Background: Polycystic ovary syndrome (PCOS) is a highly heterogeneous endocrine-metabolic disorder. Ovarian stromal cells influence follicular development and ovulation by secreting cytokines. Glycolysis, a central pathway of glucose metabolism, plays a crucial role in the pathogenesis of PCOS. However, the precise mechanisms underlying dysregulated glycolysis in ovarian stromal cells in PCOS remain unclear.Methods: Seurat and CellChat were employed to analyze single-cell RNA sequencing (scRNA-seq) data, incorporating glycolysis scoring and cell-cell communication analysis. Three independent bulk RNA-seq datasets were integrated to identify key genes. Immune infiltration was assessed using CIBERSORT, ESTIMATE, and ssGSEA algorithms. Functional enrichment analysis (GO, KEGG, and Hallmark) was performed to annotate PLK2-related pathways. Finally, a dehydroepiandrosterone (DHEA)-induced PCOS rat model was constructed to validate the critical role of PLK2 expression in PCOS.Results: Single-cell sequencing analysis revealed that endothelial cells in the ovarian stroma of PCOS exhibited the highest glycolytic activity and increased intercellular communication, particularly interacting with fibroblasts via the PPIA-BSG ligand-receptor pair. Integrated transcriptomic analysis identified PLK2 as a central regulatory gene of endothelial glycolysis (AUC > 0.85). Functional enrichment analysis further demonstrated that high PLK2 expression was closely associated with extracellular matrix (ECM) remodeling and promoted chronic inflammation and ovarian fibrosis by activating the NF-κB and IL-17 signaling pathways. Immune infiltration analysis indicated that PCOS patients with high PLK2 expression exhibited enhanced pro-inflammatory responses, increased neutrophil recruitment, and impaired T-cell function, suggesting a shift toward an inflammatory ovarian microenvironment. The DHEA-induced PCOS rat model further confirmed the critical role of PLK2 in disease progression and glycolytic dysregulation.Conclusion: This study establishes PLK2 as a key regulator of glycolysis and immune imbalance in PCOS, highlighting its pivotal role in the metabolic-immune crosstalk within the ovarian microenvironment. These findings suggest that targeting PLK2 may be a potential therapeutic strategy for alleviating glycolytic dysregulation and chronic inflammation in PCOS.
Mitochondrial dysfunction and oxidative damage are closely related to the pathogenesis of Parkinson's disease (PD). The pharmacological mechanism of protocatechuic aldehyde (PCA) for PD treatment have retained unclear. The purposes of the present study were to clarify the neuroprotective effects of post-treatment of PCA for PD treatment by mitigating mitochondrial dysfunction and oxidative damage, and to further determine whether its effects were mediated by the polo-like kinase 2/phosphorylated glycogen synthase kinase 3 β/nuclear factor erythroid-2-related factor 2 (PLK2/p-GSK3β/Nrf2) pathways. We found that PCA improved 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic cell loss. Moreover, PCA increased the expressions of PLK2, p-GSK3β and Nrf2, following the decrease of α-synuclein (α-Syn) in MPTP-intoxicated mice. Cell viability was increased and the apoptosis rate was reduced by PCA in 1-methyl-4-phenylpyridinium iodide (MPP + )-incubated cells. Mitochondrial membrane potential (MMP), mitochondrial complex I activity and reactive oxygen species (ROS) levels in MPP + -incubated cells were also ameliorated by treatment with PCA. The neuroprotective effects of PCA were abolished by inhibition or knockdown of PLK2, whereas overexpression of PLK2 strengthened the protection of PCA. Furthermore, GSK3β and Nrf2 were involved in PCA-induced protection. These results indicated that PCA has therapeutic effects on PD by the PLK2/p-GSK3β/Nrf2 pathway.
Scalp cooling is the most approved treatment for preventing chemotherapy-induced alopecia (CIA). However, the protective mechanism of scalp cooling has rarely been reported. The goal of the present study was to study the relationship between paclitaxel concentration and temperature and the inhibitory effect of low temperature on paclitaxel-induced alopecia. The results showed that the dose of paclitaxel should not exceed 60–70 mg/mL during scalp cooling treatment, and the optimal cooling temperature under different paclitaxel concentrations was determined. Normal human epidermal keratinocytes (NHEK) cells were analyzed by global transcriptome analysis, functional annotation and pathway analysis of differentially expressed genes (DEGs) and ELISA kit to analyze the mechanism of low temperature therapy. The expression of HSPA8, HSPA1A and HSPA1B, which belongs to HSP70, was up-regulated by low temperature. These genes are important target genes of low temperature treatment, which were confirmed by ELISA. The up-regulation of PLK2 and the down-regulation of TXNIP expression are the upstream of mitochondrial dysfunction and ROS, inhibiting the accumulation of ROS and up-regulating the mitochondrial membrane potential. Our research partially elucidates the therapeutic mechanism of scalp cooling, which provides a new idea on the drug research and development in CIA.
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