You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.

Search for Articles:

Title / Keyword

Author / Affiliation / Email

Journal

Article Type

Advanced Search

Section

Special Issue

Volume

Issue

Number

Page

Logical OperatorOperator

Search Text

Search Type

Current Strategies in Endodontic Regeneration

Journal Description

Cells

Cells is an international, peer-reviewed, open access journal on cell biology, molecular biology, and biophysics, published semimonthly online by MDPI. The Nordic Autophagy Society (NAS) and the Spanish Society of Hematology and Hemotherapy (SEHH) are affiliated with Cells and their members receive discounts on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, CAPlus / SciFinder, and other databases.
Journal Rank: JCR - Q2 (Cell Biology) / CiteScore - Q1 (General Biochemistry, Genetics and Molecular Biology)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the first half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Sections: published in 21 topical sections.
Companion journal: Organoids.

Impact Factor: 5.2 (2024); 5-Year Impact Factor: 6.1 (2024)

Imprint Information Journal Flyer Open Access ISSN: 2073-4409

Latest Articles

16 pages, 2967 KiB

Open AccessArticle

Adeno-Associated Viral Gene Delivery of Wild-Type Human Tau Induces Progressive Hyperphosphorylation and Neuronal Cell Death in the Hippocampi of Middle-Aged Rats

by Ryan C. Gorzek, Aurelie Joly-Amado, Natalia Hurst-Calle, Graham L. Gabrielson, Maxine Miller, Sue Osting, Kevin R. Nash and Corinna Burger

Cells 2025, 14(16), 1238; https://doi.org/10.3390/cells14161238 - 11 Aug 2025

Tau aggregation and the subsequent formation of neurofibrillary tangles are hallmarks of Alzheimer’s disease (AD) and other dementias. While accumulation of tau aggregates is believed to contribute to cell death and neurodegeneration, tau aggregation and hyperphosphorylation are also correlated with cognitive impairment in [...] Read more.

Tau aggregation and the subsequent formation of neurofibrillary tangles are hallmarks of Alzheimer’s disease (AD) and other dementias. While accumulation of tau aggregates is believed to contribute to cell death and neurodegeneration, tau aggregation and hyperphosphorylation are also correlated with cognitive impairment in AD. To understand the role of tau in neurodegeneration, we used adeno-associated virus serotype 9 (AAV9) to express human wild-type 4-repeat, 0-N-terminus tau isoform (AAV-htau) in the Cornu ammonis area 1 (CA1) region of the dorsal hippocampus of adult 6-month-old Fischer 344 rats. AAV expressing green fluorescent protein (AAV-GFP) or uninjected rats were used as controls. To characterize early phenotypes, we investigated pathological changes at 3, 8, and 12 weeks post-injection of AAV-htau. Our results show that at 3 weeks post-injection, there was already robust expression of human tau in the CA1 region of animals injected with AAV-htau compared to those injected with AAV-GFP or the uninjected controls. At 12 weeks post-injection, area CA1 showed a statistically significant reduction in cell number and a thinner neuronal layer all throughout the anterior dorsal hippocampus, as well as redistribution to the somatodendritic areas of CA1. We also found hyperphosphorylation of tau at all three timepoints. In spite of this pathology, we did not find any hippocampal-dependent cognitive impairment in rats overexpressing human tau. These results provide evidence of AAV-htau as a progressive model of tauopathy pathology to study changes in phosphorylation status and neuronal cell death that might precede cognitive impairment. Full article

(This article belongs to the Special Issue Experimental Systems to Model Aging Processes)

► Show Figures

Figure 1

22 pages, 1700 KiB

Open AccessReview

Microbial Metabolites and Cardiovascular Dysfunction: A New Era of Diagnostics and Therapy

by Jitendra Kumar

Cells 2025, 14(16), 1237; https://doi.org/10.3390/cells14161237 - 11 Aug 2025

Cardiovascular diseases (CVDs) pose a significant threat to human life and mortality worldwide, encompassing a variety of conditions that affect the heart and blood vessels. These diseases are influenced by both genetic and environmental factors, which play a critical role in their development. [...] Read more.

Cardiovascular diseases (CVDs) pose a significant threat to human life and mortality worldwide, encompassing a variety of conditions that affect the heart and blood vessels. These diseases are influenced by both genetic and environmental factors, which play a critical role in their development. Recent research has highlighted the importance of gut microbes—the diverse community of bacteria in the gastrointestinal tract—that function as a “super organ” within the human body. These microbes have a remarkable impact on metabolic pathways and are increasingly recognized for their role in serious conditions like CVDs. They contribute to metabolic regulation, provide essential nutrients and vitamins, and help protect against diseases. Various internal and external factors influence the dynamic relationship between the human host and gut microbiota, thereby regulating overall metabolism. This review explores the complex connection between gut microbiota and microbial metabolites—such as short-chain fatty acids (SCFAs), bile acids (BAs), and trimethylamine N-oxide (TMAO)—and their potential influence on the development and progression of CVDs. We also examine the interaction between dietary interventions and gut microbes in the context of conditions including atherosclerosis, obesity, type 2 diabetes, heart failure, hypertension, atrial fibrillation, and myocardial infarction. Gaining a deeper understanding of the gut microbiota’s role in maintaining physiological balance creates exciting possibilities for identifying novel diagnostic biomarkers and therapeutic targets for treating CVDs. This knowledge offers hope for early disease prediction, improved clinical management, and innovative treatments. Full article

