Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献_第2页

Astragaloside IV alleviates heatstroke brain injury and neuroinflammation in male mice by regulating microglial polarization via the PI3K/Akt signaling pathway. 黄芪皂苷IV通过PI3K/Akt信号通路调节小胶质细胞极化，减轻雄性小鼠的中暑脑损伤和神经炎症。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.biopha.2024.117545

Zeze Wang, Zhen Luo, Yulong Tan, Genlin He, Ping Li, Xiaoqian Liu, Tingting Shen, Yishan Liu, Xuesen Yang, Xue Luo

{"title":"Astragaloside IV alleviates heatstroke brain injury and neuroinflammation in male mice by regulating microglial polarization via the PI3K/Akt signaling pathway.","authors":"Zeze Wang, Zhen Luo, Yulong Tan, Genlin He, Ping Li, Xiaoqian Liu, Tingting Shen, Yishan Liu, Xuesen Yang, Xue Luo","doi":"10.1016/j.biopha.2024.117545","DOIUrl":"10.1016/j.biopha.2024.117545","url":null,"abstract":"Heatstroke is a condition caused by overheating of the body that leads to severe central nervous system dysfunction. Although there have been numerous studies on the pathological process of heatstroke, effective treatment methods are lacking. Astragaloside IV can protect the brain from inflammation and brain damage in various inflammation-related diseases, but it has not yet been used clinically for the treatment of heatstroke. Therefore, the aim of this study was to explore the neuroprotective effect of Astragaloside IV on heatstroke-induced central nervous system damage and its mechanism. Brain injury model under heatstroke was established using artificial climate simulation cabin. By scoring neurological deficits, performing histological and immunofluorescence staining of microglia, and detecting cytokine levels, we determined that Astragaloside IV alleviated brain injury and neuroinflammation. To further explore the potential molecular mechanism, RNA sequencing was performed to investigate the differences in the brain. The results revealed that the PI3K/AKT pathway is involved. In vitro experiments further confirmed that Astragaloside IV can abrogate the phenotypic changes in microglia induced by heatstroke. Moreover, Astragaloside IV promotes the polarization of M2 microglia by activating the PI3K/AKT pathway. In summary, these results indicate that Astragaloside IV alleviates neuroinflammation and brain injury induced by heatstroke through the PI3K/AKT pathway. Astragaloside IV is a commonly used therapeutic agent in the clinic, but its use in the treatment of heatstroke-induced brain injury has not been explored. This study reveals that Astragaloside IV may be a new therapeutic agent for the treatment of heatstroke-induced brain injury.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117545"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Empagliflozin attenuating renal interstitial fibrosis in diabetic kidney disease by inhibiting lymphangiogenesis and lymphatic endothelial-to-mesenchymal transition via the VEGF-C/VEGFR3 pathway. 恩格列净通过VEGF-C/VEGFR3途径抑制淋巴管生成和淋巴管内皮细胞向间质转化，从而减轻糖尿病肾病的肾间质纤维化。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.biopha.2024.117589

Jiaan Huang, Yan Liu, Mengting Shi, Xiaoyun Zhang, Yan Zhong, Shuai Guo, Yun Ma, Limin Pan, Fan Yang, Yuehua Wang

