Ming Ren, Lu-Lu Sun, Yu-Chi Tu, Li Feng, Li-Jun Yao
Ischemia-reperfusion injury (IRI) is a complex phenomenon. Although researchers have long been aware of IRI, its complex signaling events and potential therapeutic targets are still an active research area. The role of reactive oxygen species in IRI has garnered great interest among scientists. Recent studies have found that reactive oxygen species produced by IRI can activate redox-sensitive transient receptor potential channels (redox TRPs). The discovery of redox TRPs provides a new perspective for understanding the mechanism of IRI.
缺血再灌注损伤(IRI)是一种复杂的现象。尽管研究人员早已意识到 IRI 的存在,但其复杂的信号传递事件和潜在的治疗靶点仍是一个活跃的研究领域。活性氧在 IRI 中的作用引起了科学家们的极大兴趣。最新研究发现,IRI 产生的活性氧可激活氧化还原敏感性瞬时受体电位通道(氧化还原 TRPs)。氧化还原 TRPs 的发现为了解 IRI 的机理提供了一个新的视角。
{"title":"Redox TRPs in Ischemia-Reperfusion Injury and Their Pharmacological Value.","authors":"Ming Ren, Lu-Lu Sun, Yu-Chi Tu, Li Feng, Li-Jun Yao","doi":"10.31083/j.fbl2905170","DOIUrl":"https://doi.org/10.31083/j.fbl2905170","url":null,"abstract":"<p><p>Ischemia-reperfusion injury (IRI) is a complex phenomenon. Although researchers have long been aware of IRI, its complex signaling events and potential therapeutic targets are still an active research area. The role of reactive oxygen species in IRI has garnered great interest among scientists. Recent studies have found that reactive oxygen species produced by IRI can activate redox-sensitive transient receptor potential channels (redox TRPs). The discovery of redox TRPs provides a new perspective for understanding the mechanism of IRI.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176298","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}
Jie Zhang, Lei Cao, Lijuan Lyu, Wenqian Qi, Wei Yang, Ruiqing Ren, Chunyu Kao, Yun Zhang, Cheng Zhang, Meng Zhang
Transforming growth factor-β (TGF-β) activated kinase 1 (TAK1), also named mitogen-activated protein kinase 7 (MAPK7), forms a pivotal signaling complex with TAK1-binding proteins (TAB1, TAB2, and TAB3), orchestrating critical biological processes, including immune responses, cell growth, apoptosis, and stress responses. Activation of TAK1 by stimuli, such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and Toll-like receptors (TLRs), underscores its central role in cellular signaling. Given the critical role of the TAK1-binding protein (TAK1-TAB) complex in cellular signaling and its impact on various biological processes, this review seeks to understand how ubiquitination thoroughly regulates the TAK1-TAB complex. This understanding is vital for developing targeted therapies for diseases where this signaling pathway is dysregulated. The exploration is significant as it unveils new insights into the activity, stability, and assembly of the complex, underscoring its therapeutic potential in disease modulation.
{"title":"Regulation of TAK-TAB Complex Activation through Ubiquitylation.","authors":"Jie Zhang, Lei Cao, Lijuan Lyu, Wenqian Qi, Wei Yang, Ruiqing Ren, Chunyu Kao, Yun Zhang, Cheng Zhang, Meng Zhang","doi":"10.31083/j.fbl2905169","DOIUrl":"https://doi.org/10.31083/j.fbl2905169","url":null,"abstract":"<p><p>Transforming growth factor-β (TGF-β) activated kinase 1 (TAK1), also named mitogen-activated protein kinase 7 (MAPK7), forms a pivotal signaling complex with TAK1-binding proteins (TAB1, TAB2, and TAB3), orchestrating critical biological processes, including immune responses, cell growth, apoptosis, and stress responses. Activation of TAK1 by stimuli, such as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and Toll-like receptors (TLRs), underscores its central role in cellular signaling. Given the critical role of the TAK1-binding protein (TAK1-TAB) complex in cellular signaling and its impact on various biological processes, this review seeks to understand how ubiquitination thoroughly regulates the TAK1-TAB complex. This understanding is vital for developing targeted therapies for diseases where this signaling pathway is dysregulated. The exploration is significant as it unveils new insights into the activity, stability, and assembly of the complex, underscoring its therapeutic potential in disease modulation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176383","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}
Huihui Ke, Juan Shao, Jiachang Hu, Xumin Song, Hongyu Han, Zhanpeng Zhu, Xinying Zhou, Li Chen, Ying Shan
Background: Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis.
Methods: Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth in vivo, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10.
Results: ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells.
Conclusions: Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.
