Clinics
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2025
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IF 2.4
Shan Xu,Xuming Lin,Fengling Jia
Objective Retinoblastoma (RB) is a type of intraocular tumor in childhood with a high lethality rate. N4-acetylcytosine (ac 4 C) modification is known to regulate multiple cancers, which is mediated by the only known ac 4 C writer N-Acetyltransferase 10 (NAT10). In this study, the authors aimed to reveal the mechanism of RB progression regulated by ac 4 C modification. Method Phenotypically, dot blot assay and quantitative real-time PCR were used to detect the ac 4 C levels and NAT10 expression in clinical samples and RB cell lines. Then, NAT10 was knocked down to assess its effect on glycolysis. Mechanically, RNA immunoprecipitation assay, immunofluorescence assay, and dual luciferase report were used to explore the mRNA modified by NAT10-mediated ac 4 C modification. Mice xenograft model was used to determine the effect of NAT10 on tumor growth in vivo . Results The present results demonstrated that the levels of ac 4 C and NAT10 were increased in cancer tissues and RB cell lines. Furthermore, NAT10 knockdown inhibited the glycolysis in RB cell lines. Moreover, the authors revealed that NAT10 knockdown decreased the ac 4 C modification and mRNA stability of HK1, while the inhibition of glycolysis by NAT10 knockdown was reversed by HK1 overexpression. Finally, NAT10 knockdown relieved the growth of tumors in mice models. Conclusion The authors illustrated that NAT10 plays an important role in the progression of RB by regulating the ac 4 C modification on HK1 mRNA and affects its stability, which may provide a novel theoretical basis for the treatment of RB.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Dong Liu,Meihua Shan,Rong Zeng,Meng He,Xufang Dai,Lu Lu,Mingzhen Yang,Haiyan He,Yang Zhang,Li Xiang,An Chen,Liangbo Sun,Fengtian He,Jiqin Lian
N6-methyladenosine (m6A) serves as the most abundant posttranscription modification. However, the role of m6A in tumorigenesis and chemotherapeutic drugs sensitivity remains largely unclear. Present research focuses on the potential function of the m6A writer KIAA1429 in tumor development and sorafenib sensitivity in liver cancer. We found that the level of KIAA1429 was significantly elevated in liver cancer tissues and cells and was closely associated with poorer prognosis. Functionally, KIAA1429 promoted the proliferation and Warburg effect of liver cancer cells in vitro and in vivo . RNA-seq and MeRIP-seq analysis revealed the glycolysis was one of the most affected pathways by KIAA1429, and m6A-modified HK1 was the most likely targeted gene to regulate the Warburg effect. KIAA1429 depletion decreased Warburg effect and increased sorafenib sensitivity in liver cancer. Mechanistically, KIAA1429 could affect the m6A level of HK1 mRNA through directly binding with it. Moreover, KIAA1429 cooperated with the m6A reader HuR to enhance HK1 mRNA stability, thereby upregulating its expression. These findings demonstrated that KIAA1429/HK1 axis decreases the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect, which may provide a novel therapeutic target for liver cancer treatment
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2020
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IF 7.182
Yu-Heng Mao,Ang-Xin Song,Long-Qing Li,Yan Yang,Zhong-Ping Yao,Jian-Yong Wu
This work was to examine the impact of power ultrasound (US) on the molecular properties of a high-molecular weight (MW) exopolysaccharide (EPS) from the Cs-HK1 medicinal fungus and the utilization, and prebiotic function of the US-treated EPS fractions in human fecal microflora in vitro . The US treatment caused notable reduction of intrinsic viscosity, average MW and aggregate size of EPS in water but no significant changes in the molecular structure. The US-treated EPS fractions were consumed more rapidly by the fecal microflora, resulting in a higher total level of short chain fatty acids. They also affected the relative abundance in the microflora more beneficially than the original EPS. The results suggest that power US is effective for modifying and improving the prebiotic properties of high-MW polysaccharides.
研究领域:
食品科学
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微生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2025
·
IF 4
Peng Chen,Wenhao Xiao,Fanzhao Zou,Jiexin Lei,Fuchao Chen,Ruhong Zhang
This study explored the effects of methylated urolithin A (mUro A), on lipopolysaccharide (LPS)-induced cognitive impairment and anxiety- and depression-like behaviors, and their molecular mechanism. mUro A significantly mitigated cognitive dysfunction, anxiety- and depression-like behaviors. Furthermore, mUro A improved activities of antioxidative enzymes, regulated the release of inflammatory factors, inhibited the LPS-induced generation of Aβ 1 – 42 and restored the cholinergic system balance in the AD mouse brain. Additionally, mUro A markedly attenuated microglial activation by inhibiting the Drp1/HK1/NLRP3 pathway, thereby suppressing mitochondrial inflammation. This was evidenced by the downregulation of p-Drp1 (s616), VDACs, NLRP3, ASC, cleaved caspase 1, IL-18, and IL-1β, alongside the upregulation of HK1 expression. In conclusion, mUro A mitigates AD-associated cognitive deficits by inhibiting the Drp1/HK1/NLRP3 pathway and suppressing mitochondrial inflammation.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF ALLOYS AND COMPOUNDS
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2026
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IF 6.7
Chao Ying,Xinyue Zhu,Hanxiao Li,Yi Xie,Yang Wang,Dong Tian,Shiliu Yang,Daofu Liu,Shiyue Zhu,Guannan Xiao
Antimony trisulfide (Sb 2 S 3 ) has emerged as a promising absorber material for indoor photovoltaic applications owing to its ideal bandgap (∼1.73 eV) and high absorption coefficient in the visible spectrum. However, the carrier transport efficiency of Sb 2 S 3 thin films is strongly constrained by their preferential crystallographic orientation, with the [hk1]-oriented films exhibiting approximately 100 times higher resistivity than their [hk0]-oriented counterparts. Herein, we report a facile chemical bath deposition (CBD) strategy to achieve the [hk1]-oriented Ag-doped Sb 2 S 3 thin films by incorporating trace amounts of Ag + ions into the growth solution. The effects of Ag + concentration on the crystal orientation, bandgap, chemical composition, and defect density of the resulting Ag:Sb 2 S 3 thin films, as well as the photovoltaic performance of the corresponding solar cells, were systematically investigated. The results demonstrate that the Ag:Sb 2 S 3 thin film with an optimal Ag doping concentration of 2% exhibits superior [hk1]-orientation, significantly reduced defect density, and enhanced carrier transport properties, while maintaining an ideal bandgap of ∼1.77 eV. As a result, the Ag:Sb₂S₃ solar cell achieves a photoelectric conversion efficiency of 7.01% under AM 1.5 G illumination and up to 17.22% under warm white LED illumination (2762 K, 1000 lx), representing a notable achievement for Sb 2 S 3 -based indoor solar cells.
