Pharmaceuticals
·
2025
·Vol. 18
·期 11
·1759
·
IF 4.8
Jing Hong,Fangyu Zhang,Ruizhen Zhang,Hongyang Fu,Dongang Shen,Xinyue Wang,Yuting Yang,Jiamei Wu,Lin Meng,Hongyang Lü,Xiwei Jiang,Yunli Zhao
Background: Doxorubicin (DOX) is a highly effective chemotherapy drug, but its use is limited by dose-dependent cardiotoxicity, driving the search for protective natural products. Although the herb Viscum coloratum (Kom.) Nakai is known for its cardiovascular benefits, the cardioprotective effects and mechanisms of its isolated compound, DHDK, remain unexplored. Methods: The protective effect of DHDK was first evaluated in DOX-injured H9c2 cardiomyocytes. Subsequently, an integrated network toxicology (incorporating DOX-induced toxicity targets and relevant chronic disease pathways such as aging and lipid metabolism) and pharmacology (DHDK) approach identified core targets, which were then refined through Protein–Protein Interaction (PPI) analysis and molecular docking. The underlying mechanism was investigated using lipidomics and validated through a series of in vitro assays, including CCK-8, q-PCR, biochemical tests, and flow cytometry, as well as in an in vivo rat model. Results: DHDK significantly alleviated DOX-induced cardiomyocyte toxicity. Integrated analysis identified 56 intersecting targets, with PPARG confirmed as the primary target via PPI and molecular docking. Lipidomics revealed that DHDK potently attenuated DOX-induced accumulation of pathogenic lipids (e.g., fatty acids, ceramides). Mechanistically, DHDK activated PPARG, which in turn upregulated CPT1B, a key regulator of fatty acid β-oxidation (FAO). This enhanced cell viability, ATP production, and mitochondrial membrane potential while reducing oxidative stress. These protective effects, which were abolished by the inhibition of PPARG or CPT1B, were further validated in vivo. Conclusion: This study demonstrates that DHDK exerts its cardioprotective effect by activating the PPARG-CPT1B-FAO axis, effectively correcting lipid metabolic disorders. Given that lipid dysregulation is a hallmark of various internal metabolic diseases, DHDK may also hold therapeutic potential for other heart conditions driven by metabolic disturbances, such as diabetic cardiomyopathy, highlighting its broad relevance to the field of internal diseases.
研究领域:
药理学
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肿瘤心脏病学
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代谢组学
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天然产物化学
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分子生物学
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毒理学
·
脂质组学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Ruipeng Lu,Jingjing Hong,Tong Fu,Yu Zhu,Ruiqi Tong,Di Ai,Shuai Wang,Qingsong Huang,Ceshi Chen,Zhiming Zhang,Rui Zhang,Huiling Guo,Boan Li
Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a higher number of primary breast tumors with accelerated growth and increased lung-metastases. Furthermore, treatment with FAO inhibitors effectively reduces stemness characteristics of tumor cells, breast tumor initiation, and metastasis, especially in OVOL2-deficient breast tumors. The findings suggest that targeting JAK/STAT3 pathway and FAO is a promising therapeutic strategy for OVOL2-deficient TNBC.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 106
·期 1
·e70158
·
IF 3.3
Yong Zhu,Chuanmin Yi,Jin Zhao,Lei Wang,Tao Huang,Bo Xiang,Lvhai Zhang,Xiangfang He,Linke Wu
Platinum-based and pyrimidine drugs are first-line treatments for gastric cancer (GC), but their efficacy is often affected by drug resistance. High spalt-like transcription factor 4 (SALL4) expression is associated with poor prognosis, but its role in 5-fluorouracil (5-FU) resistance is not yet clear. In this study, we investigated the effect of SALL4 on 5-FU resistance in GC cells by bioinformatics analysis, real-time quantitative reverse transcription polymerase chain reaction, cell counting kit-8, colony formation assay, and western blot. The results showed that SALL4 was highly expressed in GC and significantly correlated with the fatty acid oxidation (FAO) pathway. Knockdown of SALL4 resulted in a notable attenuation of cellular proliferative capacity and heightened susceptibility to 5-FU resistance in GC cells, while overexpression of SALL4 enhanced 5-FU resistance. Rescue assays confirmed that SALL4 fostered 5-FU resistance in GC cells by enhancing FAO. Our research confirmed that SALL4 promoted the resistance of GC cells to 5-FU by enhancing the FAO pathway. This suggests that drug development targeting SALL4 may help overcome chemotherapy resistance in GC.
