Ulcerative colitis (UC) is a type of refractory and recurrent inflammatory disorder that occurs in colon and rectum. Immune cell infiltration plays a critical role in UC progression; therefore, this study aims to explore potential biomarkers for UC and to analyze characteristics of immune cell infiltration based on the bioinformatic analysis. In this study, 248 differentially expressed genes (DEGs) were screened, and the top 20 immune-related hub genes and pathways were assessed. Moreover, four candidate diagnostic biomarkers (DPP10, S100P, AMPD1, and ASS1) were identified and validated. Immune cell infiltration analysis identified 13 differentially infiltrated immune cells (IICs) in UC samples compared to normal samples, and the result showed that two IICs only expressed in UC samples. In addition, the present research found that DPP10 was negatively correlated with neutrophils, S100P exhibited a positive correlation with resting CD4 memory T cells, AMPD1 was positively correlated with M2 macrophages, and ASS1 was inversely associated with neutrophils and positively related to CD8 T cells. Taken together, these findings indicated that DPP10, S100P, AMPD1, and ASS1 may act as diagnostic biomarkers for UC, and that differential IICs may help to illustrate the progression of UC. Graphical Abstract

Patients with ulcerative colitis (UC) are at increased risk of developing colitis-associated colon cancer. Accumulating evidence suggests that follicular T helper (T_FH) cells play a crucial role in the pathogenic process of autoimmune diseases. However, little is known about the role of T_FH cells in the development of UC. To investigate the role of T_FH cells in the development of UC, the number of T_FH cells, the level of interleukin-21 (IL-21), the numbers of B cell subsets, and clinical parameters were detected in peripheral blood from 31 UC patients and 29 healthy controls. T_FH cells and the level of IL-21 were significantly higher in UC patients than in the healthy controls. A positive correlation between T_FH and IL-21 cells was found in UC patients. Moreover, aberrant frequencies of different subsets of B cells were observed in UC patients, and a positive correlation was found between CD38⁺CD19⁺ B cells and T_FH cells and between CD86⁺CD19⁺ B cells and T_FH cells. A high number of T_FH cells were positively associated with Mayo score, serum C-reaction protein (CRP) and serum IgG in UC patients. Our data indicate that T_FH cells and IL-21 are involved in the pathogenesis of UC.

Tripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms. Ch-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model. The Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling. Novel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation. All experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.

Background: In the few reports to date, the changes in superoxide dismutase (SOD), a key factor in cellular protection against superoxide, in COVID-19 have been very inconsistent and contradictory. There is also a lack of data on COVID-19 induced by Omicron variant. Further investigation is warranted to figure out SOD alterations in COVID-19, particularly within the context of ongoing Omicron variant infection, which may provide clues to its role within COVID-19 pathogenesis and open up new avenues for COVID-19 treatment.Methods: SOD activity in 109 COVID-19 patients (including 46 severe cases and 63 mild to moderate cases) and 30 matched healthy controls were quantified. Demographic data, blood cell counts, biochemical indicators, coagulation indicators, and inflammatory markers were also recorded.Results: SOD, an important key node, experienced a significant decrease in COVID-19, with the severe patients exhibiting lower activity compared to the mild to moderate patients and control healthy. Notably, severe patients who deceased had the lowest SOD activity. Correlation analysis revealed significant correlations between SOD and inflammatory markers, organ injury markers, coagulation dysfunction indicators, nutritional markers, and lymphocytes counts. The ROC curve also showed good performance for the differentiation of severe cases and the prediction of death.Conclusion: SOD activity was significantly decreased in COVID-19 infected with Omicron variant and significantly correlated with systemic changes, and could be used as a biomarker to assess disease severity and predict mortality in COVID-19 clinical pathway management. Additionally, this finding will contribute to exploring new potential direction for the treatment of severe COVID-19 patients.

Background: Inflammatory responses and metabolic abnormalities play essential roles in the pathophysiology of osteoarthritis (OA). Our study aimed to evaluate the association between monocyte-to-high density lipoprotein-cholesterol ratio (MHR) and OA and compared it with other systemic inflammatory markers. Methods: This study recruited 323 OA cases and age- and sex-matched 283 control participants during the same period. Demographic, clinical, and imaging data and laboratory indicators were obtained from participants’ records. Systemic inflammatory markers were calculated for both cohorts. The diagnostic effectiveness of each index for distinguishing patients with OA was analyzed using receiver operating characteristic (ROC) curves. Spearman’s method and ordered logistic regression were used to analyze the association between each indicator and Kellgren and Lawrence (KL) grade. Results: MHR was significantly higher (0.38± 0.18 vs 0.25± 0.07, p < 0.0001) in OA patients than healthy controls. MHR had the largest area under the ROC curve for predicting OA. Analysis of ordered logistic regression indicated that MHR was a risk factor for OA radiological severity. Spearman correlation analysis indicated that MHR significantly correlates with the KL grade. Moreover, MHR was significantly higher in early stage patients than in healthy controls. Conclusion: These results suggest that an elevated MHR could reflect knee OA severity and might be a useful marker for diagnosis and monitoring of OA.