Biomedicine & Pharmacotherapy最新文献

{"title":"Aspirin reduces Ponatinib-induced cardiovascular toxic phenotypes and death in zebrafish","authors":"Ruiqi Yu ,&nbsp;Nana Ai ,&nbsp;Chen Huang ,&nbsp;Danni Wang ,&nbsp;Chao Bian ,&nbsp;Wei Ge ,&nbsp;Cheong-Meng Chong","doi":"10.1016/j.biopha.2024.117503","DOIUrl":"10.1016/j.biopha.2024.117503","url":null,"abstract":"<div><h3>Background</h3><div>Ponatinib (Iclusig) is an oral tyrosine kinase BCR-ABL inhibitor for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) and chronic myeloid leukemia (CML) who are resistant to the therapies with other tyrosine kinase inhibitors. However, adverse cardiovascular events caused by Ponatinib are a serious issue that affects patients' survival rates. Thus, it is necessary to search for candidate drugs to reduce the cardiovascular toxicity of Ponatinib.</div></div><div><h3>Purpose</h3><div>To investigate the effects of Aspirin on Ponatinib-induced cardiovascular toxicity in zebrafish.</div></div><div><h3>Methods</h3><div>AB strain of wild type zebrafish (<em>Danio rerio</em>), Tg (<em>cmlc2: GFP</em>) transgenic zebrafish, and Tg (<em>gata1: dsRed</em>) transgenic zebrafish were used as <em>in vivo</em> models to assess survival, blood flow, cardiac morphology, and function. Thrombus formation was detected using O-dianisidine staining. The transcriptome of zebrafish larvae treated with Ponatinib was assessed using RNA sequencing.</div></div><div><h3>Results</h3><div>Ponatinib not only reduced survival rate but also caused cardiovascular toxic events such as pericardial edema, abnormal heart structure, low heart rate, and thrombosis. In addition, whole-body transcriptome analysis showed that Ponatinib up-regulated the expression of cyclooxygenase-1 (COX-1). Compared with other antithrombotic drugs, a COX-1 inhibitor Aspirin more effectively reduced ponatinib-induced cardiovascular toxicity events and improved the survival rate of zebrafish larvae.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that Aspirin exhibits the potential to reduce Ponatinib-induced cardiovascular toxicity.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117503"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the potential of extracellular vesicle circRNAs in breast cancer: From molecular mechanisms to therapeutic horizons","authors":"Lijuan Fang ,&nbsp;Zehua Zhu ,&nbsp;Mingyue Han ,&nbsp;Shaojie Li ,&nbsp;Xiangyi Kong ,&nbsp;Lusen Yang","doi":"10.1016/j.biopha.2024.117480","DOIUrl":"10.1016/j.biopha.2024.117480","url":null,"abstract":"<div><div>Breast cancer remains the leading cause of cancer-related morbidity and mortality among women worldwide, underscoring the urgent need for novel diagnostic and therapeutic strategies. This review explores the emerging roles of circular RNAs (circRNAs) within extracellular vesicles (exosomes) in breast cancer. circRNAs, known for their stability and tissue-specific expression, are aberrantly expressed in breast cancer and regulate critical cellular processes such as proliferation, migration, and apoptosis, positioning them as promising biomarkers. Exosomes facilitate intercellular communication by delivering circRNAs, reflecting the physiological and pathological state of their source cells. This review highlights the multifaceted roles of exosomal circRNAs in promoting tumor growth, metastasis, and drug resistance through their modulation of tumor metabolism, the tumor microenvironment, and immune responses. In particular, we emphasize their contributions to chemotherapy resistance and their potential as both diagnostic markers and therapeutic targets. By synthesizing current research, this review provides novel insights into the clinical applications of exosomal circRNAs, offering a foundation for future studies aimed at improving breast cancer management through non-invasive diagnostics and targeted therapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117480"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps and cardiovascular disease: Associations and potential therapeutic approaches","authors":"Yiyue Tang ,&nbsp;Yang Jiao ,&nbsp;Xiaohua An ,&nbsp;Qingxian Tu ,&nbsp;Qianfeng