Disease Activity Research Articles

Quantitative Evaluation of Noncontrast Magnetic Resonance Enterography for Active Inflammation in Crohn Disease Using Native T 1 and T 2 Mapping.

The aim of this study was to investigate the utility of native T 1 and T 2 mapping in the bowel to evaluate disease activity in Crohn disease (CD) using endoscopy as the reference standard. This was a prospective study. Magnetic resonance imaging was performed by using a 1.5-T Philips scanner. We used a modified look-locker inversion recovery and a multiecho gradient-spin-echo sequences for single breath-hold native T 1 and T 2 maps, respectively, for the short-axis image of the intestine, and the measurement at the most severe site was compared with partial Simple Endoscopic Score for Crohn's Disease (pSES-CD, assessed by an expert endoscopist). A pSES-CD ≥ 4 indicated active disease. Statistical analyses were performed using the Student t test, Spearman correlation, and receiver operating characteristic curve analysis. A total of 27 patients (mean age ± standard deviation, 37 ± 18 years; 20 men, 7 women) were included in this study. The native T 1 value of active disease was significantly higher than that of inactive disease (1170.8 ± 100.5 milliseconds vs 924.5 ± 95.3 milliseconds; P = 0.018), but the T 2 value was not significantly different between active and inactive disease (76.1 ± 7.8 milliseconds vs 69.3 ± 10.9 milliseconds; P = 0.424). A good correlation was found between native T 1 value and pSES-CD (ρ = 0.71; P < 0.001) but not between T 2 value and pSES-CD (ρ = 0.06; P = 0.790). The area under the receiver operating characteristic curve for differentiating the disease activity was 0.96 (95% confidence interval [CI]: 0.90-1.00) for T 1 values and 0.68 (95% confidence interval: 0.41-0.96) for T 2 values. Native T 1 mapping could be potentially used as a noninvasive method to differentiate disease activity in patients with CD and may be superior to T 2 mapping for this purpose.

5-hydroxymethylcytosine as a liquid biopsy biomarker in colorectal cancer.

291 Background: 5-hydroxymethylcytosine (5hmC) is an epigenetic modification which regulates gene expression and is associated with active transcription. The optimization of 5hmC sequencing in cell-free DNA (cfDNA) could therefore enable assessment of gene activity through a liquid biopsy. We aimed to investigate the 5hmC landscape of colorectal cancer (CRC) in plasma-derived cfDNA to evaluate the potential of 5hmC modifications as a liquid biopsy-based biomarker of CRC. Methods: Genome-wide 5hmC modifications were analyzed with a low-input whole-genome 5hmC sequencing method based on selective chemical labeling in cfDNA from 72 CRC patients and 70 healthy samples. Differential 5hmC analysis between CRC and healthy samples was conducted using DESeq2 (padj &lt; 0.05 and log2FC &lt;= -1 and &gt;=1). Low-pass whole genome sequencing (LP-WGS) was performed on all cfDNA samples. Tumor fraction was estimated using ichorCNA to classify samples into high ct-fraction (&gt;=0.1) and low ct-fraction (&lt;0.1) groups. Nucleosome profiling was performed on LP-WGS to reveal chromatin accessibility patterns. Elastic Net Regression (ENR) was applied to identify changes in 5hmC levels for classifying samples as cancerous or healthy. Results: Differential cfDNA 5hmC levels of 139 genes distinguished high ct-fraction CRC (n=16) and healthy samples (n=70). Although the remaining CRC samples (n=56) had similar ct-fractions as the healthy samples, as estimated by ichorCNA, we found a differentially hydroxymethylated gene signature could discriminate between these low ct-fraction CRC and healthy samples. Nucleosome profiling analysis with LP-WGS in cfDNA was used to identify active transcriptional drivers of the genes with increased 5hmC levels. The analysis revealed increased chromatin accessibility near the binding sites for the transcription factor caudal-related homeobox transcription factor 2 ( CDX2 ), a master transcriptional regulator of intestinal cell fate and cancer, in CRC patients relative to healthy samples. Corroborating this, CDX2 and its downstream targets had increased 5hmC levels in cfDNA in CRC relative to healthy samples, consistent with colorectal-derived tumor DNA in CRC plasma samples. Conclusions: Genes with differential 5hmC levels in cfDNA can discriminate CRC and healthy samples. Our 5hmC signature identified CRC samples that did not harbor copy number gains or losses; which is typically used to estimate ct-fraction and routinely included in targeted ctDNA sequencing assays. Integration of 5hmC and LP-WGS can be used to identify gene activation in disease. In the context of CRC, CDX2 displayed increased chromosome accessibility in the promoters of its target genes which in turn displayed increased 5hmC levels. Further studies are aimed at optimizing and validating 5hmC-based biomarkers throughout patient treatment.

