Pub Date : 2024-08-20DOI: 10.1016/j.biopha.2024.117312
Anthracyclines are broad-spectrum anticancer drugs, but their clinical use is limited due to their severe cardiotoxicity. Anthracycline-induced cardiotoxicity (AIC) remains a significant cause of heart disease-related mortality in many cancer survivors. The underlying mechanisms of AIC have been explored over the past few decades. Reactive oxygen species and drug-induced inhibition of topoisomerase II beta are well-studied mechanisms, with mitochondria being a prominently investigated organelle. Emerging mechanisms such as ferroptosis, Ca2+ overload, autophagy and inflammation mediators have been implicated in recent years. In this review, our goal is to summarize and update the roles of various mechanisms in AIC, focusing on different cellular levels and further explore promising therapeutic approaches targeting these organelles or pathways.
蒽环类是广谱抗癌药物,但由于其严重的心脏毒性,其临床应用受到限制。蒽环类药物诱发的心脏毒性(AIC)仍然是许多癌症幸存者死于心脏病的一个重要原因。过去几十年来,人们一直在探索 AIC 的基本机制。活性氧和药物诱导的拓扑异构酶 II beta 抑制是研究较多的机制,线粒体是研究较多的细胞器。近年来,新出现的机制,如铁蛋白沉积、Ca2+ 超载、自噬和炎症介质也被牵涉其中。在这篇综述中,我们的目标是总结和更新各种机制在 AIC 中的作用,重点关注不同细胞水平,并进一步探讨针对这些细胞器或途径的有前景的治疗方法。
{"title":"Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective","authors":"","doi":"10.1016/j.biopha.2024.117312","DOIUrl":"10.1016/j.biopha.2024.117312","url":null,"abstract":"<div><p>Anthracyclines are broad-spectrum anticancer drugs, but their clinical use is limited due to their severe cardiotoxicity. Anthracycline-induced cardiotoxicity (AIC) remains a significant cause of heart disease-related mortality in many cancer survivors. The underlying mechanisms of AIC have been explored over the past few decades. Reactive oxygen species and drug-induced inhibition of topoisomerase II beta are well-studied mechanisms, with mitochondria being a prominently investigated organelle. Emerging mechanisms such as ferroptosis, Ca<sup>2+</sup> overload, autophagy and inflammation mediators have been implicated in recent years. In this review, our goal is to summarize and update the roles of various mechanisms in AIC, focusing on different cellular levels and further explore promising therapeutic approaches targeting these organelles or pathways.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S075333222401196X/pdfft?md5=7e81829c98ce3aec0f4b6775ed711fec&pid=1-s2.0-S075333222401196X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012958","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 : 2024-08-20DOI: 10.1016/j.biopha.2024.117296
Over the past decades, cancer immunotherapy has encountered challenges such as immunogenicity, inefficiency, and cytotoxicity. Consequently, exosome-based cancer immunotherapy has gained rapid traction as a promising alternative. Exosomes, a type of extracellular vesicles (EVs) ranging from 50 to 150 nm, are self-originating and exhibit fewer side effects compared to traditional therapies. Exosome-based immunotherapy encompasses three significant areas: cancer vaccination, co-inhibitory checkpoints, and adoptive T-cell therapy. Each of these fields leverages the inherent advantages of exosomes, demonstrating substantial potential for individualized tumor therapy and precision medicine. This review aims to elucidate the reasons behind the promise of exosome-based nanoparticles as cancer therapies by examining their characteristics and summarizing the latest research advancements in cancer immunotherapy.
