{"title":"Promoting effect and immunologic role of secretogranin II on bladder cancer progression via regulating MAPK and NF-κB pathways","authors":"Jiawei Zhou, Caitao Dong, Jing Tan, Guijun Wang, Zhen Li, Sheng Li, Ziqi He","doi":"10.1007/s10495-023-01898-2","DOIUrl":"10.1007/s10495-023-01898-2","url":null,"abstract":"<div><p>Bladder cancer (BLCA) is ranked among the top ten most prevalent cancers worldwide and is the second most common malignant tumor within the field of urology. The limited effectiveness of immune targeted therapy in treating BLCA, due to its high metastasis and recurrence rates, necessitates the identification of new therapeutic targets. Secretogranin II (SCG2), a member of the chromaffin granin/secreted granin family, plays a crucial role in the regulated release of peptides and hormones. The role of SCG2 in the tumor microenvironment (TME) of lung adenocarcinoma and colon cancer has been established, but its functional significance in BLCA remains uncertain. This study aimed to investigate SCG2 expression in 15 bladder cancer tissue samples and their corresponding adjacent control tissues. The potential involvement of SCG2 in BLCA progression was assessed using various techniques, including analysis of public databases, immunohistochemistry, Western Blotting, immunofluorescence, wound-healing assay, Transwell assay, and xenograft tumor formation experiments in nude mice. This study provided novel evidence indicating that SCG2 plays a pivotal role in facilitating the proliferation, migration, and invasion of BLCA by activating the MEK/Erk and MEK/IKK/NF-κB signaling pathways, as well as by promoting M2 macrophage polarization. These findings propose the potential of SCG2 as a molecular target for immunotherapy in human BLCA.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"121 - 141"},"PeriodicalIF":6.1,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-10-05DOI: 10.1007/s10495-023-01899-1
Ana Carolina Guerta Salina, Letícia de Aquino Penteado, Naiara Naiana Dejani, Ludmilla Silva-Pereira, Breno Vilas Boas Raimundo, Gabriel Ferranti Corrêa, Karen Cristina Oliveira, Leandra Naira Zambelli Ramalho, Mèdéton Mahoussi Michaël Boko, Vânia L. D. Bonato, C. Henrique Serezani, Alexandra Ivo Medeiros
{"title":"Different bacterial cargo in apoptotic cells drive distinct macrophage phenotypes","authors":"Ana Carolina Guerta Salina, Letícia de Aquino Penteado, Naiara Naiana Dejani, Ludmilla Silva-Pereira, Breno Vilas Boas Raimundo, Gabriel Ferranti Corrêa, Karen Cristina Oliveira, Leandra Naira Zambelli Ramalho, Mèdéton Mahoussi Michaël Boko, Vânia L. D. Bonato, C. Henrique Serezani, Alexandra Ivo Medeiros","doi":"10.1007/s10495-023-01899-1","DOIUrl":"10.1007/s10495-023-01899-1","url":null,"abstract":"<div><p>The removal of dead cells (efferocytosis) contributes to the resolution of the infection and preservation of the tissue. Depending on the environment milieu, macrophages may show inflammatory (M1) or anti-inflammatory (M2) phenotypes. Inflammatory leukocytes are recruited during infection, followed by the accumulation of infected and non-infected apoptotic cells (AC). Efferocytosis of non-infected AC promotes TGF-β, IL-10, and PGE<sub>2</sub> production and the polarization of anti-inflammatory macrophages. These M2 macrophages acquire an efficient ability to remove apoptotic cells that are involved in tissue repair and resolution of inflammation. On the other hand, the impact of efferocytosis of infected apoptotic cells on macrophage activation profile remains unknown. Here, we are showing that the efferocytosis of gram-positive <i>Streptococcus pneumoniae</i>-AC (<i>Sp</i>-AC) or gram-negative <i>Klebsiella pneumoniae</i>-AC (<i>Kp</i>-AC) promotes distinct gene expression and cytokine signature in macrophages. Whereas the efferocytosis of <i>Kp</i>-AC triggered a predominant M1 phenotype in vitro and in vivo, the efferocytosis of <i>Sp</i>-AC promoted a mixed M1/M2 activation in vitro and in vivo in a model of allergic asthma. Together, these findings suggest that the nature of the pathogen and antigen load into AC may have different impacts on inducing macrophage polarization.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 3-4","pages":"321 - 330"},"PeriodicalIF":6.1,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-10-04DOI: 10.1007/s10495-023-01892-8
Rafael Cardoso Maciel Costa Silva