Angiopoietin-2 and D-dimer add prognostic information to clinical risk in pulmonary arterial hypertension

Thrombosis and endothelial injury are pathologic hallmarks of pulmonary arterial hypertension (PAH). We aimed to evaluate whether markers of endothelial dysfunction and coagulation in the blood would provide insight into disease activity, treatment response, and outcomes in PAH. MethodsWe prospectively collected baseline and 3-month follow-up blood samples from treatment-naïve PAH patients (n=22) and those who had a clinical indication to intensify therapy (n=19). In addition, we recruited 12 healthy people and clinically stable PAH patients (n=45) as controls who had two blood samples collected twice within 14 days. We generated platelet-free plasma and measured D-dimer, angiopoietin-2, thrombin time, soluble P-selectin, von Willebrand factor, and vascular endothelial growth factor. We assessed treatment response with Reveal Lite 2 scores (all patients had NT-pro-BNP, 6-minute-walk, and functional class assessment at both visits) and followed clinical outcomes for 3 years. ResultsAngiopoietin-2 levels were elevated and fell with response to effective therapy (drop in Reveal Lite 2 score). At follow-up, persistently elevated angiopoietin-2 levels predicted clinical events and even identified low-risk participants who subsequently had events. D-dimer levels were also elevated in PAH patients but didn’t change in response to therapy. Several other abnormalities in endothelial and platelet activation were identified (including elevated soluble P-selectin, elevated von Willebrand factor, and elevated vascular endothelial growth factor) but these did not change with treatment or predict outcome. ConclusionsAngiopoietin-2 and D-dimer are elevated in PAH patients and may add prognostic information to routine clinical assessment.

The characteristics and associated factors of hand dysfunction in patients with rheumatoid arthritis

Objective: To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA). Methods: A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses. Results: A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale (OR=1.375, 95%CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count (OR=1.151, 95%CI 1.063-1.246) and provider global assessment of disease activity (OR=1.381, 95%CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions: Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.

Circulatory age-associated B cells: Their distinct transcriptomic characteristics and clinical significance in drug-naïve patients with rheumatoid arthritis.

Age-associated B cells (ABCs) have been implicated in the pathogenesis of autoimmune diseases. However, the global gene expression and clinical significance of circulatory ABCs in rheumatoid arthritis (RA) remain poorly understood. Here, single-cell RNA sequencing identified nine B cell subsets in peripheral blood of RA patients, including ABCs. Increased phagocytosis and antigen presentation were functionally enriched by the genes expressed differentially in ABCs. Network analysis and in vitro experiments demonstrated SYK as a key regulator defining the myeloid-like phenotypes in ABCs. Flow cytometry showed that the proportion of ABCs correlated with RA activity and serum tumor necrosis factor-alpha level. Notably, ABCs above a cutoff threshold specifically distinguished RA from healthy controls and indicated higher disease activity. This study highlights the myeloid characteristics of circulatory ABCs regulated by SYK in RA. Increased ABCs may reflect disease activity and could serve as a potential biomarker in RA.

VEGF in psoriatic arthritis: Systematic review and meta-analysis.