{"title":"Exosome-based nanoparticles and cancer immunotherapy","authors":"","doi":"10.1016/j.biopha.2024.117296","DOIUrl":"10.1016/j.biopha.2024.117296","url":null,"abstract":"<div><p>Over the past decades, cancer immunotherapy has encountered challenges such as immunogenicity, inefficiency, and cytotoxicity. Consequently, exosome-based cancer immunotherapy has gained rapid traction as a promising alternative. Exosomes, a type of extracellular vesicles (EVs) ranging from 50 to 150 nm, are self-originating and exhibit fewer side effects compared to traditional therapies. Exosome-based immunotherapy encompasses three significant areas: cancer vaccination, co-inhibitory checkpoints, and adoptive T-cell therapy. Each of these fields leverages the inherent advantages of exosomes, demonstrating substantial potential for individualized tumor therapy and precision medicine. This review aims to elucidate the reasons behind the promise of exosome-based nanoparticles as cancer therapies by examining their characteristics and summarizing the latest research advancements in cancer immunotherapy.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011806/pdfft?md5=16318b1a8b64874f35d3b55046ed6a26&pid=1-s2.0-S0753332224011806-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012935","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 : 2024-08-19DOI: 10.1016/j.biopha.2024.117302
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex disorder with an unknown cause. However, the dysbiosis of the gut microbiome has been found to play a role in IBD etiology, including exacerbated immune responses and defective intestinal barrier integrity. The gut microbiome can also be a potential biomarker for several diseases, including IBD. Currently, conventional treatments targeting pro-inflammatory cytokines and pathways in IBD-associated dysbiosis do not yield effective results. Other therapies that directly target the dysbiotic microbiome for effective outcomes are emerging. We review the role of the gut microbiome in health and IBD and its potential as a diagnostic, prognostic, and therapeutic target for IBD. This review also explores emerging therapeutic advancements that target gut microbiome-associated alterations in IBD, such as nanoparticle or encapsulation delivery, fecal microbiota transplantation, nutritional therapies, microbiome/probiotic engineering, phage therapy, mesenchymal stem cells (MSCs), gut proteins, and herbal formulas.
{"title":"The emerging role of the gut microbiota and its application in inflammatory bowel disease","authors":"","doi":"10.1016/j.biopha.2024.117302","DOIUrl":"10.1016/j.biopha.2024.117302","url":null,"abstract":"<div><p>Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex disorder with an unknown cause. However, the dysbiosis of the gut microbiome has been found to play a role in IBD etiology, including exacerbated immune responses and defective intestinal barrier integrity. The gut microbiome can also be a potential biomarker for several diseases, including IBD. Currently, conventional treatments targeting pro-inflammatory cytokines and pathways in IBD-associated dysbiosis do not yield effective results. Other therapies that directly target the dysbiotic microbiome for effective outcomes are emerging. We review the role of the gut microbiome in health and IBD and its potential as a diagnostic, prognostic, and therapeutic target for IBD. This review also explores emerging therapeutic advancements that target gut microbiome-associated alterations in IBD, such as nanoparticle or encapsulation delivery, fecal microbiota transplantation, nutritional therapies, microbiome/probiotic engineering, phage therapy, mesenchymal stem cells (MSCs), gut proteins, and herbal formulas.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011867/pdfft?md5=8cfca8d5d6df099a6ab52709f2a664f1&pid=1-s2.0-S0753332224011867-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007139","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 : 2024-08-18DOI: 10.1016/j.biopha.2024.117272
Calpain, a key member of the Calpain cysteine protease superfamily, performs limited protein hydrolysis in a calcium-dependent manner. Its activity is tightly regulated due to the potential for non-specific cleavage of various intracellular proteins upon aberrant activation. A thorough review of the literature from 2010 to 2023 reveals 121 references discussing cardiovascular and cerebrovascular diseases. Dysregulation of the Calpain system is associated with various pathological phenomena, including lipid metabolism disorders, inflammation, apoptosis, and excitotoxicity. Although recent studies have revealed the significant role of Calpain in cardiovascular and cerebrovascular diseases, the precise mechanisms remain incompletely understood. Exploring the potential of Calpain inhibition as a therapeutic approach for the treatment of cardiovascular and cerebrovascular diseases may emerge as a compelling area of interest for future calpain research.
