Pub Date : 2024-09-19DOI: 10.1016/j.biopha.2024.117438
Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies.
{"title":"The therapeutic potential of andrographolide in cancer treatment","authors":"","doi":"10.1016/j.biopha.2024.117438","DOIUrl":"10.1016/j.biopha.2024.117438","url":null,"abstract":"<div><p>Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013246/pdfft?md5=55e0265f6c3492e35c427b86a2827c75&pid=1-s2.0-S0753332224013246-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242771","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}
Pub Date : 2024-09-18DOI: 10.1016/j.biopha.2024.117417
<div><p>The effect of baicalin methyl ester (BME) on the regulation of mice intestinal barrier in the inflammatory response was studied in vivo and in vitro. Thirty six C57/BL mice were randomly divided into six groups (n = 6): control group; LPS group (LPS 3.5 mg/kg given intraperitoneal [ip] on day 7 of the study only), PBS group, and three BME groups (low: 50 mg/kg; medium: 100 mg/kg; high: 200 mg/kg) orally dosed with BME for 7d and LPS ip on day 7. All mice were sacrificed on day 8, and jejunum tissue collected for histopathology (H&E and PAS staining), protein expression of pro-inflammatory factors (TNF-α, IL-6, IL-8, IFN-γ) by ELISA, and intestinal tight junction proteins (ZO-1, occludin, claudin-1 and claudin-4) by Western Blot. Compared with the control group, LPS significantly increased the serum cytokines DAO (<em>p</em> < 0.01) and DLA (<em>p</em> < 0.01), u<em>p</em>regulated the expression of pro-inflammatory factors, MLCK proteins (<em>p</em> <0.05) and increased the MLCK/ZO-1ratio (<em>p</em> <0.001). LPS also decreased the expression of claudin-4 (<em>p</em> < 0.01) in the jejunum and induced an inflammatory response damaging the jejunal mucosal barrier. Pretreatment with BME (100–200 mg/kg) significantly decreased the cytokines DAO (<em>p</em> < 0.05) and DLA (<em>p</em> < 0.01) in the serum, pro-inflammatory factors in the jejunum, significantly down-regulated the expression of MLCK (<em>p</em> <0.05) and the ratio of MLCK/ZO-1(<em>p</em> <0.001) but upregulated the expressions of ZO-1(<em>p</em> < 0.01), occludin (<em>p</em> < 0.05), claudin-1(<em>p</em> < 0.05) and claudin-4 (<em>p</em> < 0.05), and thereby restored the intestinal tissue structure, suggestive of alleviation of LPS-induced intestinal inflammation by BME. In vitro, MODE-K cells (derived from mice intestinal epithelium) were exposed to BME at 0 (control group-No LPS), 10, 20 and 40 μM BME for 24 h prior to LPS addition at 50 μg/mL for 2 h. LPS significantly increased the expression of pro-inflammatory factors, MLCK (<em>p</em> < 0.01) and the ratio of MLCK/ZO-1(<em>p</em> <0.001), decreased the expressions of ZO-1 (<em>p</em> < 0.05), occludin (<em>p</em> < 0.01), claudin-1 (<em>p</em> < 0.01) and claudin-4 (<em>p</em> < 0.01) in MODE-K cells compared with the control group. Compared with the LPS group, BME (10 – 40 μM) significantly decreased the expression of pro-inflammatory factors, MLCK (<em>p</em> < 0.05) and the ratio of MLCK/ZO-1(<em>p</em> <0.01) but increased the expressions of ZO-1(<em>p</em> < 0.01), occludin (<em>p</em> < 0.05) and claudin-4(<em>p</em> < 0.01) indicating an up-regulation of the expression of tight junction proteins by BME. On addition of extrinsic TNF-α plus LPS, the TNF- α level increased (<em>p</em> < 0.001) in MODE-K cells and the protein expression of MLCK (<em>p</em> < 0.01) was markedly up-regulated. Molecular docking predicted BME interacted wit