{"title":"Fas ligand intracellular signaling: does PSTPIP mediate T cell death?","authors":"Rafael Cardoso Maciel Costa Silva","doi":"10.1007/s10495-023-01892-8","DOIUrl":"10.1007/s10495-023-01892-8","url":null,"abstract":"<div><p>Fas and Fas ligand (FasL)-induced cell death is critical for the appropriate regulation of immune responses, especially those mediated by T cells. In this letter, several studies are discussed that reinforce the importance of FasL intracellular signaling for CD4 + T cell death, which might involve PSTPIP phosphatase and/or MAPKs.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"1 - 2"},"PeriodicalIF":6.1,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41102654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification and validation of a novel necroptosis-related molecular signature to evaluate prognosis and immune features in breast cancer","authors":"Fan Zhang, Chenxue Qi, Zhipeng Yao, Haojun Xu, Guoren Zhou, Congzhu Li, Hongping Xia","doi":"10.1007/s10495-023-01887-5","DOIUrl":"10.1007/s10495-023-01887-5","url":null,"abstract":"<div><p>Necroptosis has been shown to play an important role in the development of tumors. However, the characteristics of the necroptosis-related subtypes and the associated immune cell infiltration in the tumor microenvironment (TME) of breast cancer (BRCA) remain unclear. In this study, we identified three clusters related to necroptosis using the expression patterns of necroptosis-relevant genes (NRGs), and found that these three clusters had different clinicopathological features, prognosis and immune cell infiltration in the TME. Cluster 2 was characterized by less infiltration of immune cells in the TME and was associated with a worse prognosis. Then, a necroptosis risk score (NRS) composed of 14 NRGs was constructed using the least absolute shrinkage and selection operator regression (LASSO) Cox regression method. Based on NRS, all BRCA patients in the TCGA datasets were classified into a low-risk group and a high-risk group. Patients in the low-risk group were characterized by longer overall survival (OS), lower mutation burden, and higher infiltration level of immune cells in the TME. Moreover, the NRS was significantly associated with chemotherapeutic drug sensitivity. Finally, the knockdown of VDAC1 reduced the proliferation and migration of BRCA cells, and promoted cell death induced by necroptosis inducer. This study identified a novel necroptosis-related subtype of BRCA, and a comprehensive analysis of NRGs in BRCA revealed its potential roles in prognosis, clinicopathological features, TME, chemotherapy, tumor proliferation, and tumor necroptosis. These results may improve our understanding of NRGs in BRCA and provide a reference for developing individualized therapeutic strategies.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1628 - 1645"},"PeriodicalIF":7.2,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41116897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-10-03DOI: 10.1007/s10495-023-01896-4
Hanyao Guo, Meixia Wang, Yanan Shang, Bo Zhang, Sidi Zhang, Xiaoyu Liu, Pengxiu Cao, Yumei Fan, Ke Tan
{"title":"Apoptosis-related prognostic biomarkers and potential targets for acute kidney injury based on machine learning algorithm and in vivo experiments","authors":"Hanyao Guo, Meixia Wang, Yanan Shang, Bo Zhang, Sidi Zhang, Xiaoyu Liu, Pengxiu Cao, Yumei Fan, Ke Tan","doi":"10.1007/s10495-023-01896-4","DOIUrl":"10.1007/s10495-023-01896-4","url":null,"abstract":"<div><p>Acute kidney injury (AKI) is a common critical illness in hospitalized patients, characterized by a rapid decline in kidney function over a short period, which can seriously endanger the patient’s life. Currently, there is a lack of precise and universal AKI diagnostic biomarkers in clinical practice. In this study, weighted gene coexpression network analysis (WGCNA), differential expression analysis, univariate and multivariate logistic regression analyses, receiver operating characteristic (ROC) curves, and immune cell infiltration were performed to identify apoptosis-related biomarkers that can be used for AKI diagnosis. Three core apoptosis-related genes (ARGs), CBFB, EGF and COL1A1, were identified as AKI biomarkers. More importantly, an apoptosis-related signature containing three hub ARGs was validated as a diagnostic model. The hub genes exhibited good correlations with glomerular filtration rate (GFR) and serum creatinine (SCr) in the Nephroseq kidney disease database. Additionally, CIBERSORT immune infiltration analysis indicated that these core ARGs may affect immune cell recruitment and infiltration in AKI patients. Subsequently, we investigated the alteration of the expression levels of three core ARGs in AKI samples using single-cell RNA sequencing analysis and analyzed the cell types that mainly expressed these ARGs. More importantly, the expression of core ARGs was validated in folic acid- and cisplatin-induced AKI mouse models. In summary, our study identified three diagnostic biomarkers for AKI, explored the roles of ARGs in AKI progression and provided new ideas for the clinical diagnosis and treatment of AKI.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 3-4","pages":"303 - 320"},"PeriodicalIF":6.1,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-27DOI: 10.1007/s10495-023-01890-w
