CellsPub Date : 2024-11-04DOI: 10.3390/cells13211820
Yulia Suzdaltseva, Anastasia Selezneva, Nikita Sergeev, Sergey L Kiselev
{"title":"Initial WNT/β-Catenin or BMP Activation Modulates Inflammatory Response of Mesodermal Progenitors Derived from Human Induced Pluripotent Stem Cells.","authors":"Yulia Suzdaltseva, Anastasia Selezneva, Nikita Sergeev, Sergey L Kiselev","doi":"10.3390/cells13211820","DOIUrl":"10.3390/cells13211820","url":null,"abstract":"<p><p>Wound healing in adults largely depends on the functional state of multipotent mesenchymal stromal cells (MSCs). Human fetal tissues at the early stages of development are known to heal quickly with a full-quality restoration of the original structure. The differences in the molecular mechanisms that determine the functional activity of mesodermal cells in fetuses and adults remain virtually unknown. Using two independent human induced pluripotent stem cell (iPSC) lines, we examined the effects of the initial WNT and BMP activation on the differentiation of iPSCs via mesodermal progenitors into MSCs and highlighted the functions of these cells that are altered by the proinflammatory microenvironment. The WNT-induced mesoderm commitment of the iPSCs enhanced the expression of paraxial mesoderm (PM)-specific markers, while the BMP4-primed iPSCs exhibited increased levels of lateral mesoderm (LM)-specific genes. The inflammatory status and migration rate of the isogenic iPSC-derived mesoderm cells were assessed via gene expression analysis and scratch assay under the receptor-dependent activation of the proinflammatory IFN-γ or TNF-α signaling pathway. Reduced <i>IDO1</i> and <i>ICAM1</i> expression levels were detected in the WNT- and BMP-induced MSC progenitors compared to the isogenic MSCs in response to stimulation with IFN-γ and TNF-α. The WNT- and BMP-induced MSC progenitors exhibited a higher migration rate than isogenic MSCs upon IFN-γ exposure. The established isogenic cellular model will provide new opportunities to elucidate the mechanisms of regeneration and novel therapeutics for wound healing.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-04DOI: 10.3390/cells13211818
Antonio Gómez-Mercader, Luis Monzón-Atienza, Daniel Montero, Jimena Bravo, Félix Acosta
{"title":"Fish Cell Spheroids, a Promising In Vitro Model to Mimic In Vivo Research: A Review.","authors":"Antonio Gómez-Mercader, Luis Monzón-Atienza, Daniel Montero, Jimena Bravo, Félix Acosta","doi":"10.3390/cells13211818","DOIUrl":"10.3390/cells13211818","url":null,"abstract":"<p><p>In vitro cell culture systems serve as instrumental platforms for probing biological phenomena and elucidating intricate cellular mechanisms. These systems afford researchers the opportunity to scrutinize cellular responses within a regulated environment, thereby circumventing the ethical and logistical challenges associated with in vivo experimentation. Three-dimensional (3D) cell cultures have emerged as a viable alternative to mimic in vivo environments. Within this context, spheroids are recognized as one of the most straightforward and efficacious models, presenting a promising substitute for conventional monolayer cultures. The application of 3D cultures of fish cells remains limited, focusing mainly on physiological and morphological characterization studies. However, given the capacity of spheroids to emulate in vivo conditions, researchers are exploring diverse applications of these 3D cultures. These include eco-toxicology, immunology, drug screening, endocrinology, and metabolism studies, employing a variety of cell types such as fibroblasts, hepatocytes, embryonic cells, gonadal cells, gastrointestinal cells, and pituitary cells. This review provides a succinct overview, concentrating on the most frequently employed methods for generating fish cell spheroids and their applications to date. The aim is to compile and highlight the significant contributions of these methods to the field and their potential for future research.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-04DOI: 10.3390/cells13211819
Peng He, Manshu Zou, Chanjuan Zhang, Yaning Shi, Li Qin
{"title":"Celastrol-Loaded Hyaluronic Acid/Cancer Cell Membrane Lipid Nanoparticles for Targeted Hepatocellular Carcinoma Prevention.","authors":"Peng He, Manshu Zou, Chanjuan Zhang, Yaning Shi, Li Qin","doi":"10.3390/cells13211819","DOIUrl":"10.3390/cells13211819","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-04DOI: 10.3390/cells13211815
Cristina Sánchez-Martínez, Esther Grueso, Tania Calvo-López, Jorge Martinez-Ortega, Ana Ruiz, José M Almendral
