Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献_第5页

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

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

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

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

Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3. 通过抑制药物输出泵 MRP3 使胆管癌对化疗敏感

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-13 DOI: 10.1016/j.biopha.2024.117533

Maitane Asensio, Oscar Briz, Elisa Herraez, Laura Perez-Silva, Ricardo Espinosa-Escudero, Diego Bueno-Sacristan, Ana Peleteiro-Vigil, Helen Hammer, Oliver Pötz, Onat Kadioglu, Jesus M Banales, Maria L Martinez-Chantar, Matias A Avila, Rocio I R Macias, Thomas Efferth, Jose J G Marin, Elisa Lozano

{"title":"Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3.","authors":"Maitane Asensio, Oscar Briz, Elisa Herraez, Laura Perez-Silva, Ricardo Espinosa-Escudero, Diego Bueno-Sacristan, Ana Peleteiro-Vigil, Helen Hammer, Oliver Pötz, Onat Kadioglu, Jesus M Banales, Maria L Martinez-Chantar, Matias A Avila, Rocio I R Macias, Thomas Efferth, Jose J G Marin, Elisa Lozano","doi":"10.1016/j.biopha.2024.117533","DOIUrl":"10.1016/j.biopha.2024.117533","url":null,"abstract":"Aims: Drug export through ABC proteins hinders cancer response to chemotherapy. Here, we have evaluated the relevance of MRP3 (ABCC3) in cholangiocarcinoma (CCA) as a potential target to overcome drug resistance.Methods: Gene expression was analyzed in silico using the TCGA-CHOL database and experimentally (mRNA and protein) in resected CCA tumors. The effect of manipulating MRP3 function/expression was evaluated in vitro and in vivo.Results: High MRP3 expression at the plasma membrane of human CCA cells was found. MRP3 overexpression in HEK293T cells selectively impaired the cytotoxic effect of etoposide, cisplatin, SN-38, and mitoxantrone. Reduced MRP3 activity with shRNAs or pan-MRP blockers enhanced the sensitivity to these drugs. MRP3 interaction with natural and semisynthetic compounds (≈40,000) was evaluated by virtual drug screening and molecular docking. Two identified potential MRP3 inhibitors (EM-114, EM-188), and sorafenib impaired MRP3 transport activity and enhanced sensitivity of CCA cells to etoposide and cisplatin. The antitumor effect of cisplatin in the mouse xenograft model was enhanced by co-treatment with sorafenib, which was accompanied by a higher intratumor accumulation of cisplatin.Conclusions: Genetic and pharmacological MRP3 inhibition enhances the anti-CCA effect of several drugs, which constitutes a promising strategy to improve the response to chemotherapy in CCA patients.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117533"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483000","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

Novel [¹⁸F]FPG-interleukin-2 conjugate for monitoring immune checkpoint therapy with positron emission tomography. 利用正电子发射断层扫描监测免疫检查点疗法的新型[18F]FPG-白介素-2共轭物。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1016/j.biopha.2024.117617

Pragalath Sadasivam, Siddesh V Hartimath, Shivashankar Khanapur, Boominathan Ramasamy, Peter Cheng, Chin Zan Feng, David Green, Julian L Goggi, Edward G Robins, Ran Yan