{"title":"Baicalin methyl ester prevents the LPS – induced mice intestinal barrier damage in vivo and in vitro via P65/TNF-α/MLCK/ZO-1 signal pathway","authors":"","doi":"10.1016/j.biopha.2024.117417","DOIUrl":"10.1016/j.biopha.2024.117417","url":null,"abstract":"<div><p>The effect of baicalin methyl ester (BME) on the regulation of mice intestinal barrier in the inflammatory response was studied in vivo and in vitro. Thirty six C57/BL mice were randomly divided into six groups (n = 6): control group; LPS group (LPS 3.5 mg/kg given intraperitoneal [ip] on day 7 of the study only), PBS group, and three BME groups (low: 50 mg/kg; medium: 100 mg/kg; high: 200 mg/kg) orally dosed with BME for 7d and LPS ip on day 7. All mice were sacrificed on day 8, and jejunum tissue collected for histopathology (H&E and PAS staining), protein expression of pro-inflammatory factors (TNF-α, IL-6, IL-8, IFN-γ) by ELISA, and intestinal tight junction proteins (ZO-1, occludin, claudin-1 and claudin-4) by Western Blot. Compared with the control group, LPS significantly increased the serum cytokines DAO (<em>p</em> < 0.01) and DLA (<em>p</em> < 0.01), u<em>p</em>regulated the expression of pro-inflammatory factors, MLCK proteins (<em>p</em> <0.05) and increased the MLCK/ZO-1ratio (<em>p</em> <0.001). LPS also decreased the expression of claudin-4 (<em>p</em> < 0.01) in the jejunum and induced an inflammatory response damaging the jejunal mucosal barrier. Pretreatment with BME (100–200 mg/kg) significantly decreased the cytokines DAO (<em>p</em> < 0.05) and DLA (<em>p</em> < 0.01) in the serum, pro-inflammatory factors in the jejunum, significantly down-regulated the expression of MLCK (<em>p</em> <0.05) and the ratio of MLCK/ZO-1(<em>p</em> <0.001) but upregulated the expressions of ZO-1(<em>p</em> < 0.01), occludin (<em>p</em> < 0.05), claudin-1(<em>p</em> < 0.05) and claudin-4 (<em>p</em> < 0.05), and thereby restored the intestinal tissue structure, suggestive of alleviation of LPS-induced intestinal inflammation by BME. In vitro, MODE-K cells (derived from mice intestinal epithelium) were exposed to BME at 0 (control group-No LPS), 10, 20 and 40 μM BME for 24 h prior to LPS addition at 50 μg/mL for 2 h. LPS significantly increased the expression of pro-inflammatory factors, MLCK (<em>p</em> < 0.01) and the ratio of MLCK/ZO-1(<em>p</em> <0.001), decreased the expressions of ZO-1 (<em>p</em> < 0.05), occludin (<em>p</em> < 0.01), claudin-1 (<em>p</em> < 0.01) and claudin-4 (<em>p</em> < 0.01) in MODE-K cells compared with the control group. Compared with the LPS group, BME (10 – 40 μM) significantly decreased the expression of pro-inflammatory factors, MLCK (<em>p</em> < 0.05) and the ratio of MLCK/ZO-1(<em>p</em> <0.01) but increased the expressions of ZO-1(<em>p</em> < 0.01), occludin (<em>p</em> < 0.05) and claudin-4(<em>p</em> < 0.01) indicating an up-regulation of the expression of tight junction proteins by BME. On addition of extrinsic TNF-α plus LPS, the TNF- α level increased (<em>p</em> < 0.001) in MODE-K cells and the protein expression of MLCK (<em>p</em> < 0.01) was markedly up-regulated. Molecular docking predicted BME interacted wit","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013027/pdfft?md5=b2452643e5a7a7b6390a9196678be563&pid=1-s2.0-S0753332224013027-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242773","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}
Pub Date : 2024-09-17DOI: 10.1016/j.biopha.2024.117429
Background
Orlistat (Orli) is an anti-obesity medication that has been approved by the US Food and Drug Administration. It has relatively limited oral bioavailability with promising inhibitory effects on cell proliferation as well as reducing the growth of tumors.
Aims
This investigation was done to evaluate the potential protective effect of Tamoxifen/Orlistat nanocrystals alone or in combination against Solid Ehrlich Carcinoma (SEC) and to clarify the possible underlying influences.
