Objective: To assess the correlation between HMGB1 expression and the patient prognosis in a multicancer context. Methods: The potential oncogenic role of HMGB1 was explored in forty tumors through the TCGA, GEO, and Oncomine datasets. We analyzed the clinical prognostic value and antitumor immunotherapy of HMGB1 in a multicancer context using GEO (GSE111636). Results: High expression of HMGB1 is present in multicancer cases, and its low expression is closely associated with the prognostic survival of patients, in terms of both overall and disease-free survival in ACC and LUAD. Further investigation revealed that the high expression of gastric and lung cancer is closely associated with low risk and better prognosis of patients based on COX and Kaplan–Meier analysis of OS, FP and PPS. HMGB1 expression was found to be significantly correlated with cancer-associated fibroblast and CD8⁺ T cell infiltration in the TME. The analysis of GO functional annotation/KEGG pathways indicates that HMGB1 may regulate tumor immunity-related pathways, such as the tumor immunotherapy response in colorectal cancer. The function of four genes as hubs are confirmed by in vitro HMGB1 knockdown which led to inhibition of cell proliferation and metastasis in SW620 and SW480 cells. Conclusion: HMGB1 is a potential novel biomarker for improving clinical prognosis and antitumor immunotherapy efficacy. CDK1, HMGB2, SSRP1, and H2AFV may serve as key nodes for HMGB1 in colorectal cancer.

Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa. In recent years, there have been an increasing number of studies on the anti‐inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti‐inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α) in mice. ATG significantly reduced the percentage of CD11b⁺Ly6G⁺ neutrophils and F4/80⁺ macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b‐positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS‐stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG‐induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG‐induced acute peritonitis in mice.

CircRNAs are a class of endogenous long non-coding RNAs with a single-stranded circular structure. Most circRNAs are relatively stable, highly conserved, and specifically expressed in tissue during the cell and developmental stages. Many circRNAs have been discovered in OSCC. OSCC is one of the most severe and frequent forms of head and neck cancer today, with a poor prognosis and low overall survival rate. Due to its prevalence, OSCC is a global health concern, characterized by genetic and epigenomic changes. However, the mechanism remains vague. With the advancement of biotechnology, a large number of circRNAs have been discovered in mammalian cells. CircRNAs are dysregulated in OSCC tissues and thus associated with the clinicopathological characteristics and prognosis of OSCC patients. Research studies have demonstrated that circRNAs can serve as biomarkers for OSCC diagnosis and treatment. Here, we summarized the properties, functions, and biogenesis of circRNAs, focusing on the progress of current research on circRNAs in OSCC.

The aim of this study was to evaluate the association between Ferredoxin 1 (FDX1) expression and the prognostic survival of tumor patients and predict the efficacy of immunotherapy response to antitumor drug sensitivity. FDX1 plays an oncogenic role in thirty-three types of tumors, based on TCGA and GEO databases, and further experimental validation in vitro was provided through multiple cell lines. FDX1 was expressed highly in multiple types of cancer and differently linked to the survival prognosis of tumorous patients. A high phosphorylation level was correlated with the FDX1 site of S177 in lung cancer. FDX1 exhibited a significant association with infiltrated cancer-associated fibroblasts and CD8⁺ T cells. Moreover, FDX1 demonstrated correlations with immune and molecular subtypes, as well as functional enrichments in GO/KEGG pathways. Additionally, FDX1 displayed relationships with the tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and RNA and DNA synthesis (RNAss/DNAss) within the tumor microenvironment. Notably, FDX1 exhibited a strong connection with immune checkpoint genes in the co-expression network. The validity of these findings was further confirmed through Western blotting, RT-qPCR, and flow cytometry experiments conducted on WM115 and A375 tumor cells. Elevated FDX1 expression has been linked to the enhanced effectiveness of PD-L1 blockade immunotherapy in melanoma, as observed in the GSE22155 and GSE172320 cohorts. Autodocking simulations have suggested that FDX1 may influence drug resistance by affecting the binding sites of antitumor drugs. Collectively, these findings propose that FDX1 could serve as a novel and valuable biomarker and represent an immunotherapeutic target for augmenting immune responses in various human cancers when used in combination with immune checkpoint inhibitors.

The fundamental biological characteristics of tumor cells are characterized by irregularities in signaling and metabolic pathways, which are evident through increased glucose uptake, altered mitochondrial function, and the ability to evade growth signals. Interventions such as fasting or fasting-mimicking diets represent a promising strategy that can elicit distinct responses in normal cells compared to tumor cells. These dietary strategies can alter the circulating levels of various hormones and metabolites, including blood glucose, insulin, glucagon, growth hormone, insulin-like growth factor, glucocorticoids, and epinephrine, thereby potentially exerting an anticancer effect. Additionally, elevated levels of insulin-like growth factor-binding proteins and ketone bodies may increase tumor cells’ dependence on their own metabolites, ultimately leading to their apoptosis. The combination of fasting or fasting-mimicking diets with radiotherapy or chemotherapeutic agents has demonstrated enhanced anticancer efficacy. This paper aims to classify fasting, elucidate the mechanisms that underlie its effects, assess its impact on various cancer types, and discuss its clinical applications. We will underscore the differential effects of fasting on normal and cancer cells, the mechanisms responsible for these effects, and the imperative for clinical implementation.

Although it is believed that chronic inflammatory and degenerative diseases of the central nervous system are mediated by autoimmune Th17 cells, the underlying mechanisms remain largely unexplored. Recent studies and our research have revealed that Sp3 was blocked in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE). However, it remained unclear why it is silent and how it regulates Th17 cell differentiation in MS. This study aimed to explore the impact of Sp3 on Th17 cell-mediated EAE and the underlying mechanism. The effect of Sp3 on the clinical symptoms of EAE was evaluated by scoring, histochemistry, and fast blue (FB) techniques, scRNA-seq data analysis, flow cytometry, ELISA, PCR, WB, immunofluorescence and reporter gene techniques were used to explore the molecular mechanism of Sp3 regulating Th17 cell differentiation. Injection of overexpression Sp3 lentivirus could significantly ameliorate the EAE progress and clinical symptoms and prevent the polarization of Th1 and Th17 cells both in vivo and in vitro. We confirmed the occurrence of EAE in Sp3^+/+CD4Cre mice and Sp3^+/- knockout mice. Furthermore, we identified Sp3 as a target of miR-223, which is found to be upregulated in the blood of MS patients, as well as in EAE and Th17 cells. Moreover, knockdown of miR-223 led to a marked improvement in EAE symptoms and a suppression of Th1 and Th17 cell polarization in vivo and in vitro. Mechanistically, Sp3 significantly suppressed RORγt expression and the phosphorylation of Stat3 and Smad2/3 by directly upregulating Socs3. Interestingly, Socs3 was found to regulate Sp3 expression in response to TGF-β1 via a feedback loop. Moreover, Socs3 modulated phospho-Smad2/3 by binding to and degrading the transforming growth factor-β receptor II (TβRII). Thus, our study suggests a novel mechanism involving miR-223/Sp3/Socs3/TGF-β signaling as a potential therapeutic strategy for targeting Th17 cells in immunotherapy.