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Fei Yan

Publications and source records attributed to Fei Yan.

3 recordsLinked to original sources

Ergothioneine Alleviated the Apoptosis of HK Cells by Regulating Ferroptosis.

INTRODUCTION/OBJECTIVE: Ergothioneine (EGT) is a naturally occurring antioxidant with protective effects on various human cell types. The impact of this substance on HK-2 cells, a human renal proximal tubular epithelial cell line, and the associated molecular mechanisms remain incompletely elucidated. METHODS: The present study aims to elucidate the effects of EGT on apoptosis induced by RAS-selective Lethal Molecule 3 (RSL3) and Erastin in HK-2 cells, as well as the potential mechanisms involved. The renal cortical proximal tubular epithelial HK-2 cells were cultured and exposed to RSL3 and Erastin, with or without EGT treatment. Cell viability and apoptosis were assessed using the Cell Counting Kit-8 (CCK-8) assay, while the detection of ferrous ion content and mitochondrial membrane potential changes was accomplished through the utilisation of flow cytometry and the JC-1 staining method, respectively. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, proteomic analysis, and western blotting were employed to explore the molecular pathways involved. RESULTS: The data demonstrated that RSL3 and Erastin exhibited a substantial inhibitory effect on HK-2 cell proliferation, concomitant with the accumulation of intracellular ferrous ions and a shift in mitochondrial membrane potential. The EGT treatment effectively mitigated RSL3- and Erastin-induced apoptosis in HK-2 cells. GO and KEGG enrichment analysis demonstrated that EGT suppressed pathways and functions associated with oxidative stress during ferroptosis. Proteomics analysis further demonstrated that EGT modulated various biological processes, molecular functions, and cellular components in HK-2 cells. The protective mechanism of EGT against RSL3- and Erastin-induced HK-2 cells was potentially mediated through regulation of ferroptosis. The results of the western blot analysis demonstrated that EGT modulated the expression levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 member 11 (SLC7A11) in HK-2 cells. CONCLUSION: These data demonstrated that EGT exerts an alleviating effect on the apoptosis of HK-2 cells induced by RSL3 and Erastin by modulating ferroptosis. These findings suggest that EGT has the potential to serve as a therapeutic candidate for the treatment of kidney diseases in the future.

Ergothioneine

Inflammatory Serum Olink Proteomics in Cancer-Related Pain Treated with Opioids: A Pilot Cross-Sectional and Longitudinal Study.

Opioid analgesia shows substantial interindividual variability in cancer patients, yet the underlying serum inflammatory alterations remain poorly characterized. This study collected plasma samples from 44 cancer pain patients before and after opioid initiation, quantifying 92 immunoinflammation proteins by Olink proteomics. Cross-sectional analysis identified nine differentially expressed proteins between responders and nonresponders. A five-protein nomogram involving TGF-α, EN-RAGE, CASP-8, ST1A1, and IL-10RA demonstrated superior predictive performance for opioid efficacy (AUC 0.902) compared to traditional CRP (AUC 0.625). Longitudinal analysis of this population revealed upregulation of β-NGF, MCP-4, IL-1alpha, and IL-13, and downregulation of CD6, IL-12beta, and SCF after treatment. STRING analysis clustered these proteins into three functional groups: efficacy-related (NGF), bowel-inflammation-related (IL-12/IL-13), and CD6-related. Notably, expression of IL-12β showed a significant efficacy-constipation interaction: constipation completely reversed the efficacy-IL-12 association, and higher IL-12 levels predicted favorable response only in nonconstipated patients. These findings established a pretreatment protein signature for predicting opioid efficacy and revealed systemic immune reprogramming following opioid therapy.

Humans

Novel Genetic Loci in Early-Onset Gout Derived From Whole-Genome Sequencing of an Adolescent Gout Cohort.

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset &#x2264;30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 &#xd7; 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

Humans