{"title":"Novel [18F]FPG-interleukin-2 conjugate for monitoring immune checkpoint therapy with positron emission tomography.","authors":"Pragalath Sadasivam, Siddesh V Hartimath, Shivashankar Khanapur, Boominathan Ramasamy, Peter Cheng, Chin Zan Feng, David Green, Julian L Goggi, Edward G Robins, Ran Yan","doi":"10.1016/j.biopha.2024.117617","DOIUrl":"10.1016/j.biopha.2024.117617","url":null,"abstract":"18F-interleukin-2 based PET imaging of activated T cells serves as a potential tool for non-invasive response prediction, treatment evaluation, and patient stratification in cancer immune checkpoint therapy. Herein, we report the radiolabelling of interleukin-2 (IL-2) with a novel arginine selective bioconjugation reagent, 4-[18F]fluorophenylglyoxal ([18F]FPG). Good non-decay corrected bioconjugation efficiencies of 29 ± 4 % (n = 5) were obtained for the [18F]FPG-IL-2. [18F]FPG-IL-2 uptake by the phytohemagglutinin-activated Jurkat cells (50.5 ± 1.2 %, n = 3) was significantly higher compared to the non-activated Jurkat cells (12.9 ± 1.1 %, n = 3). The [18F]FPG-IL-2 uptake was blocked by the pre-treatment of activated Jurkat cells with excess native IL-2 (22.3 ± 2.2 %, n = 3). Dynamic PET imaging and ex vivo biodistribution study of [18F]FPG-IL-2 in healthy and CT26 tumour bearing mice demonstrated hepatobiliary and renal clearance with minimal uptake in other organs and CT26 tumours. [18F]FPG-IL-2 PET imaging was applied to non-invasively monitor immune checkpoint therapy in CT26 tumour bearing mice, treated with IgG (control), ⍺PD-1 (monotherapy), and ⍺PD-1+⍺CTLA-4 (combination therapy). Significant uptake was observed in the spleens and tumours of the mice in the combination therapy group, which was associated with increased cytotoxic CD8+ T-cell infiltration and reduced tumour volumes. [18F]FPG-IL-2 based PET imaging has the potential to monitor immune checkpoint therapy.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117617"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549526","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

Developing a novel P-glycoprotein inhibitor and pairing it with oral paclitaxel liposomes for enhanced cancer therapy. 开发新型 P 糖蛋白抑制剂，并将其与口服紫杉醇脂质体配对，以增强癌症治疗效果。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-19 DOI: 10.1016/j.biopha.2024.117577

Sikai Deng, Weiwei Li, Qiyu Chen, Jianqun Shao, Junbo Zhang, Yuji Wang, Yinghuan Li

{"title":"Developing a novel P-glycoprotein inhibitor and pairing it with oral paclitaxel liposomes for enhanced cancer therapy.","authors":"Sikai Deng, Weiwei Li, Qiyu Chen, Jianqun Shao, Junbo Zhang, Yuji Wang, Yinghuan Li","doi":"10.1016/j.biopha.2024.117577","DOIUrl":"10.1016/j.biopha.2024.117577","url":null,"abstract":"The mucus layer and intestine epithelium pose challenges to the bioavailability of orally administered paclitaxel (PTX). A novel P-glycoprotein inhibitor, (S)-2-decanoylamino-3-(1-naphthyl)propionyl-leucyl-valine (PgpI), was synthesized in this study. Its structure was characterized using 1H NMR, 13C NMR, ESI-MS and IR spectroscopies. The efficacy and in vivo toxicity of PgpI were comprehensively evaluated by R8-PEG@PLs&PgpI, i.e., the oral combination of PgpI and octaarginine R8-PEG-DSPE modified PTX liposomes (R8-PEG@PLs), for lung cancer treatment. The joint forms between PgpI and R8-PEG@PLs were investigated and the affinity of PgpI for intestinal P-glycoprotein remained unaffected when combined externally with R8-PEG@PLs (R8-PEG@PLs&PgpI), compared to the diminished affinity for internal combination. The primary endocytic pathway for R8-PEG@PLs&PgpI in Caco-2 cells was the lipid raft, with increased percentage of macropinocytosis compared to unmodified PTX liposomes (PLs). The established physiology-based cellular kinetic models revealed that the net internalization rate of PTX was 2.3 times higher in R8-PEG@PLs&PgpI than in PLs, correlating with in vivo 2.2 times of antitumor rate. R8-PEG@PLs&PgpI may address the deficits of PLs in human lung A549 tumor-bearing mice due to the lower drug concentration than in normal mice. The external combination of R8-PEG@PLs&PgpI, offering maximal efficacy and security of PgpI, is promising for oral PTX delivery.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117577"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482968","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

Agmatine attenuates the severity of immunometabolic disorders by suppressing macrophage polarization: an in vivo study using an ulcerative colitis mouse model. 鸦胆子碱通过抑制巨噬细胞极化减轻免疫代谢紊乱的严重程度：利用溃疡性结肠炎小鼠模型进行的体内研究。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-15 DOI: 10.1016/j.biopha.2024.117549

Suyue Zhang, Zhen Sun, Yajuan Li, Xinjian Du, Kun Qian, Le Yang, Guangyan Jia, Jiye Yin, Sha Liao, Zhe Zhou

