The aim of this study was to observe the therapeutic effect of curcumin chitosan microspheres (CCM) on ulcerative colitis (UC) in rats. Rat UC model was prepared by 2,4,6-trinitrobenzenesulfonic acid (TNBS) method. All animals were divided into blank control group (BCG), model control group (MCG), mesalazine enteric-coated tablets group (MECT), curcumin chitosan microsphere low (CCML), medium (CCMM) and high dose groups (CCMH). Starting from the third day after model establishment, the rats were intra-gastrically administered for 10 days. On the 14th day of the experiment, the rats were sacrificed. The colon tissues and serum samples were collected and the expression of NF-κB P65 protein was detected by immune histochemical streptavidin-perosidase (SP) method. The levels of IL-1β, IL-4 and IL-6 in serum were determined by Enzyme Linked Immunosorbent Assay (ELISA). The colonic mucosal injury score of MCG was increased; The serum IL-1β and IL-6 levels were increased, while the IL-4 content was decreased; The expression of NF-κB in the colonic mucosa was reduced after TNBS challenge. The histological injury scores of colonic mucosa, the serum levels of IL-1β and IL-6 in CCM-treated rats were significantly decreased (P < 0.01) as compared with MECT group. While, the content of IL-4 was significantly higher than that of MCG and MECT groups (P < 0.01). Curcumin chitosan microspheres provide a potential therapeutic strategy for treating UC in clinic.
Objective: To observe the clinical effect of curcumin chitosan microsphere (CCM) on ulcerative colitis. Methods: Our group selected 75 cases with ulcerative colitis (UC) receiving treatment at The First Affiliated Hospital of Nanchang University as observation group, and 75 cases that were healthy and received examination at the same time as control group. We detected serum miR-224-3p, TLR4, TNF-α and NF-κB levels using the double antibody sandwich ELISA (DAS-ELISA). In animal experiments, our team applied DSS to induce IBD mice models, allocated into control group, model group, sulfasalazine group, curcumin group and CCM high dose group, CCM medium dose group, and CCM low dose group, in total 7 groups (n = 10). After molding, on 3rd day our team began intragastric administration for 10 days. On 14th d, we sacrificed the mice, conducted HE staining, observed changes in the pathological form of bowel tissue in each group, and gave inflammation scores. Taking the colon tissue and serum, our team applied ELISA to detect inflammatory factors such as TNF-α, TLR4, IFN-γ levels in supernate of tissue homogenate, as well as performed western blot to detect SDF-1, CXCR4, miR-224-3p protein expression levels in intestinal tissue. Results: TNF-α, TLR4, NF-κB expressions in observation group were signally elevated while miR-224-3p expression visually decreased. In control group, TNF-α, TLR4, NF-κB expressions in observation group were signally decreased while miR-224-3p expression visually elevated, the difference was significant (P < 0.05). After treatment, serum TNF-α, TLR4, NF-κB expressions in sulfasalazine group, curcumin group, CCM low, medium and high dose groups were signally reduced, while IFN-γ expression was elevated significantly, when comparing with those in model control group, the difference was significant (P < 0.01). Compared CCM low, medium and high dose groups with sulfasalazine group, there was a significant difference in efficacy (P < 0.05). Compared CCM low, medium and high dose groups with curcumin group, there was a significant difference in efficacy (P < 0.05). We applied western blot to detect SDF-1, CXCR4, and miR-224-3p protein expression levels, finding that CCM enhanced in SDF-1, CXCR4, and miR-224-3p protein expression levels, with significant differences when comparing with those in model control and curcumin groups. Conclusion: CCM may elevate IFN-γ level and enhance SDF-1, CXCR4, and miR-224-3p protein expression levels through inhibiting TNF-α, NF-κB, and TLR4 expressions, thus reducing inflammatory response as well as damage to colon tissue in mice with UC through anti-inflammatory effects.
Objective. To explore the role of conjunctival microvasculation combined with echocardiography in evaluating the prognosis of pulmonary arterial hypertension in systemic lupus erythematosus (SLE-PAH). Methods. We prospectively compared the conjunctival microvascular changes in 17 SLE-PAH patients and 34 SLE patients without PAH in our hospital from January 2020 to December 2020, and we observed the characteristics of conjunctival microvascular changes in SLE-PAH patients. We analyzed the correlation between the corresponding conjunctival microvascular changes and cardiopulmonary function and evaluated the predictive value of the vessel density (VD) and the microvascular flow index (MFI) of conjunctival microvasculation combined with echocardiography in SLE-PAH. Results. Compared with SLE patients without PAH, the ischemic areas in conjunctival microvasculation were significantly increased in SLE-PAH patients. The VD and MFI of conjunctival microvasculation are significantly correlated with N-terminal prohormone of brain natriuretic peptide and 6-minute walking distance. Combined with the VD and MFI, it can improve the accuracy of echocardiography in assessing the risk of death due to SLE-PAH (94.1% vs. 82.2%). Conclusion. The ischemic area, VD, and MFI of conjunctival microvasculation in SLE-PAH patients can indicate the occurrence of severe SLE-PAH and improve the accuracy of echocardiography in evaluating the prognosis of SLE-PAH.