Materials and methods
The liquid antisolvent precipitation technique (bottom-up technology) was utilized to manufacture Orlistat Nanocrystals. To explore potential causes for the anti-tumor action, female Swiss Albino mice bearing SEC were randomly assigned into five equal groups (n = 6). Group 1: Tumor control group, group 2: Tam group: tamoxifen (0.01 g/kg, IP), group 3: Free-Orli group: orlistat (0.24 g/kg, IP), group 4: Nano-Orli: orlistat nanocrystals (0.24 g/kg, IP), group 5: Tam–Nano-Orli: Both doses of Tam and Nano-Orli. All treatments were administered for 16 days.
Key findings
The untreated mice showed development in the tumor volume and weight. As well as histopathology results from these mice revealed many tumor large cells as well as solid sheets of malignant cells. Also, untreated mice showed raised VEGF and TGF-1beta content. Moreover, results of gene expression in the SEC-bearing mice noted upregulation in HIF-1α, MMP-9, Bcl-2, and P27 gene expression and downregulation of TXNIP, BAX, and P53 gene expression. On the other hand, administrated TAM, Free-Orli, Nano-Orli, and a combination of Tam-Nano-Orli distinctly suppressed the tumor effects on estimated parameters with special reference to Tam-Nano-Orli.
Significance
The developed Tamoxifen/Orlistat nanocrystals combination could be considered a promising approach to augment antitumor effects.
{"title":"Therapeutic efficiency of Tamoxifen/Orlistat nanocrystals against solid ehrlich carcinoma via targeting TXNIP/HIF1-α/MMP-9/P27 and BAX/Bcl2/P53 signaling pathways","authors":"","doi":"10.1016/j.biopha.2024.117429","DOIUrl":"10.1016/j.biopha.2024.117429","url":null,"abstract":"<div><h3>Background</h3><p>Orlistat (Orli) is an anti-obesity medication that has been approved by the US Food and Drug Administration. It has relatively limited oral bioavailability with promising inhibitory effects on cell proliferation as well as reducing the growth of tumors.</p></div><div><h3>Aims</h3><p>This investigation was done to evaluate the potential protective effect of Tamoxifen/Orlistat nanocrystals alone or in combination against Solid Ehrlich Carcinoma (SEC) and to clarify the possible underlying influences.</p></div><div><h3>Materials and methods</h3><p>The liquid antisolvent precipitation technique (bottom-up technology) was utilized to manufacture Orlistat Nanocrystals. To explore potential causes for the anti-tumor action, female Swiss Albino mice bearing SEC were randomly assigned into five equal groups (n = 6). Group 1: Tumor control group, group 2: Tam group: tamoxifen (0.01 g/kg, IP), group 3: Free-Orli group: orlistat (0.24 g/kg, IP), group 4: Nano-Orli: orlistat nanocrystals (0.24 g/kg, IP), group 5: Tam–Nano-Orli: Both doses of Tam and Nano-Orli. All treatments were administered for 16 days.</p></div><div><h3>Key findings</h3><p>The untreated mice showed development in the tumor volume and weight. As well as histopathology results from these mice revealed many tumor large cells as well as solid sheets of malignant cells. Also, untreated mice showed raised VEGF and TGF-1beta content. Moreover, results of gene expression in the SEC-bearing mice noted upregulation in HIF-1α, MMP-9, Bcl-2, and P27 gene expression and downregulation of TXNIP, BAX, and P53 gene expression. On the other hand, administrated TAM, Free-Orli, Nano-Orli, and a combination of Tam-Nano-Orli distinctly suppressed the tumor effects on estimated parameters with special reference to Tam-Nano-Orli.</p></div><div><h3>Significance</h3><p>The developed Tamoxifen/Orlistat nanocrystals combination could be considered a promising approach to augment antitumor effects.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013143/pdfft?md5=8518ac68cd6cc612f52e595cfe2f35cf&pid=1-s2.0-S0753332224013143-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242772","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}
Pub Date : 2024-09-14DOI: 10.1016/j.biopha.2024.117375
The perioperative period encompasses all phases of patient care from the decision to perform surgery until full recovery. Ferroptosis, a newly identified type of regulated cell death, influences a wide array of diseases, including those affecting the prognosis and regression of surgical patients, such as ischemia-reperfusion injury and perioperative cognitive dysfunction. This review systematically examines perioperative factors impacting ferroptosis such as surgical trauma-induced stress, tissue hypoxia, anesthetics, hypothermia, and blood transfusion. By analyzing their intrinsic relationships, we aim to improve intraoperative management, enhance perioperative safety, prevent complications, and support high-quality postoperative recovery, ultimately improving patient outcomes.