{"title":"Calpain: The regulatory point of cardiovascular and cerebrovascular diseases","authors":"","doi":"10.1016/j.biopha.2024.117272","DOIUrl":"10.1016/j.biopha.2024.117272","url":null,"abstract":"<div><p>Calpain, a key member of the Calpain cysteine protease superfamily, performs limited protein hydrolysis in a calcium-dependent manner. Its activity is tightly regulated due to the potential for non-specific cleavage of various intracellular proteins upon aberrant activation. A thorough review of the literature from 2010 to 2023 reveals 121 references discussing cardiovascular and cerebrovascular diseases. Dysregulation of the Calpain system is associated with various pathological phenomena, including lipid metabolism disorders, inflammation, apoptosis, and excitotoxicity. Although recent studies have revealed the significant role of Calpain in cardiovascular and cerebrovascular diseases, the precise mechanisms remain incompletely understood. Exploring the potential of Calpain inhibition as a therapeutic approach for the treatment of cardiovascular and cerebrovascular diseases may emerge as a compelling area of interest for future calpain research.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011569/pdfft?md5=6d1d08da8178d373220c74e064784d67&pid=1-s2.0-S0753332224011569-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997073","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 : 2024-08-18DOI: 10.1016/j.biopha.2024.117303
The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject of debate. Here, we examined the effects of a PPARβ/δ agonist on the pathogenesis of liver fibrosis and the activation of hepatic stellate cells (HSCs), the main effector cells in liver fibrosis, in response to the pro-fibrotic stimulus transforming growth factor-β (TGF-β). The PPARβ/δ agonist GW501516 completely prevented glucose intolerance and peripheral insulin resistance, blocked the accumulation of collagen in the liver, and attenuated the expression of inflammatory and fibrogenic genes in mice fed a choline-deficient high-fat diet (CD-HFD). The antifibrogenic effect of GW501516 observed in the livers CD-HFD-fed mice could occur through an action on HSCs since primary HSCs isolated from Ppard-/- mice showed increased mRNA levels of the profibrotic gene Col1a1. Moreover, PPARβ/δ activation abrogated TGF-β1-mediated cell migration (an indicator of cell activation) in LX-2 cells (immortalized activated human HSCs). Likewise, GW501516 attenuated the phosphorylation of the main downstream intracellular protein target of TGF-β1, suppressor of mothers against decapentaplegic (SMAD)3, as well as the levels of the SMAD3 co-activator p300 via the activation of AMP-activated protein kinase (AMPK) and the subsequent inhibition of extracellular signal-regulated kinase-1/2 (ERK1/2) in LX-2 cells. Overall, these findings uncover a new mechanism by which the activation of AMPK by a PPARβ/δ agonist reduces TGF-β1-mediated activation of HSCs and fibrosis via the reduction of both SMAD3 phosphorylation and p300 levels.
{"title":"PPARβ/δ attenuates hepatic fibrosis by reducing SMAD3 phosphorylation and p300 levels via AMPK in hepatic stellate cells","authors":"","doi":"10.1016/j.biopha.2024.117303","DOIUrl":"10.1016/j.biopha.2024.117303","url":null,"abstract":"<div><p>The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject of debate. Here, we examined the effects of a PPARβ/δ agonist on the pathogenesis of liver fibrosis and the activation of hepatic stellate cells (HSCs), the main effector cells in liver fibrosis, in response to the pro-fibrotic stimulus transforming growth factor-β (TGF-β). The PPARβ/δ agonist GW501516 completely prevented glucose intolerance and peripheral insulin resistance, blocked the accumulation of collagen in the liver, and attenuated the expression of inflammatory and fibrogenic genes in mice fed a choline-deficient high-fat diet (CD-HFD). The antifibrogenic effect of GW501516 observed in the livers CD-HFD-fed mice could occur through an action on HSCs since primary HSCs isolated from <em>Ppard</em><sup>-/-</sup> mice showed increased mRNA levels of the profibrotic gene <em>Col1a1.</em> Moreover, PPARβ/δ activation abrogated TGF-β1-mediated cell migration (an indicator of cell activation) in LX-2 cells (immortalized activated human HSCs). Likewise, GW501516 attenuated the phosphorylation of the main downstream intracellular protein target of TGF-β1, suppressor of mothers against decapentaplegic (SMAD)3, as well as the levels of the SMAD3 co-activator p300 via the activation of AMP-activated protein kinase (AMPK) and the subsequent inhibition of extracellular signal-regulated kinase-1/2 (ERK1/2) in LX-2 cells. Overall, these findings uncover a new mechanism by which the activation of AMPK by a PPARβ/δ agonist reduces TGF-β1-mediated activation of HSCs and fibrosis via the reduction of both SMAD3 phosphorylation and p300 levels.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011879/pdfft?md5=5359b31fb8858c802f6fc333645b155e&pid=1-s2.0-S0753332224011879-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997074","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 : 2024-08-16DOI: 10.1016/j.biopha.2024.117306
