ACS Applied Materials & Interfaces
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2023
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IF 9.5
Zhenchao Tao,Jingguo Wang,Haitao Wu,Jiaru Hu,Lu Li,Yuhang Zhou,Qi Zheng,Lisha Zha,Zhengbao Zha
In response to diffused ionizing radiation damage throughout the body caused by nuclear leaks and inaccurate radiotherapy, radioprotectants with considerable free radical scavenging capacities, along with negligible adverse effects, are highly regarded. Herein, unlike being performed as toxic chemotherapeutic drug candidates, molybdenum-based polyoxometalate nanoclusters (Mo-POM NCs) were developed as a non-toxic potent radioprotectant with impressive free radical scavenging capacities for ionizing radiation protection. In comparison to the clinically used radioprotectant drug amifostine (AM), the as-prepared Mo-POM NCs exhibited effective shielding capacity by virtue of their antioxidant properties resulting from a valence shift of molybdenum ions, alleviating not only ionizing radiation-induced DNA damage but also disruption of the radiation-sensitive hematopoietic system. More encouragingly, without trouble with long-term retention in the body, ultra-small sized Mo-POM NCs prepared by the mimetic Folin–Ciocalteu assay can be removed from the body through the renal-urinary pathway and the hepato-enteral excretory system after completing the mission of radiation protection. This work broadened the biological applications of metal-based POM chemotherapeutic drugs to act as a neozoic radioprotectant.
研究领域:
放射防护
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纳米技术
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药理学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Ying-Da Zang,Hai-Jie Wu,Xin-Yi Chen,Zhi-Ling Ma,Chuang-Jun Li,Jie Ma,Xiao-Guang Chen,Li Sheng,Sen Zhang,Dong-Ming Zhang
Cisplatin is a widely used drug for the clinical treatment of tumors. However, nephrotoxicity limits its widespread use. A series of compounds including eight analogs (G3-G10) and 40 simplifiers (G11-G50) were synthesized based on the total synthesis of Psiguamer A and B, which were novel meroterpenoids with unusual skeletons from the leaves of Psidium guajava. Among these compounds, (d)-G8 showed the strongest protective effect on cisplatin-induced acute kidney injury (AKI) in vitro and vivo, and slightly enhanced the antitumor efficacy of cisplatin. A mechanistic study showed that (d)-G8 promoted the efflux of cisplatin via upregulating the copper transporting efflux proteins ATP7A and ATP7B. It enhanced autophagy through the activation of the adenosine monophosphate–activated protein kinase (AMPK) signaling pathway. (d)-G8 showed no acute toxicity or apparent pathological damage in the healthy mice at a single dose of 1 g/kg. This study provides a promising lead against cisplatin-induced AKI.
研究领域:
药理学
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药物化学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2024
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IF 5.3
Huan Liu,Longsheng Wang,Xiaokai Shi,Lei Yin,Wei Zhai,Shenglin Gao,Yonghui Chen,Tao Zhang
Current therapeutic options for renal cell carcinoma (RCC) are very limited, which is largely due to inadequate comprehension of molecular pathological mechanisms as well as RCC's resistance to chemotherapy. Dual-specificity phosphatase 6 (DUSP6) has been associated with numerous human diseases. However, its role in RCC is not well understood. Here, we show that diminished DUSP6 expression is linked to RCC progression and unfavorable prognosis. Mechanistically, DUSP6 serves as a tumor suppressor in RCC by intervening the TAF10 and BSCL2 via the ERK-AKT pathway. Further, DUSP6 is also transcriptionally regulated by HNF-4a. Moreover, docking experiments have indicated that DUSP6 expression is enhanced when bound by Calcium saccharate, which also inhibits RCC cell proliferation, metabolic rewiring, and sunitinib resistance. In conclusion, our study identifies Calcium saccharate as a prospective pharmacological therapeutic approach for RCC.