Objectives. To investigate consistency between eye sign and nailfold video capillaroscopy (NVC) in systemic sclerosis (SSc) patients and to evaluate eye sign with various parameters of disease and potential pulmonary involvement. Methods. A total of 60 SSc patients and 20 healthy individuals were enrolled. 20 SSc patients were complicated with pulmonary arterial hypertension (PAH); 20 SSc patients with interstitial lung diseases (ILD); 20 SSc patients without pulmonary involvement. All subjects were assessed using the methods of NVC and eye sign. Skin involvement was evaluated by modified Rodnan skin score (mRSS) and disease activity according to Medsger’s severity score (MSS). Clinical manifestations and the presence of autoantibodies were carefully recorded. Any correlations between were evaluated with the Spearman correlation coefficient test. Results. According to the morphological changes revealed by NVC, 3 types of NVC patterns have been characterized (early pattern, active pattern, and late pattern). Eye sign showed distinguishing morphologic changes in three patterns of NVC and pulmonary involvements (PAH vs ILD) in SSc. A positive linear correlation was found between scores of eye sign and NVC in all patients with SSc (r = 0.629, P = 0.001 ). A positive correlation of eye sign was found in all SSc patients with mRSS (r = 0.748, P = 0.045 ) and MSS (r = 0.636, P = 0.001 ). Conclusions. The study demonstrates that eye sign had a high consistency with NVC for the evaluation of the microcirculation in SSc patients and exhibited specific patterns in the early, active, and late phases of SSc. Eye sign can be used as a reliable method to classify and monitor SSc patients and replace the measurement of NVC.
Objectives To ascertain whether microvascular alterations of eye sign combined with intrathecal concentrations of interleukin‐6 (IL‐6) can predict the development of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Cerebrospinal fluid (CSF) and serum samples of IL‐6 were collected and measured at the same time for patients with SLE who were consecutively enrolled. Patients with a diagnosis of NPSLE were identified. Eye sign examinations according to our criteria were performed and scored for all SLE patients. Demographic and clinical parameters were compared between groups to identify potential predictors for NPSLE using multivariable logistic regression analysis. The performance of potential predictors from eye sign along with IL‐6 in the CSF was assessed. Results A total of 120 patients with SLE were enrolled; 30 with NPSLE and 90 with non‐NPSLE. No significant positive correlation was observed between CSF level and serum level of IL‐6. CSF IL‐6 was significant higher in the NPSLE group than the non‐NPSLE (P < 0.001) group. Multivariable logistic analysis revealed that total score, ramified loops, and microangioma of eye sign were predictors for NPSLE after adjusting for SLE Disease Activity Index (SLEDAI) and antiphospholipid antibody (APL). Total score, ramified loops, microangioma of eye sign, and SLEDAI remain significant predictors for NPSLE after adjusting for CSF IL‐6. Using receiver operating characteristics curve analysis, the cut‐off point of potential predictors was applied in multivariable logistic analysis; APL, total score, ramified loops, and microangioma of eye sign remain significant predictors for NPSLE after adjusting for CSF IL‐6. Conclusion Specific microvascular alterations of eye sign are predictors for the development of NPSLE in addition to increased IL‐6 in the CSF.
In this study, we aim to investigate retinal thickness (RT) and superficial vascular density (SVD) differences between patients with systemic sclerosis (SSc) and healthy controls (HCs) by optical coherence tomography angiography (OCTA). Sixteen patients with a definitive SSc diagnosis without clinical signs of retinopathy and 16 normal control subjects were recruited. All individuals underwent OCTA scanning to assess macular RT and SVD. We divided each image into nine subregions as the early treatment diabetic retinopathy study (ETDRS). Visual acuity (VA) was considerably different between patients with SSc (32 eyes) and control subjects (32 eyes) ( p < 0.001 ). Compared to the control group, individuals with SSc had decreased inner RT in inner superior, outer superior, outer temporal, inner temporal, center, and inner nasal regions ( p < 0.05 ). Outer RT was decreased in the outer and inner temporal regions, and full RT was decreased in the regions of outer superior, inner superior, inner temporal, and outer temporal, in comparison to the control group ( p < 0.05 ). Patients with SSc had significant reduction of SVD in the inner and outer of both superior and temporal, besides outer nasal regions than controls. ( p < 0.05 ). Moreover, SVD was significantly associated with the outer temporal region of patients suffering from SSc ( p < 0.05 ). Diagnostic Sensitivity of RT and SVD of Inner Superior Regions in SSc, as indicated by areas under curves of the Receiver Operating Characteristic (ROC), were 0.874 (95% CI: 0.786–0.962) and 0.827 (95% CI: 0.704–0.950), respectively. In conclusion, VA may be affected by RT variations inside the macula in patients with SSc. Measuring RT with OCTA could be a useful predictor of early diagnosis.