Jiang","doi":"10.1016/j.biopha.2024.117476","DOIUrl":"10.1016/j.biopha.2024.117476","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) is a significant global health concern, ranking among the top five causes of disability-adjusted life-years (DALY) in 190 countries and territories. Neutrophils, key players in the innate immune system, combat infections by releasing neutrophil extracellular traps (NETs) composed of DNA, histones, elastase, myeloperoxidase, and antimicrobial peptides. This paper explores the relationship between NETs and cardiovascular diseases, focusing on conditions such as heart failure, pulmonary hypertension, atrial fibrillation, and ischemia-reperfusion injury. Particularly, it delves into the impact of NETs on atrial fibrillation and pulmonary hypertension, as well as the role of myeloperoxidase (MPO) and neutrophil elastase (NE) in these diseases. Furthermore, the potential of targeting NETs for the treatment of cardiovascular diseases is discussed.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117476"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of nitrile-containing isoquinoline-related natural product derivatives as coronavirus entry inhibitors in silico and in vitro","authors":"Nasim Shahhamzehei ,&nbsp;Sara Abdelfatah ,&nbsp;Hannah S. Schwarzer-Sperber ,&nbsp;Kathrin Sutter ,&nbsp;Rümeysa Yücer ,&nbsp;Gerhard Bringmann ,&nbsp;Roland Schwarzer ,&nbsp;Thomas Efferth","doi":"10.1016/j.biopha.2024.117517","DOIUrl":"10.1016/j.biopha.2024.117517","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections and deaths worldwide since its emergence in Wuhan, China, in late 2019. Natural product inhibitors targeting the interaction between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 (ACE2), crucial for viral attachment and cellular entry, are of significant interest as potential antiviral agents. In this study a library of nitrile- and sulfur-containing natural product derived compounds were used for virtual drug screening against the RBD of the SARS-CoV-2 spike protein. The top 18 compounds from docking were tested for their efficacy to inhibit virus entry. In vitro experiments revealed that compounds <strong>9</strong>, <strong>14</strong>, and <strong>15</strong> inhibited SARS-CoV-2 pseudovirus and live virus entry in HEK-ACE2 and Vero E6 host cells at low micromolar IC₅₀ values. Cell viability assays showed these compounds exerted low cytotoxicity towards MRC5, Vero E6, and HEK-ACE2 cell lines. Microscale thermophoresis revealed all three compounds strongly bound to the RBDs of SARS-CoV-2, SARS-CoV-2 XBB, SARS-CoV-1, MERS-CoV, and HCoV-HKU1, with their K_d values increasing as RBD sequence similarity decreased. Molecular docking studies indicated compounds <strong>9</strong>, <strong>14</strong>, and <strong>15</strong> bound to the SARS-CoV-2 spike protein RBD and interacted with hotspot amino acid residues required for the RBD-ACE2 interaction and cellular infection. These three nitrile-containing candidates, particularly compound <strong>15</strong>, should be considered for further development as potential pan-coronavirus entry inhibitors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117517"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research advances in signaling pathways related to the malignant progression of HSIL to invasive cervical cancer: A review","authors":"Huifang Wang ,&nbsp;Chang Liu ,&nbsp;Keer Jin ,&nbsp;Xiang Li ,&nbsp;Jiaxin Zheng ,&nbsp;Danbo Wang","doi":"10.1016/j.biopha.2024.117483","DOIUrl":"10.1016/j.biopha.2024.117483","url":null,"abstract":"<div><div>The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/β-catenin, Notch, NF-κB, MAPK, TGF-β, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117483"},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy","authors":"Juan Chen ,&nbsp;Zi-yun Hu ,&nbsp;Yu Ma ,&nbsp;Shan Jiang ,&nbsp;Jiu-yu Yin ,&nbsp;Yu-kai Wang ,&nbsp;Yong-gui Wu ,&nbsp;Xue-qi Liu","doi":"10.1016/j.biopha.2024.117499","DOIUrl":"10.1016/j.biopha.2024.117499","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae (<em>Euodia rutaecarpa</em> (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-β1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-β1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117499"},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbiosis