scores in DSS-induced colitis mice. Additionally, ginsenoside RT4 regulates miR-144-3p expression in DSS-induced colitis mice, and we further confirmed that the solute carrier family 7 member 11 (SLC7A11) was the target gene of miR-144-3p by database analysis. Finally, ginsenoside RT4 inhibits the activation of the miR-144-3p/SLC7A11 signaling pathway, which alleviates colitis. Ginsenoside RT4 significantly decreased the expression of pro-inflammatory cytokines TNF-α and IL-1β and increased the anti-inflammatory cytokine IL-10. These findings suggest that ginsenoside RT4 may have therapeutic potential for treating ulcerative colitis by downregulating levels of miR-144-3p/SLC7A11 signaling pathway, which are expected to be useful in treating clinical ulcerative colitis.

Oral intake of titanium dioxide nanoparticles affect the course and prognosis of ulcerative colitis in mice: involvement of the ROS-TXNIP-NLRP3 inflammasome pathway

BackgroundTitanium dioxide (TiO2), no matter in nanoscale or micron sizes, has been widely used in food industry as additives for decades. Given the potential impact of TiO2 on the gastrointestinal epithelial and parenchymal cells, including goblet cells, the public consumers may suffer the risk of diseases caused by its widespread dissemination in food products. We therefore set out to investigate the impact of TiO2 NPs on the course and prognosis of ulcerative colitis by oral gavaging TiO2 NPs at the doses levels of 0, 30, 100, and 300 mg/kg during the induction (7 days, from day 1 to day 7) and recovery (10 days, from day 8 to day 17) phases of colitis in mice.ResultsThe ulcerative colitis (UC) disease model was established by administrating of 2.5% dextran sulfate sodium (DSS) solution. Our results show that TiO2 NPs significantly enhanced the severity of DSS-induced colitis, decreased the body weight, increased the disease activity index (DAI) and colonic mucosa damage index (CMDI) scores, shortened the colonic length, increased the inflammatory infiltration in the colon. The most significant changes occurred in the low dose (30 mg/kg) group of TiO2 NPs exposure during the development phase of UC and the high dose (300 mg/kg) group of TiO2 NPs during UC self-healing phase. Increased reactive oxygen species (ROS) level and upregulation of anti-oxidant enzymes including total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT), demonstrate that the TiO2 NP exposure has triggered oxidative stress in mice. Moreover, the upregulation of caspase-1 mRNA and increased expression of thioredoxin interacting protein (TXNIP) further demonstrate the involvement of the ROS-TXNIP-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in aggravating the development of UC.ConclusionOral intake of TiO2 NPs could affect the course of acute colitis in exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.Graphical

Panax quinquefolius polysaccharides ameliorate ulcerative colitis in mice induced by dextran sulfate sodium.

This study aimed to investigate the ameliorative effect of the polysaccharides of Panax quinquefolius (WQP) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice and to explore its mechanism. Male C57BL/6J mice were randomly divided into the control group (C), model group (DSS), positivecontrol mesalazine (100 mg/kg, Y) group, and low (50 mg/kg, L), medium (100 mg/kg, M) and high dose (200 mg/kg, H) of WQP groups. The UC model was induced by free drinking water with 2.5% DSS for 7 days. During the experiment, the general condition of the mice was observed, and the disease activity index (DAI) was scored. The conventional HE staining was used to observe pathological changes in mice's colon, and the ELISA method was used to detect the levels of interleukin-6 (IL-6), IL-4, IL-8, IL-10, IL-1β and tumor necrosis factor-α (TNF-α) in mice's colon. The changes in gut microbiota in mice were detected by high-throughput sequencing; the concentration of short-chain fatty acids (SCFAs) was determined by gas chromatography; the expression of related proteins was detected by Western blot. Compared with the DSS group, the WQP group showed a significantly lower DAI score of mice and an alleviated colon tissue injury. In the middle- and high-dose polysaccharides groups, the levels of pro-inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the colonic tissue were significantly decreased (P<0.05), while the levels of IL-4 and IL-10 were significantly increased (P<0.05). The 16S rRNA gene sequencing results showed that different doses of WQP could regulate the composition and diversity of gut microbiota and improve its structure. Specifically, at the phylum level, group H showed an increased relative abundance of Bacteroidetes and a decreased relative abundance of Firmicutes compared with the DSS group, which was closer to the case in group C. At the family level, the relative abundance of Rikenellaceae in L, M and H groups increased significantly, close to that in group C. At the genus level, the relative abundance of Bacteroides, Shigella and Oscillospira in the H group increased significantly, while that of Lactobacillus and Prevotella decreased significantly. The high-dose WQP group could significantly increase the contents of acetic acid, propionic acid, butyric acid, and total SCFAs. Different doses of WQP also increased the expression levels of tight junction proteins ZO-1, Occludin and Claudin-1. To sum up, WQP can regulate the gut microbiota structure of UC mice, accelerate the recovery of gut microbiota, and increase the content of Faecal SCFAs and the expression level of tight junction proteins in UC mice. This study can provide new ideas for the treatment and prevention of UC and theoretical references for the application of WQP.

Investigating the potential associated factors and developing a risk model for interstitial lung disease in Chinese patients with systemic lupus erythematosus.

This study aimed to explore the risk factors for interstitial lung disease (ILD) in Chinese patients with systemic lupus erythematosus (SLE). This study recruited 40 SLE patients with ILD (SLE-ILD) and 40 SLE patients without ILD (SLE-non-ILD). Clinical data were collected from all patients, including basic clinical characteristics, affected organ systems, biochemical indexes, autoantibodies, and immunocytes. Compared with the SLE-non-ILD patients, SLE-ILD patients presented older age (p < 0.001), dry cough (p = 0.006), "velcro-like" crackles (p = 0.021), Raynaud's phenomenon (p = 0.040), elevated complement 3 (C3) level (p = 0.044), and lower SLE disease activity index score (p = 0.013) and cluster of difference-3cell count (p = 0.043). Multivariate logistic regression analysis showed that older age (p < 0.001, odds ratio [OR]: 1.212), female sex (p = 0.022, OR: 37.075), renal involvement (p = 0.011, OR: 20.039), C3 level (p = 0.037, OR: 63.126), immunoglobulin (Ig) M level (p = 0.005, OR: 5.082), and positive anti-U1 small ribonucleoprotein antibody (anti-nRNP) result (p = 0.003, OR: 19.886) were independent ILD risk factors in SLE patients. Consequently, the ILD risk model in patients with SLE was constructed based on statistically significant variables from the multivariate logistic regression analysis, which significantly correlated with ILD risk, with an area under the curve of 0.887 (95% confidence interval: 0.815-0.960) using receiver operating characteristic curve analysis. Age, female sex, renal involvement, C3 level, IgM level, and a positive anti-nRNP result are independent risk factors for ILD. Furthermore, their combination model is closely associated with an increased ILD risk in Chinese patients with SLE.