{"title":"ARHGAP10, Transcriptionally Regulated by Sodium Butyrate, Promotes Ferroptosis of Ovarian Cancer Cells.","authors":"Huihui Ke, Juan Shao, Jiachang Hu, Xumin Song, Hongyu Han, Zhanpeng Zhu, Xinying Zhou, Li Chen, Ying Shan","doi":"10.31083/j.fbl2905167","DOIUrl":"https://doi.org/10.31083/j.fbl2905167","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis.</p><p><strong>Methods: </strong>Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth <i>in vivo</i>, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10.</p><p><strong>Results: </strong>ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells.</p><p><strong>Conclusions: </strong>Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176080","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}
The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.
这篇综述重点介绍了有关源自植物的天然蒽醌(AQs)的最新知识,以及它们在一种名为光动力疗法(PDT)的独家药物治疗和缓解方法中的应用潜力。光动力疗法的绿色方法与植物或其他天然来源的光敏剂(PS)和可见光谱激发光有关。由于植物作为草本植物具有独特的保健特性,而且可获得具有医疗价值的化合物的比例很高,因此对植物的研究具有很高的研究兴趣。迄今为止,许多具有治疗特性的天然化合物已为人所知,并仍在研究之中。一些天然醌类化合物已经过评估,并被临床批准为抗肿瘤药物。最近,科学界对这些天然醌类化合物的兴趣已经超出了它们的普通医疗应用,而是转向了它们作为天然 PS 的光特性。本研究对从高等植物中分离出来的 AQ 衍生物作为光敏剂应用于光导透射疗法的最新知识进行了系统的搜索。天然醌类化合物自古以来就被认为具有天然染料的功能。最近,人们开始探索 AQs,因为它们具有生物活性,包括光敏特性,可用于光导放疗,尤其是针对没有其他替代品的医疗问题。现有文献综述表明,天然 AQ 具有用于光导疗法的宝贵 PS 的特性。这种方法以光活性化合物的应用和氧气介质中的光排列为基础,可以避免有害的一般细胞毒性。此外,在对常见的抗癌和抗菌药物耐药性进行评估后发现,PDT 的耐药性发生率非常低。天然 AQ 具有天然来源多、生物相容性好、毒性低、副作用小、耐药性低、光敏性好、治疗能力强等优点,因此一直是科学界进一步开发的重点。在已知的 AQs 中,只有金丝桃素已被用于抗癌临床 PDT 研究。目前,人们正在对天然 PS 进行深入研究,以便在未来将其应用于没有其他有效治疗方法的疾病的光透射疗法中。
{"title":"Plants-occurring Anthraquinones as Photosensitive Compounds for Photodynamic Method: A Critical Overview.","authors":"Vanya Mantareva, Diana Braikova, Irina Lazarova, Tsanislava Genova","doi":"10.31083/j.fbl2905168","DOIUrl":"https://doi.org/10.31083/j.fbl2905168","url":null,"abstract":"<p><p>The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176289","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}
Imtiaz Ahmad, Saeed Ahmad, Esra Küpeli Akkol, Huma Rao, Muhammad Nadeem Shahzad, Mehwish Nawaz, Bilal Ahmad Ghalloo, Wayne Thomas Shier, Eduardo Sobarzo-Sánchez
The Editors-in-Chief have retracted the article titled "[Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays]" ([1]) due to significant concerns regarding the reliability and integrity of the data presented. After the publication of the article, several issues were brought to our attention regarding the originality and authenticity of the visual data within the manuscript. Specifically, Figure 4 of the article contains images that are identical to those in the previously published papers [2, 3]. This duplication of images raises serious questions about the validity of the results and the adherence to ethical standards of research. Despite multiple attempts to contact the authors for an explanation and an opportunity to address these concerns, no satisfactory response was provided. Given the lack of accountability and the serious nature of the academic misconduct implied, the Editor-in-Chief, after careful consideration and in accordance with the publication's ethical guidelines, has decided to retract the article.