{"title":"Agmatine attenuates the severity of immunometabolic disorders by suppressing macrophage polarization: an in vivo study using an ulcerative colitis mouse model.","authors":"Suyue Zhang, Zhen Sun, Yajuan Li, Xinjian Du, Kun Qian, Le Yang, Guangyan Jia, Jiye Yin, Sha Liao, Zhe Zhou","doi":"10.1016/j.biopha.2024.117549","DOIUrl":"10.1016/j.biopha.2024.117549","url":null,"abstract":"Agmatine, an endogenous polyamine generated by the gut microbiota, positively affects host lifespan by regulating mononuclear cell or macrophage function. Although the regulatory pathways governing monocyte/macrophage differentiation have been well studied, the influence of the microbiome and its metabolites on monocyte/macrophage function have not been fully elucidated. To address this, we aimed to investigate the mechanisms whereby agmatine inhibits immunometabolic disorders using the colon of ulcerative colitis (UC) model mice. Agmatine (10 mM) attenuated pathological damage to colonic tissue and significantly improved the survival rate of UC model mice. In particular, treatment of UC model mice with 0.4, 2, and 10 mM agmatine resulted in mortality rates of 70 %, 20 %, 10 %, and 0 %, respectively. In a macrophage-depletion model, agmatine regulated the inflammatory microenvironment by affecting macrophages: it reduced the proportion of M1 macrophages and increased that of M2 macrophages in UC model mice. In cultured macrophages, agmatine inhibited lipopolysaccharide-induced inflammatory cytokine and NO secretion, as detected by enzyme-linked immunosorbent assay and the Griess assay, respectively. Agmatine partially reduced inflammatory factor production by inhibiting histone deacetylase, as detected by fluorometric assay. These findings provide evidence that agmatine efficiently suppresses macrophage polarization in UC mice, highlighting its potential as an anti-inflammatory agent against UC.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117549"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482986","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

Targeting hypoxia in combination with paclitaxel to enhance therapeutic efficacy in breast and ovarian cancer. 以缺氧为靶点，结合紫杉醇提高乳腺癌和卵巢癌的疗效。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1016/j.biopha.2024.117601

Laura Svajda, Ivan Ranđelović, Sára Eszter Surguta, Marcell Baranyi, Mihály Cserepes, József Tóvári

{"title":"Targeting hypoxia in combination with paclitaxel to enhance therapeutic efficacy in breast and ovarian cancer.","authors":"Laura Svajda, Ivan Ranđelović, Sára Eszter Surguta, Marcell Baranyi, Mihály Cserepes, József Tóvári","doi":"10.1016/j.biopha.2024.117601","DOIUrl":"10.1016/j.biopha.2024.117601","url":null,"abstract":"The poor vascularization of solid tumors results in oxygen-deprived areas within the tumor mass. This phenomenon is defined as tumor hypoxia and is considered to be a major contributor to tumor progression in breast and ovarian cancers due to hypoxia-cascade-promoted increased metastasizing capacity. Hence, targeting hypoxia is a strategic cancer treatment approach, however, the hypoxia-modulating drugs face several limitations in monotherapies. Here, we investigated the impact of the potent hypoxia-inducible factor inhibitory compound acriflavine on tumor cell proliferation, migration, and metabolism under hypoxic conditions. We identified that acriflavine inhibited the proliferation of breast and ovarian tumor cells. To model the potential benefits of additional hypoxia response inhibition next to standard chemotherapy, we combined acriflavine with a frequently used chemotherapeutic agent, paclitaxel. In most breast and ovarian cancer cell lines used, we identified additive effects between the two drugs. The most significant findings were detected in triple-negative breast cancer cell lines, where we observed synergism. The drug combination effectively impeded tumor growth and metastasis formation in an in vivo orthotopic triple-negative breast cancer model as well. Additionally, we demonstrated that an epithelial-mesenchymal transition inhibitory drug, rolipram, combined with acriflavine and paclitaxel, notably reduced the motility of hypoxic triple-negative breast cancer cells. In conclusion, we identified novel drug combinations that can potentially combat triple-negative breast cancer by inhibiting hypoxia signaling and hindering cell migration and metastasis formation.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117601"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549527","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}

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