{"title":"Empagliflozin attenuating renal interstitial fibrosis in diabetic kidney disease by inhibiting lymphangiogenesis and lymphatic endothelial-to-mesenchymal transition via the VEGF-C/VEGFR3 pathway.","authors":"Jiaan Huang, Yan Liu, Mengting Shi, Xiaoyun Zhang, Yan Zhong, Shuai Guo, Yun Ma, Limin Pan, Fan Yang, Yuehua Wang","doi":"10.1016/j.biopha.2024.117589","DOIUrl":"10.1016/j.biopha.2024.117589","url":null,"abstract":"Renal interstitial fibrosis (RIF) is a significant pathological change in diabetic kidney disease (DKD) that can be induced by endothelial-to-mesenchymal transition (EndMT). Lymphangiogenesis, mediated by the vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) pathway, plays a crucial role in the development of RIF in DKD. Although numerous studies have demonstrated the efficacy of empagliflozin in treating renal injury, its effects on lymphangiogenesis in DKD-related RIF and the underlying mechanisms remain unclear. In the present study, significant lymphangiogenesis was assessed in the renal interstitium of patients with DKD. We subsequently explored the relationship between DKD-related RIF and lymphangiogenesis in mouse models, high-glucose (HG)-stimulated renal HK-2 cell lines, and human lymphatic endothelial cells (hLECs). Additionally, we evaluated the effects of empagliflozin on these processes. The results revealed that HG induces lymphangiogenesis, which exacerbates RIF by promoting inflammatory responses. Furthermore, hLECs directly contributed to the progression of DKD-related RIF through EndMT. Further analysis revealed that tubular epithelial cells (TECs) act as effector cells for VEGF-C, with the epithelial-to-mesenchymal transition (EMT) of TECs occurring concurrently with the EndMT of lymphatic vessels. Empagliflozin inhibited RIF in DKD by suppressing the VEGF-C/VEGFR3 pathway and reducing lymphangiogenesis. In conclusion, this study elucidates the interplay between lymphangiogenesis, EndMT, and RIF in DKD and provides new insights into the mechanism by which empagliflozin treats DKD.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117589"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel synthetic compound, deferiprone-resveratrol hybrid (DFP-RVT), promotes hepatoprotective effects and ameliorates iron-induced oxidative stress in iron-overloaded β-thalassemic mice. 一种新型合成化合物--去铁酮-白藜芦醇混合物（DFP-RVT）可促进肝脏保护作用，并改善铁过载型β地中海贫血小鼠因铁引起的氧化应激。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI: 10.1016/j.biopha.2024.117570

Jin Li, Hataichanok Chuljerm, Kornvipa Settakorn, Honghong Xu, Yongmin Ma, Woranontee Korsieporn, Narisara Paradee, Somdet Srichairatanakool, Pimpisid Koonyosying

{"title":"A novel synthetic compound, deferiprone-resveratrol hybrid (DFP-RVT), promotes hepatoprotective effects and ameliorates iron-induced oxidative stress in iron-overloaded β-thalassemic mice.","authors":"Jin Li, Hataichanok Chuljerm, Kornvipa Settakorn, Honghong Xu, Yongmin Ma, Woranontee Korsieporn, Narisara Paradee, Somdet Srichairatanakool, Pimpisid Koonyosying","doi":"10.1016/j.biopha.2024.117570","DOIUrl":"10.1016/j.biopha.2024.117570","url":null,"abstract":"A high amount of iron in β-thalassemia patients can lead to oxidative stress and organ dysfunction, especially liver, the main iron accumulated organ. Iron catabolism causes the generation of reactive oxygen species (ROS), triggering liver inflammation, fibrosis, and cirrhosis. Deferiprone-resveratrol hybrid (DFP-RVT) is chemically synthesized by combining deferiprone (DFP) and resveratrol (RVT) which shows an iron-chelating property along with antioxidant activity. This study explored the hepatoprotective effect of DFP-RVT in iron overloaded β-knockout (BKO) thalassemic mice. The results revealed that DFP-RVT treatment improved liver function in iron-overloaded BKO mice by reducing liver enzymes and increasing hepcidin levels compared to iron overload control mice. Both DFP alone and DFP-RVT treatment groups demonstrated iron chelation effects by decreasing liver iron content (LIC), iron profiles, and iron deposition in the liver. Moreover, DFP-RVT powerfully showed antioxidant properties by decreasing liver and plasma thiobarbituric acid reactive substances (TBARs) and increasing reduced glutathione (GSH) and superoxide dismutase (SOD). Interestingly, transforming growth factor β1 (TGFβ1), which can contribute to chronic liver disease through liver injury, inflammation, fibrosis, and cirrhosis, is highly expressed in iron-overloaded mice. However, both DFP and DFP-RVT treatment significantly reduced TGFβ1 levels compared to the iron-overloaded group. Therefore, DFP-RVT could be a potent hepatoprotective compound through the mobilization of iron, reduction of ROS, improvement of liver enzymes, and alleviation of liver damage, potentially relieving liver dysfunction in iron-overloaded BKO mice.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117570"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway. L-NRB通过调节P11-Htr4信号通路缓解肌萎缩性脊髓侧索硬化症。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-19 DOI: 10.1016/j.biopha.2024.117588