► Show Figures

Figure 1

15 pages, 2451 KiB

Open AccessArticle

Systematic Comparison of Temperature Effects on Antibody Performance via Automated Image Analysis: A Key for Primary Ciliary Dyskinesia Diagnostic

by Hanna Przystalowska-Maciola, Malgorzata Dabrowska, Ewa Zietkiewicz and Bukowy-Bieryllo Zuzanna

Cells 2025, 14(16), 1236; https://doi.org/10.3390/cells14161236 - 11 Aug 2025

Immunofluorescence (IF) microscopy of ciliated epithelium is gaining increased popularity as a pre-genetic diagnostic method in primary ciliary dyskinesia (PCD). Ensuring reliable IF-based diagnostics in PCD requires robust standardization of staining methods and antibody performance. We applied whole slide scanning and automated image [...] Read more.

Immunofluorescence (IF) microscopy of ciliated epithelium is gaining increased popularity as a pre-genetic diagnostic method in primary ciliary dyskinesia (PCD). Ensuring reliable IF-based diagnostics in PCD requires robust standardization of staining methods and antibody performance. We applied whole slide scanning and automated image analysis to systematically evaluate the influence of various sample storage conditions on the specificity of IF staining. We tested eight polyclonal antibodies targeting diverse axonemal protein epitopes, routinely used for PCD diagnostics, under seven different temperature and time combinations. The storage conditions simulated handling of epithelial brushing on glass slides: after material collection at the clinic, during transport, or after reception at the diagnostic laboratory. Our study revealed that proper slide storage conditions are essential for the reliable PCD diagnosis via IF staining. We suggest continuous storage at −80 °C or −20 °C for slides prepared at the diagnostic laboratory, and storage at −20 °C or 4 °C for slides prepared remotely and shipped. Moreover, the IF sensitivity to slide storage conditions differs among antibodies targeting various ciliary elements, with molecular ruler proteins being particularly sensitive to prolonged storage at room temperature. We emphasize the inclusion of additional control slides to mitigate the inter-individual differences and the crucial correlation of IF results with comprehensive patient clinical history for enhanced diagnostic reliability. Full article

(This article belongs to the Special Issue Imaging Methods in Cell Biology)

► Show Figures

Figure 1

22 pages, 6386 KiB

Open AccessArticle

Identification of Epigenetic Regulatory Networks of Gene Methylation–miRNA–Transcription Factor Feed-Forward Loops in Basal-like Breast Cancer

by Larissa M. Okano, Alexandre L. K. de Azevedo, Tamyres M. Carvalho, Jean Resende, Jessica M. Magno, Bonald C. Figueiredo, Tathiane M. Malta, Mauro A. A. Castro and Luciane R. Cavalli

Cells 2025, 14(16), 1235; https://doi.org/10.3390/cells14161235 - 10 Aug 2025

Basal-like breast cancer (BLBC) is associated with poor prognosis, high recurrence rates, and limited therapeutic options, largely due to its molecular heterogeneity and complexity, which include epigenetic alterations. This study investigated epigenetic regulatory networks in BLBC by analyzing DNA methylation in distal cis-regulatory [...] Read more.

Basal-like breast cancer (BLBC) is associated with poor prognosis, high recurrence rates, and limited therapeutic options, largely due to its molecular heterogeneity and complexity, which include epigenetic alterations. This study investigated epigenetic regulatory networks in BLBC by analyzing DNA methylation in distal cis-regulatory regions and its impact on genes, transcription factors (TFs), and microRNAs (miRNAs) expression. Data from TCGA were processed using the ELMER and DESeq2 tools to identify differentially methylated regions and differentially expressed genes, TFs, and miRNAs. The FANMOD algorithm was used to identify the regulatory interactions uncovering the feed-forward loops (FFLs). The analysis identified 110 TF-mediated FFLs, 43 miRNA-mediated FFLs, and five composite FFLs, involving 18 hypermethylated and 32 hypomethylated genes, eight upregulated and nine downregulated TFs, and 21 upregulated and seven downregulated miRNAs. The TF-mediated FFLs major regulators involved the AR, EBF1, FOS, FOXM1, and TEAD4 TFs, while key miRNAs were miR-3662, miR-429, and miR-4434. Enriched pathways involved cAMP, ErbB, FoxO, p53, TGF-beta, Rap1, and Ras signaling. Differences in hallmark gene set categories reflected distinct methylation and miRNA expression profiles. Overall, this integrative analysis mapped the intricate epigenetic landscape of BLBC, emphasizing the role of FFLs as regulatory motifs that integrate DNA methylation, TFs, and miRNAs in orchestrating disease’s development and progression and offering potential targets for future diagnostic and therapeutic strategies. Overall, this integrative analysis mapped the intricate epigenetic landscape of BLBC, emphasizing the role of FFLs as regulatory motifs that integrate DNA methylation, TFs, and miRNAs in orchestrating the disease’s development and progression, and offering potential targets for future diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Epigenetic Regulatory Networks in Cancer: Understanding the Mechanisms of Disease Progression)

► Show Figures

Figure 1

18 pages, 14588 KiB

Open AccessArticle

HO-1 Suppression by Co-Culture-Derived IL-6 Alleviates Ferritinophagy-Dependent Oxidative Stress to Potentiate Myogenic Differentiation

by Mengyuan Zhang, Siyu Liu, Yongheng Wang, Shan Shan and Ming Cang

Cells 2025, 14(16), 1234; https://doi.org/10.3390/cells14161234 - 10 Aug 2025

Fibro-adipogenic progenitor cells (FAPs) support muscle tissue homeostasis, regulate muscle growth, injury repair, and fibrosis, and activate muscle progenitor cell differentiation to promote regeneration. We aimed to investigate the effects of co-culturing FAPs with muscle satellite cells (MuSCs) on myogenic differentiation. Proteomic profiling [...] Read more.

