Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

{"title":"Buparlisib and ponatinib inhibit aggressiveness of cholangiocarcinoma cells via suppression of IRS1-related pathway by targeting oxidative stress resistance.","authors":"Waleeporn Kaewlert, Chadamas Sakonsinsiri, Worachart Lert-Itthiporn, Panupong Mahalapbutr, Saba Ali, Thanyada Rungrotmongkol, Apinya Jusakul, Napat Armartmuntree, Chawalit Pairojkul, Guofei Feng, Ning Ma, Somchai Pinlaor, Mariko Murata, Raynoo Thanan","doi":"10.1016/j.biopha.2024.117569","DOIUrl":"10.1016/j.biopha.2024.117569","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is an oxidative stress-driven liver cancer with bile duct epithelial cell phenotypes and currently lacks effective treatments, making targeted drug therapy urgently needed. Oxidative stress plays a critical role in CCA carcinogenesis, involving cells with oxidative stress resistance via upregulation of the PI3K and MEKK3 signaling pathways. In this study, we investigated the antineoplastic efficacy of a PI3K inhibitor (buparlisib) and a multi-tyrosine kinase inhibitor (ponatinib) on CCA. The cytotoxicity of the drug combination was studied in vitro using CCA cell lines and in vivo using CCA xenograft models. It was found that the drug combination suppressed growth, colony formation, and migration abilities of CCA cells and induced oxidative damage, cell cycle arrest, and autophagy by suppressing MEKK3 and YAP1 through inhibition of insulin receptor substrate 1 (IRS1) signaling. Moreover, the drugs would potentially bind to the IRS1 protein, significanly decreasing IRS1 phosphorylation. Additionally, the drug combination significantly diminished the expression of YAP1, the cell proliferation marker and an antioxidant regulator, and increased oxidative stress-responsive markers in the xenograft model. In conclusion, targeting oxidative stress resistance with combined buparlisib and ponatinib suppressed tumor growth and migration by repressing IRS1-related pathways and ultimately inducing oxidative damage, suggesting the potential for targeted therapy and clinical trials in CCA patients over the use of a single drug.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117569"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482964","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}

{"title":"Combined dapagliflozin and roxadustat effectively protected heart and kidney against cardiorenal syndrome-induced damage in rodent through activation of cell stress-Nfr2/ARE signalings and stabilizing HIF-1α.","authors":"Pei-Hsun Sung, Ya Yue, Yi-Ling Chen, John Y Chiang, Ben-Chung Cheng, Chih-Chao Yang, Han-Tan Chai, Hon-Kan Yip","doi":"10.1016/j.biopha.2024.117567","DOIUrl":"10.1016/j.biopha.2024.117567","url":null,"abstract":"<p><strong>Background: </strong>This study tested whether combined dapagliflozin (DAPA) and roxadustat (ROX) therapy was superior to a singular therapy in protecting heart and kidney functions in rats with cardiorenal syndrome (CRS).</p><p><strong>Methods and results: </strong>An in vitro study demonstrated that the cell survival (PI3K/Akt/mTOR)/cell stress (ERK1/2, JNK/p-38) signaling was significantly activated by combination therapy with ROX-DAPA (all p<0.001). Additionally, these two signaling pathways further significantly upregulated the hypoxia-induced factor (HIF)-1α which, in turn, significantly upregulated Nrf2/ARE (HO-1/NQO-1) and angiogenesis/cell-growth factors (EPO/SDF-1α/VEGF/FGF/IGF-2) and downregulated hypoxia-inducible factor prolyl-4-hydroxylase-1 (all p<0.001). Adult-male SD rats were categorized into Groups 1 (sham-operated control)/2 (CRS)/3 (CRS+ROX)/4 (CRS+DAPA)/5 (CRS+ROX+DAPA). By Day 60 after rodent CRS induction, the levels of BUN/creatinine and the ratio of urine protein to creatinine were lowest in Group 1, highest in Group 2, and significantly lower in Group 5 than in Groups 3 and 4; however, they were similar in the latter two groups, whereas the left-ventricular-ejection-fraction exhibited the opposite trend of creatinine among the groups (all p<0.0001). The protein expression levels of cell-survival (p-PI3K/p-Akt-p-mTOR)/cell-stress (p-JNK/p-p38/p-ERK1/2)/Nrf2-ARE (HO-1/NQO-1/SIRT1/SIRT3) signaling factors and angiogenesis factors (HIF-1α/VEGF/SDF-1α/FGF/IGF-2/EPO) significantly and progressively increased from Groups 1-5 (all p<0.0001).</p><p><strong>Conclusion: </strong>Combined DAPA-ROX therapy has a synergistic effect on protecting heart and kidney functions against CRS-induced damage in rodents.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117567"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482966","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}

