Ferroptosis, a novel type of regulated cell death mediated by iron-dependent lipid oxidation, was discovered a decade ago. Significant progress has been made in our knowledge of ferroptosis and immune dysfunction. This review covers recent advancements in the interaction of ferroptosis and the immune system, with an emphasis on autoimmune diseases. The critical regulators of ferroptosis are summarized in the context of reactive oxygen species biology, lipid metabolism, and iron homeostasis. The molecular crosstalk between ferroptosis and different immune cells is also highlighted. Future research is expected to yield new insights into the mechanisms governing ferroptosis and its potential therapeutic benefits in autoimmune diseases.

Liver fibrosis is an excessive wound-healing response triggered by chronic liver injury. It may eventually progress to cirrhosis, liver failure or liver cancer. Currently, there are no effective therapeutic strategies available. Deacetylasperulosidic acid methyl ester (DAM), a natural iridoid compound derived from Rubiaceae plants, possesses potential anti-inflammatory activity. However, its role in liver fibrosis and the underlying mechanisms remain unclear. Given the critical involvement of inflammation and gut microbiota dysbiosis in the development of liver fibrosis, this study aimed to investigate whether DAM could ameliorate liver fibrosis by modulating hepatic inflammation and intestinal dysbiosis. Using a carbon tetrachloride (CCl₄)-induced liver fibrosis model in mice, we evaluated DAM’s effects via histopathology, serum biochemical assays, liver fibrosis marker detection, intestinal barrier analysis and 16S rRNA gene sequencing. DAM treatment significantly alleviated hepatic histopathological damage, reduced serum levels of ALT, AST and γ-GT, inhibited hepatic collagen deposition (HA, LN, IV-C and PC Ⅲ) and reduced the expression of the fibrotic markers α-SMA and Col1a1. Furthermore, DAM markedly inhibited the hepatic expression of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, demonstrating its anti-inflammatory properties. DAM also attenuated intestinal structural damage, enhanced the expression of tight junction proteins Claudin-1, ZO-1 and Occludin, and improved intestinal barrier integrity, thereby reducing endotoxin translocation. 16S rRNA gene sequencing further revealed that DAM improved CCl₄-induced gut microbiota dysbiosis by reducing the abundance of pro-inflammatory genera such as Faecalibaculum and Dubosiella, thereby contributing to the restoration of microbial homeostasis. Collectively, DAM effectively ameliorates CCl₄-induced liver fibrosis by modulating hepatic inflammation and gut microbiota dysbiosis and may serve as a promising candidate for the prevention and treatment of liver fibrosis.

Background: The current studies on metronomic chemotherapy in mCRC are all aimed at patients after multi-line therapy failure, and only a few studies have focused on maintenance treatment after successful first-line therapy. Methods: The PubMed, Embase, Cochrane Library, Wanfang, CNKI, and VIP were searched, and the relevant data was extracted, including media progression-free survival (mPFS), media overall survival (mOS), and grade 3/4 adverse events (AEs). Results: We included 4 randomized controlled trials (RCTs), 2 RCTs showed that metronomic maintenance chemotherapy could significantly improve mPFS compared to observation group; another RCT showed that metronomic maintenance chemotherapy group did not have low mPFS than the bevacizumab maintenance treatment (MT). The final RCT showed that dual-agent metronomic chemotherapy combined with bevacizumab MT did not improve mPFS compared with bevacizumab MT. The 3 RCTs showed that the metronomic maintenance therapy could not effectively improve mOS in mCRC compared to observation group or bevacizumab MT, while another RCT reported that the mOS in metronomic maintenance chemotherapy group was similar to bevacizumab MT. AEs was mostly mild and manageable. Grade ≥ 3 AEs are mostly nonhematological toxicity, and no deaths related to AEs were reported. Conclusion: This systematic review indicates that metronomic chemotherapy for mCRC MT can improve mPFS in some patients and is relatively safe. However, improvements in OS in most RCTs are arguable. Therefore, we need further studies to verify its long-term efficacy.

To systematically assess the effectiveness and toxicity of metronomic oral cyclophosphamide (MOC) on recurrent or platinum-refractory ovarian cancer. We searched the Cochrane Library, Embase, PubMed, CNKI, Weipu, and Wanfang databases for eligible studies. A descriptive statistical method was used to analyze the pooled results. Ratios and means were merged to analyze the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the rate of serious adverse events (SAEs). Subgroup analysis, sensitivity analysis, and examination of publication bias were conducted for heterogeneity test and quality assurance of the results. The ORR and DCR by MOC were 25% (95% CI 12–41) and 61% (95% CI 43–77), respectively. The median PFS and OS were 4.29 months (95% CI 2.62–5.97) and 11.26 months (95% CI 8.13–14.39), respectively. The rate of SAEs was 41% (95% CI 30–52). The most frequent SAEs were gastrointestinal toxicity 6% (95% CI 1–12), lymphopenia 6% (95% CI 1–13), and neutropenia 5% (95% CI 2–9). In the subgroup analysis, the ORR and DCR in the subgroup of MOC combined with bevacizumab/pazopanib were 42% (95% CI 26–58) and 82% (95% CI 63–95), respectively. The median PFS and OS were 7.32 months (95% CI 5.93–8.70) and 17.35 months (95% CI 12.89–21.82), respectively. MOC has a certain effect in clinical response on patients with recurrent or platinum-refractory ovarian cancers, especially when MOC combined with bevacizumab/pazopanib. However, there is a high risk of SAEs.

Hemorrhagic shock with tissue trauma (HS/T) leads to the activation of a system-wide immune-inflammatory response that involves all organs and body compartments. Recent advances in single-cell analysis permit the simultaneous assessment of transcriptomic patterns in a large number of cells making it feasible to survey the landscape of immune cell responses across numerous anatomic sites. Here, we used single-cell RNA sequencing of leukocytes from the blood, liver, and spleen to identify the major shifts in gene expression by cell type and compartment in a mouse HS/T model. At 6 h, dramatic changes in gene expression were observed across multiple-cell types and in all compartments in wild-type mice. Monocytes from circulation and liver exhibited a significant upregulation of genes associated with chemotaxis and migration and a simultaneous suppression of genes associated with interferon signaling and antigen presentation. In contrast, liver conventional DC exhibited a unique pattern compared with other myeloid cells that included a pronounced increase in major histocompatibility complex class II (MHCII) gene expression. The dominant pattern across all compartments for B and T cells was a suppression of genes associated with cell activation and signaling after HS/T. Using complement factor 3 (C3) knockout mice we unveiled a role for C3 in the suppression of monocyte Major Histocompatibility Complex class II expression and activation of gene expression associated with migration, phagocytosis and cytokine upregulation, and an unexpected role in promoting interferon-signaling in a subset of B and T cells across all three compartments after HS/T. This transcriptomic landscape study of immune cells provides new insights into the host immune response to trauma, as well as a rich resource for further investigation of trauma-induced immune responses and complement in driving interferon signaling.