Uridine metabolism is extensively reported to be involved in combating oxidative stress. Redox-imbalance-mediated ferroptosis plays a pivotal role in sepsis-induced acute lung injury (ALI). This study aims to explore the role of uridine metabolism in sepsis-induced ALI and the regulatory mechanism of uridine in ferroptosis. The Gene Expression Omnibus (GEO) datasets including lung tissues in lipopolysaccharides (LPS) -induced ALI model or human blood sample of sepsis were collected. In vivo and vitro, LPS was injected into mice or administered to THP-1 cells to generate sepsis or inflammatory models. We identified that uridine phosphorylase 1 (UPP1) was upregulated in lung tissues and septic blood samples and uridine significantly alleviated lung injury, inflammation, tissue iron level and lipid peroxidation. Nonetheless, the expression of ferroptosis biomarkers, including SLC7A11, GPX4 and HO-1, were upregulated, while lipid synthesis gene (ACSL4) expression was greatly restricted by uridine supplementation. Moreover, pretreatment of ferroptosis inducer (Erastin or Era) weakened while inhibitor (Ferrostatin-1 or Fer-1) strengthened the protective effects of uridine. Mechanistically, uridine inhibited macrophage ferroptosis by activating Nrf2 signaling pathway. In conclusion, uridine metabolism dysregulation is a novel accelerator for sepsis-induced ALI and uridine supplementation may offer a potential avenue for ameliorating sepsis-induced ALI by suppressing ferroptosis.

Ischemia-reperfusion (I/R) is a pathological process that occurs in numerous organs throughout the human body and is frequently associated with severe cellular damage and death. Puerarin is an isoflavone compound extracted from the root of Pueraria lobata and has pharmacological effects such as dilating cerebral vessels and anti-free radical generation in cerebral ischemic tissues. With the deepening of experimental research and clinical research on puerarin, it has been found that puerarin has a protective effect on ischemia-reperfusion injury (IRI) of the heart, brain, spinal cord, lung, intestine and other organs. In summary, puerarin has a vast range of pharmacological effects and significant protective effects, and it also has obvious advantages in the clinical protection of patients with organ IRI. With the deepening of experimental pharmacological research and clinical research, it is expected to be an effective drug for IRI treatment. In this review, we summarize the current knowledge of the protective effect of puerarin on I/R organ injury and its possible underlying molecular mechanisms.

Increasing evidence has confirmed the close connection between inflammatory response and tumorigenesis. However, the relationship between inflammatory response genes (IRGs) and the prognosis of lung adenocarcinoma (LUAD) as well as the response to drug therapy remains poorly investigated. Here, we comprehensively analyzed IRGs RNA expression profiling and clinical features of over 2000 LUAD patients from 12 public datasets. The Cox regression method and LASSO analysis were combined to develop a novel IRG signature for risk stratification and drug efficacy prediction in LUAD patients. Enriched pathways, tumor microenvironment (TME), genomic and somatic mutation landscape in different subgroups were evaluated and compared with each other. This established IRG signature including 11 IRGs (ADM, GPC3, IL7R, NMI, NMURI, PSEN1, PTPRE, PVR, SEMA4D, SERPINE1, SPHK1), could well categorize patients into significantly different prognostic subgroups, and have better predictive in independently assessing survival as compared to a single clinical factor. High IRG scores (IRGS) patients might benefit more from immunotherapy and chemotherapy. Comprehensive analysis uncovered significant differences in enriched pathways, TME, genomic and somatic mutation landscape between the two subgroups. Additionally, integrating the IRGS and TNM stage, a reliable prognostic nomogram was developed to optimize survival prediction, and validated in an independent external dataset for clinical application. Take together, the proposed IRG signature in this study is a promising biomarker for risk stratification and drug efficacy prediction in LUAD patients. This study may be meaningful for explaining the responses of clinical therapeutic drugs and providing new strategies for administrating sufferer of LUAD.

Background Although the relationship between inflammatory response and tumor has been gradually recognized, the potential implications of of inflammatory response genes in lung adenocarcinoma (LUAD) remains poorly investigated. Methods RNA sequencing and clinical data were obtained from multiple independent datasets (GSE29013, GSE30219, GSE31210, GSE37745, GSE42127, GSE50081, GSE68465, GSE72094, TCGA and GTEx). Unsupervised clustering analysis was used to identify different tumor subtypes, and LASSO and Cox regression analysis were applied to construct a novel scoring tool. We employed multiple algorithms (ssGSEA, CIBERSORT, MCP counter, and ESTIMATE) to better characterize the LUAD tumor microenvironment (TME) and immune landscapes. GSVA and Metascape analysis were performed to investigate the biological processes and pathway activity. Furthermore, ‘pRRophetic’ R package was used to evaluate the half inhibitory concentration (IC50) of each sample to infer drug sensitivity. Results We identified three distinct tumor subtypes, which were related to different clinical outcomes, biological pathways, and immune characteristics. A scoring tool called inflammatory response gene score (IRGS) was established and well validated in multiple independent cohorts, which could well divide patients into two subgroups with significantly different prognosis. High IRGS patients, characterized by increased genomic variants and mutation burden, presented a worse prognosis, and might show a more favorable response to immunotherapy and chemotherapy. Additionally, based on the cross-talk between TNM stage, IRGS and patients clinical outcomes, we redefined the LUAD stage, which was called ‘IRGS-Stage’. The novel staging system could distinguish patients with different prognosis, with better predictive ability than the conventional TNM staging. Conclusions Inflammatory response genes present important potential value in the prognosis, immunity and drug sensitivity of LUAD. The proposed IRGS and IRGS-Stage may be promising biomarkers for estimating clinical outcomes in LUAD patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-022-01340-7.

Background Histone acetylation (HA) is an important and common epigenetic pathway, which could be hijacked by tumor cells during carcinogenesis and cancer progression. However, the important role of HA across human cancers remains elusive. Methods In this study, we performed a comprehensive analysis at multiple levels, aiming to systematically describe the molecular characteristics and clinical relevance of HA regulators in more than 10000 tumor samples representing 33 cancer types. Results We found a highly heterogeneous genetic alteration landscape of HA regulators across different human cancer types. CNV alteration may be one of the major mechanisms leading to the expression perturbations in HA regulators. Furthermore, expression perturbations of HA regulators correlated with the activity of multiple hallmark oncogenic pathways. HA regulators were found to be potentially useful for the prognostic stratification of kidney renal clear cell carcinoma (KIRC). Additionally, we identified HDAC3 as a potential oncogene in lung adenocarcinoma (LUAD). Conclusion Overall, our results highlights the importance of HA regulators in cancer development, which may contribute to the development of clinical strategies for cancer treatment.