{"title":"Dihydromyricetin treats pulmonary hypertension by modulating CKLF1/CCR5 axis-induced pulmonary vascular cell pyroptosis.","authors":"Qian Yan, Ping Li, Shasha Liu, Yang Sun, Chen Chen, Junpeng Long, Yuting Lin, Jinping Liang, Hanlong Wang, Ling Zhang, Hongbin Wang, Huiqin Wang, Songwei Yang, Meiyu Lin, Xuan Liu, Jiao Yao, Zhifeng Tian, Naihong Chen, Yantao Yang, Qidi Ai","doi":"10.1016/j.biopha.2024.117614","DOIUrl":"10.1016/j.biopha.2024.117614","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by elevated pulmonary artery pressure and vascular remodeling, resulting in poor prognosis and increased mortality rates. Chemokine-like factor 1 (CKLF1) plays a significant role in inducing inflammation and cell proliferation, both of which are critical processes in the pathogenesis of various diseases. Dihydromyricetin (DMY) has garnered attention for its potent anti-inflammatory properties. This study evaluated the protective effects of DMY against PH, demonstrating that DMY treatment can mitigate pyroptosis in pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) in vivo via the CKLF1/CCR5 axis. Results indicated significant improvements in hemodynamics, inflammatory responses, fibrosis, vascular remodeling, and right ventricular hypertrophy in PH rats following DMY treatment. Furthermore, the interaction between CKLF1 and CCR5 was investigated in CKLF1^-/- rats after PH induction. DMY was found to downregulate CKLF1 expression and the inflammatory response in the lungs, with its therapeutic efficacy diminished following CKLF1 knockdown. This study underscores the therapeutic potential of DMY in the management of PH and lays a foundation for future research and clinical applications.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117614"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514588","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}

{"title":"Corrigendum \"The protective effect of shikonin on renal tubular epithelial cell injury induced by high glucose\" [Biomed. Pharmacother. 98 (2018) 701-708].","authors":"Yuna Tong, Junlan Chuan, Lan Bai, Jianyou Shi, Lei Zhong, Xingmei Duan, Yuxuan Zhu","doi":"10.1016/j.biopha.2024.117624","DOIUrl":"10.1016/j.biopha.2024.117624","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117624"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570481","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}

{"title":"Kefir peptides mitigate L-NAME-induced preeclampsia in rats through modulating hypertension and endothelial dysfunction.","authors":"Yu-Hsuan Chen, Yo-Cheng Chang, Wan-Ju Wu, Min Chen, Chih-Ching Yen, Ying-Wei Lan, Hsu-Chen Cheng, Chuan-Mu Chen","doi":"10.1016/j.biopha.2024.117592","DOIUrl":"10.1016/j.biopha.2024.117592","url":null,"abstract":"<p><strong>Aim: </strong>Preeclampsia is a complex and serious pregnancy disorder that leads to maternal and neonatal mortality worldwide. Kefir peptides (KPs), derived from various prebiotic fermentations in whole milk by kefir grains, were investigated for their potential therapeutic effects. In this study, we used the L-NAME in drinking water to induce a preeclampsia-like condition in spontaneous hypertension stroke-prone (SHRSP) pregnant rats.</p><p><strong>Main methods: </strong>The rats were assigned to five groups: the normal group (WKY rats), the untreated group (SHRSP rat control pregnant), the L-NAME/Mock group (SHRSP rats fed with L-NAME water), the L-NAME/KPs-LD group (SHRSP rats fed with L-NAME water and low-dose KPs diets), and the L-NAME/KPs-HD group (SHRSP rats fed with L-NAME water and high-dose KPs diets) for a 20-day experiment. Chorioallantois membrane (CAM) assay was applied for ex vivo angiogenesis study of KPs treatment.</p><p><strong>Key findings: </strong>Data showed that rats in the L-NAME group developed severe hypertension, proteinuria, placental damage, and embryo resorption. Pre-administration of KPs significantly reduced hypertension, proteinuria, improved generalized endothelial dysfunction, and decreased levels of anti-HIF-1α, sFLT1, anti-TNF-α, and IL-6 in the placenta of SHRSP rats. In ex vivo CAM study, L-NAME administration in chicken embryos resulted in lower vessel density and hemorrhage; however, angiogenesis was observed after KPs-HD treatment.</p><p><strong>Significance: </strong>The results indicate that kefir peptides improve renal lesions, prevent renal parenchyma damage, and balance endothelial and angiogenic dysfunction in both maternal and fetal sites in L-NAME-induced SHRSP pregnant rats.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117592"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570492","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}