and diabetic foot ulcers: A metabolic perspective of Staphylococcus aureus infection","authors":"Ruisi Liu ,&nbsp;Jiawei Feng ,&nbsp;Yiming Ni ,&nbsp;Kaixin Chen ,&nbsp;Yuqing Wang ,&nbsp;Ting Zhang ,&nbsp;Mingmei Zhou ,&nbsp;Cheng Zhao","doi":"10.1016/j.biopha.2024.117498","DOIUrl":"10.1016/j.biopha.2024.117498","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> (<em>S. aureus</em>) infection is the most prevalent and resistant bacterial infection, posing a worldwide health risk. Compared with healthy people, diabetes patients with weak immune function and abnormal metabolism are more vulnerable to bacterial infection, which aggravates the intensity of infection and causes a series of common and dangerous complications, such as diabetes foot ulcer (DFU). Due to metabolic abnormalities of diabetic patients, <em>S. aureus</em> on the skin surface of DFU transitions from a commensal to an invasive infection. During this process, <em>S. aureus</em> resists a series of unfavorable conditions for bacterial growth by altering energy utilization and metabolic patterns, and secretes various virulence factors, causing persistent infection. With the emergence of multiple super-resistant bacteria, antibiotic treatment is no longer the only treatment option, and developing new drugs and therapies is urgent. Regulating the metabolic signaling pathway of <em>S. aureus</em> plays a decisive role in regulating its virulence factors and impacts adjuvant therapy for DFU. This article focuses on studying the impact of regulating metabolic signals on the virulence of <em>S. aureus</em> from a metabolism perspective. It provides an outlook on the future direction of the novel development of antimicrobial therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117498"},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-treatment with notoginsenoside R1 from Panax notoginseng protects against high-altitude-induced pulmonary edema by inhibiting pyroptosis through the NLRP3/caspase-1/GSDMD pathway","authors":"Demei Huang ,&nbsp;Yilan Wang ,&nbsp;Caixia Pei ,&nbsp;Xiu Zhang ,&nbsp;Zherui Shen ,&nbsp;Nan Jia ,&nbsp;Sijing Zhao ,&nbsp;Guang Li ,&nbsp;Zhenxing Wang","doi":"10.1016/j.biopha.2024.117512","DOIUrl":"10.1016/j.biopha.2024.117512","url":null,"abstract":"<div><div>High-altitude pulmonary edema (HAPE) is a potentially fatal condition that occurs when exposed to high-altitude hypoxia environments. Currently, there is no effective treatment for HAPE, and available interventions focus on providing relief. Notoginsenoside R1 (NGR1), a major active constituent of <em>Panax notoginseng (Burkill) F.H.Chen</em> (sānqī), has demonstrated heart and lung-protective effects under hypobaric hypoxia. However, there is a lack of clarity regarding the precise mechanisms that underlie the protective effects of NGR1 against inflammation. In this study, a rat model of HAPE was developed to assess the effect of NGR1 on this pathology. High-altitude hypoxia corresponding to 6000 m altitude was simulated with a hypobaric chamber. We found that NGR1 dose-dependently alleviated pulmonary oxidative stress damage and inflammatory response, and prevented acid-base balance disruption. In addition, NGR1 restored the expression levels of hypoxia-inducible factor-1 alpha, vascular endothelial growth factor, and aquaporin protein-5, correlated with the development of pulmonary edema induced by hypobaric hypoxia. Furthermore, NGR1 pre-treatment remarkably mitigated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-induced pyroptosis, and this effect was partially counteracted by the use of an NLRP3 agonist. Thus, NGR1 may exert a lung-protective effect against HAPE by ameliorating hypoxia-induced lung edema, oxidative damage, and inflammation through inhibition of the NLRP3/Caspase-1/ GSDMD signaling pathway.