About 5%–10% of the world's population is affected by gastric ulcers, which can result in gastrointestinal perforation and bleeding. Consequently, we aimed to investigate whether blocking TNF-α type 1 receptor (TNFR1) with CAY10500 could diminish experimentally induced gastric ulcer (GU) in rats by modulating vascularization.
Rats were administered with a single oral dose of 80 mg/kg of indomethacin to produce gastric ulcers. Subsequently, some rats were given 1 mg/kg of CAY10500 orally. Gastric samples were used to assess the genetic expression and protein levels of TNFR1, VEGF, ERK, PI3K, AKT (also known as PKB), and ICAM-1. Gastric sections underwent electron microscopic examination and were subjected to hematoxylin and eosin staining and immunostaining using anti-TNFR1, anti-VEGF, and anti-ICAM-1 antibodies.
CAY10500 demonstrated the ability to inhibit the expression of TNFR1. Examination of micro-images of GU using electron microscopy or H/E staining revealed extensive necrosis, resulting in the complete loss of regular ultrastructural features of epithelial nuclei and cytoplasmic organelles, as well as the loss of tight junctions and disruption of cell membranes. Significantly, the administration of CAY10500 mitigated these effects. Furthermore, CAY10500 significantly elevated the expressions of VEGF, ERK, PI3K, and AKT, which was associated with a significant reduction in the expression of ICAM-1.
CAY10500 effectively improved experimentally induced GU in rats. It works by inhibiting TNFR1 and activating angiogenesis and cell proliferation pathways, leading to gastric tissue healing. CAY10500 significantly reduced the adhesion molecule pathways.
Miller−Fisher syndrome (MFS) is a recognized clinical variant of Guillain−Barré syndrome (GBS), characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia. When accompanied by additional symptoms such as bulbar palsy, limb weakness, or lethargy, it is termed MFS overlap syndrome.
This report describes a male patient diagnosed with MFS overlap syndrome, presenting with ophthalmoplegia, ataxia, bulbar palsy, numbness in both arms, positive GM4 IgG antibodies, a persistent, intractable headache, and a delayed onset of left-sided peripheral facial palsy. The patient had a preceding suspected case of chlamydial pneumonia before symptom onset, and his condition improved significantly following treatment with intravenous immunoglobulin.
This case suggests that chlamydial pneumonia might predispose individuals to GBS. Patients with MFS/pharyngeal-cervical-brachial (PCB) overlap syndrome may exhibit atypical symptoms, including persistent, intractable headaches, and delayed peripheral facial paralysis. Atypical symptoms should not delay the diagnosis and treatment of GBS once other conditions have been adequately excluded. The presence of anti-GM4 antibodies, often found alongside other anti-ganglioside antibodies, may serve as a critical immunological factor in MFS/PCB overlap syndrome.
Colon cancer is recognized as one of the predominant reasons of death globally. The ongoing cancer treatment techniques have not been successful; so, a strong and unique platform is needed. Interestingly, it has been discovered that stem cells offer a valuable and promising platform in cancer treatment. The goal of this study is to explore the influences of hAMSCs secretome on HT-29 colon cancer cells by analyzing TNF-α/TGF-βR/c-MYC signaling pathway, expression of interleukins (IL)-4/6/8, and cyclin-dependent kinase (CDK) inhibitory proteins (p15INK4B and p21CIP1) using a hanging drop 3D cell culture model.
In this study, a coculture system was employed. After 3 days, hAMSCs' secretome was collected and its effects on tumor formation, inflammation, and cell invasion were analyzed using Western blot, scratch assay, qPCR, and ELISA.
The study revealed a decrease in the TGF-βR/SMADs/c-MYC signaling pathway and an increase in levels of p15INK4B, p21CIP1, TNF-α, and IL-4/6/8. Additionally, a decrease in invasion was detected in HT-29 cells treated with hAMSCs.
Our results could be useful in developing a new approach to treating cancer using hAMSCs' secretome.
In rheumatism patients, the immune system erroneously attacks the body′s own tissues. This impairs the body′s defense against external pathogens and is a contributing factor to the occurrence of tuberculosis infection. The primary objective of this investigation was to examine the risk factors for the progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB) in patients with rheumatic diseases (RD).