Fibro-adipogenic progenitor cells (FAPs) support muscle tissue homeostasis, regulate muscle growth, injury repair, and fibrosis, and activate muscle progenitor cell differentiation to promote regeneration. We aimed to investigate the effects of co-culturing FAPs with muscle satellite cells (MuSCs) on myogenic differentiation. Proteomic profiling of co-culture supernatants identified significant DCX, IMP2A, NUDT16L1, SLC38A2, and IL-6 upregulation. Comparative transcriptomics of mono-cultured versus co-cultured MuSCs revealed differential expression of oxidative stress-related genes (HMOX1, ALOX5, GSTM3, TRPM2, PADI1, and CTSL). Pathway enrichment analyses highlighted cell cycle regulation, TNF signaling, and ferroptosis. Gene ontology analysis of MuSCs indicated significant gene enrichment in myosin-related components. Combined transcriptomic and proteomic analyses demonstrated HO-1 downregulation at the transcriptional and translational levels, with altered pathways being predominantly related to myosin filament, muscle system process, and muscle contraction cellular components. HO-1 knockdown reduced intracellular iron accumulation in MuSCs, suppressing iron-dependent autophagy. This alleviated oxidative stress and promoted myogenic differentiation. Exogenous IL-6 (0.1 ng/mL) downregulated HO-1 expression, initiating an identical regulatory cascade, while HO-1 overexpression reversed the IL-6-mediated reduction in the expression of the autophagy markers LC3 and ATG5, suppressing myogenic enhancement. This establishes the co-culture-induced IL-6/HO-1 axis as a core regulator of iron-dependent oxidative stress and autophagy during myogenic differentiation. Full article

(This article belongs to the Section Stem Cells)

25 pages, 2409 KiB

Open AccessArticle

Multi-Omic Characterization of Epithelial–Mesenchymal Transition: Lipidomic and Metabolomic Profiles as Key Markers of TGF-β-Induced Transition in Huh7 Hepatocellular Carcinoma

by Agnese Bertoldi, Gaia Cusumano, Eleonora Calzoni, Husam B. R. Alabed, Roberto Maria Pellegrino, Sandra Buratta, Lorena Urbanelli and Carla Emiliani

Cells 2025, 14(16), 1233; https://doi.org/10.3390/cells14161233 - 10 Aug 2025

Epithelial–mesenchymal transition (EMT) is a key process in cancer progression and fibrogenesis. In this study, EMT was induced in Huh7 hepatocellular carcinoma cells via TGF-β1 treatment, and the resulting lipidomic and metabolomic alterations were characterized. Morphological changes and protein marker analyses confirmed the [...] Read more.

Epithelial–mesenchymal transition (EMT) is a key process in cancer progression and fibrogenesis. In this study, EMT was induced in Huh7 hepatocellular carcinoma cells via TGF-β1 treatment, and the resulting lipidomic and metabolomic alterations were characterized. Morphological changes and protein marker analyses confirmed the transition to a mesenchymal phenotype, with reduced E-cadherin and increased vimentin and N-cadherin expression. Lipidomic profiling revealed a dose-dependent reorganization of membrane lipids, with a pronounced increase in the levels of ceramides, cholesteryl esters, and lysophospholipids, consistent with alterations in membrane structure, potential cellular stress, and modulation of inflammatory pathways. Changes in the content of phospholipid classes, including phosphatidylethanolamines and phosphatidylserines, indicate possible variations in membrane dynamics and potentially point to modifications in mitochondrial function, cellular stress responses, and redox balance. Metabolomic analysis further indicates an alteration of choline and phosphatidylcholine metabolism, consistent with a shift from de novo membrane synthesis toward lipid turnover. Reduced glycolytic capacity and modified acylcarnitine levels indicated impaired metabolic flexibility and mitochondrial efficiency. The integration of phenotypic, lipidomic, and metabolomic data suggests that TGF-β1 induces EMT and drives a coordinated metabolic reprogramming. These findings highlight the involvement of lipid and energy metabolism in sustaining EMT and suggest that specific metabolic reprogramming events characterize the mesenchymal shift in hepatocellular carcinoma. By exploring this process in a tumor-specific context, we aim to deepen our understanding of EMT complexity and its implications for tumor progression and therapeutic vulnerability. Full article

(This article belongs to the Special Issue Cell Migration and Invasion)

► Show Figures

Figure 1

20 pages, 1922 KiB

Open AccessReview

Recent Therapies and Biomarkers in Mucinous Ovarian Carcinoma

by Grzegorz Przywara, Oliwia Biegańska, Emilia Biczak, Aleksander Białoń, Dominik Fidorowicz, Alicja Dankowska, Zofia Łapińska and Julita Kulbacka

Cells 2025, 14(16), 1232; https://doi.org/10.3390/cells14161232 - 9 Aug 2025

Mucinous ovarian carcinoma (MOC) represents a rare and biologically distinct subtype of ovarian cancer, characterized by poor response to standard platinum-based chemotherapy and a unique molecular profile, including frequent KRAS mutations and HER2 amplifications. Recent advancements in targeted therapy, such as HER2 inhibitors [...] Read more.