Yunfeng Pan, Xiao Sun, Yu Tian, Miao Yu, Yun Luo, Xiaobo Sun

{"title":"L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway.","authors":"Yunfeng Pan, Xiao Sun, Yu Tian, Miao Yu, Yun Luo, Xiaobo Sun","doi":"10.1016/j.biopha.2024.117588","DOIUrl":"10.1016/j.biopha.2024.117588","url":null,"abstract":"Introduction: L-NRB is a compound formed as a ring cleavage product of butylphthalide and borneol in a molar ratio 1:2. This study aimed to explore the therapeutic effect of L-NRB on amyotrophic lateral sclerosis (ALS) and its possible mechanism.Methods: SOD1-G93A mice were used as an ALS model. Behavioral tests, histopathological staining, Nissl staining, immunohistochemistry, enzyme-linked immunosorbent assays, and Western blotting were used to analyze the therapeutic effect. The underlying mechanism of L-NRB in treating ALS was investigated using transcriptomic analyses.Results: It was found that L-NRB alleviated motor dysfunction, pathological changes in the gastrocnemius muscle, and motor neuron injuries. The results indicated that L-NRB had a neuroprotective function associated with the inhibition of neuroinflammation. The anti-apoptotic effect of L-NRB was found to be related to the regulation of the P11-Htr4 signaling pathway.Conclusion: In summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117588"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of inflammatory mediators underlies the antitumor effect of the combination of morusin and docetaxel on prostate cancer cells. 炎症介质的调节是吗丁啉和多西他赛联合疗法对前列腺癌细胞产生抗肿瘤作用的基础。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-19 DOI: 10.1016/j.biopha.2024.117572

Sana A Fadil, Dina A I Albadawi, Khalid Z Alshali, Hossam M Abdallah, Mona M Saber

{"title":"Modulation of inflammatory mediators underlies the antitumor effect of the combination of morusin and docetaxel on prostate cancer cells.","authors":"Sana A Fadil, Dina A I Albadawi, Khalid Z Alshali, Hossam M Abdallah, Mona M Saber","doi":"10.1016/j.biopha.2024.117572","DOIUrl":"10.1016/j.biopha.2024.117572","url":null,"abstract":"Prostate cancer stands as a prominent contributor to male mortality in cancer cases. Docetaxel (Doc) is a commonly used treatment, but some patients do not respond well due to drug toxicity and resistance. Morusin, a prenylated flavonoid found in Morus alba, show strong anticancer properties. The aim of this study was to investigate the combined effect of morusin and docetaxel on prostate cancer cells, while exploring the underlying mechanisms. The IC50 values of morusin, docetaxel, and their combination on PC3 cells were evaluated using the sulforhodamine-B (SRB) assay. In addition, various markers including glutathione (GSH), malondialdehyde (MDA), inflammatory mediators (IL-6, TNF-α, NF-κB, and IL-10), NQO1, NRF2, and apoptotic markers (Bax and Bcl2) were evaluated. Co-administration of morusin and Doc significantly reduced Doc IC50 value, indicating enhanced cytotoxicity. The combination therapy affected inflammatory mediators by increasing IL-6 levels and reducing elevated TNF-α and NF-κB levels. Furthermore, the combination reduced GSH levels and augmented MDA, NQO1 and NRF2 levels, which have a crucial role in the cellular response to oxidative stress. Moreover, morusin enhanced apoptosis induced by Doc through increasing Bax levels and decreasing Bcl-2 expression. Molecular docking analyses confirmed morusins' activity against the target proteins studied. In conclusion, the combination of morusin and docetaxel showed enhanced efficacy at lower drug concentrations in treating prostate cancer. The combination therapy may reduce drug resistance by modulating inflammatory mediators and regulating antioxidant markers. The results of this study indicate the possibility of morusin in being a supplementary treatment option for prostate cancer.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117572"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic oligonucleotide ASC1R shows excellent tolerability and remarkable efficacy in reducing SARS-CoV-2 mRNA levels in C57BL/6 mice. 治疗性寡核苷酸 ASC1R 在降低 C57BL/6 小鼠的 SARS-CoV-2 mRNA 水平方面显示出极佳的耐受性和显著的疗效。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-22 DOI: 10.1016/j.biopha.2024.117587