Spinal cord injury (SCI) is a central nervous system injury that leads to neurological dysfunction or paralysis, which seriously affects patients' quality of life and causes a heavy social and economic burden. The pathological mechanism of SCI has not been fully revealed, resulting in unsatisfactory clinical treatment. Therefore, more research is urgently needed to reveal its precise pathological mechanism. Numerous studies have shown that inflammation is closely related to various pathological processes in SCI. Inflammatory response is an important pathological process leading to secondary injury, and sustained inflammatory response can exacerbate the injury and hinder the recovery of neurological function after injury. Epigenetic modification is considered to be an important regulatory mechanism in the pathological process of many diseases. Epigenetic modification mainly affects the function and characteristics of genes through the reversibility of mechanisms such as DNA methylation, histone modification, and regulation of non-coding RNA, thus having a significant impact on the pathological process of diseases and the survival state of the body. Recently, the role of epigenetic modification in the inflammatory response of SCI has gradually entered the field of view of researchers, and epigenetic modification may be a potential means to treat SCI. In this paper, we review the effects and mechanisms of different types of epigenetic modifications (including histone modifications, DNA methylation, and non-coding RNAs) on post-SCI inflammation and their potential therapeutic effects on inflammation to improve our understanding of the secondary SCI stage. This review aims to help identify new markers, signaling pathways and targeted drugs, and provide theoretical basis and new strategies for the diagnosis and treatment of SCI.
{"title":"Epigenetic modifications of inflammation in spinal cord injury","authors":"","doi":"10.1016/j.biopha.2024.117306","DOIUrl":"10.1016/j.biopha.2024.117306","url":null,"abstract":"<div><p>Spinal cord injury (SCI) is a central nervous system injury that leads to neurological dysfunction or paralysis, which seriously affects patients' quality of life and causes a heavy social and economic burden. The pathological mechanism of SCI has not been fully revealed, resulting in unsatisfactory clinical treatment. Therefore, more research is urgently needed to reveal its precise pathological mechanism. Numerous studies have shown that inflammation is closely related to various pathological processes in SCI. Inflammatory response is an important pathological process leading to secondary injury, and sustained inflammatory response can exacerbate the injury and hinder the recovery of neurological function after injury. Epigenetic modification is considered to be an important regulatory mechanism in the pathological process of many diseases. Epigenetic modification mainly affects the function and characteristics of genes through the reversibility of mechanisms such as DNA methylation, histone modification, and regulation of non-coding RNA, thus having a significant impact on the pathological process of diseases and the survival state of the body. Recently, the role of epigenetic modification in the inflammatory response of SCI has gradually entered the field of view of researchers, and epigenetic modification may be a potential means to treat SCI. In this paper, we review the effects and mechanisms of different types of epigenetic modifications (including histone modifications, DNA methylation, and non-coding RNAs) on post-SCI inflammation and their potential therapeutic effects on inflammation to improve our understanding of the secondary SCI stage. This review aims to help identify new markers, signaling pathways and targeted drugs, and provide theoretical basis and new strategies for the diagnosis and treatment of SCI.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011909/pdfft?md5=b954902eee5c3705c039b03c04a2d3d9&pid=1-s2.0-S0753332224011909-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992753","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 : 2024-08-16DOI: 10.1016/j.biopha.2024.117307
Wound healing requires interplay between cells and molecules. Recent evidence has demonstrated that liquid bandages promote wound healing by forming a protective barrier against contamination, attenuating inflammation, and enhancing re-epithelialization and angiogenesis. In this study, we evaluated the wound healing activity of pyroxylin-based liquid bandage (LiQuiPlast®) in eight-week-old C57BL/6 male mice by generating a single 4 mm diameter full-thickness excisional skin wound on the dorsum. In the LiQuiPlast® group, the liquid bandage was applied on day 0 and was replaced every four days. Wound size was monitored every day for two weeks. The results showed that LiQuiPlast® was mechanically active (induced wound contraction), which promoted a significant wound size reduction (27 %−39 %, compared to the control group) on days 1–4 postinjury. In addition, a significant reduction in wound size was observed again in the LiQuiPlast® group (25 %−29 %, compared to the controls) on days 8−9 postinjury. LiQuiPlast®-treated wounds showed no scab. Immunohistochemistry analyses displayed a reduction in neutrophils and tumor necrosis factor-α levels in LiQuiPlast®-treated wounds, compared to the control group on day 4 postinjury (the inflammatory phase). In addition, LiQuiPlast®-treated mice had enhanced keratinocyte proliferation than control mice during this time. On day 13 postinjury, LiQuiPlast® significantly reduced hypertrophic scarring and enhanced expression and reorganization of collagen fiber compared to control mice. In conclusion, we show that LiQuiPlast® acts as a mechanically active protective film, which promotes moist wound healing by promoting wound contraction, no scab formation, attenuated inflammation, enhanced keratinocyte proliferation, and decreased scarring.