Mucinous ovarian carcinoma (MOC) represents a rare and biologically distinct subtype of ovarian cancer, characterized by poor response to standard platinum-based chemotherapy and a unique molecular profile, including frequent KRAS mutations and HER2 amplifications. Recent advancements in targeted therapy, such as HER2 inhibitors and KRAS^G12C inhibitors, offer promising avenues for personalized treatment. Immunotherapy, particularly checkpoint inhibitors, shows potential in tumors with high PD-L1 expression or tumor mutational burden. Novel strategies, including antibody–drug conjugates, synthetic lethality approaches, and Wnt/β-catenin pathway inhibitors, are reshaping the therapeutic landscape. Despite these developments, challenges such as intratumoral heterogeneity and therapy resistance persist, underscoring the need for innovative clinical trial designs and combination regimens. This review synthesizes the latest advancements in MOC therapies, highlighting opportunities for improved outcomes in this challenging malignancy. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Tumor Pathogenesis)

► Show Figures

Figure 1

21 pages, 7811 KiB

Open AccessArticle

Cepharanthine Enhances MHC-I Antigen Presentation and Anti-Tumor Immunity in Melanoma via Autophagy Inhibition

by He Luo, Dan Chen, Jing Zhou, Dingye Wang, Qingsong Du, Qianwei Cai, Sixian Lv, Xu Zhao, Guangxian Zhang, Yuhui Tan, He Jin, Xiaoyi Liu, Hua Yi and Jieying Guan

Cells 2025, 14(16), 1231; https://doi.org/10.3390/cells14161231 - 9 Aug 2025

Major histocompatibility complex class I (MHC-I)-mediated antigen presentation plays a pivotal role in anti-tumor immunity by enabling CD8⁺ T cells to recognize and eliminate malignant cells. In melanoma, modulation of this pathway is critical for improving the efficacy of immunotherapies. Our study [...] Read more.

Major histocompatibility complex class I (MHC-I)-mediated antigen presentation plays a pivotal role in anti-tumor immunity by enabling CD8⁺ T cells to recognize and eliminate malignant cells. In melanoma, modulation of this pathway is critical for improving the efficacy of immunotherapies. Our study demonstrates that the natural compound Cepharanthine (CEP) exhibits notable antitumor activity by enhancing MHC-I-mediated antigen presentation. CEP treatment upregulated MHC-I expression (both membrane-bound and total levels) in melanoma cells in a concentration-dependent manner, thereby improving antigen-presenting capacity. Interestingly, when autophagy was pharmacologically blocked using Bafilomycin A1, co-treatment with CEP did not lead to further elevation of MHC-I expression, suggesting that CEP’s effect is mediated through disruption of the autophagic pathway. Mechanistically, CEP induced autophagosome accumulation, as evidenced by an increase in GFP-LC3 puncta. Fluorescence imaging further confirmed that CEP selectively impaired lysosomal acidification without affecting autophagosome–lysosome fusion, thereby inhibiting late-stage autophagic flux. Furthermore, CEP treatment promoted CD8⁺ T cell infiltration into tumor tissues and enhanced the antitumor efficacy of anti-PD-1 therapy, resulting in greater tumor suppression compared to either treatment alone. The study elucidates how CEP’s selective lysosomal inhibition creates a tumor microenvironment more susceptible to immune surveillance, primarily through preserved MHC-I surface expression and subsequent T cell recognition. This work highlights CEP as a promising immunomodulatory agent and provides a potential strategy for improving the outcomes of immune checkpoint blockade therapy. Full article

(This article belongs to the Special Issue Cancer Immunotherapy Harnessing Innate and Adaptive Immune Effector Cells and PD-1 Immune Checkpoint Inhibitors)

► Show Figures

Figure 1

20 pages, 10292 KiB

Open AccessArticle

An Ex Vivo Intervertebral Disc Slice Culture Model for Studying Disc Degeneration and Immune Cell Interactions

by Eunha G. Oh, Li Xiao, Zhiwen Xu, Yuan Xing, Yi Zhang, Parastoo Anbaei, Jialun A. Chi, Li Jin, Rebecca R. Pompano and Xudong Li

Cells 2025, 14(16), 1230; https://doi.org/10.3390/cells14161230 - 8 Aug 2025

Intervertebral disc degeneration is a leading cause of back and leg pain and a major contributor to disability worldwide. Despite its prevalence, treatments remain limited due to incomplete understanding of its pathology. In vivo models pose challenges for controlled conditions, while in vitro [...] Read more.