Psoriatic arthritis (PsA), a chronic autoimmune disease of unclear aetiology, is associated with dysregulated angiogenesis due to the proliferation, migration, and differentiation of endothelial cells. Vascular endothelial growth factor (VEGF) plays a key role such that PsA patients exhibit skin and joint symptoms, e.g., pain and stiffness, with morphologic alterations in blood vessels. To more fully examine this phenomenon, a systematic review and meta-analysis compliant with the PRISMA guidelines (PROSPERO CRD42024572653) was conducted using subgroup and meta-regression analyses. Secondary analyses on disease activity and response to treatment were also included. In the twelve selected studies, VEGF was significantly higher in PsA vs healthy controls (SMD=0.544, 95% CI 0.253-0.835;p<0.001) with moderate heterogeneity across studies. Subgroup analysis revealed that the SMD in prospectively conducted studies was significantly higher vs those conducted retrospectively (p=0.005). Furthermore, methotrexate or sulfasalazine treatment did not affect VEGF which remained significantly higher than controls. Moreover, VEGF was lower in those with inactive disease and in those receiving disease modifying agents in pre-post studies. These findings suggest that VEGF is a promising candidate biomarker in PsA and worthy of further prospective studies to investigate its utility in monitoring disease progress and response to treatment.

An online mindfulness-based intervention for adults with Inflammatory Bowel Disease & psychological distress: A feasibility randomized controlled trial of the Mind4IBD program

ObjectiveThe bidirectional relationship between disease activity and mental health in inflammatory bowel disease (IBD) has prompted investigations into the efficacy of psychotherapies, such as mindfulness-based interventions (MBI), for improving biopsychosocial outcomes. Therefore, the aim is to examine the feasibility, acceptability, and preliminary efficacy of an online-delivered, self-directed MBI, adapted to individuals with IBD and psychological distress, in comparison to wait-list control (WLC). Methods50 adults with IBD were randomized to WLC (N = 25) or intervention (N = 25) groups. The intervention (MIND4IBD program) consisted of six, weekly, 15-min videos (with guided meditations). Feasibility was examined through recruitment and retention rates, while acceptability was examined through intervention satisfaction ratings and qualitative feedback. Preliminary efficacy was examined using linear mixed models for group differences in outcomes between baseline and post-intervention. ResultsPrimary Outcomes. The retention rate for the WLC group was 92 %, while the retention rate for the intervention group was 48 %. However, 16 % of participants allocated to the intervention group never began the intervention, therefore this resulted in a retention rate of 71 % of participants who began the intervention. Acceptability was high with an average intervention satisfaction rating of 83/100. Secondary Outcomes. When compared with the WLC, the MIND4IBD program improved total mindfulness levels (b = 0.29, 95 %CI [0.11,0.47], p = 0.004) with a large effect size (β = 0.54, b = 0.19, 95 %CI [0.04,0.34], p = 0.014). Themes based on participants' intervention feedback included: 1) beginning of journey with mindfulness, 2) the beneficial impact of mindfulness, 3) why adapting the intervention to IBD is important, 4) views on program delivery, and 5) mixed reactions to AI generated presenters. ConclusionMIND4IBD is feasible and acceptable for individuals with IBD and psychological distress. Participants' total mindfulness levels increased significantly in the intervention group compared to WLC. Most participants provided positive intervention feedback. These findings warrant a full-scale RCT to determine MIND4IBD's efficacy for IBD.

Pregnancy outcomes in Greek women with inflammatory bowel disease: a longitudinal national retrospective study.