{"title":"Corrigendum to \"MicroRNA-30c functions as a tumor suppressor via targeting SNAI1 in esophageal squamous cell carcinoma\" [Biomed. Pharmacother. 98 (2018) 680-686].","authors":"Teng Ma, Ye Zhao, Qitong Lu, Yun Lu, Zhiyong Liu, Tao Xue, Yongfeng Shao","doi":"10.1016/j.biopha.2024.117376","DOIUrl":"10.1016/j.biopha.2024.117376","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117376"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127638","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}

{"title":"Studies on absorption mechanism and pharmacokinetic properties of albendazole-bile acid conjugate: In vivo and in vitro.","authors":"Zhimei Guo, Shizhen Tang, Kaili Nie, Jingshuai Liu, Chunhui Hu","doi":"10.1016/j.biopha.2024.117400","DOIUrl":"10.1016/j.biopha.2024.117400","url":null,"abstract":"<p><strong>Purpose: </strong>To improve the oral bioavailability of albendazole (ABZ), a series of albendazole-bile acid conjugates (ABCs) were synthesized. ABC's transmembrane transport mechanism and in vivo pharmacokinetic properties were preliminarily studied.</p><p><strong>Methods: </strong>The transmembrane transport mechanism of ABCs was studied using the Caco-2 monolayer cell model and intestinal perfusion model. The concentration of ABCs and ABZ were evaluated using High-Performance Liquid Chromatography (HPLC) and HPLC-Mass Spectrometry (HPLC-MS/MS).</p><p><strong>Results: </strong>Compared to ABZ, better permeability was observed for different types and concentrations of ABCs using the Caco-2 monolayer cell model, with ABC-C8 showing the highest permeability. The transmembrane transport of ABCs was affected by ASBT inhibitors, indicating an ASBT-mediated active transport mechanism. Additionally, introducing cholic acid resulted in ABZ no longer being a substrate for P-gp, MRP2, and BCRP, effectively reversing ABZ efflux. In vivo unidirectional intestinal perfusion results in rats showed that ABCs altered the absorption site of ABZ from the jejunum to the ileum. The absorption efficiency of ABCs in each intestinal segment was higher than that of ABZ, and the transmembrane transport efficiency decreased with increasing concentrations of ASBT inhibitors. This further confirmed the presence of both passive diffusion and ASBT-mediated active transport mechanisms in the transport of ABCs. The solubility of ABCs in gastric juice and pharmacokinetics in rats showed that ABZ-C4 exhibited enhanced solubility. Moreover, ABCs significantly increased oral bioavailability compared to ABZ, with ABC-C4 showing an approximately 31-fold increase in bioavailability.</p><p><strong>Conclusion: </strong>The transmembrane transport mechanism of ABCs involves a combination of ASBT-mediated active transport and passive diffusion. Moreover, the incorporation of BAs successfully reverses the efflux of ABZ by efflux proteins. Among the synthesized conjugates, ABC-C4 demonstrated superior dissolution behavior both in vitro and in vivo.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"179 ","pages":"117400"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147108","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}

{"title":"Corrigendum to \"Monastrol suppresses invasion and metastasis in human colorectal cancer cells by targeting fascin independent of kinesin-Eg5 pathway\" [Biomed. Pharmacother. 175 (2024) 116785].","authors":"Begoña Alburquerque-González, Silvia Montoro-García, Ángel Bernabé-García, Manuel Bernabé-García, Priscila Campioni-Rodrigues, Alejandro Rodríguez-Martínez, Irene Luque, Tuula Salo, Alfonso Pérez-Garrido, Horacio Pérez-Sánchez, María Luisa Cayuela, Ginés Luengo-Gil, Enrico Luchinat, Fatima Postigo-Corrales, Tommaso Staderini, Francisco José Nicolás, Pablo Conesa-Zamora","doi":"10.1016/j.biopha.2024.117411","DOIUrl":"10.1016/j.biopha.2024.117411","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117411"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303323","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}

{"title":"Retraction notice to 'Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate' [Biomedicine & Pharmacotherapy, Volume 171 (2024) 116055].","authors":"Alexiane Pradelle, Sabine Mainbourg, Steeve Provencher, Emmanuel Massy, Guillaume Grenet, Jean-Christophe Lega","doi":"10.1016/j.biopha.2024.117353","DOIUrl":"10.1016/j.biopha.2024.117353","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117353"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082834","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}

{"title":"Corrigendum to \"Exploring the molecular mechanisms of MSC-derived exosomes in Alzheimer's disease: Focus on autophagy, insulin and PI3K/Akt/mTOR signaling pathways\" [Biomed. Pharmacother. 176 (2024) 116836].","authors":"Faris Q B Alenzi","doi":"10.1016/j.biopha.2024.117381","DOIUrl":"10.1016/j.biopha.2024.117381","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117381"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134760","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}