Shikai Jin, Pu-Ste Liu, Daheng Zheng, Xin Xie
{"title":"The interplay of miRNAs and ferroptosis in diseases related to iron overload","authors":"Shikai Jin, Pu-Ste Liu, Daheng Zheng, Xin Xie","doi":"10.1007/s10495-023-01890-w","DOIUrl":"10.1007/s10495-023-01890-w","url":null,"abstract":"<div><p>Ferroptosis has been conceptualized as a novel cell death modality distinct from apoptosis, necroptosis, pyroptosis and autophagic cell death. The sensitivity of cellular ferroptosis is regulated at multiple layers, including polyunsaturated fatty acid metabolism, glutathione-GPX4 axis, iron homeostasis, mitochondria and other parallel pathways. In addition, microRNAs (miRNAs) have been implicated in modulating ferroptosis susceptibility through targeting different players involved in the execution or avoidance of ferroptosis. A growing body of evidence pinpoints the deregulation of miRNA-regulated ferroptosis as a critical factor in the development and progression of various pathophysiological conditions related to iron overload. The revelation of mechanisms of miRNA-dependent ferroptosis provides novel insights into the etiology of diseases and offers opportunities for therapeutic intervention. In this review, we discuss the interplay of emerging miRNA regulators and ferroptosis players under different pathological conditions, such as cancers, ischemia/reperfusion, neurodegenerative diseases, acute kidney injury and cardiomyopathy. We emphasize on the relevance of miRNA-regulated ferroptosis to disease progression and the targetability for therapeutic interventions.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"45 - 65"},"PeriodicalIF":6.1,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-26DOI: 10.1007/s10495-023-01895-5
Patrycja Nowak-Sliwinska, Arjan W. Griffioen
{"title":"Rising impact of cell death research","authors":"Patrycja Nowak-Sliwinska, Arjan W. Griffioen","doi":"10.1007/s10495-023-01895-5","DOIUrl":"10.1007/s10495-023-01895-5","url":null,"abstract":"","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"28 11-12","pages":"1503 - 1504"},"PeriodicalIF":7.2,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41109689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-26DOI: 10.1007/s10495-023-01889-3
Yi Zheng, Jiachen Li, Bo Liu, Zhihong Xie, Yuanhang He, Dongbo Xue, Dali Zhao, Chenjun Hao
{"title":"Global trends in PANoptosis research: bibliometrics and knowledge graph analysis","authors":"Yi Zheng, Jiachen Li, Bo Liu, Zhihong Xie, Yuanhang He, Dongbo Xue, Dali Zhao, Chenjun Hao","doi":"10.1007/s10495-023-01889-3","DOIUrl":"10.1007/s10495-023-01889-3","url":null,"abstract":"<div><p>PANoptosis has recently been discovered as a new type of cell death. PANoptosis mainly refers to the significant interaction among the three programmed cell death pathways of apoptosis, necroptosis, and pyroptosis. Despite this, only a few studies have examined the systematic literature in this area. By analyzing the bibliometric data for PANoptosis, we can visualize the current hotspots and predicted trends in research. This study analyzed bibliometric indicators using the Histcite Pro 2.0 tool, which searches the Web of Science for PANoptosis literature published between 2016 and 2022. A bibliometric analysis was performed using Histcite Pro 2.0, while research trends and hotspots were visualized using VOSviewer, CiteSpace and BioBERT. The output of related literature was low in the four years from the first presentation of PANoptosis in 2016 to 2020. The volume of relevant literature grew exponentially between 2020 and 2022. The United States and China play a leading role in this field. Although China started late, its research in this field is developing rapidly. As research progressed, more focus was placed on the relationship between PANoptosis and pyroptosis, as well as apoptosis and necrosis. Now is a rapid development stage of PANoptosis research. Most of the research focuses on the cellular level, and the focus is more on the treatment of tumor-related diseases. The current focus of this area is PANoptosis mechanisms in cancer and inflammation. It can be seen from the burst analysis of keywords that caspase1 and host defense have consistently been research hotspots in the field of PANoptosis, while the frequency of NLRC4, causes of autoinflammation, recognition, NLRP3, and Gasdermin D has gradually increased, all of which have become research hotspots in recent years. Finally, we used the BioBERT biomedical language model to mine the most documented genes and diseases in the PANoptosis field articles, pointing out the direction for subsequent research steps. According to a bibliometric analysis, researchers have shown an increased interest in PANoptosis over the past few years. Researchers initially focused on the molecular mechanism of PANoptosis and pyroptosis, apoptosis, and necroptosis. The role of PANoptosis in diseases and conditions such as inflammation and tumors is one of the current research hotspots in this area. The focus is more on treating inflammation-related diseases, which will become the key development direction of future research.