{"title":"RETRACTED: Ahmad <i>et al</i>. Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by <i>Leucophyllum frutescens</i> (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays. <i>Front. Biosci. (Landmark Ed)</i> 2023, 28(8), 184.","authors":"Imtiaz Ahmad, Saeed Ahmad, Esra Küpeli Akkol, Huma Rao, Muhammad Nadeem Shahzad, Mehwish Nawaz, Bilal Ahmad Ghalloo, Wayne Thomas Shier, Eduardo Sobarzo-Sánchez","doi":"10.31083/j.fbl2808184R","DOIUrl":"https://doi.org/10.31083/j.fbl2808184R","url":null,"abstract":"<p><p>The Editors-in-Chief have retracted the article titled \"[Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays]\" ([1]) due to significant concerns regarding the reliability and integrity of the data presented. After the publication of the article, several issues were brought to our attention regarding the originality and authenticity of the visual data within the manuscript. Specifically, Figure 4 of the article contains images that are identical to those in the previously published papers [2, 3]. This duplication of images raises serious questions about the validity of the results and the adherence to ethical standards of research. Despite multiple attempts to contact the authors for an explanation and an opportunity to address these concerns, no satisfactory response was provided. Given the lack of accountability and the serious nature of the academic misconduct implied, the Editor-in-Chief, after careful consideration and in accordance with the publication's ethical guidelines, has decided to retract the article.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868995","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}
Hai Liang, Longhai Li, Baoyu Huang, Gang Cheng, Jiafu Ao, Shuli Hao
Objective: The aims of this study were to evaluate the correlation between chemokine (C-X-C) ligand 7 (CXCL7) expression and glycolysis and to explore the prognostic significance of CXCL7 in colorectal cancer (CRC).
Methods: The expression of CXCL7 and lactate dehydrogenase A (LDH-A) was measured by immunohistochemistry in tissue from 158 CRC patients. Patients were divided into high expression and low expression groups based on receiver operating characteristic curves and a cut-off value. The correlation between CXCL7 and LDH-A expression was evaluated. The overall survival (OS) times of CRC patients were explored. The risk factors related to prognosis were assessed.
Results: Significantly higher expression of CXCL7 and LDH-A was detected in CRC tissue than in non-CRC tissue, and was associated with N stage and tumor-node-metastasis (TNM) stage. CXCL7 expression was strongly correlated with LDH-A expression in CRC tissue. High expression of CXCL7 was validated as an independent risk factor for OS.
Conclusion: Increased expression of CXCL7 was positively correlated with LDH-A expression and was an independent risk factor for CRC prognosis.
{"title":"The Chemokine CXCL7 is Correlated with LDH-A and Predicts the Prognosis of Patients with Colorectal Cancer.","authors":"Hai Liang, Longhai Li, Baoyu Huang, Gang Cheng, Jiafu Ao, Shuli Hao","doi":"10.31083/j.fbl2904166","DOIUrl":"10.31083/j.fbl2904166","url":null,"abstract":"<p><strong>Objective: </strong>The aims of this study were to evaluate the correlation between chemokine (C-X-C) ligand 7 (CXCL7) expression and glycolysis and to explore the prognostic significance of CXCL7 in colorectal cancer (CRC).</p><p><strong>Methods: </strong>The expression of CXCL7 and lactate dehydrogenase A (LDH-A) was measured by immunohistochemistry in tissue from 158 CRC patients. Patients were divided into high expression and low expression groups based on receiver operating characteristic curves and a cut-off value. The correlation between CXCL7 and LDH-A expression was evaluated. The overall survival (OS) times of CRC patients were explored. The risk factors related to prognosis were assessed.</p><p><strong>Results: </strong>Significantly higher expression of CXCL7 and LDH-A was detected in CRC tissue than in non-CRC tissue, and was associated with N stage and tumor-node-metastasis (TNM) stage. CXCL7 expression was strongly correlated with LDH-A expression in CRC tissue. High expression of CXCL7 was validated as an independent risk factor for OS.</p><p><strong>Conclusion: </strong>Increased expression of CXCL7 was positively correlated with LDH-A expression and was an independent risk factor for CRC prognosis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856069","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}
Lu-Rong Yu, Xian-Zhong Han, Ying-Zi Tang, Dan Liu, Xian-Qin Luo, Xue-Wen Qiu, Jie Feng, Wen-Xiao Yuan, Jia-Yu Ding
Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored.
Methods: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens.
Results: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues.
Conclusions: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.
{"title":"Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.","authors":"Lu-Rong Yu, Xian-Zhong Han, Ying-Zi Tang, Dan Liu, Xian-Qin Luo, Xue-Wen Qiu, Jie Feng, Wen-Xiao Yuan, Jia-Yu Ding","doi":"10.31083/j.fbl2904160","DOIUrl":"10.31083/j.fbl2904160","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored.</p><p><strong>Methods: </strong>Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens.</p><p><strong>Results: </strong>Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues.</p><p><strong>Conclusions: </strong>Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872303","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}
Smaragdi Antonopoulou, Evdokia K Mitsou, Adamantini Kyriacou, Elizabeth Fragopoulou, Maria Detopoulou
Objective: The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects.
Methods: A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention.