BackgroundThe decrease of IL-2 level is believed to play an important role in the disease occurrence and development of SLE, but the relevant mechanisms have not been fully clarified. Many studies have found that the level of soluble interleukin 2 receptor α (sIL-2Rα) in SLE patients is significantly increased. Considering the fact that sIL-2Rα has the ability to bind IL-2, we want to know whether the increased sIL-2Rα has some impact on the level and function of IL-2 in SLE patients.MethodsNew onset SLE patients, treated SLE patients and healthy volunteers were recruited. The levels of serum IL-2, IL-2 mRNA in CD3+ T cells and serum sIL-2Rα were detected and compared in these subjects. Two mixed solid-phase sandwich ELISA system were designed to measure exclusively the heterodimers complex of sIL-2Rα/IL-2. The sera from SLE patients were pretreated with or without immune complex dissociation solution and detected for IL-2 levels. IL-2 standard or serum from HCs were used to co-incubate with recombinant sIL-2Rα or serum samples with high levels of sIL-2Rα and detected for IL-2 levels by ELISA. The inhibitory effect of sIL-2Rα on IL-2 biological activity was investigated by CTLL-2 cell proliferation assay. The frequencies and absolute counts of Treg cells were detected by flow cytometry before and after the addition of recombinant sIL-2Rα.ResultsThe levels of serum IL-2 in SLE patients were significantly decreased and negatively correlated with SLEDAI. However, there was no significant difference in IL-2 mRNA levels in CD3+ T cells between SLE patients and healthy controls. The levels of serum sIL-2Rα in SLE patients were significantly increased, positively correlated with the SLEDAI and negatively correlated with the levels of serum IL-2. sIL-2Rα was shown to bind to IL-2 to form immune complex, resulting in false reduction in the detection level of serum IL-2 and significant decrease in biological activity of IL-2. The increase of sIL-2Rα was demonstrated to be one of the important mechanisms for the obstruction of Treg cells differentiation in SLE patients.ConclusionIncreased serum sIL-2Rα can bind to IL-2, leading to obstruction of IL-2 activity and Treg cells differentiation.
ObjectiveTo explore risk factors for developing osteonecrosis in patients with systemic lupus erythematosus (SLE).MethodsTwenty-six SLE patients with osteonecrosis from January 2018 to December 2019 were described. Fifty SLE patients without osteonecrosis were selected as controls from the SLE database (total 2,680) of our hospital during the same period. Clinical manifestations and laboratory tests were recorded and analyzed, especially antibodies. Univariate and multivariate analyses were used to evaluate possible associated risk factors.ResultsTwenty-six (3 male, 23 female) SLE patients with osteonecrosis were confirmed by X-ray and magnetic resonance imaging. The median course from SLE onset to osteonecrosis onset was 45 (range 2–302) months. Seven (27%) patients had a single joint involved and 19 (73%) patients had two or more joints involved. Besides, the incidence of femoral head osteonecrosis (FHON), knee ON, and humerus head ON were 85% (22/26), 27% (7/26), and 12%(3/26), respectively. The multivariate logistic regression analysis showed that the score of European Consensus Lupus Activity Measurement (ECLAM) at SLE onset [odds ratio (OR) 1.37; 95% confidence interval (CI) 1.07–1.75], a cumulative dose of prednisone above 10 g (OR 15.49; 95% CI 3.38–84.61), and positive of independent anti-RNP antibodies (OR 3.35; 95% CI 0.80–10.73) were significantly associated with osteonecrosis in SLE.ConclusionThe score of ECLAM at SLE onset, a cumulative dose of prednisone above 10 g, and positive anti-RNP antibodies are associated with osteonecrosis in SLE. Herein, we reported for the first time that anti-RNP antibodies were associated with osteonecrosis in SLE patients and might be a novel predictor.
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