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Abundant evidence has indicated that the prognosis of cutaneous melanoma (CM) patients is highly complicated by the tumour immune microenvironment. We retrieved the clinical data and gene expression data of CM patients in The Cancer Genome Atlas (TCGA) database for modelling and validation analysis. Based on single-sample gene set enrichment analysis (ssGSEA) and consensus clustering analysis, CM patients were classified into three immune level groups, and the differences in the tumour immune microenvironment and clinical characteristics were evaluated. Seven immune-related CM prognostic molecules, including three mRNAs (SUCO, BTN3A1 and TBC1D2), three lncRNAs (HLA-DQB1-AS1, C9orf139 and C22orf34) and one miRNA (hsa-miR-17-5p), were screened by differential expression analysis, ceRNA network analysis, LASSO Cox regression analysis and univariate Cox regression analysis. Their biological functions were mainly concentrated in the phospholipid metabolic process, transcription regulator complex, protein serine/threonine kinase activity and MAPK signalling pathway. We established a novel prognostic model for CM integrating clinical variables and immune molecules that showed promising predictive performance demonstrated by receiver operating characteristic curves (AUC ≥ 0.74), providing a scientific basis for predicting the prognosis and improving the clinical outcomes of CM patients. [ABSTRACT FROM AUTHOR]

Abundant evidence has indicated that the prognosis of cutaneous melanoma (CM) patients is highly complicated by the tumour immune microenvironment. We retrieved the clinical data and gene expression data of CM patients in The Cancer Genome Atlas (TCGA) database for modelling and validation analysis. Based on single-sample gene set enrichment analysis (ssGSEA) and consensus clustering analysis, CM patients were classified into three immune level groups, and the differences in the tumour immune microenvironment and clinical characteristics were evaluated. Seven immune-related CM prognostic molecules, including three mRNAs (SUCO, BTN3A1 and TBC1D2), three lncRNAs (HLA-DQB1-AS1, C9orf139 and C22orf34) and one miRNA (hsa-miR-17-5p), were screened by differential expression analysis, ceRNA network analysis, LASSO Cox regression analysis and univariate Cox regression analysis. Their biological functions were mainly concentrated in the phospholipid metabolic process, transcription regulator complex, protein serine/threonine kinase activity and MAPK signalling pathway. We established a novel prognostic model for CM integrating clinical variables and immune molecules that showed promising predictive performance demonstrated by receiver operating characteristic curves (AUC ≥ 0.74), providing a scientific basis for predicting the prognosis and improving the clinical outcomes of CM patients. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum–gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum–gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA. [ABSTRACT FROM AUTHOR]

In biomedical data mining, the gene dimension is often much larger than the sample size. To solve this problem, we need to use a feature selection algorithm to select feature gene subsets with a strong correlation with phenotype to ensure the accuracy of subsequent analysis. This paper presents a new three-stage hybrid feature gene selection method, that combines a variance filter, extremely randomized tree, and whale optimization algorithm. First, a variance filter is used to reduce the dimension of the feature gene space, and an extremely randomized tree is used to further reduce the feature gene set. Finally, the whale optimization algorithm is used to select the optimal feature gene subset. We evaluate the proposed method with three different classifiers in seven published gene expression profile datasets and compare it with other advanced feature selection algorithms. The results show that the proposed method has significant advantages in a variety of evaluation indicators. [ABSTRACT FROM AUTHOR]

RNA modification is a key regulatory mechanism involved in tumorigenesis, tumor progression, and the immune response. However, the potential role of RNA modification "writer" genes in the immune microenvironment of gliomas and their effect on the response to immunotherapy remains unclear. The purpose of this study was to evaluate the role of RNA modification "writer" gene in the prognosis and immunotherapy response of low-grade glioma (LGG). The consensus non-negative matrix factorization (CNMF) method was used to identify different RNA modification subtypes. We used a novel eigengene screening method, the variable neighborhood learning Harris Hawks optimizer (VNLHHO), to screen for eigengenes among the RNA modification subtypes. We constructed a principal components analysis score(PCA_score)-based prognostic prediction model and validated it using an independent cohort. We also analyzed the association between PCA_score and the immune and molecular features of LGG. The results suggested that LGG can be divided into two different RNA modification-based subtypes with distinct prognostic and molecular features. High PCA_score was significantly associated with a poor prognosis in LGG and was an independent prognostic factor. A nomogram containing PCA_score and clinical features was constructed, and it showed a significant predictive value. PCA_score was negatively correlated with tumor purity and the abundance of CD4+ T cells in LGG patients. LGG patients with high PCA_score had lower Tumor Immune Dysfunction and Exclusion scores and showed an immunotherapy response. In conclusion, we report a novel RNA modification-based prognostic model for LGG that lays the foundation for evaluating LGG prognosis and developing more effective therapeutic strategies for these tumors. [ABSTRACT FROM AUTHOR]