Intervertebral disc degeneration is a leading cause of back and leg pain and a major contributor to disability worldwide. Despite its prevalence, treatments remain limited due to incomplete understanding of its pathology. In vivo models pose challenges for controlled conditions, while in vitro cell cultures lack key cell–cell and cell–matrix interactions. To address these limitations, we developed a novel tissue slice culture model of mouse discs, in which intact mouse discs were sliced down to 300 μm thickness with a vibratome and cultured ex vivo at various time points. The cell viability, matrix components, structure integrity, inflammatory responses, and macrophage interactions were evaluated with biochemistry, gene expression, histology, and 3D imaging analyses. Disc slices maintained structural integrity and cell viability, with preserved extracellular matrix in the annulus fibrosus (AF) and mild degeneration in nucleus pulposus (NP) by day 5. Interleukin-1 (IL-1) induced disc degeneration manifested by increased glycosaminoglycan release in media and reduced aggrecan and collagen II mRNA levels in disc cells. Cultured disc slices promoted macrophages towards pro-inflammatory phenotype with elevated mRNA levels of il-1α, il-6, and inos. Macrophage overlay and 3D imaging demonstrated macrophage infiltration into the NP and AF tissues up to ~100 µm in depth. The disc tissue slice model captures key features of intervertebral discs and can be used for investigating mechanisms of disc degeneration and therapeutic evaluation. Full article

(This article belongs to the Special Issue Novel Insights into Mechanism and Treatment of Degenerative Disc Disease)

► Show Figures

Figure 1

16 pages, 3848 KiB

Open AccessArticle

Reversing Preeclampsia Pathology: AXL Inhibition Restores Mitochondrial Function and ECM Balance

by Archarlie Chou, Benjamin Davidson, Paul R. Reynolds, Brett E. Pickett and Juan A. Arroyo

Cells 2025, 14(16), 1229; https://doi.org/10.3390/cells14161229 - 8 Aug 2025

Preeclampsia (PE) is a leading cause of maternal and fetal morbidity that affects 2–8% of pregnancies worldwide, driven by placental dysfunction and systemic inflammation. Growth arrest-specific protein 6 (Gas6) and its receptor AXL play pivotal roles in PE pathogenesis, promoting trophoblast impairment and [...] Read more.

Preeclampsia (PE) is a leading cause of maternal and fetal morbidity that affects 2–8% of pregnancies worldwide, driven by placental dysfunction and systemic inflammation. Growth arrest-specific protein 6 (Gas6) and its receptor AXL play pivotal roles in PE pathogenesis, promoting trophoblast impairment and vascular dysregulation. This study investigated the transcriptomic reversal effects of AXL Receptor Tyrosine Kinase (AXL) inhibition in a Gas6-induced rat model of PE using RNA sequencing (RNA-seq). Pregnant rats were administered Gas6 to induce PE-like symptoms such as hypertension and proteinuria; a subset also received the AXL inhibitor R428. RNA-seq of placental tissues revealed 2331 differentially expressed genes (DEGs) in Gas6-AXLi versus Gas6 (1277 upregulated, 1054 downregulated). Protein–protein interaction networks and Gene Ontology enrichment highlighted upregulated mitochondrial functions, including electron transport chain components (e.g., NDUFC2, COX5A), suggesting enhanced energy metabolism. In the secondary analysis that compared Gas6 to Control, Gas6-upregulated extracellular matrix proteins (e.g., COL4A1, LAMC1) linked to fibrosis were reversed by AXL inhibition, indicating ameliorated placental remodeling. AXL inhibition activated compensatory pathways beyond Gas6 blockade, unveiling novel mechanisms for PE resolution. These findings position AXL inhibitors as promising therapeutics, offering insights into mitochondrial and fibrotic targets to mitigate this enigmatic disorder. Full article

► Show Figures

Figure 1

35 pages, 1462 KiB

Open AccessReview

The Influence of Irisin on Selected Organs—The Liver, Kidneys, and Lungs: The Role of Physical Exercise

by Maria Ciałowicz, Marek Woźniewski, Eugenia Murawska-Ciałowicz and Piotr Dzięgiel

Cells 2025, 14(16), 1228; https://doi.org/10.3390/cells14161228 - 8 Aug 2025

In recent years, irisin has garnered significant interest among researchers. It is a myokine released by skeletal muscles during physical exercise. Its expression occurs not only in skeletal muscles but also in other organs such as the liver, kidneys, and lungs, where it [...] Read more.

In recent years, irisin has garnered significant interest among researchers. It is a myokine released by skeletal muscles during physical exercise. Its expression occurs not only in skeletal muscles but also in other organs such as the liver, kidneys, and lungs, where it fulfills important metabolic and protective functions. Irisin is involved in the regulation of energy homeostasis, promotes the browning of adipose tissue, plays a protective role, and influences the body’s adaptation to physical exercise. In the context of internal organ function, studies suggest its potential role in protecting the kidneys from damage, modulating inflammatory processes in the lungs, and supporting liver regeneration. This literature review focuses on analyzing the therapeutic effects of irisin in these organs in relation to the role of physical exercise. Full article

(This article belongs to the Section Tissues and Organs)

► Show Figures

Figure 1

22 pages, 2971 KiB

Open AccessArticle

Pig Liver Esterase Hydrolysis of 2-Arachidonoglycerol Exacerbates PRRSV-Induced Inflammation via PI3K-Akt-NF-κB Pathway

by Yuelin Fu, Huiwen Zhu, Qiling Xiao, Qi Chen, Qiongqiong Zhou, Xiliang Wang and Deshi Shi

Cells 2025, 14(16), 1227; https://doi.org/10.3390/cells14161227 - 8 Aug 2025

Inflammation is essential for host defense but requires strict regulation to prevent immunopathology. This study reveals how pig liver esterase (PLE) in alveolar macrophages (PAMs) modulates PRRSV-induced inflammation through endocannabinoid metabolism. We identified PLE6 as the dominant hydrolytically active subtype in PAMs. Functional [...] Read more.

