Zongkui Wang

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal barrier disruption and dysregulated immune responses. While Intravenous Immunoglobulin (IVIG) is widely used for its immunomodulatory effects in various autoimmune conditions, its specific therapeutic mechanisms and molecular targets in colitis remain to be fully elucidated. Objective: To elucidate the therapeutic mechanisms of IVIG in dextran sodium sulfate (DSS)-induced colitis, with a focus on pyroptosis regulation via the NOD-like receptor (NLR) signaling pathway. Methods: Colitis was induced in mice via DSS administration. IVIG was administered intravenously during disease progression. Colon tissues underwent proteomic profiling, and key targets (GBP5, NLRP3, Pro-Caspase-1, GSDMD) were validated by Western blotting (WB), while interleukin (IL)-1β and IL-18 levels were quantified via ELISA. Results: IVIG significantly attenuated weight loss, Disease Activity Index (DAI) scores, colon shortening, and histopathological damage. Proteomics analysis identified 172 differentially expressed proteins between DSS and DSS + IVIG groups, with pronounced downregulation of GBP5 and NLR pathway components. IVIG suppressed GBP5/NLRP3/CASP1 activation, reduced GSDMD cleavage, and significantly decreased IL-1β production (while showing a decreasing trend for IL-18). Conclusions: IVIG ameliorates colitis by inhibiting the GBP5/NLRP3/CASP1-mediated pyroptosis pathway, highlighting its potential as a targeted therapy for ulcerative colitis.

Background: Intestinal inflammation encompasses a range of conditions, including inflammatory bowel disease (IBD), radiation-induced enteritis, and chemotherapy- or toxin-induced epithelial injury. Although intravenous immunoglobulin (IVIg) is widely used in autoimmune and inflammatory disorders, its role in these forms of intestinal injury has not been systematically evaluated. Objective: This systematic review aimed to summarize the existing animal and clinical evidence on the therapeutic effects of IVIg in intestinal inflammation. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four electronic databases (PubMed, Web of Science, Embase, and China National Knowledge Infrastructure) were systematically searched for studies published from January 1, 2000 to February 3, 2026. Eligible studies included animal and clinical investigations evaluating the role of IVIg in the context of intestinal inflammation. Data were narratively synthesized, and risk of bias was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool for animal studies and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) for non-randomized clinical studies. Results: Ten studies were included: seven animal and three clinical studies. IVIg generally exhibited anti-inflammatory and epithelial-protective effects across models of Dextran Sulfate Sodium (DSS)-induced colitis, radiation-induced enteritis, chemotherapy-induced mucositis, and toxin-induced epithelial damage. Reported mechanisms included interleukin (IL)-10 signaling, Fcγ receptor modulation, ferroptosis inhibition, and microbiota-mediated immune regulation. Human data were restricted to small, retrospective, uncontrolled cohorts of patients with refractory or steroid-resistant IBD, often with contraindications to standard immunosuppressive therapy. In these studies, some patients experienced short-term clinical improvement, but responses were variable, long-term outcomes were frequently unsatisfactory, and the overall risk of bias was serious to critical. Conclusion: Current animal and clinical data suggest that IVIg can modulate intestinal inflammation and epithelial injury but are insufficient to support its use as a standard therapy for IBD or other intestinal inflammatory conditions. At present, IVIg should be considered, at most, as an adjunctive or rescue option in carefully selected, refractory cases in which guideline-recommended therapies are ineffective or contraindicated. Further work is needed to improve the rigour and transparency of preclinical studies and to conduct small, well-designed prospective clinical studies in clearly defined niche indications to clarify any potential role of IVIg within the expanding therapeutic armamentarium for intestinal inflammation. PROSPERO ID (CRD420251051592).

