Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献_第4页

Simeprevir induces ferroptosis through β-TrCP/Nrf2/GPX4 axis in triple-negative breast cancer cells. 西美瑞韦通过β-TrCP/Nrf2/GPX4轴在三阴性乳腺癌细胞中诱导铁蛋白沉积。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.biopha.2024.117558

Zhirong Lin, Zifei Liu, Xinyu Yang, Zhilong Pan, Yaxin Feng, Yunyi Zhang, Huiping Chen, Liyan Lao, Jianing Chen, Fujun Shi, Chang Gong, Wenfeng Zeng

{"title":"Simeprevir induces ferroptosis through β-TrCP/Nrf2/GPX4 axis in triple-negative breast cancer cells.","authors":"Zhirong Lin, Zifei Liu, Xinyu Yang, Zhilong Pan, Yaxin Feng, Yunyi Zhang, Huiping Chen, Liyan Lao, Jianing Chen, Fujun Shi, Chang Gong, Wenfeng Zeng","doi":"10.1016/j.biopha.2024.117558","DOIUrl":"10.1016/j.biopha.2024.117558","url":null,"abstract":"The effective treatment regimens of triple-negative breast cancer (TNBC), a specific subtype of breast cancer (BC) with proneness to relapse and poor prognosis, are still lacking. Simeprevir (SIM), approved for hepatitis C infection treatment, has been proved to be a competitive drug for the treatment of various solid tumors recently. However, the anti-tumor mechanisms of SIM and therapeutic effects on TNBC are uncertain. In this study, we suggested that SIM effectively restrained the growth of MDA-MB-231 and BT-549 cells, two cell lines from TNBC. The RNA sequencing revealed that ferroptosis signaling was activated in SIM-treated TNBC cells. SIM induced ferroptosis in TNBC cells through reduced glutathione (GSH) levels, increased iron levels, ROS and lipid peroxidation. Mechanistically, SIM promoted the expression of β-TrCP to inhibit the Nrf2/GPX4 axis in TNBC cells, leading to ferroptosis. Moreover, SIM administration into the xenografts formed by MDA-MB-231 dramatically suppressed the tumor progression by inducing ferroptosis in vivo. Collectively, this finding reveals that SIM may serve as a competitive therapeutic strategy to inhibit TNBC.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117558"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483001","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

Expediting the development of robust 5-FU-resistant colorectal cancer models using innovative combined in vivo and in vitro strategies. 利用创新的体内和体外联合策略，加快开发稳健的 5-FU 抗性结直肠癌模型。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-23 DOI: 10.1016/j.biopha.2024.117576

Ming Shao, Yunran Gao, Xiling Xu, Jiyuan Shi, Zunyun Wang, Juan Du

{"title":"Expediting the development of robust 5-FU-resistant colorectal cancer models using innovative combined in vivo and in vitro strategies.","authors":"Ming Shao, Yunran Gao, Xiling Xu, Jiyuan Shi, Zunyun Wang, Juan Du","doi":"10.1016/j.biopha.2024.117576","DOIUrl":"10.1016/j.biopha.2024.117576","url":null,"abstract":"Background: 5-Fluorouracil (5-FU) is a cornerstone in colorectal cancer therapy, but resistance has compromised its efficacy, necessitating detailed research into resistance mechanisms. Traditional methods for developing 5-FU-resistant cell lines are lengthy, unstable, and often unrepresentative of clinical scenarios.Methods: We devised a rapid approach to create 5-FU-resistant colorectal cancer cells using an integrated in vivo/in vitro methodology. HCT116 cells were pretreated with 5-FU, then implanted into nude mice. Tumor growth was monitored, and cells from the tumors were cultured to establish the HCT116-Tumor cell line. Cells from 5-FU-exposed tumors received increasing 5-FU doses to induce resistance, creating the tumor-derived resistant (TR) cell line. Cells cultured without 5-FU were termed tumor-derived parental (TP) cells. An in vitro 5-FU resistance model, CR, served as a benchmark. Resistance metrics were evaluated using CCK-8 assays, Western Blotting, flow cytometry, and in vivo studies. Proteomics identified resistance-related differentially expressed proteins (DEPs).Results: Low-dose 5-FU pretreatment accelerated tumor growth. Combining in vivo and in vitro methods, we developed 5-FU-resistant TR cells within two and a half months, faster than the ten-month conventional protocol. TR cells showed stronger and more durable 5-FU resistance than CR cells, with inhibited apoptosis, autophagy, and ferroptosis, and activation of MDR1. Proteomic analysis indicated more DEPs in TR cells, suggesting unique resistance mechanisms. Animal studies confirmed enhanced drug resistance in TR cells.Conclusions: Our integrated approach rapidly develops colorectal cancer cells with robust 5-FU resistance, offering a potent model for exploring multiple resistance pathways and counter-resistance strategies.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117576"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514589","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