Veronika Nemethova, Petra Babiakova, Michal Selc, Kristina Jakic, Lucia Uhelska, Boglarka Teglasova, Peter Makovicky, Andrea Babelova, Filip Razga

{"title":"Therapeutic oligonucleotide ASC1R shows excellent tolerability and remarkable efficacy in reducing SARS-CoV-2 mRNA levels in C57BL/6 mice.","authors":"Veronika Nemethova, Petra Babiakova, Michal Selc, Kristina Jakic, Lucia Uhelska, Boglarka Teglasova, Peter Makovicky, Andrea Babelova, Filip Razga","doi":"10.1016/j.biopha.2024.117587","DOIUrl":"10.1016/j.biopha.2024.117587","url":null,"abstract":"The coronavirus pandemic has resulted in over 775 million cases and 7 million deaths worldwide, driving efforts to develop therapeutic strategies to control the viral infection. Therapeutic oligonucleotides have shown promise in treating many pathological conditions, including those of viral origin. The present study assessed the in vivo efficacy and safety of ASC1R, a novel therapeutic oligonucleotide of unconventional design targeting the conserved viral RdRp sequence essential for replication. In functional studies, ASC1R was administered to transfected C57BL/6 mice at doses of 1 and 10 mg/kg. Safety assessments included acute toxicity evaluations at doses ranging from 30 to 100 mg/kg, and subacute toxicity evaluations of repeated doses of 1 and 10 mg/kg. Evaluations included general clinical observations, findings at necropsy, measurements of organ weight, and histopathological examinations of the liver, lungs, spleen, and kidneys. ASC1R effectively reduced RdRp levels >94 % within 24 hours following a single 1 mg/kg dose, with no observed organ toxicity. Acute and subacute toxicity assessments found that mice receiving high (≥30 mg/kg) or repeated (10 mg/kg for 7 days) doses of ASC1R showed an increase in relative spleen weight, without histopathological changes. The marked ability of a single low dose of ASC1R (1 mg/kg) to reduce viral RNA suggests its potential for clinical applications, balancing therapeutic efficacy with minimal side effects. Our findings indicate that ASC1R has promise as a viable treatment option for patients with COVID-19.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117587"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fully human monoclonal antibody targeting the cysteine-rich substrate-interacting region of ADAM17 on cancer cells. 靶向癌细胞 ADAM17 富半胱氨酸底物相互作用区的全人源单克隆抗体。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI: 10.1016/j.biopha.2024.117605

Nayanendu Saha, Sang Gyu Lee, Eeva-Christine Brockmann, M Jason de la Cruz, Yehuda Goldgur, Rachelle P Mendoza, Elisa de Stanchina, Tanzy M Love, Josh Marvald, Yan Xu, Kai Xu, Juha P Himanen, Urpo Lamminmäki, Darren Veach, Dimitar B Nikolov

{"title":"Fully human monoclonal antibody targeting the cysteine-rich substrate-interacting region of ADAM17 on cancer cells.","authors":"Nayanendu Saha, Sang Gyu Lee, Eeva-Christine Brockmann, M Jason de la Cruz, Yehuda Goldgur, Rachelle P Mendoza, Elisa de Stanchina, Tanzy M Love, Josh Marvald, Yan Xu, Kai Xu, Juha P Himanen, Urpo Lamminmäki, Darren Veach, Dimitar B Nikolov","doi":"10.1016/j.biopha.2024.117605","DOIUrl":"10.1016/j.biopha.2024.117605","url":null,"abstract":"ADAM17 sheds EGFR/erbB ligands and triggers oncogenic pathways that lead to the progression of solid tumors. We targeted the ADAM17 disintegrin and cysteine rich domain region (D+C) to generate a panel of single-chain antibody fragments (scFvs) that selectively bind to the D or C domains of ADAM17, but not of ADAM10 or ADAM19. From the panel, we selected one scFv, referred to as C12, based on its high binding affinity towards the target, and re-formatted it to a full IgG for further studies. High-resolution cryo-electron microscopy studies documented that the mAb binds to the ADAM17 C-domain that in ADAM proteases, notably ADAM10 and ADAM17, is known to impart substrate-specificity. The C12 mAb significantly inhibited EGFR phosphorylation in cancer cell lines by hindering the cleavage of EGFR ligands tethered to the cell surface. This inhibition provides a mechanism for potential anti-tumor effects, and indeed C12 diminished the viability of a variety of EGFR-expressing cancer cell lines. Cell-based ELISA studies revealed that C12 preferentially bound to activated ADAM17 present on tumor cells, as compared to the autoinhibited ADAM17 that is the predominant form on HEK293 and other non-tumor cells. C12 also exhibited tumor growth inhibition in an ovarian cancer xenograft mouse model. Consistent with its selective tumor cell binding in vitro, radioimmuno PET (positron emission tomography) imaging with 89Zr-DFO-C12 in mouse xenograft models confirmed tumoral accumulation of the C12 mAb.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117605"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "miR-615-3p promotes proliferation and migration and inhibits apoptosis through its potential target CELF2 in gastric cancer" [Biomed. Pharmacother. 101, May 2018, pp. 406-413]. 对 "miR-615-3p通过其潜在靶点CELF2促进胃癌的增殖和迁移并抑制凋亡 "的更正[《生物医学。药物治疗学》101，2018年5月，第406-413页]。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-29 DOI: 10.1016/j.biopha.2024.117622