研究领域:
肿瘤学
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分子生物学
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药理学
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生物化学
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癌症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Chemical and Biological Technologies in Agriculture
·
2025
·Vol. 12
·期 1
·1-16
·
IF 5.2
Liang Zhiqing,Wang Zhi,Shen Xiaojuan,Chen Ruitao,Peng Yuansong,Cai Yafan,Zeng Shan,Zhuang Wei,Yang Jianping,Liu Dong,Wang Shilei,Xu Jingliang,Ying Hanjie
Chinese distiller grains (CDGs) are a primary by-product of the Baijiu production process. This research focused on converting CDGs into high-protein, low-fiber, and non-toxic feed through the synergistic effects of the synthetic microbial community in solid-state fermentation (SMC-SSF) of CDGs. After fermentation promoted by inorganic nitrogen, the protein content indicated 33.32%. Concurrently, crude fiber, ethanol, lactic acid, and acetic acid content were decreased by 20.46%, 64.28%, 64.28%, and 90.96%, respectively. Additionally, zearalenone and aflatoxin B1 content decreased by 9.32% and 63.75%. The organic acid, ethanol, and mycotoxin content in fermented CDGs (FCDGs) complied with the standards of Food and Agriculture Organization (FAO). While the digestibility was enhanced 62.46%, it also showed the effective antimicrobial activity against Escherichia coli and Staphylococcus aureus. This study provides a viable pathway for producing protein feed with enhanced probiotic characteristics.
研究领域:
生物技术
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微生物学
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食品科学
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动物营养
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环境科学
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应用微生物学
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产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Qinfei Zhou,Lihong Liu,Nian Liu,Bin He,Ligang Hu,Lina Wang
With the extensive application of nanotechnology, metal nanoparticles (MNPs) have been widely used, thus are universally detected in the environment. This has caused increasingly concerns due to their toxicity and the potential health risks they pose to humans. In this work, the concentrations and particle size distributions of MNPs and concentrations of associated metal ionic species in shellfish seafood (clams and oysters) were investigated using single particle inductively coupled plasma mass spectrometry (sp-ICP-MS) and inductively coupled plasma mass spectrometry (ICP-MS). The MNPs in the clam and oyster tissues were extracted via an alkaline digestion method with a recovery rate of 95.9% (for gold nanoparticles (AuNPs)). Then total concentrations of 41 metal elements were measured in the two types of seafood, of which 20 were selected for sp-ICP-MS analysis. The results showed that 5 types of MNPs were detectable in clams (Y, La, Ce, Pr, Gd) and 5 types of MNPs were detectable in oysters (Y, La, Ce, Pr, Nd). Size distributions of MNPs in clams and oysters were in the range of 35–55 nm and 30–65 nm, respectively. Nanoparticle concentrations in clams and oysters ranged from 0.6 to 37.7 ng/g and 4.2–19.7 ng/g, and accounted for 3.4%–50% and 5.5%–46% of the total metal content, respectively. Based on this analysis, the health risks of metals in the two kinds of seafood were evaluated by comparing the Provisional Tolerable Weekly Intake (PTWI) with limits recommended by the World Health Organization (WHO)/Food and Agriculture Organization (FAO). These results provide important information about the presence of metal nanoparticles in seafood and, to the best of our knowledge, this is the first time that the nanoparticles of rare earth elements have been detected and reported in bivalve mollusc tissues.
研究领域:
环境科学
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分析化学
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毒理学
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食品安全
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）