Sodium bicarbonate potentiates the antitumor effects of Olaparib in ovarian cancer via cGMP/PKG-mediated ROS scavenging and M1 macrophage transformation. 碳酸氢钠通过cGMP/PKG介导的ROS清除和M1巨噬细胞转化增强奥拉帕利对卵巢癌的抗肿瘤作用

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-22 DOI: 10.1016/j.biopha.2024.117509

Xiao Li, Yaoqi Sun, Jing Guo, Yujie Cheng, Wei Lu, Weihong Yang, Lian Wang, Zhongping Cheng

{"title":"Sodium bicarbonate potentiates the antitumor effects of Olaparib in ovarian cancer via cGMP/PKG-mediated ROS scavenging and M1 macrophage transformation.","authors":"Xiao Li, Yaoqi Sun, Jing Guo, Yujie Cheng, Wei Lu, Weihong Yang, Lian Wang, Zhongping Cheng","doi":"10.1016/j.biopha.2024.117509","DOIUrl":"10.1016/j.biopha.2024.117509","url":null,"abstract":"The high metabolic requirements of cancer cells result in excess accumulation of H+ in the tumor microenvironment. Therefore, the extracellular pH of solid tumors is acidic, whereas the pH of normal tissues is more alkaline. The acidic tumor environment is correlated with tumor metastasis, immune escape, and chemoresistance, but the underlying mechanisms remain elusive. Herein, we demonstrate that sodium bicarbonate, a weakly alkaline compound, induces cytotoxicity in ovarian cancer cells and hinders cancer migration and invasion in vitro. The anti-cancer efficacy of Olaparib can be significantly augmented when combined with sodium bicarbonate. In vivo experiments suggest that the combinatorial treatment of sodium bicarbonate and Olaparib is biocompatible and more effective at inhibiting ovarian cancer growth than either treatment alone. Additionally, RNA-sequencing results reveal that the differentially expressed genes are enriched in pathways related to reactive oxygen species (ROS) generation, such as the cGMP/PKG pathway. The combined treatment increases M1 macrophage composition in tumors and reduces the accumulation of excessive ROS. These findings strongly suggest that sodium bicarbonate holds great potential as an adjuvant treatment by scavenging ROS accumulation and promoting M1 macrophage composition, thereby enhancing Olaparib's anti-cancer activity.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117509"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514596","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

Polypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs. 使用基于细胞的多重检测平台 safetyProfiler 对蛋白质靶家族和细胞通路进行多药理学分析，揭示药物的疗效、效力和副作用。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.biopha.2024.117523

Lukša Popović, Ben Brankatschk, Giulia Palladino, Moritz J Rossner, Michael C Wehr

{"title":"Polypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs.","authors":"Lukša Popović, Ben Brankatschk, Giulia Palladino, Moritz J Rossner, Michael C Wehr","doi":"10.1016/j.biopha.2024.117523","DOIUrl":"10.1016/j.biopha.2024.117523","url":null,"abstract":"Selectivity profiling is key for assessing the pharmacological properties of multi-target drugs. We have developed a cell-based and barcoded assay encompassing ten druggable targets, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), nuclear receptors, a protease as well as their key downstream pathways and profiled 17 drugs in living cells for efficacy, potency, and side effects. Notably, this multiplex assay, termed safetyProfiler assay, enabled the simultaneous assessment of multiple target and pathway activities, shedding light on the polypharmacological profile of compounds. For example, the neuroleptics clozapine, paliperidone, and risperidone potently inhibited primary targets DRD2 and HTR2A as well as cAMP and calcium pathways. However, while paliperidone and risperidone also potently inhibited the secondary target ADRA1A and mitogen-activated protein kinase (MAPK) downstream pathways, clozapine only exhibited mild antagonistic effects on ADRA1A and lacked MAPK inhibition downstream of DRD2 and HTR2A. Furthermore, we present data on the selectivity for bazedoxifene, an estrogen receptor antagonist currently undergoing clinical phase 2 trials for breast cancer, on MAPK signaling. Additionally, precise potency data for LY2452473, an androgen receptor antagonist, that completed a phase 2 clinical trial for prostate cancer, are presented. The non-selective kinase inhibitor staurosporine was observed to potently inactivate the two RTKs EGFR and ERBB4 as well as MAPK signaling, while eliciting stress-related cAMP responses. Our findings underscore the value of comprehensive profiling in elucidating the pharmacological properties of established and novel therapeutics, thereby facilitating the development of novel multi-target drugs with enhanced efficacy and selectivity.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117523"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482996","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

