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Introduction: The relationship between the expression of opioid-associated receptors and cancer outcomes is complex and varies among studies.Methods: This study focused on six opioid-related receptors (OPRM1, OPRD1, OPRK1, OPRL1, OGFR, and TLR4) and their impact on cancer patient survival. Bioinformatics analysis was conducted on 33 cancer types from The Cancer Genome Atlas database to examine their expression, clinical correlations, mechanisms in the tumor microenvironment, and potential for immunotherapy. Due to significantly lower expression of OPRM1, OPRD1, and OPRK1 compared to OGFR and TLR4, the analysis concentrated on the latter two genes.Results: OGFR was highly expressed in 16 tumor types, while TLR4 showed low expression in 13. Validation from external samples, the Gene Expression Omnibus, and the Human Protein Atlas supported these findings. The diagnostic value of these two genes was demonstrated using the Genotype-Tissue Expression database. Univariate Cox regression models and Kaplan-Meier curves confirmed OGFR's impact on prognosis in a cancer type-specific manner, while high TLR4 expression was associated with a favorable prognosis. Analysis of the tumor microenvironment using a deconvolution algorithm linked OGFR to CD8+ T cells and TLR4 to macrophages. Single-cell datasets further validated this correlation. In 25 immune checkpoint blockade treatment cohorts, TLR4 expression showed promise as an immunotherapy efficacy predictor in non-small cell lung cancer, urothelial carcinoma, and melanoma.Conclusion: In a pan-cancer analysis of 33 tissues, OGFR was consistently highly expressed, while TLR4 had low expression. Both genes have diagnostic and prognostic significance and are linked to immune cells in the tumor microenvironment. TLR4 has potential as an immunotherapeutic response marker. [ABSTRACT FROM AUTHOR]

Fish skin is the first barrier against external invasion, and also an important interface for communication between males and females during reproduction. Nonetheless, sexual dimorphism in the physiology of fish skins is still poorly understood. Herein, transcriptomes of skin were comparatively analysed between males and females in spinyhead croaker, Collichthys lucidus. Totally, 170 differentially expressed genes (DEG) were detected, including 79 female‐biased genes and 91 male‐biased genes. Gene ontology (GO) annotation items of the DEGs were mainly enriched in biological process items (86.2%), including regulation of biological processes, responses to chemical and biological stimuli, transport and secretion, movement, immune response, tissue development, etc. In KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis, the male‐biased genes were enriched in pathways including those related to immunity such as the TNF signalling pathway and IL‐17 signalling pathway, whereas the female‐biased genes were enriched in pathways including those related to female steroids such as ovarian steroidogenesis and oestrogen signalling pathway. In addition, odf3 was found to be a male‐specific expression gene, being a candidate marker for phenotypic sex. Thus, the sexual difference in gene expression in fish skin in spawning season was uncovered by transcriptome analysis for the first time, providing new insights into sexual dimorphism in the physiology and functions of fish skin. [ABSTRACT FROM AUTHOR]

Cystic fibrosis is characterized by recurring pulmonary exacerbations that lead to the deterioration of lung function and eventual lung failure. Excessive inflammatory responses by airway epithelia have been linked to the overproduction of the inflammatory cytokine IL-6 and IL-8. The mechanism by which this occurs is not fully understood, but normal IL-1β mediated activation of the production of these cytokines occurs via H2O2 dependent signaling. Therefore, we speculated that CFTR dysfunction causes alterations in the regulation of steady state H2O2. We found significantly elevated levels of H2O2 in three cultured epithelial cellmodels of CF, one primary and two immortalized. Increases in H2O2 heavily contributed to the excessive IL-6 and IL-8 production in CF epithelia. Proteomic analysis of three in vitro and two in vivo models revealed a decrease in antioxidant proteins that regulate H2O2 processing, by ≥2 fold in CF vs. matched normal controls. When cells are stimulated, differential expression in CF versus normal is enhanced; corresponding to an increase in H2O2 mediated production of IL-6 and IL-8. The cause of this redox imbalance is a decrease by ∼70% in CF cells versus normal in the expression and activity of the transcription factor Nrf-2. Inhibition of CFTR function in normal cells produced this phenotype, while N-acetyl cysteine, selenium, an activator of Nrf-2, and the overexpression of Nrf-2 all normalized H2O2 processing and decreased IL-6 and IL-8 to normal levels, in CF cells. We conclude that a paradoxical decrease in Nrf-2 driven antioxidant responses in CF epithelia results in an increase in steady state H2O2, which in turn contributes to the overproduction of the pro-inflammatory cytokines IL-6 and IL-8. Treatment with antioxidants can ameliorate exaggerated cytokine production without affecting normal responses. [ABSTRACT FROM AUTHOR]