Colorectal cancer (CRC) is a prevalent malignant tumour, with its incidence and mortality rates consistently ranking among the highest and exhibiting an upward trend. Extensive screening and early diagnosis are crucial for managing CRC progression and improving patient prognosis. This study aims to construct a novel analytical framework for integrating the sequencing data from tumour tissue and peripheral blood. By integrating and analysing the multi-omics data and clinical data from tumour tissues and peripheral blood, we confirmed that the LTB4R gene is significantly upregulated not only in tumour tissues but also in the peripheral blood of CRC patients. Further single-cell RNA sequencing (scRNA-seq) and immune cell correlation analyses revealed that Leukotriene B4 receptor 1 (LTB4R) is primarily expressed in macrophages, T cells, and other immune cells, with a significant negative correlation observed with M1-type macrophages, suggesting its potential pro-tumourigenic role in CRC by suppressing M1 macrophage. Additionally, simulated gene knockout analysis (scTenifoldKnk) demonstrated that LTB4R knockout significantly impacts immune-related pathways, including immune response and immune receptor activity. These findings not only highlight the potential of LTB4R as a peripheral blood diagnostic marker for CRC but also elucidate its involvement in tumour progression, offering novel insights for early clinical diagnosis and tumour screening systems.

Background Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of IVIg in CIM. Methods A murine model of doxorubicin (Dox)-induced intestinal mucositis and an organoid model of small intestinal injury were used to explore the protective effects of IVIg on CIM. Immunostaining, transmission electron microscopy (TEM), western blotting (WB), and proteomic analysis were used to further investigate ferroptosis in intestinal epithelial cells and the underlying mechanisms. Results In the murine model of Dox-induced intestinal mucositis, intestinal epithelial barrier was destroyed and ferroptosis increased, characterized by weight loss, hematological injury, inflammation, mitochondrial atrophy in intestinal epithelial cells, lipid peroxidation, impairment of tight junctions, and damage to intestinal microvilli. IVIg treatment significantly ameliorated intestinal epithelial barrier damage and reduced ferroptosis both in vitro and in vivo. Proteomic analysis revealed that the FcγR-mediated phagocytosis signaling pathway was involved in the therapeutic effects of IVIg on CIM mice. WB results demonstrated that key proteins downstream of this pathway, Syk, PI3K, and Akt, showed increased phosphorylation in CIM mice, whereas IVIg treatment significantly reduced the phosphorylation levels. Furthermore, the inhibitory effects of IVIg on Dox-induced activation of the Syk/PI3K/Akt axis and ferroptosis, as well as its protective effects on intestinal inflammation and intestinal barrier damage, were reversed by 740Y-P (an PI3K activator) or SC79 (an Akt activator). Conclusions Our findings highlight that IVIg ameliorates CIM by inhibiting ferroptosis via the Syk/PI3K/Akt axis. These results suggest that IVIg may represent a potential therapeutic approach for CIM.

Objective: The purpose of the present study was to evaluate whether intravenous immunoglobulin (IVIG) increases live birth rates and improves neonatal results in patients with antiphospholipid antibodies (aPL) at high-risk for miscarriage. Background: Positivity of aPL in pregnant women is a high-risk factor for miscarriage, and IVIG treatment has emerged as a potential intervention. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was employed to search multiple electronic databases for articles published until August 20, 2023, including PubMed, Web of Science, Embase, Scopus and Medline. The inclusion criteria encompassed studies assessing the efficacy of IVIG in aPL-positive patients with a high risk of miscarriage. Relevant articles were assessed for the quality and data were extracted for analysis. Two independent reviewers performed study selection, data extraction, and quality assessments. The risk of bias was evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.3. Results: This systematic review included nine randomized controlled trials, with 366 aPL-positive women at high risk of miscarriage. These studies included in this review were randomized controlled trials. The primary outcome measures were successful pregnancy outcomes and live birth rates. The secondary outcomes included obstetric complications, and neonatal outcomes (such as birth weight and live-birth rate). The comparison between the intervention and control groups revealed no significant differences in terms of obstetric complications and neonatal outcomes. The group receiving IVIG treatment had a higher prevalence of preterm deliveries than controls (OR = 2.05, I² = 46%, 95% CI [0.58–5.24]), but also exhibited a partial improvement in live birth rates (OR = 2.86, I² = 52%, 95% CI [1.04–7.90]), because it reduced the number of miscarriages (OR = 0.35, I² = 52%, 95% CI [0.13–0.96]). Conclusion: Based on the available evidence, IVIG intervention appears to be a potentially effective approach for managing of aPL-positive pregnant women with high risk of miscarriage. While IVIG shows significant potential in tripling the chances of having a live-born child, further large-scale randomized controlled trials are necessary, preferably comparing IVIG with hydroxychloroquine or lifestyle and dietary interventions, to refine treatment protocols and ensure the most effective application.