{"title":"Comprehensive review of perioperative factors influencing ferroptosis","authors":"","doi":"10.1016/j.biopha.2024.117375","DOIUrl":"10.1016/j.biopha.2024.117375","url":null,"abstract":"<div><p>The perioperative period encompasses all phases of patient care from the decision to perform surgery until full recovery. Ferroptosis, a newly identified type of regulated cell death, influences a wide array of diseases, including those affecting the prognosis and regression of surgical patients, such as ischemia-reperfusion injury and perioperative cognitive dysfunction. This review systematically examines perioperative factors impacting ferroptosis such as surgical trauma-induced stress, tissue hypoxia, anesthetics, hypothermia, and blood transfusion. By analyzing their intrinsic relationships, we aim to improve intraoperative management, enhance perioperative safety, prevent complications, and support high-quality postoperative recovery, ultimately improving patient outcomes.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224012605/pdfft?md5=eee926d68ae8ee106aca74d443c0ded7&pid=1-s2.0-S0753332224012605-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230279","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}
Pub Date : 2024-09-13DOI: 10.1016/j.biopha.2024.117416
Podocan, a small leucine-rich repeat protein, is expressed in HIV-associated nephropathy, the cardiovascular system, and smooth muscle. Studies have linked PODN and PODNL to cancers such as osteosarcoma, glioma, and stomach cancer. Research has primarily focused on podocan's role in renal podocytes, injured smooth muscle cells, and various tumor cells. Bioinformatics studies have examined the role of PODN as a biomarker in tumors. Our research summarizes the modulatory role of podocan in smooth muscle and tumor proliferation through its suppression of cell proliferation and promotion of cell differentiation via various signaling pathways, including Wnt/β-catenin, TGF-β, and Akt/mTOR. We aim to provide a comprehensive overview of PODN's involvement in smooth muscle, cardiovascular system, and tumors by integrating current and past research. This review aims to enhance understanding and inform in the diagnosis, prognosis, and treatment of various diseases.
{"title":"Podocan unraveled: Understanding its role in tumor proliferation and smooth muscle regulation","authors":"","doi":"10.1016/j.biopha.2024.117416","DOIUrl":"10.1016/j.biopha.2024.117416","url":null,"abstract":"<div><p>Podocan, a small leucine-rich repeat protein, is expressed in HIV-associated nephropathy, the cardiovascular system, and smooth muscle. Studies have linked PODN and PODNL to cancers such as osteosarcoma, glioma, and stomach cancer. Research has primarily focused on podocan's role in renal podocytes, injured smooth muscle cells, and various tumor cells. Bioinformatics studies have examined the role of PODN as a biomarker in tumors. Our research summarizes the modulatory role of podocan in smooth muscle and tumor proliferation through its suppression of cell proliferation and promotion of cell differentiation via various signaling pathways, including Wnt/β-catenin, TGF-β, and Akt/mTOR. We aim to provide a comprehensive overview of PODN's involvement in smooth muscle, cardiovascular system, and tumors by integrating current and past research. This review aims to enhance understanding and inform in the diagnosis, prognosis, and treatment of various diseases.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013015/pdfft?md5=47643939a3ee3bbc4c69944de1383d1f&pid=1-s2.0-S0753332224013015-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230278","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}
Pub Date : 2024-09-12DOI: 10.1016/j.biopha.2024.117436
The occurrence and development of tumors are closely associated with abnormalities in the immune system's structure and function, with tumor immunotherapy being intricately linked to the tumor microenvironment (TME). Early studies on lymphocytes within the TME primarily concentrated on T cells. However, as research has advanced, the multifaceted roles of tumor-infiltrating B cells (TIL-Bs) in tumor immunity, encompassing both anti-tumor and pro-tumor effects, have garnered increasing attention. This paper explored the composition of the TME and the biological characteristics of TIL-Bs, investigating the dual roles within the TME to offer new insights and strategies for tumor immunotherapy.