RD cover a wide range of disorders affecting the skeletal system, joints, and adjacent soft tissues. When the human body is infected by Mycobacterium tuberculosis, the condition is classified as either LTBI or ATB, depending on the presence or absence of typical clinical symptoms. A retrospective study was conducted at the Xijing Hospital of the Fourth Military Medical University. Specifically, the Laboratory Information System was used to investigate patients diagnosed with RD from January 2012 to October 2022.
The study included a total of 32,235 individuals diagnosed with rheumatism, of whom only 18.60% were screened for LTBI. The overall incidence of LTBI was 25.33%. Among the 629 RD inpatients with LTBI, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) accounted for half, and 56.44% received glucocorticoid (GC) therapy. Risk-factor assessment for ATB was conducted in 247 cases. A GC dose of 20 mg/day or more was an independent risk factor for LTBI activation (odds ratio = 3.59, 95% CI: 1.26–10.29, p = 0.017).
In China, RD patients have a relatively high risk of LTBI. In clinical practice, LTBI screening should be routinely performed for RD patients before initiating GC therapy at a dose of ≥ 20 mg/day. For patients with SLE and RA undergoing continuous GC treatment, close monitoring is essential. In addition, clinicians should enhance the diagnostic pathways and treatment management for these patients to prevent the occurrence of ATB.
Generalized modules for membrane antigens (GMMA) are outer membrane vesicles derived from gram-negative bacteria that can be used to design affordable subunit vaccines. GMMA are highly immunogenic and capable to induce an optimal antigen-specific humoral immune response both in animals and humans. Despite their potent immunogenicity, GMMA are usually formulated with aluminum salts (alum) to reduce their potential systemic reactogenicity. GMMA, in fact, contain agonists of toll-like receptor 4 (TLR4) and TLR2 that possess pro-inflammatory activity. The adsorption of GMMA onto alum is believed to reduce their systemic exposure. However, it has been found that GMMA formulated without alum did not induce concerning signs of systemic reactogenicity in the rabbit model. Here, we asked whether GMMA promote local reactogenicity.
We immunized mice intramuscularly with GMMA alone or adsorbed to alum and analyzed the injection site during 7 days after treatment.
We found that GMMA alone promoted only mild inflammation within the muscle, whereas the presence of alum induced severe muscle inflammation, as expected. Thus, in the mouse model, GMMA demonstrated to possess mild local reactogenic potential, while alum is confirmed a major driver of local reactogenicity.
Our results further support the idea to investigate the reactogenicity of GMMA formulated without alum in clinical studies.
Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disorder predominantly involving the axial skeleton. Understanding the cytokine and chemokine signatures in AS is crucial for elucidating disease mechanisms and identifying potential diagnostic biomarkers.
Serum samples from 31 AS patients and 20 age-matched healthy controls (HCs) were analyzed. The concentrations of 54 cytokines, chemokines, and angiogenesis-related factors were measured using a Meso Scale Discovery (MSD) electrochemiluminescence immunoassay. Data analysis included statistical comparison of serum cytokine levels, heatmap clustering, principal component analysis (PCA), and receiver operating characteristic (ROC) curve analysis. Validation was performed using peripheral blood mononuclear cells (PBMCs) from SKG mice, a spontaneous animal model of AS, through quantitative real-time PCR.
Compared with HCs, AS patients showed significantly higher serum concentrations of 12 cytokines (TNF-α, TNF-β, IL-17A, IL-17D, VEGFA, ICAM1, SAA, IP-10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13) and significantly lower concentrations of nine cytokines (IL-4, IL-8, IL-17C, MIP-1α/CCL3, eotaxin-3/CCL26, PlGF, VEGF-C, VEGF-D, and bFGF) (all p < 0.05). Heatmap clustering and PCA demonstrated a clear separation between AS patients and HCs. ROC curve analysis showed excellent diagnostic accuracy for IP-10/CXCL10 (AUC = 1.00), VEGF-D (AUC = 0.98), IL-17A (AUC = 0.87), TNF-α (AUC = 0.85), and ICAM1 (AUC = 0.84). Positive correlations were observed between IL-17A and MIP-3α/CCL20, and between VEGFA and sFlt-1, indicating coordinated inflammatory and angiogenic pathways. Validation experiments in SKG mice confirmed elevated IP-10/CXCL10 and reduced VEGF-D expression, supporting cross-species relevance.