Inflammatory bowel disease (IBD) commonly affects patients of reproductive age. The effect of disease activity on the outcome of pregnancy and its impact on neonatal health are areas of intense research. Α national retrospective study of pregnancies in women with IBD between 2010 and 2020 was carried out in 22 IBD reference centers in Greece. 223 pregnancies in 175 IBD patients [122 Crohn's disease (CD)] were included. Mean age at diagnosis was 26 years (12-44) with a mean duration of 7.4 (0-23). Pregnancy as a result of IVF occurred in 15 cases (6.7%). At the beginning of gestation, 165 patients (74%) were under treatment: 48 (29%) with anti-tumor necrosis factor alpha agents, 43 (26%) with azathioprine, 101 (61%) with 5-aminosalicylates, and 12 (7%) with steroids. Forty-nine cases (22%) of IBD flares were recorded: Two-thirds ( n = 30) were in clinical remission at the onset of pregnancy, whereas treatment with corticosteroids was required in 22 (45%). Patients with ulcerative colitis were at greater risk for flare compared to those with CD ( P < 0.001). All but two pregnancies (99.1%) resulted in an uncomplicated delivery. In 147 cases (67.1%), c-section was performed. Two late fetal deaths (0.9%) were reported, both in patients with persistently active disease. After delivery, 75 patients (34%) presented with a disease flare, associated with active disease at the beginning of pregnancy ( P < 0.001). The majority of Greek patients with IBD have a favorable pregnancy outcome. Active inflammation during gestation and a diagnosis of ulcerative colitis are negatively associated with pregnancy outcomes.

317 Changes in microglia phenotype precede microvascular dysfunction and sympathetic activation in chronic kidney disease

317 Changes in microglia phenotype precede microvascular dysfunction and sympathetic activation in chronic kidney disease

The effect of tonsillectomy on clinical manifestations in Familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most prevalent genetic autoinflammatory disease worldwide. There are several novel advancements in pathophysiology, genetic testing, diagnosis, comorbidities, disease-related damage, and treatment strategies. This study aimed to assess the effect of tonsillectomy on FMF disease severity and activity. This prospective randomized cohort study was conducted on 43 patients diagnosed with FMF and chronic tonsillitis, who were divided randomly into two groups: Group I, a case group including 23 patients subjected to tonsillectomy and medical treatment using colchicine; Group II, a control group consisting of 20 cases receiving only colchicine. The monthly frequency of the attacks and average duration of the three symptoms, such as fever, abdominal/chest pain, and musculoskeletal pain in days, were evaluated and recorded. A highly significant reduction in the monthly frequency of attacks, duration of fever, abdominal/chest pain, and musculoskeletal pain was observed three months after management in both study groups (p<0.00001 for all). Evaluation of the values of both groups revealed a significant increase in the degree of change for the duration of fever, abdominal/chest pain in Group I relative to Group II (p=0.0003 and 0.006 respectively) and a significant increase in the degree of change for musculoskeletal pain in Group II relative to Group I (p=0.007). Survival analysis showed a nonsignificant difference between the two groups regarding the resolution of fever, abdominal/chest pain, and musculoskeletal pain at 12, 18, and 24 months (p=0.26, 0.08, and 0.42, respectively) CONCLUSION: Tonsillectomy operation combined with colchicine resulted in a greater but nonsignificant decrease in the monthly frequency of the FMF attacks and a significant greater decrease in the duration of fever and abdominal/chest pain compared with the use of colchicine alone. Further research is recommended to confirm these results on a larger scale.

Is there a relationship between vitamin D levels and graft versus host disease?

Vitamin D deficiency is common in adult patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT). Since vitamin D is an important regulatory factor for the immune system, vitamin D deficiency may have effects on antitumor activity, relapse rates, graft versus host disease (GVHD) occurrence and infection rates in allo-HSCT. We aimed to investigate the effects of vitamin D levels on the outcome of allo-HSCT. This study included 211 patients who underwent allo-HSCT at seven transplant centers in Türkiye. The impact of pretransplant vitamin D level on overall survival (OS), relapse rate, GVHD occurrence and engraftment times was analyzed retrospectively RESULTS: Pretransplant vitamin D levels were not related to the neutrophil engraftment day (p: 0.887), relapse rate (p: 0.433) and GVHD occurrence (p: 0.391). At a median follow-up of 14 months, OS was 84.8 % and median OS was not reached. Univariate Cox Regression analysis showed that higher levels of vitamin D (>12 ng/mL) affected the survival rates (p = 0.029) (HR: 0.392: 95 % CI: 10.170-0.907). In our study, pretransplant vitamin D levels were not related to GVHD occurrence, relapse rate and engraftment times. However, we found that higher levels of pretransplant vitamin D levels (threshold is 12 ng/mL) were associated with increased survival. Further studies with a larger population are necessary to reveal the role of vitamin D in patients undergoing allo-HSCT.