Results: Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of Bifidobacterium spp., Clostridium perfringens group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of Lactobacillus and C. perfringens group was detected after the intake of the plain yogurt. The increase in the levels of C. perfringens group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of C. perfringens group were also associated with lower PAF action assessed as ex vivo human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels.
Conclusion: Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects.
{"title":"Does Yogurt Enriched with Platelet-Activating Factor Inhibitors from Olive Oil By-Products Affect Gut Microbiota and Faecal Metabolites in Healthy Overweight Subjects? (A randomized, parallel, three arm trial.).","authors":"Smaragdi Antonopoulou, Evdokia K Mitsou, Adamantini Kyriacou, Elizabeth Fragopoulou, Maria Detopoulou","doi":"10.31083/j.fbl2904159","DOIUrl":"10.31083/j.fbl2904159","url":null,"abstract":"<p><strong>Objective: </strong>The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects.</p><p><strong>Methods: </strong>A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention.</p><p><strong>Results: </strong>Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of <i>Bifidobacterium</i> spp., <i>Clostridium perfringens</i> group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of <i>Lactobacillus</i> and <i>C. perfringens</i> group was detected after the intake of the plain yogurt. The increase in the levels of <i>C. perfringens</i> group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of <i>C. perfringens</i> group were also associated with lower PAF action assessed as <i>ex vivo</i> human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels.</p><p><strong>Conclusion: </strong>Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov (NCT02259205).</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862868","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}
Zaven A Karalyan, Susanna A Ghonyan, Davit A Poghosyan, Lina H Hakobyan, Hranush R Avagyan, Aida S Avetisyan, Liana O Abroyan, Arpine A Poghosyan, Sona A Hakobyan, Gayane P Manukyan
Background: The African swine fever (ASF) virus (ASFV) and ASF-like viral sequences were identified in human samples and sewage as well as in different water environments. Pigs regularly experience infections by the ASFV. The considerable stability of the virus in the environment suggests that there is ongoing and long-term contact between humans and the ASFV. However, humans exhibit resistance to the ASFV, and the decisive factor in developing infection in the body is most likely the reaction of target macrophages to the virus. Therefore, this study aimed to characterize the responses of human macrophages to the virus and explore the distinct features of the viral replication cycle within human macrophages.
Methods: The ASFV Armenia/07 strain was used in all experiments. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the ASFV gene expression; flow cytometry analysis was performed to evaluate the effects of the inactive and active ASFV (inASFV and aASFV) treatments on the phenotype of THP-1-derived macrophages (Mφ0) and inflammatory markers. Moreover, other methods such as cell viability and apoptosis assays, staining techniques, phagocytosis assay, lysosome-associated membrane protein (LAMP-1) cytometry, and cytokine detection were used during experiments.
Results: Our findings showed that the virus initiated replication by entering human macrophages. Subsequently, the virus shed its capsid and initiated the transcription of numerous viral genes, and at least some of these genes executed their functions. In THP-1-derived macrophages (Mφ0), the ASFV implemented several functions to suppress cell activity, although the timing of their implementation was slower compared with virus-sensitive porcine alveolar macrophages (PAMs). Additionally, the virus could not complete the entire replication cycle in human Mφ0, as indicated by the absence of viral factories and a decrease in infectious titers of the virus with each subsequent passage. Overall, the infection of Mφ0 with the ASFV caused significant alterations in their phenotype and functions, such as increased TLR2, TLR3, CD80, CD36, CD163, CXCR2, and surface LAMP-1 expression. Increased production of the tumor necrosis factor (TNF) and interleukin (IL)-10 and decreased production of interferon (IFN)-α were also observed. Taken together, the virus enters human THP-1-derived macrophages, starts transcription, and causes immunological responses by target cells but cannot complete the replicative cycle.