The colony-stimulating factor-1 receptor inhibitor edicotinib counteracts multidrug resistance in cancer cells by inhibiting ABCG2-mediated drug efflux. 集落刺激因子-1受体抑制剂埃迪替尼通过抑制ABCG2介导的药物外流来对抗癌细胞的多药耐药性。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-15 DOI: 10.1016/j.biopha.2024.117554

Yen-Ching Li, Yun-Chieh Lee, Megumi Murakami, Yang-Hui Huang, Tai-Ho Hung, Yu-Shan Wu, Suresh V Ambudkar, Chung-Pu Wu

{"title":"The colony-stimulating factor-1 receptor inhibitor edicotinib counteracts multidrug resistance in cancer cells by inhibiting ABCG2-mediated drug efflux.","authors":"Yen-Ching Li, Yun-Chieh Lee, Megumi Murakami, Yang-Hui Huang, Tai-Ho Hung, Yu-Shan Wu, Suresh V Ambudkar, Chung-Pu Wu","doi":"10.1016/j.biopha.2024.117554","DOIUrl":"10.1016/j.biopha.2024.117554","url":null,"abstract":"Chemotherapy treatment faces a major obstacle with the emergence of multidrug resistance (MDR), often attributed to the elevated expression of ATP-binding cassette (ABC) transporters such as ABCG2 and ABCB1 in cancer cells. These transporters hinder the efficacy of cytotoxic drugs via ATP hydrolysis-dependent efflux, leading to diminished intracellular drug levels. The scarcity of approved treatments for multidrug resistant cancers necessitates exploration of alternative strategies, including drug repositioning of molecular targeted agents to counteract ABCG2-mediated MDR in multidrug-resistant cancer cells. This study investigates the potential of edicotinib, a selective colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase inhibitor that is currently undergoing clinical trials for various diseases, to reverse MDR in ABCG2-overexpressing cancer cells. Our findings reveal that by attenuating the drug-efflux function of ABCG2 without altering its expression, edicotinib improves drug-induced apoptosis and reverses MDR in ABCG2-overexpressing multidrug-resistant cancer cells at non-toxic concentrations. Through ATPase activity analysis and molecular docking, potential interaction sites for edicotinib on ABCG2 were identified. These results underscore an additional pharmacological benefit of edicotinib against ABCG2 activity, suggesting its potential incorporation into combination therapies for patients with ABCG2-overexpressing tumors. Further research is warranted to validate these findings and explore their clinical implications.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117554"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483005","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

Cereblon mediates macrophage differentiation and microglial phagocytosis by regulating calpain protease activity. Cereblon通过调节钙蛋白酶活性介导巨噬细胞分化和小胶质细胞吞噬。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-24 DOI: 10.1016/j.biopha.2024.117606

Liang Zhou, Qing Sun, Dan Cao

{"title":"Cereblon mediates macrophage differentiation and microglial phagocytosis by regulating calpain protease activity.","authors":"Liang Zhou, Qing Sun, Dan Cao","doi":"10.1016/j.biopha.2024.117606","DOIUrl":"10.1016/j.biopha.2024.117606","url":null,"abstract":"Autoimmune diseases encompass over 80 distinct types, affecting approximately 7.6-9.4 % of the population globally. The intricate interplay between genetic predispositions and environmental triggers complicates early diagnosis and intervention. Abnormal macrophage differentiation and proliferation have been identified as key contributors to the pathogenesis of these conditions, though the precise molecular pathways remain poorly understood. Recent studies suggest that cereblon (CRBN), a target for immunomodulatory drugs like thalidomide, lenalidomide, and pomalidomide, may offer therapeutic potential for autoimmune diseases such as systemic lupus erythematosus. In this study, quantitative proteomics revealed that CRBN downregulated the calpain regulatory subunit, calpain small subunit 1 (CAPNS1), in macrophages. Subsequent biochemical assays demonstrated that CRBN modulated calpain activity, impacting autophagy processes during macrophage differentiation and microglial phagocytosis. Histological evaluation of CRBN-deficient mice indicated a marked increase in microglial populations in the brain. These findings highlight potential therapeutic targets and present new avenues for the treatment of autoimmune diseases.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117606"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514587","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

Acetate supplementation improves neurological outcomes by preventing hyperglycemia and suppressing Serpina3n expression in CA1 region after cardiac arrest and cardiopulmonary resuscitation. 心脏骤停和心肺复苏后，通过预防高血糖和抑制CA1区Serpina3n的表达，补充醋酸盐可改善神经系统的预后。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-28 DOI: 10.1016/j.biopha.2024.117615

