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The apelin receptor (APJ) is a key player in tumour angiogenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of the apelin/APJ pathway in HCC using a multi‐omics approach and identify potential therapeutic biomarkers. Differentially expressed genes related to the apelin/APJ axis were identified from bulk transcriptomics to reveal HCC‐associated disparities. Single‐cell and spatial transcriptomics were used to localize and analyse the function of these genes. Machine learning models were constructed to predict outcomes based on apelin/APJ expression, and experimental validation was conducted to explore the pathway's impact on HCC angiogenesis. Single cell analysis revealed an overexpression of APJ/Aplin in the endothelium. The stemness of endothelial cell (EC) with high apelin/APJ was enhanced, as well as the expression of TGFb, oxidative stresses and PI3K/AKT pathway genes. Spatial transcriptomics confirmed that EC populations with high APJ scores were enriched within the tumour. Machine learning models showed high prognostic accuracy. High APJ expression was linked to worse outcomes (p = 0.001), and AUC values were high (1 year, 3 year, 5 year) (0.95, 0.97, 0.98). Immune suppression and non‐responsiveness of immune therapy were also seen in high‐risk groups. The experimental validation showed that silencing apelin reduced angiogenesis (p < 0.05), endothelial proliferation, decreased expression of ANG2, KLF2, VEGFA and lower ERK1/2 phosphorylation. Apelin may serve as a potential therapeutic target in HCC, given its role in promoting tumour angiogenesis and poor patient outcomes. [ABSTRACT FROM AUTHOR]

Defining radioiodine-refractory differentiated thyroid cancer: efficacy and safety of lenvatinib by radioiodine-refractory criteria in the SELECT trial. What's more, Nair's paper, published in 2015, was a summary of the FDA's approval of lenvatinib for radioiodine-resistant thyroid cancer treatment, and the data here were identical to those in the SELECT study. Keywords: lenvatinib; meta-analysis; radioiodine-refractory thyroid carcinoma; systematic review EN lenvatinib meta-analysis radioiodine-refractory thyroid carcinoma systematic review 275 276 2 01/03/23 20230201 NES 230201 We read with great interest the paper by Yan et al., sharing the perspective that lenvatinib is beneficial for the treatment of radioiodine-refractory thyroid cancer in terms of the extension of progression-free survival (PFS) and overall survival (OS).[1] We greatly appreciated the authors' contributions in studying the treatment of thyroid cancer refractory to radioactive iodine, however, it seems to be some critical problems when the authors drew to this conclusion. [Extracted from the article]

Radiation-induced lung injury (RILI) is a common complication during thoracic radiotherapy which impairs the quality of life in patients and limits radiation doses. Jiawei Maxing Shigan Tang (JMST), which is a modified decoction made of Ephedra, Apricot Kernel, Gypsum, and Licorice, can alleviate the symptoms of RILI in patients. Previous studies and preliminary findings suggested a potential molecular mechanism of JMST in the treatment of RILI. Further studies are needed. To elucidate the mechanisms of how regulatory T cells (Tregs) promote RILI and the effect of JMST on Tregs, as well as the corresponding pathway. CD4+CD25+ Tregs were isolated from rats, and the supernatant's TGF-β1 level was examined by using enzyme-linked immunosorbent assay (ELISA). Type II alveolar epithelial cells (AECs) were co-cultured with the supernatant of Tregs, and the expression levels of epithelial-to-mesenchymal transition (EMT)-related and TGF-β1/Smad signaling pathway-related proteins were analyzed by using western blotting (WB). Afterward, the Tregs were incubated with different concentrations of JMST. The cell viability and TGF-β1 concentration were confirmed by cell counting kit-8 (CCK-8) assay and ELISA, respectively. The optimized concentration of JMST was applied in vitro and vivo experiments. The specific mechanism was investigated through the combination of using flow cytometry, lung histopathology analysis, ELISA, and WB. Radiation could promote Tregs to secrete TGF-β1. After radiation, the expression levels of Smad2/3, phosphorylated Smad2/3 (p-Smad2/3), Smad4 and mesenchymal markers Vimentin and α-SMA were all increased, while the expression level of epithelial markers E-cadherin was decreased. The expression levels of these proteins were reversed after interventions involving Treg cell activation inhibition or TGF-β1 receptor inhibitor. JMST reduced the number of Tregs in lung tissue and alleviated the degree of pulmonary fibrosis. The expression of Smad2/3, p-Smad2/3, Smad4, TGF-β1, Vimentin, and α-SMA were significantly downregulated, while the E-cadherin was upregulated, through the intervention of JMST. Tregs could mediate EMT through TGF-β1/Smad pathway. JMST inhibits EMT via TGF-β1/Smad pathway by regulating Tregs, therefore alleviating RILI. [Display omitted] • Regulatory T cells (Tregs) mediate epithelial-to-mesenchymal transition (EMT) through TGF-β1/Smad pathway. • Jiawei Maxing Shigan Tang (JMST) could regulate Tregs. • JMST could alleviate radiation-induced lung injury (RILI) by inhibiting EMT via TGF-β1/Smadpathway mediated by Tregs. [ABSTRACT FROM AUTHOR]

