Abstract Background: Heart failure is a complex clinical syndrome, and there is growing evidence that ferroptosis is related to heart failure. This study sought to identify a new diagnostic model for ferroptosis-related genes in heart failure patients and analyze the signature genes associated with ferroptosis in heart failure. Methods: The ferroptosis-related genes were found on the FerrDbwebsite, and the heart failure microarray datasets (GSE5406, GSE57338, GSE1145) were screened from the GEO database. The "limma" package in R software was then used to analyze the ferroptosis-related differentially expressed genes (DEGs), and functional enrichment analysis was carried out for ferroptosis-related DEGs. The differentially expressed ferroptosis-related genes were then screened using LASSO regression and SVM-RFE algorithms. The intersection was then used to get the signature genes. The signature genes served as the foundation for the diagnostic model. The diagnostic model was created using a nomogram and receiver operating characteristic curve (ROC), and the model's precision was assessed. The expression of the signature genes' signaling pathways was examined using GSEA. The CIBERSORT algorithm was then used to analyze immune cell infiltration and correlation analysis in the immune systems of heart failure patients. Finally, the testing set was used to evaluate the diagnostic and predictive value of signature genes in heart failure. Results: The training set (GSE5406) was used to screen 127 ferroptosis-related differentially expressed genes, including 44 up-regulated and 83 down-regulated genes. Ferroptosis was significantly enriched for genes that were differentially expressed according to KEGG analysis, and oxidative stress was significantly enriched in genes according to GO-BP analysis. A diagnostic model and nomogram were successfully constructed based on the five differential genes with an area under the curve (AUC):0.952 (95% CI: 0.894-0.993), using the diagnostic model to differentiate between the normal control group and the heart failure group. Five ferroptosis-related differential genes (BECN1, SLC39A14, QSOX1, DAZAP1, TMSB4X) were screened and identified. Additionally, CD4-naive T cells were discovered to be related to heart failure patients. Finally, the diagnostic performance in the testing set (GSE57338, GSE1145) was confirmed, further demonstrating the accuracy and reliability of the study's findings. Conclusion: A novel diagnostic model with significant value for heart failure was successfully established after five ferroptosis-related genes were screened and identified. Additionally, it might be beneficial for treating patients with heart failure and aid in understanding the part ferroptosis plays in the pathogenesis of the condition.
Abstract The simultaneous application of photothermal therapy (PTT) and photodynamic therapy (PDT) offers substantial advantages in cancer treatment. However, their synergistic anticancer efficacy is often limited by tumor hypoxia, and thermotolerance induced by high expression of heat shock proteins (HSP). Fortunately, hydrogen sulfide (H 2 S), known for its direct cytotoxic effect on tumor cells, has been recognized for its ability to enhance PTT and PDT. The effectiveness of H 2 S in these therapies is challenged by its low loading efficiency, poor stability, and short diffusion distance. To address these issues, a nanoscale emulsion drop template created through the salting‐out effect is employed to construct a robust H 2 S delivery system. Polydopamine (PDA), chosen for its interfacial polymerization tendency and excellent photothermal conversion rate, is utilized as a carrier for the H 2 S donor (ADT) and Zinc phthalocyanine (ZnPc) to fabricate a novel nanomedicine termed APZ NPs. The temperature‐responsive APZ NPs are designed to release H 2 S during the PTT process. Elevated H 2 S levels promoted vasodilation, thereby enhancing the enhanced permeability and retention effect (EPR) of APZ NPs within solid tumors. This strategy effectively alleviated tumor hypoxia by disrupting the mitochondrial respiratory chain and mitigated tumor cell heat tolerance by inhibiting HSP expression.
Copper (Cu) pollution is one of environmental problems that adversely affects the growth and development of plants. However, knowledge of lignin metabolism associated with Cu-induced phytotoxicity mechanism is insufficient. The objective of this study was to reveal the mechanisms underlying Cu-induced phytotoxicity by evaluating changes in the photosynthetic characteristics and lignin metabolism in the seedlings of wheat cultivar 'Longchun 30'. Treatment with varying concentrations of Cu clearly retarded seedling growth, as demonstrated by a reduction in the growth parameters. Cu exposure reduced the photosynthetic pigment content, gas exchange parameters, and chlorophyll fluorescence parameters, including the maximum photosynthetic efficiency, potential efficiency of photosystem II (PS II), photochemical efficiency of PS II in light, photochemical quenching, actual photochemical efficiency, quantum yield of PS II electron transport, and electron transport rate, but notably increased the nonphotochemical quenching and quantum yield of regulatory energy dissipation. Additionally, a significant increase was observed in the amount of cell wall lignin in wheat leaves and roots under Cu exposure. This increase was positively associated with the up-regulation of enzymes related to lignin synthesis, such as phenylalanine ammonia-lyase, 4-coumarate:CoA ligase, cinnamyl alcohol dehydrogenase, laccase, cell wall bound (CW-bound) guaiacol peroxidase, and CW-bound conifer alcohol peroxidase, and TaPAL, Ta4CL, TaCAD, and TaLAC expression. Correlation analysis revealed that lignin levels in the cell wall were negatively correlated with the growth of wheat leaves and roots. Taken together, Cu exposure inhibited photosynthesis in wheat seedlings, resulting from a reduction in photosynthetic pigment content, light energy conversion, and photosynthetic electron transport in the leaves of Cu-stressed seedlings, and the Cu-inhibitory effect on seedling growth was related to the inhibition of photosynthesis and an increase in cell wall lignification.
The aim of this study was to determine the effects of VEGF treatment on focal cerebral ischemia in rats. Rats were administered PBS or VEGF at concentrations of 10, 20 or 30 µg/ml. The effects of VEGF on the rat infarct volume and neurological deficits were investigated. Transmission electron microscopy was used to observe the ultrastructure of the cerebral cortex. Treatments with VEGF reduced the infarct volume and improved neurological functions. VEGF increased microvessel generation and also inhibited apoptosis in the cerebral cortex and basal ganglia. For the rats in the 30 µg/ml VEGF group, an even higher number of proliferative endothelial cells were observed by electron microscopy. In conclusion, VEGF treatment has protective effects on focal cerebral ischemia in rats.
The incidence of stroke in young adults has a trend of increasing year by year, and its etiology and risk factors are more complex than those in the traditional stroke in the elderly. This article reviews the clinical research in this field.
Key words:
Stroke; Brain ischemia; Etiology; Risk factors; Adolescent
The aim of the current study was to examine the prognostic value of copeptin for acute intracerebral hemorrhage (ICH) patients. A total of 120 patients were recruited. The plasma copeptin levels were measured using sandwich immunoassays. The hematoma volume, Glasgow coma scale (GCS) and ICH score were evaluated. The 90-day functional outcomes were measured with the modified Rankin scale (mRS). Copeptin correlated positively with hematoma volume (r=0.61, P=0.000), Hemphill scores (r=0.78, P=0.000) and white blood cell counts (r=0.58, P=0.000), whereas copeptin correlated negatively with GCS scores (r=-0.79, P=0.000). Copeptin levels were also higher in patients with an unfavorable functional outcome at 90 days than in patients with a favorable outcome (4.14±0.87 vs. 3.09±0.30 ng/ml; t=8.001, P=0.00). Monovariate logistic regression analysis results suggest that copeptin is a predictor of the 90-day functional outcomes of ICH patients (OR=3.17, 95% CI 2.01-4.35, P=0.003. Multivariate logistic regression analysis results indicate that copeptin is an independent predictor of the 90-day functional outcomes of ICH patients.
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