肿瘤的发生和发展与免疫系统的结构和功能异常密切相关,而肿瘤免疫疗法与肿瘤微环境(TME)密切相关。早期对肿瘤微环境中淋巴细胞的研究主要集中在 T 细胞上。然而,随着研究的深入,肿瘤浸润 B 细胞(TIL-Bs)在肿瘤免疫中的多方面作用(包括抗肿瘤和促肿瘤作用)日益受到关注。本文探讨了TME的组成和TIL-Bs的生物学特性,研究了TME内的双重作用,为肿瘤免疫疗法提供新的见解和策略。
{"title":"Tumor-infiltrating B cells: Their dual mechanistic roles in the tumor microenvironment","authors":"","doi":"10.1016/j.biopha.2024.117436","DOIUrl":"10.1016/j.biopha.2024.117436","url":null,"abstract":"<div><p>The occurrence and development of tumors are closely associated with abnormalities in the immune system's structure and function, with tumor immunotherapy being intricately linked to the tumor microenvironment (TME). Early studies on lymphocytes within the TME primarily concentrated on T cells. However, as research has advanced, the multifaceted roles of tumor-infiltrating B cells (TIL-Bs) in tumor immunity, encompassing both anti-tumor and pro-tumor effects, have garnered increasing attention. This paper explored the composition of the TME and the biological characteristics of TIL-Bs, investigating the dual roles within the TME to offer new insights and strategies for tumor immunotherapy.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013222/pdfft?md5=76f9a880a55c32eebd04ab7ee6428a57&pid=1-s2.0-S0753332224013222-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172972","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}
Pub Date : 2024-09-11DOI: 10.1016/j.biopha.2024.117407
Mitochondrial autophagy (mitophagy) is very important process for the maintenance of cellular homeostasis, functionality and survival. Its dysregulation is associated with high risk and progression numerous serious diseases (e.g., oncological, neurodegenerative and cardiovascular ones). Therefore, targeting mitophagy mechanisms is very hot topic in the biological and medicinal research. The interrelationships between the regulation of mitophagy and iron homeostasis are now becoming apparent. In short, mitochondria are central point for the regulation of iron homeostasis, but change in intracellular cheatable iron level can induce/repress mitophagy. In this review, relationships between iron homeostasis and mitophagy are thoroughly discussed and described. Also, therapeutic applicability of mitophagy chelators in the context of individual diseases is comprehensively and critically evaluated.
{"title":"Iron chelators as mitophagy agents: Potential and limitations","authors":"","doi":"10.1016/j.biopha.2024.117407","DOIUrl":"10.1016/j.biopha.2024.117407","url":null,"abstract":"<div><p>Mitochondrial autophagy (mitophagy) is very important process for the maintenance of cellular homeostasis, functionality and survival. Its dysregulation is associated with high risk and progression numerous serious diseases (e.g., oncological, neurodegenerative and cardiovascular ones). Therefore, targeting mitophagy mechanisms is very hot topic in the biological and medicinal research. The interrelationships between the regulation of mitophagy and iron homeostasis are now becoming apparent. In short, mitochondria are central point for the regulation of iron homeostasis, but change in intracellular cheatable iron level can induce/repress mitophagy. In this review, relationships between iron homeostasis and mitophagy are thoroughly discussed and described. Also, therapeutic applicability of mitophagy chelators in the context of individual diseases is comprehensively and critically evaluated.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224012927/pdfft?md5=6da4c3dc73d33554b9faa7859c8ec76f&pid=1-s2.0-S0753332224012927-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167356","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}
Pub Date : 2024-09-10DOI: 10.1016/j.biopha.2024.117430
Targeting checkpoints for immune cell activation has been acknowledged known as one of the most effective way to activate anti-tumor immune responses. Among them, drugs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for clinical treatment though several more are in advanced stages of development, which demonstrated durable response rates and manageable safety profile. However, its therapy efficacy is unsatisfactory in pancreatic cancer (PC), which can be limited by the overall condition of patients, the pathological type of PC, the expression level of tumor related genes, etc. To improve clinical efficiency, various researches have been conducted, and the efficacy of combination therapy showed significantly improvement compared to monotherapy. This review analyzed current strategies based on anti-CTLA-4 combination immunotherapy, providing totally new idea for future research.