Inflammation is essential for host defense but requires strict regulation to prevent immunopathology. This study reveals how pig liver esterase (PLE) in alveolar macrophages (PAMs) modulates PRRSV-induced inflammation through endocannabinoid metabolism. We identified PLE6 as the dominant hydrolytically active subtype in PAMs. Functional studies demonstrated that PLE promotes pro-inflammatory cytokine expression during PRRSV infection, while its substrate 2-arachidonoylglycerol (2-AG) exerts anti-inflammatory effects. Animal experiments confirmed that PLE inhibition reduces pulmonary inflammation and tissue damage in PRRSV-infected piglets. Transcriptomic and mechanistic analyses revealed that PLE hydrolyzes 2-AG to activate the PI3K-Akt-NF-κB pathway, particularly through enhanced phosphorylation of Akt and p65. These findings establish a novel pathological mechanism where PLE-mediated 2-AG degradation disrupts endocannabinoid homeostasis, amplifying PRRSV-induced inflammation. The study provides therapeutic insights for targeting endocannabinoid hydrolysis to control inflammatory diseases. Full article

► Show Figures

Figure 1

32 pages, 2379 KiB

Open AccessArticle

A Better Understanding of Atrial-like and Ventricular-like Action Potentials in Stem Cell-Derived Cardiomyocytes: The Underestimated Role of the L-Type Ca²⁺ Current

by Arie O. Verkerk, Christiaan C. Veerman, Maaike Hoekstra, Harsha D. Devalla and Ronald Wilders

Cells 2025, 14(16), 1226; https://doi.org/10.3390/cells14161226 - 8 Aug 2025

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) tend to show a mixed population of action potential (AP) types, including atrial-like (A-like) and ventricular-like (V-like) APs. In the present study, we investigated the membrane currents underlying these two AP types in hESC-CMs. These were generated [...] Read more.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) tend to show a mixed population of action potential (AP) types, including atrial-like (A-like) and ventricular-like (V-like) APs. In the present study, we investigated the membrane currents underlying these two AP types in hESC-CMs. These were generated using standard (Std) and retinoic acid (RA)-based differentiation protocols. Patch clamp methodology was used to correlate AP morphology with major cardiac ion currents by applying alternating current and voltage clamp protocols to each cell, and to measure L-type Ca²⁺ current (I_Ca,L) and Na⁺-Ca²⁺ exchange current (I_NCX) in detail, whereas Ca²⁺ transients were measured ratiometrically using Indo-1. A- and V-like APs were found in both Std and RA-treated hESC-CMs and the AP plateau amplitude (AP_plat), as a measure of fast phase-1 repolarization, appeared the best AP criterion to separate these two AP types. Traditional voltage clamp experiments revealed a significantly smaller I_Ca,L density in RA-treated hESC-CMs, as well as larger densities of the transient outward and delayed rectifier K⁺ currents (I_to1 and I_K, respectively), without changes in the inward rectifier K⁺ current (I_K1). The AP_plat showed strong and moderate correlations with the densities of I_Ca,L and I_K, respectively, in the absence of a clear-cut correlation with the density of I_to1. Using pre-recorded, typical A- and V-like APs, AP clamp demonstrated that the I_Ca,L-mediated Ca²⁺ influx during the V-like AP in Std hESC-CMs is 3.15 times larger than the influx during the A-like AP in RA-treated hESC-CMs. Ca²⁺ transients of A-like hESC-CMs have a lower diastolic and systolic level, as well as a lower amplitude, than those of Std hESC-CMs, while their duration is shorter due to enhanced SERCA activity. In conclusion, I_Ca,L is an important determinant of the differently shaped A- and V-like APs in hESC-CMs. Furthermore, the Ca²⁺ homeostasis differs between A- and V-like hESC-CMs due to the smaller I_Ca,L and enhanced SERCA activity during A-like APs, resulting in a strongly reduced Ca²⁺ influx, which will cause a substantial reduction in I_NCX, further contributing to the shorter A-like APs. Full article

(This article belongs to the Section Cells of the Cardiovascular System)

► Show Figures

Figure 1

27 pages, 651 KiB

Open AccessReview

From COPD to Smoke-Related Arteriopathy: The Mechanical and Immune–Inflammatory Landscape Underlying Lung Cancer Distant Spreading—A Narrative Review

by Giulia M. Stella, Francesco Rocco Bertuccio, Cristina Novy, Chandra Bortolotto, Ilaria Salzillo, Fabio Perrotta, Vito D’Agnano, Valentina Conio, Vittorio Arici, Pietro Cerveri, Andrea Bianco, Angelo Guido Corsico and Antonio Bozzani

Cells 2025, 14(16), 1225; https://doi.org/10.3390/cells14161225 - 8 Aug 2025

Metastatic dissemination defines a complex phenomenon driven by genetic forces and, importantly, determined by interaction between cancer cells and the surrounding stroma. Although the biologic and immune reactions which characterize the process have been widely and extensively evaluated, fewer data are available regarding [...] Read more.

