Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with renal cell carcinoma.

BACKGROUND: There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC). OBJECTIVE: We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs). METHODS: Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature. CONCLUSION: The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.

CACNA1C mutation as a prognosis predictor of immune checkpoint inhibitor in skin cutaneous melanoma.

Aims: There is an urgent need for appropriate biomarkers that can precisely and reliably predict immunotherapy efficacy, as immunotherapy responses can differ in skin cutaneous melanoma (SKCM) patients. Methods: In this study, univariate regression models and survival analysis were used to examine the link between calcium voltage-gated channel subunit alpha 1C (CACNA1C) mutation status and immunotherapy outcome in SKCM patients receiving immunotherapy. Mutational landscape, immunogenicity, tumor microenvironment and pathway-enrichment analyses were also performed. Results: The CACNA1C mutation group had a better prognosis, higher immunogenicity, lower endothelial cell infiltration, significant enrichment of antitumor immune response pathways and significant downregulation of protumor pathways. Conclusion: CACNA1C mutation status is anticipated to be a biomarker for predicting melanoma immunotherapy effectiveness.

Aims: The treatment to make the immune system work better is also used to treat a skin cancer called skin cutaneous melanoma (SKCM). We need new ways to predict if the treatment will work. Methods: We looked at two groups of people getting the treatment to make the immune system work better. One group had a special change in their bodies, and the other group did not. We looked at how this change affected the patients. We also looked at how to make their immune system stronger. Results: We found that people with mutations tend to have better chances of getting better from their sickness. Conclusion: We think that this might be a good way to tell if immunotherapy will work well for this type of SKCM.

Structural characteristics, functional properties, antioxidant and hypoglycemic activities of pectins from feijoa (Acca sellowiana) peel.

The structure characteristics, functional properties, antioxidant and hypoglycemic activities of pectins extracted from feijoa peel with water (FP-W), acid (FP-A) and alkali (FP-B) were investigated. Results showed that the feijoa peel pectins (FPs) were mainly composed of galacturonic acid, arabinose, galactose and rhamnose. FP-W and FP-A had higher proportion of homogalacturonan domain, degree of esterification and molecular weight (for main component) than FP-B; FP-B owned the highest yield, protein and polyphenol contents. FP-W had a compact and smooth surface morphology unlike FP-A and FP-B. FP-W and FP-A had better thermal stability than FP-B. The rheological analysis suggested that the FPs exhibited pseudoplastic fluid behavior, and the elastic characteristics were dominant. Results showed that FP-W and FP-B had superior antioxidant and hypoglycemic activities than FP-A. According to correlation analysis, monosaccharide composition, sugar ratios and degree of acetylation were chief factors affecting the functional properties, antioxidant and hypoglycemic activities of the FPs.

Mutations Status of NOTCH Signaling Pathway Predict Prognosis of Immune Checkpoint Inhibitors in Colorectal Cancer.

Purpose: In recent years, tumour immunotherapy has ushered in a new era of oncology treatment. However, the use of immune checkpoint inhibitors (ICIs) in the treatment of CRC remains limited. There is an urgent clinical need for precise biomarkers that can aid in the screening and treatment of CRC subtypes. Therefore, we focused on the NOTCH pathway mutation status and conducted a systematic analysis for its predictive value of ICI therapy efficacy. Methods: We collected mutational and clinical data from cohorts of CRC patients treated with ICIs. The relationship between NOTCH pathway mutations (NOTCH-MT) and CRC immunotherapy prognosis was analysed using univariate and multivariate Cox regression models. CRC cohort data from The Cancer Genome Atlas (TCGA) database were combined to obtain a comprehensive overview of immunogenicity and tumour microenvironment (TME) differences among different NOTCH pathway mutation statuses. Results: We observed greater infiltration of M1 macrophages, CD8+ T cells, neutrophils, and activated natural killer (NK) cells with NOTCH-MT status. Immunogenicity was also significantly higher in patients with NOTCH-MT, as were tumour mutational burden (TMB), neoantigen load (NAL), and the number of mutations in DNA damage repair (DDR) pathways. Conclusion: NOTCH-MT status was strongly associated with the prognosis of CRC patients treated with ICIs and is expected to serve as a novel biomarker and therapeutic target for CRC.

Chemical structure and antioxidant activity of a neutral polysaccharide from Asteris Radix et Rhizoma.

Asteris Radix et Rhizoma (AR) has been widely used as a herbal medicine for treating various symptoms and possesses a number of bioactivities. A neutral polysaccharide ARP-1 was isolated from AR with weight-average molecular weight of 214 kDa. The heteropolysaccharide ARP-1 was composed of fucose, arabinose, galactose, glucose and mannose with a molar ratio of 0.40:14.25:10.22:1.06:0.41. Linkage and NMR analysis showed that ARP-1 had a backbone containing →3,6)-ß-d-Galp-(1→ and →6)-ß-d-Galp-(1 â†’ residues, and oligosaccharide side chains containing Araf and Galp units were attached to the backbone at C-3 of →3,6)-ß-d-Galp-(1 â†’ residues. Antioxidant activity assays showed that ARP-1 exhibited potent antioxidant activities, including ABTS, hydroxy and DPPH radicals scavenging and reducing power. Besides, ARP-1 decreased the production of ROS and MDA, and improved the activities of SOD, which resulted in the protection of PC12 cells against H2O2-induced oxidative stress. The findings indicated that ARP-1 might be used as a potential natural antioxidant.