靶向检查点激活免疫细胞已被公认为激活抗肿瘤免疫反应的最有效方法之一。其中,以细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)为靶点的药物已被批准用于临床治疗,还有几种药物正处于开发的后期阶段,这些药物显示出持久的应答率和可控的安全性。然而,其对胰腺癌(PC)的疗效并不理想,这可能受到患者整体情况、PC 病理类型、肿瘤相关基因表达水平等因素的限制。为了提高临床疗效,人们开展了各种研究,与单药治疗相比,联合治疗的疗效显著提高。本综述分析了目前基于抗CTLA-4联合免疫疗法的策略,为今后的研究提供了全新的思路。
{"title":"Advances of immune-checkpoint inhibition of CTLA-4 in pancreatic cancer","authors":"","doi":"10.1016/j.biopha.2024.117430","DOIUrl":"10.1016/j.biopha.2024.117430","url":null,"abstract":"<div><p>Targeting checkpoints for immune cell activation has been acknowledged known as one of the most effective way to activate anti-tumor immune responses. Among them, drugs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for clinical treatment though several more are in advanced stages of development, which demonstrated durable response rates and manageable safety profile. However, its therapy efficacy is unsatisfactory in pancreatic cancer (PC), which can be limited by the overall condition of patients, the pathological type of PC, the expression level of tumor related genes, etc. To improve clinical efficiency, various researches have been conducted, and the efficacy of combination therapy showed significantly improvement compared to monotherapy. This review analyzed current strategies based on anti-CTLA-4 combination immunotherapy, providing totally new idea for future research.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013155/pdfft?md5=32755b7149ee8c79ed3040f7cf10c3fc&pid=1-s2.0-S0753332224013155-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164084","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}
Pub Date : 2024-09-09DOI: 10.1016/j.biopha.2024.117420
Radiotherapy, a precise modality for treating malignant tumors, has undergone rapid advancements in primary and clinical research. The mechanisms underlying tumor radioresistance have become significant research. With the introduction and in-depth study of cancer stem cells (CSCs) theory, CSCs have been identified as the primary factor contributing to the development of tumor radioresistance. The “stemness” of CSCs is a biological characteristic of a small subset of cells within tumor tissues, characterized by self-renewal solid ability. This characteristic leads to resistance to radiotherapy, chemotherapy, and targeted therapies, driving tumor recurrence and metastasis. Another study revealed that cellular autophagy plays a pivotal role in maintaining the “stemness” of CSCs. Autophagy is a cellular mechanism that degrades proteins and organelles to generate nutrients and energy in response to stress. This process maintains cellular homeostasis and contributes to CSCs radioresistance. Furthermore, ionizing radiation (IR) facilitates epithelial-to-mesenchymal transition (EMT), vascular regeneration, and other tumor processes by influencing the infiltration of M2-type tumor-associated macrophages (TAMs). IR promotes the activation of the classical immunosuppressive “switch,” PD-1/PD-L1, which diminishes T-cell secretion, leading to immune evasion and promoting radioresistance. Interestingly, recent studies have found that the immune pathway PD-1/PD-L1 is closely related to cellular autophagy. However, the interrelationships between immunity, autophagy, and radioresistance of CSCs and the regulatory mechanisms involved remain unclear. Consequently, this paper reviews recent research to summarize these potential connections, aiming to establish a theoretical foundation for future studies and propose a new model for the network regulation of immunity, autophagy, and radioresistance of tumor cells.