Fei Peng, Feiyu Long, Bowen Gao, Yu Liang

{"title":"Acetate supplementation improves neurological outcomes by preventing hyperglycemia and suppressing Serpina3n expression in CA1 region after cardiac arrest and cardiopulmonary resuscitation.","authors":"Fei Peng, Feiyu Long, Bowen Gao, Yu Liang","doi":"10.1016/j.biopha.2024.117615","DOIUrl":"10.1016/j.biopha.2024.117615","url":null,"abstract":"Background: Hyperglycemia is common after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). More importantly, it is associated with a worse neurological outcome after CA/CPR. Acetate has been proven to be of great value to reprogram glucose metabolism in the whole body. Nevertheless, the impact of acetate on hyperglycemia and neurological outcomes after CA/CPR remains largely unexplored.Methods: Glucose metabolism-related parameters were examined to assess the changes of glucose metabolism in our CA/CPR model. Survival and neurological function were measured after return of spontaneous circulation. Acetate supplementation was achieved by gavage to assess the impact of acetate on CA/CPR-induced hyperglycemia. Proteomics investigation of the changes in proteins of the CA1 region were performed to explore the differences of protein expression. The correlation between acetate supplementation and improvement of neurological outcomes after CA/CPR was elucidated by Serpina3n over-expression and knockdown in CA1 region.Results: CA/CPR induces hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance with upregulation of Serpina3n in CA1 region. Acetate supplementation could attenuate hyperglycemia, reduce protein levels of Serpina3n in CA1 region, and improves neurological outcomes after CA/CPR. Mechanistically, the acetate-dependent improvement of neurological outcomes after CA/CPR and attenuation of CA/CPR-induced hyperglycemia were correlated with the down-regulation of Serpina3n in CA1 region.Conclusions: Our findings suggest that acetate supplementation improves neurological outcomes of CA/CPR mice by maintaining glucose homeostasis in the whole body and suppression of Serpina3n expression in CA1 region.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117615"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570491","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

Calcium handling abnormalities increase arrhythmia susceptibility in DMSXL myotonic dystrophy type 1 mice. 钙处理异常增加了 DMSXL 肌营养不良 1 型小鼠心律失常的易感性。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI: 10.1016/j.biopha.2024.117562

Michael Cupelli, Vamsi Krishna Murthy Ginjupalli, Jean-Baptiste Reisqs, Yvonne Sleiman, Nabil El-Sherif, Geneviève Gourdon, Jack Puymirat, Mohamed Chahine, Mohamed Boutjdir

{"title":"Calcium handling abnormalities increase arrhythmia susceptibility in DMSXL myotonic dystrophy type 1 mice.","authors":"Michael Cupelli, Vamsi Krishna Murthy Ginjupalli, Jean-Baptiste Reisqs, Yvonne Sleiman, Nabil El-Sherif, Geneviève Gourdon, Jack Puymirat, Mohamed Chahine, Mohamed Boutjdir","doi":"10.1016/j.biopha.2024.117562","DOIUrl":"10.1016/j.biopha.2024.117562","url":null,"abstract":"Background: Myotonic dystrophy type 1 (DM1) is a multiorgan disorder with significant cardiac involvement. ECG abnormalities, including arrhythmias, occur in 80 % of DM1 patients and are the second-most common cause of death after respiratory complications; however, the mechanisms underlying the arrhythmogenesis remain unclear. The objective of this study was to investigate the basis of the electrophysiological abnormalities in DM1 using the DMSXL mouse model.Methods: ECG parameters were evaluated at baseline and post flecainide challenge. Calcium transient and action potential parameters were evaluated in Langendorff-perfused hearts using fluorescence optical mapping. Calcium transient/sparks were evaluated in ventricular myocytes via confocal microscopy. Protein and mRNA levels for calcium handling proteins were evaluated using western blot and RT-qPCR, respectively.Results: DMSXL mice showed arrhythmic events on ECG including premature ventricular contractions and sinus block. DMSXL mice showed increased calcium transient time to peak without any change to voltage parameters. Calcium alternans and both sustained and non-sustained ventricular tachyarrhythmias were readily inducible in DMSXL mice. The confocal experiments also showed calcium transient alternans and increased frequency of calcium sparks in DMSXL cardiomyocytes. These calcium abnormalities were correlated with increased RyR2 phosphorylation without changes to the other calcium handling proteins.Conclusions: The DMSXL mouse model of DM1 exhibited enhanced arrhythmogenicity associated with abnormal intracellular calcium handling due to hyperphosphorylation of RyR2, pointing to RyR2 as a potential new therapeutic target in DM1 treatment.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117562"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482965","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