{"title":"VEGF-Virus Interactions: Pathogenic Mechanisms and Therapeutic Applications.","authors":"Cristina Sánchez-Martínez, Esther Grueso, Tania Calvo-López, Jorge Martinez-Ortega, Ana Ruiz, José M Almendral","doi":"10.3390/cells13211815","DOIUrl":"10.3390/cells13211815","url":null,"abstract":"<p><p>Many types of viruses directly or indirectly target the vascular endothelial growth factor (VEGF) system, which is a central regulator of vasculogenesis and angiogenesis in physiological homeostasis, causing diverse pathologies. Other viruses have been developed into effective therapeutic tools for VEGF modulation in conditions such as cancer and eye diseases. Some viruses may alter the levels of VEGF in the pathogenesis of respiratory syndromes, or they may encode VEGF-like factors, promoting vascular disruption and angiogenesis to enable viruses' systemic spread. Oncogenic viruses may express interactive factors that perturb VEGF's functional levels or downstream signaling, which increases the neovascularization and metastasis of tumors. Furthermore, many viruses are being developed as therapeutic vectors for vascular pathologies in clinical trials. Major examples are those viral vectors that inhibit the role of VEGF in the neovascularization required for cancer progression; this is achieved through the induction of immune responses, by exposing specific peptides that block signaling or by expressing anti-VEGF and anti-VEGF receptor-neutralizing antibodies. Other viruses have been engineered into effective pro- or anti-angiogenesis multitarget vectors for neovascular eye diseases, paving the way for therapies with improved safety and minimal side effects. This article critically reviews the large body of literature on these issues, highlighting those contributions that describe the molecular mechanisms, thus expanding our understanding of the VEGF-virus interactions in disease and therapy. This could facilitate the clinical use of therapeutic virus vectors in precision medicine for the VEGF system.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-04DOI: 10.3390/cells13211816
Alessandra Ferraresi, Ian Ghezzi, Amreen Salwa, Andrea Esposito, Danny N Dhanasekaran, Ciro Isidoro
{"title":"NKX3-2 Induces Ovarian Cancer Cell Migration by HDAC6-Mediated Repositioning of Lysosomes and Inhibition of Autophagy.","authors":"Alessandra Ferraresi, Ian Ghezzi, Amreen Salwa, Andrea Esposito, Danny N Dhanasekaran, Ciro Isidoro","doi":"10.3390/cells13211816","DOIUrl":"10.3390/cells13211816","url":null,"abstract":"<p><p>Several soluble factors secreted by the stromal cells and cancer cells within the tumor microenvironment facilitate the progression and invasiveness of ovarian cancer. In ovarian cancer cells, lysophosphatidic acid (LPA) modulates the transcriptome profile and promotes cell invasiveness by the downregulation of autophagy. Here, we further elucidate this mechanism by focusing on the molecular and cellular events regulating autophagy. Transcriptomic and Western blotting analyses revealed NKX3-2, a transcriptional factor, to be among the genes hyperexpressed in LPA-stimulated ovarian cancer cells. Bioinformatic analyses revealed that in ovarian cancer patients, the expression of <i>NKX3-2</i> positively correlates with genes involved in cell motility and migration, while it negatively correlates with macromolecular catabolic pathways. In various ovarian cancer cell lines, NKX3-2 silencing abrogated LPA-induced cell migration. Mechanistically, this effect is linked to the restoration of the HDAC6-mediated relocation of the lysosomes in the para-golgian area, and this results in an increase in autolysosome formation and the overall upregulation of autophagy. Silencing the expression of <i>ATG7</i> or <i>BECN1</i>, two autophagy genes, rescued the migratory phenotype of the NKX3-2-silenced ovarian cancer cells. Taken together, these data reveal the mechanism by which the LPA-NKX3-2 axis promotes the invasiveness of ovarian cancer cells and supports the possibility of targeting NKX3-2 to reduce the migratory capacity of cancer cells in response to a permissive microenvironment.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-04DOI: 10.3390/cells13211817
Alena Svobodová Kovaříková, Lenka Stixová, Aleš Kovařík, Denisa Komůrková, Soňa Legartová, Paolo Fagherazzi, Eva Bártová
{"title":"Correction: Svobodova et al. N<sup>6</sup>-Adenosine Methylation in RNA and a Reduced m<sub>3</sub>G/TMG Level in Non-Coding RNAs Appear at Microirradiation-Induced DNA Lesions. <i>Cells</i> 2020, <i>9</i>, 360.","authors":"Alena Svobodová Kovaříková, Lenka Stixová, Aleš Kovařík, Denisa Komůrková, Soňa Legartová, Paolo Fagherazzi, Eva Bártová","doi":"10.3390/cells13211817","DOIUrl":"10.3390/cells13211817","url":null,"abstract":"<p><p>The affiliation number 1, \"Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic\" changed its zip code to 612 00 [...].</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-03DOI: 10.3390/cells13211813
Snezhanna Kandrashina, Ekaterina Sherstyukova, Mikhail Shvedov, Vladimir Inozemtsev, Roman Timoshenko, Alexander Erofeev, Maxim Dokukin, Viktoria Sergunova