{"title":"Pyroxylin-based liquid bandage forms a mechanically active protective film to facilitate skin wound healing in mice","authors":"","doi":"10.1016/j.biopha.2024.117307","DOIUrl":"10.1016/j.biopha.2024.117307","url":null,"abstract":"<div><p>Wound healing requires interplay between cells and molecules. Recent evidence has demonstrated that liquid bandages promote wound healing by forming a protective barrier against contamination, attenuating inflammation, and enhancing re-epithelialization and angiogenesis. In this study, we evaluated the wound healing activity of pyroxylin-based liquid bandage (LiQuiPlast®) in eight-week-old C57BL/6 male mice by generating a single 4 mm diameter full-thickness excisional skin wound on the dorsum. In the LiQuiPlast® group, the liquid bandage was applied on day 0 and was replaced every four days. Wound size was monitored every day for two weeks. The results showed that LiQuiPlast® was mechanically active (induced wound contraction), which promoted a significant wound size reduction (27 %−39 %, compared to the control group) on days 1–4 postinjury. In addition, a significant reduction in wound size was observed again in the LiQuiPlast® group (25 %−29 %, compared to the controls) on days 8−9 postinjury. LiQuiPlast®-treated wounds showed no scab. Immunohistochemistry analyses displayed a reduction in neutrophils and tumor necrosis factor-α levels in LiQuiPlast®-treated wounds, compared to the control group on day 4 postinjury (the inflammatory phase). In addition, LiQuiPlast®-treated mice had enhanced keratinocyte proliferation than control mice during this time. On day 13 postinjury, LiQuiPlast® significantly reduced hypertrophic scarring and enhanced expression and reorganization of collagen fiber compared to control mice. In conclusion, we show that LiQuiPlast® acts as a mechanically active protective film, which promotes moist wound healing by promoting wound contraction, no scab formation, attenuated inflammation, enhanced keratinocyte proliferation, and decreased scarring.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011910/pdfft?md5=c2d121202c2e288272d0f20956f8f319&pid=1-s2.0-S0753332224011910-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992765","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 : 2024-08-16DOI: 10.1016/j.biopha.2024.117290
Hydrogen sulfide (H2S) is a gaseous signaling molecule that influences digestive and nervous system functions. Enteric glial cells (EGCs) are integral to the enteric nervous system and play a role in regulating gastrointestinal motility. This study explored the dual effects of exogenous H2S on EGCs and the influence of apoptosis-related pathways and ion channels in EGCs. We also administered honokiol for further interventional studies. The results revealed that low-concentration H2S increased the mitochondrial membrane potential (MMP) of EGCs, decreased the whole-cell membrane potential, downregulated BAX and caspase-3, upregulated Bcl2 expression, reduced apoptosis, and promoted cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also increased. A high concentration of H2S had the opposite effect. In addition, GFAP mRNA expression was upregulated in the test-low group, downregulated in the test-high group, and upregulated in the test-high + Hon group. Honokiol treatment increased MMP, reduced whole-cell membrane potential, inhibited BAX and caspase-3 expression, increased Bcl2 expression, decreased cell apoptosis, and increased cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also upregulated. In conclusion, our study showed that exogenous H2S can bidirectionally regulate EGC proliferation and apoptosis by affecting MMP and cell membrane potential via the Bcl2/BAX/caspase-3 pathway and modulate Cx43-mediated Ca2+ responses in EGCs to regulate colonic motility bidirectionally. Honokiol can ameliorate the damage to EGCs induced by high H2S concentrations through the Bcl2/BAX/caspase-3 pathway and improve colon motility by increasing Cx43 expression and Ca2+ concentration.
