PLACENTA
·
2025
·
IF 2.5
Xiaodan Tan,Xing Chen,Duanfang Zhou,Wenjia Guo,Dan Li,Xiaoli Wang,Jiali Liu,Zhe Peng,Lin Chen
Introduction Preeclampsia (PE) is a pregnancy-specific disorder associated with hypertension and multi-organ dysfunction, posing serious risks to maternal and fetal health. Early detection remains challenging, highlighting the urgent need to identify reliable molecular biomarkers for improved diagnosis and therapeutic intervention. Methods We integrated Gene Expression Omnibus (GEO) datasets (GSE10588, GSE25906, and GSE48424) and identified 671 differentially expressed genes (312 upregulated and 359 downregulated). Weighted Gene Co-expression Network Analysis (WGCNA) identified 165 genes highly correlated with PE, of which 74 overlapped with the DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on these 74 genes. Additionally, four machine learning models were applied to prioritize diagnostic biomarkers. Results GO analysis revealed enrichment in Wnt signaling, ER-to-Golgi vesicle transport, COPII-coated vesicle components, and ubiquitin-protein transferase activity. KEGG analysis indicated significant involvement in cysteine and methionine metabolism and protein processing in the endoplasmic reticulum. Among the top 20 genes from each machine learning model, Glutamate-cysteine ligase modifier subunit (GCLM) was the only overlapping gene. Its downregulation was validated in clinical samples and PE models. Functional experiments showed that lentiviral GCLM overexpression restored GSH/GPX4 levels, enhanced HUVEC viability, and reduced sFLT-1 secretion. Conclusion Our study identifies GCLM as a potential biomarker and therapeutic target for PE, offering new insight into its molecular pathogenesis and suggesting clinical relevance for diagnosis and intervention.
研究领域:
妇产科学
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分子生物学
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生物信息学
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系统生物学
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转化医学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Jingyu Weng,Lang Liu,Shuming Li,Yuangui Yang,Rui Zhou,Zhen Zhang,Yanru Liu,Lin Chen,Zeyu Feng,Zhishu Tang,Hongbo Xu
Background Lipid peroxide accumulation plays significant roles in cerebral ischemia-reperfusion injury (CIRI) through various mechanisms, including ferroptosis. Preserving the neuronal metabolic equilibrium and averting cell death during cerebral Ischemia-reperfusion are pivotal for protecting brain function. Yinaoxin granule (YNX) is a widely used Chinese herbal preparations for treating cerebrovascular diseases, but pharmacological mechanism remains ambiguous.. Purpose The aim in this study was to assess the effectiveness of YNX in treating CIRI and to investigate the underlying mechanisms. Methods The active ingredients of YNX were quantified using high-performance liquid chromatography. To explore the effects of YNX on CIRI and ferroptosis, both an in vitro oxygen-glucose deprivation and reperfusion model and a middle cerebral artery occlusion and reperfusion rat model were used. To assess the neuroprotective effects of YNX in the latter, neurological scores and cerebral blood flow were evaluated. Neuronal damage was determined through 2,3,5-triphenyltetrazolium chloride, Nissl, and H&E staining. Ferroptosis-related markers, including ferrous ion, glutathione, 4-hydroxynonenal, and malondialdehyde were also investigated. Furthermore, the gene expression and protein levels of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and glutamate-cysteine ligase modulator (GCLM) were determined. Results YNX enhanced neurological scores and cerebral blood flow, reduced infarct volume, and rescued necrotic neurons in rats. Additionally, YNX mitigated lipid peroxidation and upregulated the SLC7A11, GCLM, and GPX4 levels. The absence of Nrf2 rendered neurons more susceptible to ischemia-reperfusion damage and abrogated the anti-ferroptotic neuroprotective effects of YNX. Conclusion YNX activates the Nrf2 pathway, resulting in the transcription of genes associated with antioxidants, including SLC7A11, GCLM, and GPX4. This suggests that YNX reduces lipid peroxidation and alleviates ferroptosis-induced CIRI.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-15
·
IF 3.8
Wang Yan,Wang Shasha,Ma Chenchen,Qi Weiwei,Lv Jing,Zhang Mengqi,Wang Shibo,Wang Rui,Lu Yangyang,Qiu Wensheng
Gastric cancer (GC) is the most common malignant tumor of the gastrointestinal tract and currently has a poor clinical outcome. Turmeric’s rhizome contains a polyphenolic component called curcumin (Cur), which has been demonstrated to inhibit a variety of tumor cells, such as pancreatic, colon, lung and gastric cancers. However, it remains to be elucidated how Cur functions in GC and what molecular processes underlie it. Here, Cur showed a stronger inhibitory effect on GC cells AGS and HGC27. In addition, Cur’s inhibition of GC cells growth was accompanied by increased ROS production, triggering of the Keap1-Nrf2 signaling pathway, and increased transcription of its downstream antioxidant genes HO-1, GCLM, and NQO1. However, when a ROS scavenger NAC was used, the inhibitory effect of Cur on GC cells was reversed. Nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed or activated in cancers to shield cancer cells from oxidative damage by responding to oxidative stress (OS). Cur has been found to act as an activator of Nrf2. Notably, compared with Nrf2 knockdown and Cur alone, the combination of the two dramatically increased Cur-induced ROS overaccumulation and inhibition of GC cells proliferation, migration, and invasive abilities. Consistent with in vitro experiments, Cur combined with Nrf2 knockdown significantly inhibited tumor growth in nude mice transplanted with AGS cells. Therefore, we concluded that Nrf2 depletion enhanced Cur therapy effect in GC by inducing the excessive accumulation of ROS, indicating that this is a promising treatment strategy.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-15
·
IF 7
Lu Yang-yang,Zhu Chun-yang,Ding Yi-xin,Wang Bing,Zhao Shu-fen,Lv Jing,Chen Shu-ming,Wang Sha-sha,Wang Yan,Wang Rui,Qiu Wen-sheng,Qi Wei-wei
Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata , is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 4
·1135
·
IF 3.687
Maiquan Li,Tao Xu,Fei Zhou,Mengmeng Wang,Huaxin Song,Xing Xiao,Baiyi Lu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.Keywords:Keap1;Nrf2;Neuroprotective;PC12 cells;PhGs
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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