This study identified distinct cytokine and chemokine profiles in AS patients. IP-10/CXCL10 and VEGF-D emerged as promising diagnostic biomarkers with high discriminatory power. Several previously unreported immune mediators were also highlighted. These findings provide new insights into AS pathogenesis and suggest potential targets for future therapeutic interventions.
Intestinal γδ T-cell immune characteristics and their relationship with disease activity in Crohn's disease (CD) and ulcerative colitis (UC) remain to be fully clarified.
Biopsies from 21 CD, 21 UC and 21 healthy controls were analyzed by flow cytometry for γδ T-cell frequency, cytotoxicity (perforin, granzyme-B), activation (HLA-DR) and exhaustion (PD-1). ROC curves were used to evaluate the diagnostic performance of these indices. Vγ subsets were profiled using published scRNA-seq data.
As disease activity increased, intestinal γδ T cells in CD and UC patients decreased and could not activate. The differences were that the cytotoxicity of intestinal γδ T cells in CD patients was always normal as disease activity increased. In contrast, the cytotoxicity of intestinal γδ T cells in UC patients was suppressed. Different Vγ subsets in CD or UC patients showed different immune characteristics, which might lead to different immune characteristics of γδT cells in CD or UC patients at different disease active stages. Furthermore, γδ T cell and HLA-DR+ γδ T cell ratio were good indicators in diagnosing CD. The ratios of γδ T cell, HLA-DR+ γδ T cell, PD-1+ γδ T cell, and Perforin+ γδ T cell exhibited values for diagnosing UC. PD-1+ γδ T cell ratio was a valuable indicator to help distinguish CD from UC.
Intestinal γδ T cells exhibit both shared and divergent features in CD and UC that closely parallel disease activity, supporting their potential as immune biomarkers for diagnosis and discrimination between the two diseases.
Intracranial hypertension (IH) is a frequently observed clinical manifestation of cerebral venous thrombosis (CVT), which reflects the severity of the disease. The gold standard of intracranial pressure (ICP) is through invasive lumbar puncture.
We aimed to develop a noninvasive model combining biomarkers and clinical features to predict IH in CVT patients, facilitating early risk stratification.
The patients with CVT were consecutively enrolled in the Second Affiliated Hospital of Soochow University and the First Affiliated Hospital of Soochow University between January 2011 and June 2024, which were divided into two groups: CVT-IH group and CVT + IH group based on ICP levels. Additionally, participants were further categorized into four groups according to the cut-off of C-reactive protein (CRP) and international normalized ratio (INR) by the receiver operating characteristic (ROC) curves. Logistic regression models were employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of IH across the four subgroups.
157 individuals were finally included, 61 of whom had IH. Participants with CRP > 5.5 g/L or INR < 0.99 were more likely to experience IH. Those with high CRP and low INR conferred 9.778 times higher risk of IH compared with that of those with low CRP and high INR. Simultaneously adding CRP and INR to the basic model with established risk factors significantly improved risk discrimination and reclassification for IH of CVT patients.
Combination of CRP and INR better predicted the occurrence of IH for CVT patients, which might provide a noninvasive way of assessing ICP of CVT patients.
House dust mite allergy affects 65–130 million people worldwide. Untreated patients could develop severe allergic diseases such as atopic dermatitis and asthma.
We consecutively recruited 50 patients with a clinical diagnosis of allergic rhinitis/rhino conjunctivitis. Mite Skin Prick Tests were performed. Mite specific IgE were tested.
Ninety-six per cent of the patients had a positive prick test for Dpt, Dfar 94%, Ldt 86%, Tput 82%, and Blot 82%. Der p1 was recognized by 70%, Der p2 84%, Der p23 72%. Regarding serodominances, Der p2 was the highest one (30.2 kU/L). Forty-three patients presented sensitization to 3 Dermatophagoides pteronyssinus molecules, been 1 + 2 + 23 the main combination. Der p 1, 2, and 23 prevalence were similar in patients with intermittent or persistent allergic rhinitis. All patients with asthma recognized to Der p2 and more than 80% Der p1 and 23. In the group of patients without asthma, sensitivity to Der p23 is considerably reduced.
Ninety per cent of patients recognize Der p1, 2, and 23, alone or in any of their combinations. The high prevalence of sensitization to Der p23 (72%) stands out, that all asthmatic patients are sensitive to Der p2 and that sensitization to Der p23 in non-asthmatic patients drops to 50%.
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