A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patients

A randomised, double-masked, placebo-controlled trial evaluating the efficacy and safety of teprotumumab for active thyroid eye disease in Japanese patients

Huanglian Ganjiang Decoction alleviates DSS-induced colitis through suppressing inflammation and protecting intestinal barrier: From the perspective of disassembling prescriptions.

Huanglian Ganjiang decoction (HGD), which is composed of Chinese medicines with cold, warm, and astringent properties, has demonstrated significant therapeutic efficacy in ulcerative colitis (UC). However, the underlying mechanisms remain unclear, highlighting the need for a multi-faceted investigation. Disassembling prescriptions is a crucial approach for investigating compatibility mechanisms. Analyzing the interactions among Chinese herbs through this method can refine treatment focus and provide novel insights into TCM prescription compatibility research. Therefore, HGD was disassembled into three groups: Cold Medicine Removed (C-R), which warm medicine and astringent medicine are combined; Warm Medicine Removed (W-R), which cold medicine and astringent medicine are combined; and Astringent Medicine Removed (A-R), which cold medicine and warm medicine are combined. To elucidate the therapeutic effects of HGD and its three disassembled prescriptions against UC and to uncover their compatibility mechanisms. The chemical composition of HGD and its disassembled prescriptions (HGDADPs) was qualitatively analyzed using UPLC-MS/MS. 3% dextran sulfate sodium (DSS) was used to induce a UC mouse model. The efficacy in treating UC was evaluated by body weight loss, disease activity index (DAI), colon length, spleen index, thymus index, and histopathological score. A compound-UC target network was established utilizing the network pharmacology. The underlying mechanisms were then investigated by assessing intestinal barrier function and inflammatory responses, as well as the APOC1/P38 MAPK and TLR4/NF-κB signaling pathways through qRT-PCR, Western blotting, and immunofluorescence. Subsequently, anisomycin, a P38 MAPK agonist, was used to confirm whether C-R protects the gut barrier via the APOC1/P38 MAPK pathway. Monophosphoryl lipid A (MPLA), a TLR4 agonist, was employed to investigate whether W-R mediates its anti-inflammatory effects via the TLR4/NF-κB signaling pathway. HGDADPs improved colitis symptoms, increasing ZO-1, Occludin, Claudin-1, and E-cadherin levels while reducing blood cell counts and IL-6 and IL-1β levels. HGD was the most effective in reducing inflammation and repairing the intestinal barrier, with A-R showing similar effects. C-R excelled in repairing the barrier, while W-R was better at reducing inflammation. Network pharmacology indicated C-R inhibits the APOC1/P38 MAPK pathway, and W-R suppresses the TLR4/NF-κB pathway, aligning with Western blotting results. ANI and MPLA reversed the effects of C-R and W-R, respectively. The mechanism by which HGDADPs treat colitis is demonstrated for the first time in our study. In HGD, cold medicine serves as the "Jun", primarily exerting anti-inflammatory effects; Warm medicine acts as the "Chen", mainly protecting the intestinal mucosal barrier; And astringent medicine functions as the "Zuo", playing a synergistic role in the treatment of colitis. In addition, the combination of cold and warm medicines (A-R) was the most crucial for HGD' s compatibility. The pairing of warm and astringent medicines (C-R) significantly contributed to the restoration of the gut barrier and the inhibition of the APOC1/P38 MAPK signaling pathway. Meanwhile, the combination of cold and astringent medicines (W-R) primarily contributed to alleviating inflammation and inhibiting the TLR4/NF-κB pathway.

Quantitative assessment of transmural remission in Crohn's disease using low dose computed tomography (CT) enterography perfusion imaging: a single-centre study based on intestinal microcirculation.