{"title":"Advancements in a novel model of autophagy and immune network regulation in radioresistance of cancer stem cells","authors":"","doi":"10.1016/j.biopha.2024.117420","DOIUrl":"10.1016/j.biopha.2024.117420","url":null,"abstract":"<div><p>Radiotherapy, a precise modality for treating malignant tumors, has undergone rapid advancements in primary and clinical research. The mechanisms underlying tumor radioresistance have become significant research. With the introduction and in-depth study of cancer stem cells (CSCs) theory, CSCs have been identified as the primary factor contributing to the development of tumor radioresistance. The “stemness” of CSCs is a biological characteristic of a small subset of cells within tumor tissues, characterized by self-renewal solid ability. This characteristic leads to resistance to radiotherapy, chemotherapy, and targeted therapies, driving tumor recurrence and metastasis. Another study revealed that cellular autophagy plays a pivotal role in maintaining the “stemness” of CSCs. Autophagy is a cellular mechanism that degrades proteins and organelles to generate nutrients and energy in response to stress. This process maintains cellular homeostasis and contributes to CSCs radioresistance. Furthermore, ionizing radiation (IR) facilitates epithelial-to-mesenchymal transition (EMT), vascular regeneration, and other tumor processes by influencing the infiltration of M2-type tumor-associated macrophages (TAMs). IR promotes the activation of the classical immunosuppressive “switch,” PD-1/PD-L1, which diminishes T-cell secretion, leading to immune evasion and promoting radioresistance. Interestingly, recent studies have found that the immune pathway PD-1/PD-L1 is closely related to cellular autophagy. However, the interrelationships between immunity, autophagy, and radioresistance of CSCs and the regulatory mechanisms involved remain unclear. Consequently, this paper reviews recent research to summarize these potential connections, aiming to establish a theoretical foundation for future studies and propose a new model for the network regulation of immunity, autophagy, and radioresistance of tumor cells.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224013052/pdfft?md5=ae497e5fb1c8746c3e8521355c22cd49&pid=1-s2.0-S0753332224013052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164166","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}
Pub Date : 2024-09-09DOI: 10.1016/j.biopha.2024.117406
In recent years, ferroptosis has gradually attracted increasing attention because of its important role in tumors. Ferroptosis resistance is an important cause of tumor metastasis, recurrence and drug resistance. Exploring the initiating factors and specific mechanisms of ferroptosis has become a key strategy to block tumor progression and improve drug sensitivity. As the external space in direct contact with tumor cells, the tumor microenvironment has a great impact on the biological function of tumor cells. The relationships between abnormal environmental characteristics (hypoxia, lactic acid accumulation, etc.) in the microenvironment and ferroptosis of tumor cells has not been fully characterized. This review focuses on the characteristics of the tumor microenvironment and summarizes the mechanisms of ferroptosis under different environmental factors, aiming to provide new insights for subsequent targeted therapy. Moreover, considering the presence of anticancer drugs in the microenvironment, we further summarize the mechanisms of ferroptosis to provide new strategies for the sensitization of tumor cells to drugs.
{"title":"Emerging role of tumor microenvironmental nutrients and metabolic molecules in ferroptosis: Mechanisms and clinical implications","authors":"","doi":"10.1016/j.biopha.2024.117406","DOIUrl":"10.1016/j.biopha.2024.117406","url":null,"abstract":"<div><p>In recent years, ferroptosis has gradually attracted increasing attention because of its important role in tumors. Ferroptosis resistance is an important cause of tumor metastasis, recurrence and drug resistance. Exploring the initiating factors and specific mechanisms of ferroptosis has become a key strategy to block tumor progression and improve drug sensitivity. As the external space in direct contact with tumor cells, the tumor microenvironment has a great impact on the biological function of tumor cells. The relationships between abnormal environmental characteristics (hypoxia, lactic acid accumulation, etc.) in the microenvironment and ferroptosis of tumor cells has not been fully characterized. This review focuses on the characteristics of the tumor microenvironment and summarizes the mechanisms of ferroptosis under different environmental factors, aiming to provide new insights for subsequent targeted therapy. Moreover, considering the presence of anticancer drugs in the microenvironment, we further summarize the mechanisms of ferroptosis to provide new strategies for the sensitization of tumor cells to drugs.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224012915/pdfft?md5=a023cfe7f735427152ca773c4478179d&pid=1-s2.0-S0753332224012915-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164165","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}