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DOI
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2023
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IF 3.8
Jiaxi Chen,Mengyue Pan,Jingjie Wang,Mengling Zhang,Mingmei Feng,Xiaoming Chai,Qi Zhang,Yang Sun
Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5′-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography–mass spectrometry (GC–MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.
研究领域:
药理学
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免疫学
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微生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2024
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IF 6.9
Xia Rui-xue,Zou Pei-chen,Xie Jun-ting,Tang Ya-bin,Gong Miao-miao,Fan Fu,Aihemaiti Ayinazhaer,Liu Yu-qing,Shen Ying,Zhou Bin-bing S.,Zhu Liang,Lei Hui-min
RAS is the most frequently mutated oncoprotein for cancer driving. Understanding of RAS biology and discovery of druggable lynchpins in RAS pathway is a prerequisite for targeted therapy of RAS-mutant cancers. The recent identification of KRAS G12C inhibitor breaks the “undruggable” curse on RAS and has changed the therapy paradigm of KRAS-mutant cancers. However, KRAS mutations, let alone KRAS G12C mutation, account for only part of RAS-mutated cancers. Targeted therapies for cancers harboring other RAS mutations remain the urgent need. In this study we explored the pivotal regulatory molecules that allow for broad inhibition of RAS mutants. By comparing the expression levels of nucleotide pyrophosphatase (NPPS) in a panel of cell lines and the functional consequence of increased NPPS expression in RAS-mutant cells, we demonstrated that cancer cells with various kinds of RAS mutations depended on NPPS for growth and survival, and that this dependence conferred a vulnerability of RAS-mutant cancer to treatment of NPPS inhibition. RAS-mutant cells, compared with RAS-wildtype cells, bored and required an upregulation of NPPS. Transcriptomics and metabolomics analyses revealed a NPPS-dependent hyperglycolysis in RAS-mutant cells. We demonstrated that NPPS promoted glucose-derived glycolytic intermediates in RAS-mutant cells by enhancing its interaction with hexokinase 1 (HK1), the enzyme catalyzing the first committed step of glycolysis. Pharmacological inhibition of NPPS-HK1 axis using NPPS inhibitor Enpp-1-IN-1 or HK1 inhibitor 2-deoxyglucose (2-DG), or genetic interfere with NPPS suppressed RAS-mutant cancers in vitro and in vivo. In conclusion, this study reveals an unrecognized mechanism and druggable lynchpin for modulation of pan-mutant-RAS pathway, proposing a new potential therapeutic approach for treating RAS-mutant cancers.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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DOI
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2024
·
IF 2.7
Hongmei Chang,Siqi Zhao,Yuzhu Lei,Yunhua Hu,Yizhong Yan,Guanling Song
Titanium dioxide nanoparticles (nano-TiO 2 ) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO 2 on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO 2 for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO 2 regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO 2 significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO 2 decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO 2 . Collectively, nano-TiO 2 downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells.
研究领域:
生殖生物学
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细胞生物学
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纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
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IF 2.65
Yihua Shi,Kai Lian,Jiguang Jia
Osteosarcoma (OS) is a prevalent primary malignant bone tumor that commonly occurs in children and adolescents. Apigenin (4′,5,7-trihydroxyflavone) is one of the most researched phenolic compounds that exhibits antitumor effects in several cancers. The aim of the current study was to investigate the effect and underlying mechanisms of apigenin on OS. To address this, OS cells (SOSP-9607) were treated with different concentrations of apigenin. The proliferation, migration, invasion, stem-like properties, and Warburg effect of apigenin-treated OS cells were evaluated. Apigenin was found to suppress the proliferation of SOSP-9607 cells and inhibit epithelial-mesenchymal transition, as indicated by decreased number of migrated and invaded cells, decreased protein expression of vimentin, and increased protein expression of E-cadherin. Additionally, apigenin suppressed tumorsphere formation and reduced the proportion of SOSP-9607 cells with positive expression of the stem cell-related markers Nanog and OCT-4. Apigenin inhibited the Warburg effect in SOSP-9607 cells, as demonstrated by decreased glucose and lactic acid levels, increased citrate and ATP levels, and downregulation of GLUT1, HK1, and LDHA, which are metabolism-related enzymes related to the Warburg effect. Moreover, apigenin inhibited the phosphorylation of PI3K, Akt, and mTOR in SOSP-9607 cells. Collectively, these results indicate that apigenin suppresses the Warburg effect and stem-like properties in SOSP-9607 cells, which may be mediated by PI3K/Akt/mTOR signaling, thus, providing a novel strategy for OS treatment.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
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