{"title":"Effects of exogenous hydrogen sulfide and honokiol intervention on the proliferation, apoptosis, and calcium signaling pathway of rat enteric glial cells","authors":"","doi":"10.1016/j.biopha.2024.117290","DOIUrl":"10.1016/j.biopha.2024.117290","url":null,"abstract":"<div><p>Hydrogen sulfide (H<sub>2</sub>S) is a gaseous signaling molecule that influences digestive and nervous system functions. Enteric glial cells (EGCs) are integral to the enteric nervous system and play a role in regulating gastrointestinal motility. This study explored the dual effects of exogenous H<sub>2</sub>S on EGCs and the influence of apoptosis-related pathways and ion channels in EGCs. We also administered honokiol for further interventional studies. The results revealed that low-concentration H<sub>2</sub>S increased the mitochondrial membrane potential (MMP) of EGCs, decreased the whole-cell membrane potential, downregulated BAX and caspase-3, upregulated Bcl2 expression, reduced apoptosis, and promoted cell proliferation. The Ca<sup>2+</sup> concentration, Cx43 mRNA, and protein expression were also increased. A high concentration of H<sub>2</sub>S had the opposite effect. In addition, GFAP mRNA expression was upregulated in the test-low group, downregulated in the test-high group, and upregulated in the test-high + Hon group. Honokiol treatment increased MMP, reduced whole-cell membrane potential, inhibited BAX and caspase-3 expression, increased Bcl2 expression, decreased cell apoptosis, and increased cell proliferation. The Ca<sup>2+</sup> concentration, Cx43 mRNA, and protein expression were also upregulated. In conclusion, our study showed that exogenous H<sub>2</sub>S can bidirectionally regulate EGC proliferation and apoptosis by affecting MMP and cell membrane potential via the Bcl2/BAX/caspase-3 pathway and modulate Cx43-mediated Ca<sup>2+</sup> responses in EGCs to regulate colonic motility bidirectionally. Honokiol can ameliorate the damage to EGCs induced by high H<sub>2</sub>S concentrations through the Bcl2/BAX/caspase-3 pathway and improve colon motility by increasing Cx43 expression and Ca<sup>2+</sup> concentration.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011740/pdfft?md5=9e2b68124779972d0130d47a13feb56c&pid=1-s2.0-S0753332224011740-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992766","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 : 2024-08-16DOI: 10.1016/j.biopha.2024.117315
Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.
{"title":"c-Myc-XRCC2-FOS axis promotes the proliferation and the resistance to Doxorubicin of NSCLC","authors":"","doi":"10.1016/j.biopha.2024.117315","DOIUrl":"10.1016/j.biopha.2024.117315","url":null,"abstract":"<div><p>Lung cancer represents one of the most prevalent malignant neoplasms, commanding an alarming incidence and mortality rate globally. Non-small cell lung cancer (NSCLC), constituting approximately 80 %-90 % of all lung cancer cases, is the predominant pathological manifestation of this disease, with a disconcerting 5-year survival rate scarcely reaching 10 %. Extensive prior investigations have elucidated that the aberrant expression of X-ray repair cross-complementing gene 2 (XRCC2), a critical meiotic gene intricately involved in the DNA damage repair process, is intimately associated with tumorigenesis. Nevertheless, the precise roles and underlying mechanistic pathways of XRCC2 in NSCLC remain largely elusive. In the present study, we discerned an overexpression of XRCC2 within NSCLC patient tissues, particularly in high-grade samples, when juxtaposed with normal tissues. Targeted knockdown of XRCC2 notably impeded the proliferation of NSCLC both in vitro and in vivo. Comprehensive RNA sequencing and flow rescue assays unveiled that XRCC2 augments the proliferation of NSCLC cells through the down-regulation of FOS expression. Moreover, the c-Myc gene was definitively identified as an XRCC2 transcriptional factor by means of chromatin immunoprecipitation (ChIP) and luciferase reporter assays, whereby pharmacological attenuation of c-Myc expression, in conjunction with Doxorubicin, synergistically curtailed NSCLC cell growth both in vitro and in vivo. Collectively, our findings proffer critical insights into the novel c-Myc-XRCC2-FOS axis in promoting both proliferation and resistance to Doxorubicin in NSCLC cells, thereby extending a promising avenue for potential new diagnostic strategies and therapeutic interventions in NSCLC.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011995/pdfft?md5=0312ff5d26c309d86adde0d6f54d660e&pid=1-s2.0-S0753332224011995-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992767","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 : 2024-08-15DOI: 10.1016/j.biopha.2024.117284