To assess transmural remission in patients with Crohn's disease using low-dose small bowel computed tomography (CT) perfusion scans. Forty six patients were divided into active and remission phases based on Crohn's Disease Activity Index (CDAI) and C-reactive protein (CRP). Dual-source CT enterography with low-dose perfusion scans was conducted to generate perfusion parameter maps, including blood flow (BF), blood volume (BV), time to peak (TTP), mean transit time (MTT), and permeability of surface (PS). We compared differences in perfusion parameter values of intestinal walls, mesenteric fat, and lymph nodes between two groups. Receiver operating characteristic (ROC) curves were plotted, and area under the curve (AUC), sensitivity, specificity, and cutoff values were calculated. The BF, BV, TTP, MTT, and PS values of the intestinal wall were significantly higher in the active phase (P0.05). Additionally, lymph node BF and TTP displayed significant differences (P<0.01). Dual-source CT enterography with low-dose perfusion scans enables quantitative assessment of Crohn's disease microcirculation in intestinal walls, mesenteric fat, and lymph nodes. These quantitative indicators provide strong diagnostic efficacy and offer insights into whether the disease is in transmural remission.

Biosimilars Versus Originators in Children With Juvenile Idiopathic Arthritis: A Real-World Experience

We aimed to evaluate the efficacy, safety, and immunogenicity profile of Etanercept (ETA) and Adalimumab (ADA) biosimilars (BIOs) compared to their originators in children with juvenile idiopathic arthritis (JIA). Eighty-one JIA children treated with ETA or ADA originators or BIOs were examined at baseline (T0) and after 3- (T1), 6- (T2), 12- (T3), and 24-(T4) months after starting treatment. Lower Juvenile Arthritis Disease Activity Score 10 (JADAS-10) scores were reported at T1, T2, T3, and T4 in JIA children treated with BIOs than originators (all p < 0.05). At T1 and T3, anti-drugs antibodies levels were lower in children receiving BIOs than originators (p = 0.04 and p = 0.0007, respectively), even after adjustments (both p < 0.05). Relapses were lower for BIOs compared to originators (p < 0.001). Safety profile was comparable between the groups (p > 0.05). A better overall profile of BIOs than originators was demonstrated in JIA children, but larger confirmatory studies are needed.

Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.

TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase. This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects. A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment. TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function. Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.

Elevated frequencies of activated memory B cells in multiple sclerosis are reset to healthy control levels after B cell depletion with Ocrelizumab

In multiple sclerosis (MS) the B cell depleting drug ocrelizumab has shown high efficacy in reducing inflammatory activity. Its mechanism of action is unclear due to B cell subset complexity and unknown roles in pathogenesis. Here, we comprehensively phenotyped and quantitated peripheral blood B cell subsets before and after ocrelizumab infusion to gain insight into the fate of B cell subsets with pathogenic potential. Peripheral blood B cells were collected from treatment naïve patients at baseline and months one, three, and six following the first course of ocrelizumab treatment; at 6 months following the second treatment cycle; ~14 months following their last infusion; and from healthy controls. Flow cytometry combined with cluster analysis was used to track depletion and repletion of naïve, memory, and antibody secreting cells. By month one, naïve B cells were depleted, but a small subset of memory B cells were retained with no depletion of antibody secreting cells. Uniform manifold approximation and projection for dimension reduction analysis of flow cytometry data revealed two non-class switched naïve clusters and two class switched memory clusters. One class switched cluster was activated in MS patients but largely absent in healthy controls. Both memory B cell subsets underwent depletion after a single six-month course of ocrelizumab treatment after which their proportions were reset to heathy control levels. These observations suggest that activated class-switched memory B cells could serve as a biomarker of recent or ongoing MS disease activity to guide redosing.

Oral administration of Folium Artemisiae Argyi-derived exosome-like nanovesicles can improve ulcerative colitis by regulating intestinal microorganisms.