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"229 - 242"},"PeriodicalIF":6.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing the frontiers of colorectal cancer treatment: harnessing ferroptosis regulation","authors":"Siyue Liu, Ming Yue, Yukang Lu, Ying Wang, Shiwen Luo, Xiaoliu Liu, Jue Jiang","doi":"10.1007/s10495-023-01891-9","DOIUrl":"10.1007/s10495-023-01891-9","url":null,"abstract":"<div><p>In recent years, colorectal cancer incidence and mortality have increased significantly due to poor lifestyle choices. Despite the development of various treatments, their effectiveness against advanced/metastatic colorectal cancer remains unsatisfactory due to drug resistance. However, ferroptosis, a novel iron-dependent cell death process induced by lipid peroxidation and elevated reactive oxygen species (ROS) levels along with reduced activity of the glutathione peroxidase 4 (GPX4) antioxidant enzyme system, shows promise as a therapeutic target for colorectal cancer. This review aims to delve into the regulatory mechanisms of ferroptosis in colorectal cancer, providing valuable insights into potential therapeutic approaches. By targeting ferroptosis, new avenues can be explored for innovative therapies to combat colorectal cancer more effectively. In addition, understanding the molecular pathways involved in ferroptosis may help identify biomarkers for prognosis and treatment response, paving the way for personalized medicine approaches. Furthermore, exploring the interplay between ferroptosis and other cellular processes can uncover combination therapies that enhance treatment efficacy. Investigating the tumor microenvironment’s role in regulating ferroptosis may offer strategies to sensitize cancer cells to cell death induction, leading to improved outcomes. Overall, ferroptosis presents a promising avenue for advancing the treatment of colorectal cancer and improving patient outcomes.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"86 - 102"},"PeriodicalIF":6.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41091689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ApoptosisPub Date : 2023-09-26DOI: 10.1007/s10495-023-01894-6
Haoran Ye, Shasha He, Yuan Du, Yuchen Wang, Yahui Hu, Chunxia Zhao, Yueting Jin, Fangyu Liu, Yuhong Guo
{"title":"Involvement of CD44 and MAPK14-mediated ferroptosis in hemorrhagic shock","authors":"Haoran Ye, Shasha He, Yuan Du, Yuchen Wang, Yahui Hu, Chunxia Zhao, Yueting Jin, Fangyu Liu, Yuhong Guo","doi":"10.1007/s10495-023-01894-6","DOIUrl":"10.1007/s10495-023-01894-6","url":null,"abstract":"<div><p>To elucidate the induction of ferroptotic pathways and the transcriptional modulation of pivotal genes in the context of hemorrhagic shock. The R software was used to analyze the GSE64711 dataset, isolating genes relevant to ferroptosis. Enrichment analyses and protein interaction networks were assembled. Using WGCNA hub genes were identified and intersected with ferroptosis-related genes, highlighting hub genes CD44 and MAPK14. In a rat hemorrhagic shock model, cardiac ROS, Fe<sup>2+</sup>, MDA, and GSH levels were assessed. Key ferroptotic proteins (SLC7A11/GPX4) in myocardial tissues were examined via western blot. Hub genes, CD44 and MAPK14, expressions were confirmed through immunohistochemistry. Analyzing the GSE64711 dataset revealed 337 differentially expressed genes, including 12 linked to ferroptosis. Enrichment analysis highlighted pathways closely related to ferroptosis. Using Genemania, we found these genes mainly affect ROS metabolism and oxidative stress response. WGCNA identified CD44 and MAPK14 as hub genes. Rat myocardial tissue validation showed significant cardiac damage and elevated ROS and MDA levels, and decreased GSH levels in the hemorrhagic shock model. The ferroptotic pathway SLC7A11/GPX4 was activated, and immunohistochemistry showed a significant increase in the expression levels of CD44 and MAPK14 in the hemorrhagic shock rat model. We demonstrated the presence of tissue ferroptosis in hemorrhagic shock by combining bioinformatics analysis with in vivo experimentation. Specifically, we observed the activation of the SLC7A11/GPX4 ferroptotic pathway. Further, CD44 and MAPK14 were identified as hub genes in hemorrhagic shock.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 1-2","pages":"154 - 168"},"PeriodicalIF":6.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}