Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

{"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":"<p><p>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.</p>","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}

{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>In summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"title":"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].","authors":"Jizhao Wang, Lin Liu, Yuchen Sun, Yumo Xue, Jingkun Qu, Shupei Pan, Huajing Li, Hangying Qu, Jiansheng Wang, Jia Zhang","doi":"10.1016/j.biopha.2024.117622","DOIUrl":"10.1016/j.biopha.2024.117622","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117622"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549522","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":"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":"<p><p>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.</p>","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}

{"title":"Corrigendum to \"Calcium ion delivery by microbubble-assisted sonoporation stimulates cell death in human gastrointestinal cancer cells\" [Biomed. Pharmacother. 179 (2024) 117339].","authors":"Dawid Przystupski, Dagmara Baczyńska, Joanna Rossowska, Julita Kulbacka, Marek Ussowicz","doi":"10.1016/j.biopha.2024.117442","DOIUrl":"10.1016/j.biopha.2024.117442","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117442"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376439","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":"Metformin-mediated protection against doxorubicin-induced cardiotoxicity.","authors":"Ming-Li Sun, Jun-Min Dong, Chen Liu, Pu Li, Chao Zhang, Jie Zhen, Wei Chen","doi":"10.1016/j.biopha.2024.117535","DOIUrl":"10.1016/j.biopha.2024.117535","url":null,"abstract":"<p><strong>Background: </strong>A phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed.</p><p><strong>Objectives: </strong>The aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials.</p><p><strong>Methods: </strong>MET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups.</p><p><strong>Results: </strong>H9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting.</p><p><strong>Conclusions: </strong>We confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117535"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482992","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 \"Hominis Placenta modulates PTSD-like behaviors in SPSS-induced PTSD mice: Regulating energy metabolism and neuronal activity\" [Biomed. Pharmacother. 178 (2024) 117243].","authors":"Mudan Cai, Hee Ra Park, Eun Jin Yang","doi":"10.1016/j.biopha.2024.117443","DOIUrl":"10.1016/j.biopha.2024.117443","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117443"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334323","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}