Jianxiong Li

Background: PLK1 is associated with various malignant tumors, but its correlation with lung adenocarcinoma (LUAD) remains unclear. This research seeks to explore the differences in PLK1 expression in LUAD and evaluate the relationship between PLK1 expression and the outcomes for LUAD patients. Methods: Information on LUAD patients was sourced from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Genotype-Tissue Expression (GTEx). The XianTao Academic Online Platform was employed for systematic analysis of PLK1, including: (1) Wilcoxon rank-sum test to compare PLK1 expression between LUAD and normal tissues; (2) logistic regression analysis evaluating PLK1-clinicopathological feature relationships; (3) Kaplan–Meier and COX regression analyses assessing prognostic significance; (4) nomogram construction for survival prediction. Immunohistochemical (IHC) staining results from the Human Protein Atlas (HPA) validated PLK1 protein expression. Functional characterization using the XianTao platform included: (1) Analysis of PLK1-coexpressed genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways; (2) single-sample gene set enrichment analysis (ssGSEA) to measure immune cell infiltration in tumors with high PLK1 expression. In vitro validation included: (1) cell proliferation assessment (CCK-8 and colony formation assays); (2) apoptosis detection via Annexin V/PI staining; (3) cell cycle analysis by PI staining flow cytometry; (4) cell cycle-related protein expression evaluation using Western blotting (Cyclin B1, CDK1). Results: PLK1 expression was significantly elevated in LUAD tumor tissues compared to adjacent normal samples across multiple cohorts. Elevated PLK1 expression was strongly associated with advanced clinicopathological stages (tumor/node/metastasis (T/N/M)) and poorer overall survival. Functional enrichment analysis revealed that genes co-expressed with PLK1 were predominantly involved in cell cycle regulatory pathways. Furthermore, transcriptomic profiling indicated a significant correlation between high PLK1 expression and an immunosuppressive tumor microenvironment. Experimental validation in A549 cells demonstrated that pharmacological inhibition of PLK1 ( via GSK461364 ) effectively suppressed cell proliferation, induced G2/M phase arrest, promoted apoptosis, and led to the accumulation of Cyclin B1 and CDK1 proteins. Conclusion: PLK1 overexpression signifies aggressive disease and poor prognosis in LUAD, mechanistically linked to cell cycle dysregulation and an immunosuppressive microenvironment. Our findings nominate PLK1 as a promising therapeutic target and biomarker, warranting further investigation into PLK1-directed therapies.

Radiation-induced injury remains a significant challenge in the radiotherapy of cancer patients. Ionizing radiation causes various cellular and molecular damages, leading to both acute and chronic organ dysfunction. Its impact extends beyond interrupting standard treatment protocols and adversely affects the quality of life. Therefore, understanding the mechanisms underlying radiation-induced injury and identifying effective treatment strategies are crucial. In this review, we summarize the recent advances in the molecular and cellular mechanisms of radiation-induced injury across various organs and systems, particularly in the lung, gastrointestinal system, brain, skin, and bone. We highlight the roles of oxidative stress, DNA damage response, mitochondrial dysfunction, and epigenetics in radiation pathology, and summarize the relevant signaling pathways and cellular responses involved in radiation damage. Additionally, we discuss the common symptoms, risk factors, and current diagnostic strategies of radiation-induced injuries. Furthermore, this article provides an in-depth review of effective clinical treatments, elucidates their mechanisms of action, and highlights emerging therapeutic approaches, such as stem cell therapy, nanomedicine, and exosome-based interventions, in clinical practice. Despite significant advances in understanding radiation-induced injury, challenges remain in translating molecular insights into effective therapies. The review concludes with a call for integrated, precision medicine-based approaches to better manage radiation-induced injuries and improve patient outcomes.

Background: LRFN4, characterized by leucine-rich repeats and fibronectin type III domains, has been implicated in various human diseases. However, its role in immune regulation and cancer prognosis remains unclear.Methods: We performed a comprehensive analysis using datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTE x), UALCAN, Star Base, and Comparative Toxicogenomics Database (CTD), and observed significant dysregulation of LRFN4 in multiple cancers compared to normal tissues.Results: LRFN4 expression was strongly correlated with clinical prognosis, immune subtypes, molecular subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltration, which were measured by ESTIMATE scores. Moreover, LRFN4 expression was associated with the presence of tumor-infiltrating immune cells, particularly in gastrointestinal tumors, reflecting immune cell genetic signatures. Validation through fluorescence multiplex immunohistochemistry confirmed that the association of LRFN4 protein expression with the clinicopathological features and the immune microenvironment of gastric cancer. Flow cytometry analysis indicated that LRFN4 inhibited apoptosis in gastric cancer cell lines while enhancing cell cycle arrest in the S phase. Western Blot analysis demonstrated a positive correlation between the high expression of LRFN4 and the expression levels of cyclin D1 as well as CDK4. In contrast, a negative correlation was observed between the high expression of LRFN4 and the expression level with cleaved-caspase-3 levels.Conclusion: These findings suggest that LRFN4 may serve as a novel biomarker for cancer prognosis and a potential target for immunotherapy.

