Puerarin suppresses macrophage M1 polarization to alleviate renal inflammatory injury through antagonizing TLR4/MyD88-mediated NF-κB p65 and JNK/FoxO1 activation.

BACKGROUND: Acute kidney injury (AKI) is a clinically common and serious renal dysfunction, characterized by inflammation and damage to tubular epithelial cells. Puerarin, an isoflavone derivative isolated from Pueraria lobata, has been proven to possess exceptional effectiveness in reducing inflammation. However, the effects and underlying mechanisms of puerarin on AKI remain uncertain. PURPOSE: This study investigated the possible therapeutic effects of puerarin on AKI and explored its underlying mechanism. STUDY DESIGN AND METHODS: The effects of puerarin on AKI and macrophage polarization were investigated in lipopolysaccharide (LPS)-induced or unilateral ureteral obstruction (UUO)-induced mouse models in vivo and LPS-treated macrophages (Raw264.7) in vitro. Additionally, the effects of puerarin on inflammation-related signaling pathways were analyzed. RESULTS: Administration of puerarin effectively alleviated kidney dysfunction and reduced inflammatory response in LPS-induced and UUO-induced AKI. In vitro, puerarin treatment inhibited the polarization of M1 macrophages and the release of inflammatory factors in Raw264.7 cells stimulated by LPS. Mechanistically, puerarin downregulated the activities of NF-κB p65 and JNK/FoxO1 signaling pathways. The application of SRT1460 to activate FoxO1 or anisomycin to activate JNK eliminated puerarin-mediated inhibition of JNK/FoxO1 signaling, leading to suppression of macrophage M1 polarization and reduction of inflammatory factors. Further studies showed that puerarin bound to Toll/interleukin-1 receptor (TIR) domain of MyD88 protein, hindering its binding with TLR4, ultimately resulting in downstream NF-κB p65 and JNK/FoxO1 signaling inactivation. CONCLUSIONS: Puerarin antagonizes NF-κB p65 and JNK/FoxO1 activation via TLR4/MyD88 pathway, thereby suppressing macrophage polarization towards M1 phenotype and alleviating renal inflammatory damage.

Characterization of a predictive signature for tumor microenvironment and immunotherapy response in hepatocellular carcinoma involving neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) and other factors play a significant role in impacting the prognosis of patients with Hepatocellular carcinoma (HCC). Nevertheless, further research is warranted to fully elucidate the prognostic implications of NETs in patients with HCC. We employed a hierarchical clustering technique to examine the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data and identified subtypes associated with NETs. Subsequently, we utilized LASSO regression analysis to identify a distinct gene expression pattern within these subtypes. The strength of this signature was further validated through analysis of TCGA-LIHC and International Cancer Genome Consortium-Liver Cancer (ICGC-LIRI-JP) data. Our findings resulted in the construction of a six-gene signature related to NETs, which can predict survival outcomes in HCC patients. To enhance the predictive accuracy of our tool, we developed a nomogram that integrates the NETs signature with clinicopathological characteristics. We validated the significance of NETs in HCC patients using qRT-PCR and immunohistochemistry assays, along with in vitro experiments targeting high-risk genes. Furthermore, our exploration of the immune microenvironment uncovered augmented immune-specific metrics within the low-risk cohort, implying potential disparities in immune-related attributes between the high-risk and low-risk contingents. In summary, the NETs signature we discovered serves as a valuable biomarker and provides guidance for personalized therapy in HCC patients.

Investigating the impact of inflammatory response-related genes on renal fibrosis diagnosis: a machine learning-based study with experimental validation.

Renal fibrosis plays a crucial role in the progression of renal diseases, yet the lack of effective diagnostic markers poses challenges in scientific and clinical practices. In this study, we employed machine learning techniques to identify potential biomarkers for renal fibrosis. Utilizing two datasets from the GEO database, we applied LASSO, SVM-RFE and RF algorithms to screen for differentially expressed genes related to inflammatory responses between the renal fibrosis group and the control group. As a result, we identified four genes (CCL5, IFITM1, RIPK2, and TNFAIP6) as promising diagnostic indicators for renal fibrosis. These genes were further validated through in vivo experiments and immunohistochemistry, demonstrating their utility as reliable markers for assessing renal fibrosis. Additionally, we conducted a comprehensive analysis to explore the relationship between these candidate biomarkers, immunity, and drug sensitivity. Integrating these findings, we developed a nomogram with a high discriminative ability, achieving a concordance index of 0.933, enabling the prediction of disease risk in patients with renal fibrosis. Overall, our study presents a predictive model for renal fibrosis and highlights the significance of four potential biomarkers, facilitating clinical diagnosis and personalized treatment. This finding presents valuable insights for advancing precision medicine approaches in the management of renal fibrosis.Communicated by Ramaswamy H. Sarma.

Fabrication and biocompatibility investigation of TiO(2) films on the polymer substrates obtained via a novel and versatile route.

Titanium oxide (TiO(2)) films were successfully deposited onto the polymer substrates of polytetrafluoroethylene (PTFE), polyethylene (PE), and polyethylene terephthalate (PET), which were pre-modified with polydopamine coating (polydopamine and its coating are coded as PDA and PDAc, respectively), by a simple liquid phase deposition (LPD) process. The morphology and chemical state of the obtained TiO(2) films were characterized by field emission scanning electron microscope (FE-SEM) and X-ray photoelectron spectroscopy (XPS), respectively. Subsequently, the biocompatibility of the samples was investigated by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay and acridine orange staining of MC-3T3 osteoblast cells, and the results demonstrated that the fabricated TiO(2) films could markedly improve the in vitro cytocompatibility. So, the presented route is anticipated to be a promising surface modification methodology to improve the practical outcome of the implanted materials for its versatility and validity.