Background: According to the 2022 Global Cancer Statistics, lung cancer is the leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (LUAD), which is a histological subtype of Non- Small Cell Lung Cancer (NSCLC), accounts for 40% of primary lung cancer. Therefore, there is an urgent need to identify new prognostic markers as clinical predictive markers for LUAD., Objective: This study aimed to investigate the role of Keratin 80 (KRT80) in the prognosis of LUAD and its underlying mechanisms., Methods: Bioinformatics analysis was conducted using data retrieved from The Cancer Genome Atlas (TCGA) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were employed to predict the involved biological processes and signaling pathways, respectively. The LinkedOmics database was utilized to identify differentially expressed genes (DEGs) correlated with KRT80. Nomograms and Kaplan-Meier plots were constructed to evaluate the survival outcomes of patients diagnosed with LUAD. Moreover, TIMER was employed to conduct correlation analyses between KRT80 expression and immune cell infiltration, shedding light on the intricate interplay between KRT80 and the tumor microenvironment in LUAD. To ascertain the RNA and protein expression levels of KRT80 in LUAD and adjacent normal tissues, Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry techniques were employed, respectively., Results: Scrutiny of the TCGA dataset revealed KRT80 up-regulation across pan-cancer tissues, notably elevated in LUAD compared to healthy lung tissues. This finding was validated in our clinical samples, where Kaplan-Meier survival curves indicated poorer survival rates for high KRT80 expression in LUAD. A positive correlation was found between the transcription level of KRT80 in LUAD samples and clinical parameters, such as lymph node metastasis stage, distant metastasis, and pathological stage. Survival, logistic regression, and Cox regression analyses emphasized the clinical prognostic significance of high KRT80 expression in LUAD. Nomogram results underscored the robust predictive potential of KRT80 for the survival of LUAD patients. Gene functional enrichment analyses mainly associated KRT80 with cytokine-cytokine receptor interactions, cell cycle, apoptosis, and chemokine signaling pathways. Based on the results of the immune infiltration analysis, it can be found that the expression of KRT80 is related to the immune cell subsets and survival rate of patients with LUAD., Conclusion: Our research revealed a significant upregulation of KRT80 in LUAD, with heightened KRT80 expression correlating with unfavorable prognosis. This study represents a comprehensive and systematic evaluation of KRT80 expression in LUAD, encompassing its prognostic and diagnostic significance, as well as underlying mechanisms. Our findings suggest that KRT80 may emerge as a novel prognostic and predictive biomarker in LUAD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Radiation-induced lung toxicity, including radiation pneumonitis and pulmonary fibrosis, often occurs in patients receiving radiation therapy. Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays critical roles in radiation-induced lung toxicity. In the present study, RNA sequencing was applied to examine the whole transcriptomes of human pulmonary AEC cells (HPAEpiC) with or without radiation treatment. We found that cytokine, chemokine and cell adhesion signaling pathways were enriched in radiation-treated cells. CCL2 (C-C Motif Chemokine Ligand 2), CCL5 and CCR4 (C-C Motif Chemokine Receptor 4) were among the top enriched genes in chemokine signaling pathway. The upregulation of CCL2, CCL5 and CCR4 in response to irradiation was confirmed at both mRNA and protein levels by real-time PCR, western blotting and enzyme-linked immunosorbent assay analyses. Ophiopogonin B, a bioactive ingredient of Radix Ophiopogon japonicas , was found to attenuate radiation-induced EMT in HPAEpiC cells as demonstrated by the alteration in cell morphology, and the expression of E-cadherin and Vimentin. Ophiopogonin B could also reduce radiation-induced expression of CCL2, CCL5, CCR4 and phosphorylated ERK (p-ERK). Moreover, CCR4 knockdown, U0126 (a MEK/ERK inhibitor) or ophiopogonin B also partially blocked the EMT promoting effects of CCL2 and CCL5. Our data suggested CCL2, CCL5 and CCR4 may be potential therapeutic targets for radiation-induced lung toxicity. Ophiopogonin B, which could down-regulate CCL2, CCL5 and CCR4, may be a useful radioprotective agent., Competing Interests: None.