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117512"},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in stimuli-responsive gold nanorods for drug-delivery and targeted therapy systems","authors":"Sakineh Hajebi ,&nbsp;Mohsen Chamanara ,&nbsp;Shadi Sadat Nasiri ,&nbsp;Mahsa Ghasri ,&nbsp;Alireza Mouraki ,&nbsp;Reza Heidari ,&nbsp;Abbas Nourmohammadi","doi":"10.1016/j.biopha.2024.117493","DOIUrl":"10.1016/j.biopha.2024.117493","url":null,"abstract":"<div><div>In recent years, the use of gold nanorods (AuNRs) has garnered considerable attention in biomedical applications due to their unique optical and physicochemical properties. They have been considered as potential tools for the advanced treatment of diseases by various stimuli such as magnetic fields, pH, temperature and light in the fields of targeted therapy, imaging and drug delivery. Their biocompatibility and tunable plasmonic properties make them a versatile platform for a range of biomedical applications. While endogenous stimuli have limited cargo delivery control at specific sites, exogenous stimuli are a more favored approach despite their circumscribed penetration depth for releasing the cargo at the specific target. Dual/multi-stimuli responsive AuNTs can be triggered by multiple stimuli for enhanced control and specificity in biomedical applications. This review provides to provide a summary of the biomedical applications of stimuli-responsive AuNRs, including their endogenous and exogenous properties, as well as their dual/multi-functionality and potential for clinical delivery. This review provides a comprehensive review on the improvement of therapeutic efficacy and the effective control of drug release with AuNRs, highlights AuNRs design strategies in recent years, discusses the advantages or challenges so far in the field of AuNRs. Finally, we have addressed the clinical translation bio-integrated nanoassemblies (CTBNs) in this field.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117493"},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paclitaxel-resistance facilitates glycolytic metabolism via Hexokinase-2-regulated ABC and SLC transporter genes in ovarian clear cell carcinoma","authors":"Tsai-Yu Lin ,&nbsp;Shin-Yuan Gu ,&nbsp;Yi-Hui Lin ,&nbsp;Jou-Ho Shih ,&nbsp;Jiun-Han Lin ,&nbsp;Teh-Ying Chou ,&nbsp;Yu-Ching Lee ,&nbsp;Shwu-Fen Chang ,&nbsp;Yaw-Dong Lang","doi":"10.1016/j.biopha.2024.117452","DOIUrl":"10.1016/j.biopha.2024.117452","url":null,"abstract":"<div><div>Ovarian clear cell carcinoma (OCCC) frequently develops resistance to platinum-based therapies, which is regarded as an aggressive subtype. However, metabolic changes in paclitaxel resistance remain unclear. Herein, we present the metabolic alternations of paclitaxel resistance in bioenergetic profiling in OCCC. Paclitaxel-resistant OCCC cells were developed and metabolically active with oxygen consumption rates (OCR) compared to parental cells. Metabolite profiling analysis revealed that paclitaxel-resistant OCCC cells reduced intracellular ATP and GTP influx rates, increasing the NADH/NAD+ ratio. We further demonstrated that paclitaxel-resistant OCCC cells led to characteristic alternations of metabolite levels in energy-requiring and energy-releasing steps of glycolysis and their corresponding glycolytic enzymes. Copy number alterations and RNA sequencing analysis demonstrated that ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporter genes involved in glycolysis metabolism and molecular transport were enriched in paclitaxel-resistant OCCC cells. We first identified that Hexokinase 2 (HK2) expression is upregulated in paclitaxel-resistant OCCC cells to determine the quantity of glucose entering glycolysis. Utilizing proteolysis-targeting chimera (PROTAC) HK2 degraders, we also found that paclitaxel sensitivity, viability, and oxygen consumption rates under paclitaxel treatment were restored by HK2 degraders treatment, and decreased downstream expression of the ABC and SLC transporters was shown in OCCC cells. Taken together, these findings highlight the paclitaxel resistance in OCCC elucidates metabolic alternation, including ABC- and SLC- drug transporters, thereby affecting glycolysis metabolism in response to paclitaxel resistance, and HK2 may become a novel potential therapeutic target for paclitaxel resistance.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117452"},"PeriodicalIF":6.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}