Jizhao Wang, Lin Liu, Yuchen Sun, Yumo Xue, Jingkun Qu, Shupei Pan, Huajing Li, Hangying Qu, Jiansheng Wang, Jia Zhang

引用次数: 0

Gilteritinib reverses ABCB1-mediated multidrug resistance: Preclinical in vitro and animal investigations. 吉瑞替尼可逆转ABCB1介导的多药耐药性：临床前体外和动物实验

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1016/j.biopha.2024.117603

Meng Zhang, Mei-Ling She, Jun Chen, Xiao-Qi Zeng, Qing-Quan Xiong, Ying-Huan Cen, Jia-An Ye, Guo-Bin Qiu, Shu-Yi Yang, Guang-Hui Ren

{"title":"Gilteritinib reverses ABCB1-mediated multidrug resistance: Preclinical in vitro and animal investigations.","authors":"Meng Zhang, Mei-Ling She, Jun Chen, Xiao-Qi Zeng, Qing-Quan Xiong, Ying-Huan Cen, Jia-An Ye, Guo-Bin Qiu, Shu-Yi Yang, Guang-Hui Ren","doi":"10.1016/j.biopha.2024.117603","DOIUrl":"10.1016/j.biopha.2024.117603","url":null,"abstract":"Multi-drug resistance (MDR) poses a significant challenge to cancer treatment. Targeting ATP-binding cassette subfamily B member 1 (ABCB1) is a viable strategy for overcoming MDR. This study examined the preclinical in vitro and animal studies that used gilteritinib, a FLT3 inhibitor that reverses ABCB1-mediated MDR. At nontoxic levels, gilteritinib significantly increased the susceptibility of cancer cells overexpressing ABCB1 to chemotherapeutic drugs. Furthermore, it impaired the development of drug-resistant cell colonies and 3D spheroids. Studies on the reversal mechanism have shown that gilteritinib can directly bind to the drug-binding site of ABCB1, inhibiting drug efflux activity. Consequently, the substrate's drug cytotoxicity increases in MDR cells. Furthermore, gilteritinib increased ATPase activity while leaving ABCB1 expression and subcellular distribution unchanged and inhibited AKT or ERK activation. Docking analysis indicated that Gilteritinib could interact with the drug-binding site of the ABCB1 transporter. In vivo studies have shown that gilteritinib improves the antitumor efficacy of paclitaxel in nude mice without obvious toxic effects. In conclusion, our preclinical investigations show that gilteritinib has the potential to successfully overcome ABCB1-mediated MDR in a clinical environment when combined with substrate medicines.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117603"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Calcium ion delivery by microbubble-assisted sonoporation stimulates cell death in human gastrointestinal cancer cells" [Biomed. Pharmacother. 179 (2024) 117339]. 更正："微气泡辅助声波修复法输送钙离子刺激人胃肠癌细胞死亡" [Biomed. Pharmacother.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-04 DOI: 10.1016/j.biopha.2024.117442

Dawid Przystupski, Dagmara Baczyńska, Joanna Rossowska, Julita Kulbacka, Marek Ussowicz

引用次数: 0