{"title":"The Effect of the Acid-Base Imbalance on the Shape and Structure of Red Blood Cells.","authors":"Snezhanna Kandrashina, Ekaterina Sherstyukova, Mikhail Shvedov, Vladimir Inozemtsev, Roman Timoshenko, Alexander Erofeev, Maxim Dokukin, Viktoria Sergunova","doi":"10.3390/cells13211813","DOIUrl":"10.3390/cells13211813","url":null,"abstract":"<p><p>Red blood cells respond to fluctuations in blood plasma pH by changing the rate of biochemical and physical processes that affect the specific functions of individual cells. This study aimed to analyze the effect of pH changes on red blood cell morphology and structure. The findings revealed that an increase or decrease in pH above or below the physiological level of pH 7.4 results in the transformation of discocytes into echinocytes and causes significant alterations in the membrane, including its roughness, cytoskeleton structure, and the cell's elastic modulus. Furthermore, the study shown a strong connection between critical acidosis and alkalosis with increased intracellular reactive oxygen species production.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-03DOI: 10.3390/cells13211814
Kamil Seyrek, Johannes Espe, Elisabeth Reiss, Inna N Lavrik
{"title":"The Crosstalk of Apoptotic and Non-Apoptotic Signaling in CD95 System.","authors":"Kamil Seyrek, Johannes Espe, Elisabeth Reiss, Inna N Lavrik","doi":"10.3390/cells13211814","DOIUrl":"10.3390/cells13211814","url":null,"abstract":"<p><p>The mechanisms of CD95 (Fas/APO-1)-mediated extrinsic apoptotic pathway in cancer cells have been extensively studied. The majority of human cells express CD95, but not all these cells can induce extrinsic apoptosis. Accumulating evidence has shown that CD95 is a multifunctional protein, and its stimulation can also elicit non-apoptotic or even survival signals. It has become clear that under certain cellular contexts, due to the various checkpoints, CD95 activation can trigger both apoptotic and non-apoptotic signals. The crosstalk of death and survival signals may occur at different levels of signal transduction. The strength of the CD95 stimulation, initial levels of anti-apoptotic proteins, and posttranslational modifications of the core DISC components have been proposed to be the most important factors in the life/death decisions at CD95. Successful therapeutic targeting of CD95 signaling pathways will require a better understanding of the crosstalk between CD95-induced apoptotic and cell survival pathways. In this review, in order to gain a systematic understanding of the crosstalk between CD95-mediated apoptosis and non-apoptotic signaling, we will discuss these issues in a step-by-step way.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-02DOI: 10.3390/cells13211812
Siyi Yang, Xinyi Fan, Wei Yu
{"title":"Regulatory Mechanism of Protein Crotonylation and Its Relationship with Cancer.","authors":"Siyi Yang, Xinyi Fan, Wei Yu","doi":"10.3390/cells13211812","DOIUrl":"10.3390/cells13211812","url":null,"abstract":"<p><p>Crotonylation is a recently discovered protein acyl modification that shares many enzymes with acetylation. However, it possesses a distinct regulatory mechanism and biological function due to its unique crotonyl structure. Since the discovery of crotonylation in 2011, numerous crotonylation sites have been identified in both histones and other proteins. In recent studies, crotonylation was found to play a role in various diseases and biological processes. This paper reviews the initial discovery and regulatory mechanisms of crotonylation, including various writer, reader, and eraser proteins. Finally, we emphasize the relationship of dysregulated protein crotonylation with eight common malignancies, including cervical, prostate, liver, and lung cancer, providing new potential therapeutic targets.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CellsPub Date : 2024-11-02DOI: 10.3390/cells13211810
Arka Saha, Nancy Gavert, Thomas Brabletz, Avri Ben-Ze'ev
{"title":"A Necessary Role for Cyclin D2 Induction During Colon Cancer Progression Mediated by L1.","authors":"Arka Saha, Nancy Gavert, Thomas Brabletz, Avri Ben-Ze'ev","doi":"10.3390/cells13211810","DOIUrl":"10.3390/cells13211810","url":null,"abstract":"<p><p>The cell adhesion molecule L1CAM (L1), mainly known for its function in brain cells, is a Wnt/β-catenin signaling target gene in colorectal cancer (CRC) cells, where it promotes invasion and liver metastasis. We interrogated which genes are expressed at increased levels in human CRC tissue and induced in CRC cell lines overexpressing L1. We found increased cyclin D2 levels in CRC tissue and LS 174T and HCT 116 human CRC cells overexpressing L1. Increased cyclin D2 in CRC cells was associated with higher proliferation rates, faster motility, tumorigenesis, and liver metastasis. The suppression of cyclin D2 expression by shRNA to cyclin D2 blocked the increase in these cellular properties of L1-expressing cells. The overexpression of cyclin D2 in the absence of L1 also conferred tumorigenic properties similar to L1 expression. The pathways involved in the elevation of cyclin D2 by L1 include NF-κB, Akt, and β-catenin signaling but not the Erk pathway. We found that in a significant percentage of human CRC tissue samples, cyclin D2 is expressed at high levels in the nuclei of cancer cells. At the same time, the adjacent normal mucosa was negative for cyclin D2 staining. The results suggest that the increased cyclin D2 expression by L1 is required to induce proliferative, motile tumor development in CRC tissue and can serve as a diagnostic marker and a target for CRC therapy.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}