In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO₂ nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn²⁺‐mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long‐lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.

Background: N6-methyladenosine (m6A) RNA regulators play important roles in cancers, but their functions and mechanism have not been demonstrated clearly in gastric cancer (GC).Methods: In this study, the GC samples with clinical information and RNA transcriptome were downloaded from The Cancer Genome Atlas database. The different expression genes were compared by the absolute value and median ± standard deviation. Samples with complete information were randomly divided into a training dataset and a test dataset. The differential expression genes (DEGs) between ALKBH5-low and ALKBH5-high subgroups were identified in the training dataset and constructed a risk model by Cox and least absolute shrinkage and selection operator regression. The model was testified in test datasets, overall survival (OS) was compared with the Kaplan–Meier method, and immune cell infiltration was calculated by the CIBERSORT algorithm in the low-risk and high-risk subgroups based on the model. The protein levels of ALKBH5 were detected with immunohistochemistry. The relative expression of messenger-ribonucleic acid (mRNA) was detected with quantitative polymerase chain reaction.Results: ALKBH5 was the only regulator whose expression was lower in tumor samples than that in normal samples. The low expression of ALKBH5 led to the poor OS of GC patients and seemed to be an independent protective factor. The model based on ALKBH5-regulated genes was validated in both datasets (training/test) and displayed a potential capacity to predict a clinical prognosis. Gene Ontology analysis implied that the DEGs were involved in the immune response; CIBERSORT results indicated that ALKBH5 and its related genes could alter the immune microenvironment of GC. The protein levels of ALKBH5 were verified as lowly expressed in GC tissues. SLC7A2 and CGB3 were downregulated with ALKBH5 knockdown.Conclusions: In this study, we found that ALKBH5 might be a suppressor of GC; ALKBH5 and its related genes were latent biomarkers and immunotherapy targets.

Background N6-methyladenosine(m6A) RNA regulators play important roles in cancers, but the functions and mechanism of them have not been demonstrated clearly in gastric cancer (GC). Methods In this study, the GC samples with clinical information and RNA transcriptome were downloaded from TCGA database. The different expression genes were compared by absolute value and median ± standard deviation (sd). Samples with complete information were randomly divided into training dataset and test datasets. The differential expression genes (DEGs) between ALKBH5-low and ALKBH5-high subgroups were identified in training dataset and constructed a risk model by Cox and LASSO regression. The model was testified in test datasets, the overall survival (OS) was compared with Kaplan-Meier method and immune cells infiltration was calculated by CIBERSORT algorithm in the low-risk and high-risk subgroups based on the model. Results ALKBH5 was the only one regulator whose expression was lower in tumor samples than that in normal samples, there was the same phenomenon in GEO dataset GSE29998. Low expression of ALKBH5 led to poor overall survival of GC patients and seemed to be an independent protective factor. The model based on ALKBH5 regulated genes was validated in both two datasets (training/test) and it displayed potential capacity to predict clinical prognosis. Gene Ontology (GO) analysis implied that the DEGs were involved in immune response, CIBERSORT results indicated that ALKBH5 and its related genes could alter the immune microenvironment of GC. Conclusions In this study we found that ALKBH5 might be a suppressor of GC, ALKBH5 and its related genes were latent biomarkers and immunotherapy targets.

Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis are cell swelling, membrane perforation, and the release of cell contents. In normal physiology, pyroptosis plays a critical role in host defense against pathogen infection. However, excessive pyroptosis may cause immoderate and continuous inflammatory responses that involves in the occurrence of inflammatory diseases. Attractively, as immunogenic cell death, pyroptosis can serve as a new strategy for cancer elimination by inducing pyroptotic cell death and activating intensely antitumor immunity. To make good use of this double-edged sword, the molecular mechanisms, and therapeutic implications of pyroptosis in related diseases need to be fully elucidated. In this review, we first systematically summarize the signaling pathways of pyroptosis and then present the available evidences indicating the role of pyroptosis in inflammatory diseases and cancer. Based on this, we focus on the recent progress in strategies that inhibit pyroptosis for treatment of inflammatory diseases, and those that induce pyroptosis for cancer therapy. Overall, this should shed light on future directions and provide novel ideas for using pyroptosis as a powerful tool to fight inflammatory diseases and cancer.