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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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
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2026
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IF 3.1
Kai Deng,Gaoyuan Zhang,Qiang Yan,Shuwen Han,Yunyao Wei,Ying Mei
LRACN alleviated acute RP by reducing lung inflammation and oxidative stress. • LRACN partially reversed thoracic irradiation-induced gut microbiota dysbiosis. • Gut microbial and metabolic remodelling was associated with improved RP-related lung phenotypes. • Multi-omics linked LRACN protection to gut–lung axis modulation and a PI3K/AKT-related signalling axis. Radiation pneumonitis (RP) is a dose-limiting complication of thoracic radiotherapy, and effective preventive interventions remain limited. Lycium ruthenicum anthocyanins (LRACN) exhibit antioxidant and anti-inflammatory activities, but their effects on RP and the associated systemic mechanisms remain unclear. In this study, a mouse RP model was established by 15 Gy localised chest irradiation, and LRACN was administered orally before and after irradiation. Protective effects were evaluated using histopathology, inflammatory cytokines, and oxidative stress indices. Potential mechanisms were explored by integrating 16S rRNA sequencing, non-targeted serum metabolomics, metabolite-based target network analysis, transcriptomics, and single-cell RNA-seq. Compared with the model group, high-dose LRACN reduced injury score, collagen volume fraction, tumour necrosis factor-α, and malondialdehyde in the lung tissue by approximately 55%, 58%, 45%, and 44%, respectively. Multi-omics profiling revealed that LRACN partially restored radiation-disrupted gut microbial taxa, including Dubosiella , Ligilactobacillus , and Akkermansia , and reversed radiation-induced disturbances in serum purine and glycerophospholipid metabolism. Correlation analysis linked LRACN-responsive gut taxa and circulating metabolites with RP-related pathological, inflammatory, and oxidative indices. Integrated pathway analysis and western blotting suggested that the protective effect of LRACN was associated with reduced PI3K and Akt phosphorylation in lung tissue. These findings indicate that LRACN mitigates early RP in mice, and gut microbiota-associated metabolic remodelling may contribute to its protective effects. Download: Download high-res image (189KB) Download: Download full-size image
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Yuwei Yang,Peng Ni,Lixue Ma,Haikang Tang,Jiaming Yang,Xiaoliang Zhou,Yikun Sun,Wenqing Xu
Ethnopharmacological relevance Radiation-Induced Skin Injury (RISI) is the major cutaneous side effect met by cancer patients who received radiotherapy. Disposed earthworm (Dilong) has been historically employed for treating various ailments in ancient China. Amputated-regeneration and high radiation-tolerant are two distinctive characteristics for earthworms. These features might due to their abundant biologically active substances (65 % composed of proteins), which make them attractive candidates for radioprotector development. Aim of the study This study aimed to investigate therapeutic mechanism of regenerated E. fetida protein extract (G90′-ES2) in mitigating RISI, and reveal therapeutic potential macromolecules by proteomic analysis. Materials and methods Protein salt precipitation method was firstly adopted to obtain G90′-ES2/G90-ES2 protein complex. Their radioprotective activities were evaluated in vitro by cell viability, migration, ROS accumulation, EdU proliferation, cell cycle and apoptosis assays. A combined radiogenic injury mice model was constructed to analyze radiotherapeutic function of G90′-ES2 in vivo . Its mechanism against RISI was illustrated by RNA-Seq analysis, qPCR, and HIF Luciferase Reporter Assay. Finally, a nanoElute UPLC-MS/MS method was used to elucidate therapeutic potential macromolecules in G90′-ES2. Results We discovered that G90′-ES2 displayed higher efficacy than G90-ES2 in mitigating RISI, mainly by activating radio-resistant HIF-1 pathway, redistributing cell cycle phases (S-phase preservation), accelerating re-epithelialization, and enhancing tissue angiogenesis. The significantly up-regulated proteins (including lumbrokinase, aquaporin, RAD51C, TCTP, and SCBP2) in G90′-ES2 might hold particular importance for its therapeutic effect against RISI. Conclusions This investigation will broaden our understanding of the radiation-tolerant and regenerative capacities for earthworm; also provide medical candidates for the development of skin-specific radioprotector.
研究领域:
放射生物学
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创伤修复与再生医学
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分子药理学
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蛋白质组学
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皮肤生物学
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天然药物开发
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转化医学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2023
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IF 6.1
Haijie Wu,Xiaohu Shi,Yingda Zang,Xiaodi Zhao,Xikun Liu,Weida Wang,Wenying Shi,Clarence T.T. Wong,Li Sheng,Xiaoguang Chen,Sen Zhang
Aims Cisplatin is a widely-used drug in the clinical treatment of tumors, but kidney nephrotoxicity is one of the reasons that limits its widespread use. We previously found that 7-hydroxycoumarin-β-D-glucuronide (7-HCG) was one of metabolites of skimmin and highly enriched in the kidneys and maintained a high blood concentration in skimmin-treated rats. Therefore, we investigated whether 7-HCG has a protective effect on cisplatin-induced acute kidney injury. Materials and methods Male C57BL/6 mice were continuously administered 7-HCG for five days, and on the third day, an intraperitoneal injection of cisplatin was given to induce acute kidney injury. After 72 h, the mice were sacrificed for analysis. Serum and renal tissue were collected for renal function evaluation. RNA sequencing was used to explore mechanism, and further validated by western blot and immunohistochemistry. In addition, pharmacokinetic study of oral 7-HCG administration was performed to examine how much 7-hydroxycoumarin (7-HC) was metabolized and 7-HC possible effect on renal protection. Key findings 7-HCG significantly reduced serum BUN and SCR levels, and alleviated pathological damage in renal tissue, and reduced the renal index. RNA sequencing revealed that 7-HCG could reverse p38 MAPK regulation and apoptosis. By western blotting, it was found that 7-HCG could reduce renal injury by reducing p-p38, p-ERK, p-JNK, cleaved-caspase3 and Bax. The immunohistochemical results of cleaved-caspase3 were consistent with western blotting. 7-HCG also significantly reduced the production of ROS in kidney tissue. Pharmacokinetic experiments have shown that 7-HCG in the blood increased rapidly and was eliminated slowly, with an average t 1/2β of 18.3 h. And the concentration of 7-HCG in the target organ kidney was about 4 times higher than that in blood. Significance Our findings indicate that 7-HCG could exert its protective effect against cisplatin-induced acute kidney injury by inhibiting apoptosis via p38 MAPK regulation and elucidates its pharmacokinetics.
研究领域:
药理学
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肾病学
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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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