Ulcerative colitis (UC), an inflammatory disease characterized by intestinal barrier dysfunction, poses significant challenges because of the toxicity and adverse effects commonly associated with conventional therapies. Safer and more efficacious treatment strategies are needed. The purpose of this study was to treat UC with Folium Artemisiae Argyi exosome-like nanovesicles (FAELNs) and to explore its related mechanism to provide a safer and more effective means for the treatment of ulcerative colitis. We established an in vivo model of acute UC in mice and an in vitro inflammatory model using HT-29 human colorectal cancer cells. To evaluate the therapeutic effect of FAELNs on UC, we adopted various proxies, including changes in body weight and disease activity index (DAI) of mice, and measurement of colon length. The concentrations of myeloperoxide, interleukin (IL-1β), IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interferon-gamma in sera of mice were detected by ELISA. Immunohistochemistry, hematoxylin and eosin staining, and Alyssin blue staining were performed. The effect of HT-29 cells on oxidative stress was detected using an active oxygen probe, diacetyldichlorofluorescein, and flow cytometry. Western blotting was performed to detect the expression levels of Bax and Bcl-2 in HT-29 cells treated with FAELNs. The effects of FAELNs on IL-6 and IL-1β were detected by fluorescence quantitative PCR. Fecal 16S bacteria were detected, and the role of FAELNs was verified by α diversity and β diversity analyses, principal component analysis, species distribution, and function prediction. For microRNA sequencing of FAELNs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. To detect the metabolic and lipid groups of FAELNs, the components were identified and a pharmacological network was constructed to explore the related mechanisms and diseases. FAELNs effectively alleviated the pathogenesis of UC induced by dextran sodium sulfate in animal models, restoring the integrity of the intestinal barrier and reversing an imbalance of the intestinal microbiota. Our findings demonstrate the therapeutic potential of FAELNs in UC management, highlighting their scalability for mass production and encouraging prospects for clinical transformation.

The NLRP3 inflammasome: A central player in multiple sclerosis.

Multiple sclerosis (MS) is a neurological autoimmune condition associated with many symptoms including spasticity, pain, limb numbness and weakness. It is characterised by inflammatory demyelination and axonal degeneration of the brain and spinal cord. A range of disease-modifying therapies (DMTs) are available to suppress inflammatory disease activity in MS, however, there is a pressing need for new therapeutic avenues as DMTs have a limited ability to suppress confirmed disability progression. A body of literature indicates that innate immune inflammation is linked to MS progression. The nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing protein 3 (NLRP3) inflammasome has a well-established function in innate immunity which is closely associated with the pathogenesis of neuroinflammatory conditions. Evidence suggests that the inflammasome may be a therapeutic target in disorders such as MS and at present, inhibitors of the NLRP3 inflammasome are in pre-clinical development. Therefore, this review systematically highlights the pathogenic role of inflammasomes in MS, presenting an overview of research evidence linking inflammasome-related polymorphisms to MS susceptibility, and gathering evidence investigating NLRP3 biomarkers in MS. The role of the NLRP3 inflammasome in murine models of MS is furthermore discussed. Finally, a significant component of this review focuses on evidence that NLRP3 signalling components are novel drug targets in MS. Overall this review defines the role of the inflammasome in MS pathogenesis and identifies inflammasome inhibitor targets that warrant full investigation in MS and related disorders.

Effect of the Jiedu Tongluo Shengjin formulation on plasma immunoglobulin G (IgG) levels in patients with primary Sjögren’s syndrome

This study assessed the effect of Jiedu Tongluo Shengjin formulation on plasma IgG levels in pSS patients. 89 pSS patients were randomized into treatment (45 cases; 1 drop-out) and control (44 cases) groups using the random number table method. The control group received hydroxychloroquine sulfate and a placebo dose of Jiedu Tongluo Shengjin. The treatment group received hydroxychloroquine sulfate and the original Jiedu Tongluo Shengjin formulation. The treatment group showed significant decreases in SS disease activity index, TCM syndrome score, plasma IgG, and ESR, and significant increases in tear film break-up time, tear flow rate, salivary flow rate, C3, and C4 levels (p&lt;0.05). No significant changes were observed in the control group (p&gt;0.05). Jiedu Tongluo Shengjin effectively reduced eye and mouth dryness in pSS patients by improving inflammation and immune status.