• Overcoming the blood-spinal cord barrier to deliver prodrug. • In situ release of prodrug in response to reactive oxygen species. • Realizing multifunctional synergistic treatment of spinal cord injuries. Secondary injury has a tremendous impact on the recovery of motor function after traumatic spinal cord injury (SCI). The microenvironmental reactive oxygen species (ROS) and inflammatory bursts in the spinal cord tissues cause secondary injury that can further lead to neuronal apoptosis, which in turn exacerbates the loss of mobility and sensory function. Due to the presence of the blood–spinal cord barrier (BSCB), current clinical medicine is unable to effectively improve the microenvironment after SCI at a safe dose. In this experiment, macrophage membrane-modified ROS-responsive self-assembled methylprednisolone-S-docosahexaenoic acid prodrug nanoparticles (MΦ@MP-S-DHA) were designed to achieve targeted therapy across the BSCB. The monosulfide bond (-S-) responds to ROS in situ and attenuates ROS levels while releasing methylprednisolone (MP) and docosahexaenoic acid (DHA), which exert anti-inflammatory and neuroprotective effects. In vitro experiments have shown that MΦ@MP-S-DHA is released more rapidly by ROS. Cellular and mouse experiments further illustrated that MΦ@MP-S-DHA reduced ROS, malondialdehyde (MDA) and superoxide anion levels and maintained superoxide dismutase (SOD) activity after SCI. Moreover, MΦ@MP-S-DHA reduced the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and the levels of apoptotic factors (caspase-3 and cleaved caspase-3) after SCI. On the 28th day, the SCI mice treated with MΦ@MP-S-DHA achieved a BMS score of 6 and better recovery of hindlimb movement. Therefore, MΦ@MP-S-DHA provides a potential therapeutic strategy to effectively exert multifaceted improvements in the microenvironment after SCI. [ABSTRACT FROM AUTHOR]

[Display omitted] • GSH-AuNCs were found to accumulate endogenous zinc in the injured spinal cord. • A new mechanism based on the accumulation of endogenous zinc in the treatment of SCI was proposed. • Endogenous zinc accumulation stimulates immunotherapy. • R. The proposed treatment has memory therapeutic effects. Spinal cord injury (SCI) can cause very serious bodily harm or even paralysis. However, all clinical drugs require long-term use to relieve the disease, causing toxicity and side effects. Zinc tends to activate the self-defense system to repair SCI, but the currently reported zinc supplementation is not efficient to cure SCI due to the poor targeting effects. The zinc delivery system has been employed to improve the targeting efficiency, which also increases the complexity and toxicity of drugs. On the other hand, we envisage that if there is a drug that can accumulate and activate endogenous zinc in the lesions of the spinal cord and stimulate immunotherapy, it can not only reduce long-term drug dependence but also significantly improve the therapeutic effect on SCI. Herein, we found zinc deficiency for SCI mice, but more zinc accumulated in the lesions of the spinal cord after the administration of GSH-AuNCs in SCI mice. Meanwhile, more microglia/macrophages polarize toward M2 from M1 phenotypes after zinc accumulation which enhances immunotherapy effects. Thereafter, the inflammatory response was inhibited, which exerts a neuroprotective effect. As well as this, the current treatment showed memory effects for zinc accumulation even after stopping the drug administration, allowing endogenous zinc to continue its induction of multiple therapeutic effects. Due to the direct and memory curative function, the lesions of SCI mice were well recovered and the motor functions were also significantly improved. [ABSTRACT FROM AUTHOR]