Osteosarcoma is the most common primary bone malignancy with a challenging prognosis marked by a high rate of metastasis. The limited success of current treatments may be partially attributed to an incomplete understanding of osteosarcoma pathophysiology and to the absence of reliable in vitro models to select the best molecules for in vivo studies. Among the natural compounds relevant for osteosarcoma treatment, Licochalcone A (Lic-A) and chalcone derivatives are particularly interesting. Here, Lic-A and selected derivatives have been evaluated for their anticancer effect on multicellular tumor spheroids from MG63 and 143B osteosarcoma cell lines. A metabolic activity assay revealed Lic-A, 1i, and 1k derivatives as the most promising candidates. To delve into their mechanism of action, caspase activity assay was conducted in 2D and 3D in vitro models. Notably, apoptosis and autophagic induction was generally observed for Lic-A and 1k. The invasion assay demonstrated that Lic-A and 1k possess the ability to mitigate the spread of osteosarcoma cells within a matrix. The effectiveness of chalcone as a natural scaffold for generating potential antiproliferative agents against osteosarcoma has been demonstrated. In particular, chalcones exert their antiproliferative activity by inducing apoptosis and autophagy, and in addition they are capable of reducing cell invasion. These findings suggest Lic-A and 1k as promising antitumor agents against osteosarcoma cells.
{"title":"Chalcones induce apoptosis, autophagy and reduce spreading in osteosarcoma 3D models","authors":"","doi":"10.1016/j.biopha.2024.117284","DOIUrl":"10.1016/j.biopha.2024.117284","url":null,"abstract":"<div><p>Osteosarcoma is the most common primary bone malignancy with a challenging prognosis marked by a high rate of metastasis. The limited success of current treatments may be partially attributed to an incomplete understanding of osteosarcoma pathophysiology and to the absence of reliable <em>in vitro</em> models to select the best molecules for <em>in vivo</em> studies. Among the natural compounds relevant for osteosarcoma treatment, Licochalcone A (<strong>Lic-A</strong>) and chalcone derivatives are particularly interesting. Here, <strong>Lic-A</strong> and selected derivatives have been evaluated for their anticancer effect on multicellular tumor spheroids from MG63 and 143B osteosarcoma cell lines. A metabolic activity assay revealed <strong>Lic-A</strong>, <strong>1i</strong>, and <strong>1k</strong> derivatives as the most promising candidates. To delve into their mechanism of action, caspase activity assay was conducted in 2D and 3D <em>in vitro</em> models. Notably, apoptosis and autophagic induction was generally observed for <strong>Lic-A</strong> and <strong>1k</strong>. The invasion assay demonstrated that <strong>Lic-A</strong> and <strong>1k</strong> possess the ability to mitigate the spread of osteosarcoma cells within a matrix. The effectiveness of chalcone as a natural scaffold for generating potential antiproliferative agents against osteosarcoma has been demonstrated. In particular, chalcones exert their antiproliferative activity by inducing apoptosis and autophagy, and in addition they are capable of reducing cell invasion. These findings suggest <strong>Lic-A</strong> and <strong>1k</strong> as promising antitumor agents against osteosarcoma cells.</p></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0753332224011685/pdfft?md5=e1f27063b89f787e05a0dec3e4abab25&pid=1-s2.0-S0753332224011685-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991372","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}