The prognostic value of tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: A systematic review and meta-analysis. 头颈部鳞状细胞癌中肿瘤浸润淋巴细胞的预后价值：系统综述和荟萃分析。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI: 10.1016/j.biopha.2024.117544

Meri Torri, Adam Sandell, Ahmed Al-Samadi

{"title":"The prognostic value of tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: A systematic review and meta-analysis.","authors":"Meri Torri, Adam Sandell, Ahmed Al-Samadi","doi":"10.1016/j.biopha.2024.117544","DOIUrl":"10.1016/j.biopha.2024.117544","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is experiencing a rising incidence and mortality worldwide, emphasizing the need for reliable prognostic markers. Tumor-infiltrating lymphocytes (TILs) have emerged as a promising biomarker for predicting HNSCC prognosis, yet no systematic reviews have exclusively focused on hematoxylin and eosin (H&E)-stained formalin-fixed paraffin-embedded (FFPE) samples, which are routinely used in clinical practice. This systematic review and meta-analysis followed the PRISMA guidelines to examine the prognostic value of TILs in HNSCC using H&E-stained FFPE samples. Data were pooled from 43 studies, including 26 studies in a meta-analysis, analyzing 5037 HNSCC samples. We found that a high TIL count associated with a significantly improved overall survival (OS) (HR 0.47, 95 % CI 0.41-0.55, p < 0.0001), disease-free survival (DFS) (HR 0.55, 95 % CI 0.41-0.55, p < 0.0001), and disease-specific survival (DSS) (HR 0.58, 95 % CI 0.46-0.73, p < 0.0001). The heterogeneity was moderate for the pooled analysis (OS: I² = 40 %; DFS: I² = 39 %; DSS: I² = 51 %), but low for the subgroup analysis based on tumor site in oral, oropharyngeal, laryngeal, and nasopharyngeal cancer (OS and DFS: I² = 0-14 %). This review is the first to systematically evaluate TILs in HNSCC using H&E-stained samples, confirming their prognostic value. A high TIL count is associated with improved survival outcomes, suggesting their potential as prognostic biomarkers in clinical settings.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117544"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483006","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

Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice. 柠檬草精油和柠檬醛对双氯芬酸所致小鼠毒性的肾脏保护和肝脏保护作用

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-15 DOI: 10.1016/j.biopha.2024.117541

Mohaddeseh Abouhosseini Tabari, Masoumeh Houshyar, Atefeh Araghi, Navideh Mirzakhani, Giuseppe Crescenzo, Roberta Cardone, Claudia Zizzadoro

{"title":"Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice.","authors":"Mohaddeseh Abouhosseini Tabari, Masoumeh Houshyar, Atefeh Araghi, Navideh Mirzakhani, Giuseppe Crescenzo, Roberta Cardone, Claudia Zizzadoro","doi":"10.1016/j.biopha.2024.117541","DOIUrl":"10.1016/j.biopha.2024.117541","url":null,"abstract":"The present study was carried out to evaluate and compare the protective potential of two well-known antioxidants of herbal origin in a mouse model of acute DIC-induced nephro- and hepatotoxicity. The tested antioxidants included lemongrass essential oil (LO) and its predominant bioactive constituent citral (CIT). A third herbal product, silymarin (SILY), was used as a reference hepato-renal protective agent. DIC administration led to elevated serum urea and creatinine levels, and prompted oxidative stress along with histopathological changes in the kidney tissue. In parallel, DIC administration increased serum liver enzyme activity, decreased total protein, albumin, and globulin levels, and caused oxidative stress with associated histopathological changes in the liver tissue. Pre-treatment with LO or CIT mitigated DIC-induced alterations in all serum biochemical markers of kidney and liver health (except albumin). High-dose LO, like SILY, within kidney and liver tissues, counteracted DIC-induced oxidative stress and histomorphological alterations. By contrast, CIT failed to mitigate DIC-induced oxidative stress in the kidneys and provided only partial control of DIC-induced oxidative stress in the liver, resulting in less efficient preservation of kidney function and liver structural integrity than LO. Besides confirming the efficacy of SILY at protecting kidneys and liver against the toxicity of DIC in a rodent species different from the one tested so far (rat), this study demonstrated the preventive properties of LO and, to a lesser extent, of CIT against DIC-induced hepato-renal toxicity in mice, supporting their developmental potential as therapeutics.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117541"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482995","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