FASEB JOURNAL
·
2025
·Vol. 39
·期 11
·e70681
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IF 4.2
Yao Chen,Heqi Dai,Fei Mao,Yangbai Li,Ruizhi Feng,Yun Qian
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. However, the underlying molecular mechanism remains unclear. In this study, we employed RNA sequencing analysis to identify differentially expressed protein‐coding genes and long noncoding RNA (lncRNA) expression profiles in granulosa cells from women with and without PCOS. It was established that the level of NONHSAT233728.1 was diminished in women with PCOS. The present study demonstrated the role of NONHSAT233728.1 in granulosa cells from patients with PCOS and further investigated the potential mechanism of NONHSAT233728.1 in the KGN cell line. Additionally, the knockdown of NONHSAT233728.1 has been observed to promote cell apoptosis, inhibit cell proliferation, promote mitochondrial dysfunction, and inflammation. Western blot analyses confirmed that phospho‐extracellular regulated protein kinases (ERK)1/2 were decreased following lnc‐NONHSAT233728.1 knockdown. Consequently, we propose that ROS accumulation activates the endogenous mitochondrial apoptosis pathway, leading to granulosa cell apoptosis via the MEK/ERK1/2 pathway, which contributes to follicular atresia. We observed a negative correlation between NONHSAT233728.1 and both LH levels and the LH/FSH ratio. These findings indicate that lncRNA NONHSAT233728.1 is linked to the pathogenesis of PCOS and offer new insights into its underlying mechanisms. Through isolation and transcriptomic profiling of granulosa cells, we identified the functional significance of lncRNA NONHSAT233728.1 in polycystic ovary syndrome (PCOS) pathogenesis. Knockdown of lncRNA NONHSAT233728.1 in granulosa cells elevated ROS levels, reduced the Bcl2/Bax ratio, downregulated phospho‐ERK1/2, and increased IL‐8 secretion. These results demonstrate ROS‐mediated mitochondrial apoptosis via MEK/ERK1/2 suppression, alongside inhibited proliferation and enhanced inflammation, consistent with follicular atresia in PCOS. Negative correlations between NONHSAT233728.1 and LH/FSH ratios further support its pathogenic role.
研究领域:
生殖医学
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分子生物学
·
内分泌学
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DOI
PubMed
高影响因子
Journal of Evidence-Based Integrative Medicine
·
2024
·
IF 3.3
Shu Dong,MD,Panling Xu,MD,Peiwen Yang,MD,Juying Jiao,MD,Chien-shan Cheng,MD,PhD,Lianyu Chen,MD,PhD
BackgroundHuanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear.AimsThis study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways.MethodsA PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro, besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays.ResultsHLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2.ConclusionHLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.
研究领域:
肿瘤学
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中医药学
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药理学
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分子生物学
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系统生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Hong Chen,Yang Lili,Zhang Yifan,Li Yiming,Wu Huali
Epimedium brevicornum Maxim. (Epimedii Folium) is a traditional medicine widely utilized in China for sexual dysfunction and osteoporosis treatment. Recently, studies have reported that Epimedium flavonoid icariin displayed hair growth and melanogenic ability by targeting tyrosinase activity. Nevertheless, icariin hydrolysate icariside II and icaritin cause depigmentation due to their tyrosinase inhibition. These pigment functional discrepancies from Epimedium constituents arouse our great interest. Then, this study focused on the pigmentation effects of Epimedii Folium extract (EFE) on melanin synthesis and melanosome biogenesis/transfer, and further identified the bioactive constituents. First, in in vitro systemic studies, we discovered that the potent melanogenic and repigmented effects of EFE were dependent on concentration and amount of time in multi-melanocytes, normal human skin tissue, and vitiligo perilesional areas. In vivo, EFE exhibited repigmented effect on two kinds of depigmented models of N-phenylthiourea-induced zebrafish and hydroquinone-induced mice. Mechanistically, EFE strongly promoted tyrosinase activity and upregulated the protein expression of tyrosinase families which finally contribute to melanin biosynthesis by activating the MAPK/ERK1/2 signal pathway. In addition, EFE effectively increased melanosome number, accelerated melanosome maturity and cytoplasmic transport through the growth/extension of melanocyte dendrites, and induced melanosome transfer from melanocyte to keratinocyte for pigmentation. The six main flavonoid ingredients were identified among EFE. Compared to others, epimedin B (EB) was confirmed as a high-content, low-toxicity, and effective melanogenic compound in EFE. Taking all these together, this study systematically demonstrates the potential pigmentation effect of Epimedium brevicornum Maxim., and clarifies its related molecular mechanisms and melanogenesis basis. These results give additional insight into Epimedium herb pharmacology and may provide a novel therapy basis for hypopigmentation disorders.
研究领域:
药理学
·
皮肤科
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中医药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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