Conclusion: These findings suggest that there may be molecular limitations within human macrophages that at least partially restrict the complete replication of the ASFV. Understanding the factors that hinder viral replication in Mφ0 can provide valuable insights into the host-virus interactions and the mechanisms underlying the resistance of human macrophages to the
{"title":"Infection of Human Macrophage-Like Cells by African Swine Fever Virus.","authors":"Zaven A Karalyan, Susanna A Ghonyan, Davit A Poghosyan, Lina H Hakobyan, Hranush R Avagyan, Aida S Avetisyan, Liana O Abroyan, Arpine A Poghosyan, Sona A Hakobyan, Gayane P Manukyan","doi":"10.31083/j.fbl2904164","DOIUrl":"https://doi.org/10.31083/j.fbl2904164","url":null,"abstract":"<p><strong>Background: </strong>The African swine fever (ASF) virus (ASFV) and ASF-like viral sequences were identified in human samples and sewage as well as in different water environments. Pigs regularly experience infections by the ASFV. The considerable stability of the virus in the environment suggests that there is ongoing and long-term contact between humans and the ASFV. However, humans exhibit resistance to the ASFV, and the decisive factor in developing infection in the body is most likely the reaction of target macrophages to the virus. Therefore, this study aimed to characterize the responses of human macrophages to the virus and explore the distinct features of the viral replication cycle within human macrophages.</p><p><strong>Methods: </strong>The ASFV Armenia/07 strain was used in all experiments. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the ASFV gene expression; flow cytometry analysis was performed to evaluate the effects of the inactive and active ASFV (inASFV and aASFV) treatments on the phenotype of THP-1-derived macrophages (Mφ0) and inflammatory markers. Moreover, other methods such as cell viability and apoptosis assays, staining techniques, phagocytosis assay, lysosome-associated membrane protein (LAMP-1) cytometry, and cytokine detection were used during experiments.</p><p><strong>Results: </strong>Our findings showed that the virus initiated replication by entering human macrophages. Subsequently, the virus shed its capsid and initiated the transcription of numerous viral genes, and at least some of these genes executed their functions. In THP-1-derived macrophages (Mφ0), the ASFV implemented several functions to suppress cell activity, although the timing of their implementation was slower compared with virus-sensitive porcine alveolar macrophages (PAMs). Additionally, the virus could not complete the entire replication cycle in human Mφ0, as indicated by the absence of viral factories and a decrease in infectious titers of the virus with each subsequent passage. Overall, the infection of Mφ0 with the ASFV caused significant alterations in their phenotype and functions, such as increased TLR2, TLR3, CD80, CD36, CD163, CXCR2, and surface LAMP-1 expression. Increased production of the tumor necrosis factor (TNF) and interleukin (IL)-10 and decreased production of interferon (IFN)-α were also observed. Taken together, the virus enters human THP-1-derived macrophages, starts transcription, and causes immunological responses by target cells but cannot complete the replicative cycle.</p><p><strong>Conclusion: </strong>These findings suggest that there may be molecular limitations within human macrophages that at least partially restrict the complete replication of the ASFV. Understanding the factors that hinder viral replication in Mφ0 can provide valuable insights into the host-virus interactions and the mechanisms underlying the resistance of human macrophages to the ","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866890","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}
Baoxin Yan, Xiaoxian Yu, Xianzhen Cai, Xiaojun Huang, Bin Xie, Danchun Lian, Jinhao Chen, Weiwen Li, Ying Lin, Junjun Ye, Jilin Li
Atherosclerosis (AS) is a chronic inflammatory vascular disease that begins with endothelial activation followed by a series of inflammatory responses, plaque formation, and finally rupture. An early event in endothelial dysfunction is activation of the nuclear factor-κB (NF-κB) signaling axis. Toll-like receptors (TLRs) in endothelial cells (ECs) play an essential role in recognizing pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and lifestyle-associated molecular patterns (LAMPs). Activation of the canonical NF-κB pathway stimulates the expression of cytokines, chemokines, and an array of additional genes which activate and amplify AS-associated inflammatory responses. In this review, we discuss the involvement of TLR2/4 and NF-κB signaling in ECs during AS initiation, as well as regulation of the inflammatory response during AS by noncoding RNAs, especially microRNA (miRNA) and circular RNA (circRNA).
{"title":"A Review: The Significance of Toll-Like Receptors 2 and 4, and NF-κB Signaling in Endothelial Cells during Atherosclerosis.","authors":"Baoxin Yan, Xiaoxian Yu, Xianzhen Cai, Xiaojun Huang, Bin Xie, Danchun Lian, Jinhao Chen, Weiwen Li, Ying Lin, Junjun Ye, Jilin Li","doi":"10.31083/j.fbl2904161","DOIUrl":"10.31083/j.fbl2904161","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory vascular disease that begins with endothelial activation followed by a series of inflammatory responses, plaque formation, and finally rupture. An early event in endothelial dysfunction is activation of the nuclear factor-κB (NF-κB) signaling axis. Toll-like receptors (TLRs) in endothelial cells (ECs) play an essential role in recognizing pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and lifestyle-associated molecular patterns (LAMPs). Activation of the canonical NF-κB pathway stimulates the expression of cytokines, chemokines, and an array of additional genes which activate and amplify AS-associated inflammatory responses. In this review, we discuss the involvement of TLR2/4 and NF-κB signaling in ECs during AS initiation, as well as regulation of the inflammatory response during AS by noncoding RNAs, especially microRNA (miRNA) and circular RNA (circRNA).</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862073","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}