Metastatic dissemination defines a complex phenomenon driven by genetic forces and, importantly, determined by interaction between cancer cells and the surrounding stroma. Although the biologic and immune reactions which characterize the process have been widely and extensively evaluated, fewer data are available regarding the mechanical and physical forces to which circulating neoplastic clones are exposed. It should be hypothesized that this interaction can be modified in case of concomitant pathologic conditions, such as chronic vasculopathy, which frequently occurs in lung cancer patients. We here aim at analyzing and discussing the complex interplay between lung malignant transformation and arteriopathy, mainly focusing on the immune–inflammatory systemic reaction. Notably—in most instances—smoking-related fixed airflow obstruction, including but not limited to COPD, frequently coexists and contributes to both tumor progression and vascular complications. Attention is paid mainly to the analysis of the role of immune checkpoint inhibitors and their interaction with triple bronchodilation and antiaggregants. Understanding the biomechanical and molecular dynamics of lung cancer progression in altered vascular territories has several translational implications in defining risk stratification and in surgical planning and therapeutic targeting. Moreover, computational modeling of the physical forces which regulate the transit and extravasation of metastatic clones in altered contexts could be of help in deciphering the whole process and in determining more effective blockade strategies. Full article

► Show Figures

Figure 1

26 pages, 12045 KiB

Open AccessArticle

Notch2 Deletion Compromises Epithelial Integrity and Enamel Formation in Rodent Incisors

by Argyro Lamprou, Cristina Porcheri and Thimios A. Mitsiadis

Cells 2025, 14(15), 1224; https://doi.org/10.3390/cells14151224 - 7 Aug 2025

The evolutionarily conserved Notch signalling pathway regulates the fate, proliferation and differentiation of cells in most developing organs, thus affecting their morphogenesis and function. Here, we investigated the role of the Notch2 receptor in the generation and function of epithelial cells of the [...] Read more.

The evolutionarily conserved Notch signalling pathway regulates the fate, proliferation and differentiation of cells in most developing organs, thus affecting their morphogenesis and function. Here, we investigated the role of the Notch2 receptor in the generation and function of epithelial cells of the continuously erupting rodent incisors. We used transgenic Notch1-Cre^ERT2/+;Rosa26^mT/mG and Notch2-Cre^ERT2/+;Rosa26^mT/mG mice to compare the contribution of Notch1- and Notch2-expressing cells and their progeny in the generation of the different epithelial cell populations. Furthermore, we examined if the dental epithelium organisation and enamel structure are affected in early postnatal incisors of Keratin14^Cre/+;Notch2^fl/fl mice using immunofluorescent staining, gene expression analysis, microcomputed tomography and scanning electron microscopy. Our results showed that Notch2 deletion resulted in smaller incisors with disorganised dental epithelium and defective enamel. Delayed eruption was correlated with alterations in the proliferative and differentiation status of epithelial stem cells in the cervical loop area of the incisors. Similar results were obtained with in vitro studies, where inhibition of the Notch signalling by the CB103 blocker recapitulated the in vivo phenotype. In conclusion, this study demonstrates for the first time the importance of Notch2 in epithelial cell fate acquisition, dental epithelium organisation and enamel structure in rodent incisors. Full article

► Show Figures

Figure 1

20 pages, 2095 KiB

Open AccessReview

Exploiting TCR Repertoire Analysis to Select Therapeutic TCRs for Cancer Immunotherapy

by Ursule M. Demaël, Thunchanok Rirkkrai, Fatma Zehra Okus, Andreas Tiffeau-Mayer and Hans J. Stauss

Cells 2025, 14(15), 1223; https://doi.org/10.3390/cells14151223 - 7 Aug 2025

Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous [...] Read more.

Over the past decade, numerous innovative immunotherapy strategies have transformed the treatment of cancer and improved the survival of patients unresponsive to conventional chemotherapy and radiation therapy. Immune checkpoint inhibition approaches aim to block negative regulatory pathways that limit the function of endogenous T cells, while adoptive cell therapy produces therapeutic T cells with high functionality and defined cancer specificity. While CAR engineering successfully targets cancer surface antigens, TCR engineering enables targeting of the entire cancer proteome, including mutated neo-antigens. To date, TCR engineering strategies have focused on the identification of target cancer antigens recognised by well-characterised therapeutic TCRs. In this review, we explore whether antigen-focused approaches could be complemented by TCR-focused approaches, whereby information of the TCR repertoire of individual patients provides the basis for selecting TCRs to engineer autologous T cells for adoptive cell therapy. We discuss how TCR clonality profiles, distribution in T cell subsets, and bioinformatic screening against continuously improving TCR databases can guide the selection of TCRs for therapeutic application. We further outline in vitro approaches to prioritise TCR candidates to confirm cancer reactivity and exclude recognition of healthy autologous cells, which could provide validation for their therapeutic use even when the target antigen remains unknown. Full article

(This article belongs to the Special Issue Recent Advances in Novel Cell and Gene Therapies for the Treatment of Immune Diseases)

► Show Figures

Figure 1

22 pages, 28302 KiB

Open AccessArticle

IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma

by Feiming Hu, Chenchen Hu, Yuanli He, Lin Guo, Yuanjie Sun, Chenying Han, Xiyang Zhang, Junyi Ren, Jinduo Han, Jing Wang, Junqi Zhang, Yubo Sun, Sirui Cai, Dongbo Jiang, Kun Yang and Shuya Yang

Cells 2025, 14(15), 1222; https://doi.org/10.3390/cells14151222 - 7 Aug 2025

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and [...] Read more.

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine. Full article

(This article belongs to the Section Cell Microenvironment)

► Show Figures

Figure 1

20 pages, 6154 KiB

Open AccessArticle

Age-Related Mitochondrial Alterations Contribute to Myocardial Responses During Sepsis

by Jiayue Du, Qing Yu, Olufisayo E. Anjorin and Meijing Wang

Cells 2025, 14(15), 1221; https://doi.org/10.3390/cells14151221 - 7 Aug 2025

Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal [...] Read more.

Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article

(This article belongs to the Section Cellular Aging)

► Show Figures

Figure 1

18 pages, 2583 KiB

Open AccessFeature PaperArticle

B-Cell Lymphomas Secrete Novel Inhibitory Molecules That Disrupt HLA Class II-Mediated CD4+ T-Cell Recognition

by Jason M. God, Shereen Amria, Christine A. Cameron, Lixia Zhang, Jennifer R. Bethard and Azizul Haque

Cells 2025, 14(15), 1220; https://doi.org/10.3390/cells14151220 - 7 Aug 2025

B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), evade CD4+ T-cell immunity through novel HLA class II-associated immunosuppressive mechanisms. Despite expressing surface HLA-DR, these tumors fail to activate antigen-specific CD4+ T cells, independent of co-stimulation or [...] Read more.

B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), evade CD4+ T-cell immunity through novel HLA class II-associated immunosuppressive mechanisms. Despite expressing surface HLA-DR, these tumors fail to activate antigen-specific CD4+ T cells, independent of co-stimulation or PD-L1 checkpoint inhibition. We identified lymphoma-secreted factors that broadly disrupt HLA class II-mediated antigen presentation in both malignant B cells and dendritic cells (DCs), silencing T-cell responses. This inhibition is allele-independent (affecting DR1, DR4, DR7) but spares HLA class I-mediated CD8+ T-cell recognition, indicating a targeted immune evasion strategy. Biochemical and mass spectrometry (MALDI-MS) analyses revealed unique low-molecular-weight peptides (693–790 Da) in BL cells, absent in normal B cells, which may mediate this suppression. Functional fractionation confirmed bioactive inhibitory fractions in lymphoma lysates, further implicating tumor-intrinsic molecules in immune escape. These findings highlight a previously unrecognized axis of B-cell lymphoma immune evasion, where secreted factors disable HLA class II function across antigen-presenting cells. Therapeutically, neutralizing these immunosuppressive molecules could restore CD4+ T-cell surveillance and enhance immunotherapies in B-cell malignancies. This work underscores the importance of HLA class II dysfunction in lymphoma progression and identifies candidate targets for reversing immune suppression. Full article

(This article belongs to the Special Issue Cellular Pathology: Emerging Discoveries and Perspectives in the USA)

► Show Figures

Figure 1

32 pages, 1991 KiB

Open AccessReview

Synthetic Small-Molecule Ligands Targeted to Adenosine Receptors: Is There Potential Towards Ischemic Heart Disease?

by Qi Xu, Yaw Nana Opoku, Kalwant S. Authi and Agostino Cilibrizzi

Cells 2025, 14(15), 1219; https://doi.org/10.3390/cells14151219 - 7 Aug 2025

Ischemic heart disease (IHD) represents a leading cause of global morbidity and mortality. Despite significant advances in treatment achieved over recent decades, as well as various therapeutic strategies available to manage IHD progression currently, the global incidence of this disorder remains high. This [...] Read more.

Ischemic heart disease (IHD) represents a leading cause of global morbidity and mortality. Despite significant advances in treatment achieved over recent decades, as well as various therapeutic strategies available to manage IHD progression currently, the global incidence of this disorder remains high. This review examines essential cell biology aspects of adenosine receptors (ARs), along with the effects of known synthetic small-molecule AR ligands, to provide an up-to-date view on the therapeutic potential towards IHD treatment. In particular, we report here advancements made on a selection of AR synthetic ligands that have demonstrated efficacy in pre-clinical or clinical studies, thereby holding promise as new therapeutic candidates in the field of IHD. Although this work adds further evidence that clinically valid small-molecule therapeutic agents targeting ARs exist, their use represents an emerging area, with most drug prototypes still in the pre-clinical developmental stage and many lacking large-scale clinical trials. The future lies in identifying improved AR synthetic ligands with enhanced efficacy and selectivity, as well as reduced adverse side effects, along with establishing a platform of specific and diversified pre-clinical tests, to inform in turn the resulting clinical investigations. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cardiovascular and Metabolic Diseases)

► Show Figures

Figure 1

More Articles...

Submit to Cells Review for Cells

Journal Menu

Journal Browser

► Journal Browser

Highly Accessed Articles

View More...

Latest Books

More Books and Reprints...

E-Mail Alert

News

7 August 2025
Meet Us at the 28^th Annual Meeting of KSBNS: K-Brain 2025 & The 3^rd CJK Neuroscience Meeting (KSBNS 2025), 24–27 August 2025, Incheon, Republic of Korea

31 July 2025
MDPI INSIGHTS: The CEO's Letter #25 - 8,000 Staff Worldwide, Korea Visit, 100,000 Preprints, Malaysia Roundtable, Canada Consortium Deal

29 July 2025
Meet Us at the 5^th International Symposium on Frontiers in Molecular Science, 26–29 August 2025, Kyoto, Japan

More News & Announcements...

Topics

Propose a Topic

Topic in Cancers, Medicines, Medical Sciences, Cells, Pharmaceuticals, Biology, Biologics

Advances in Anti-Cancer Drugs: 2nd Edition Topic Editors: Armando Varela-Ramirez, Elisa Robles-Escajeda, Blanca E. Ruiz-Medina, Patricia Talamás-Rohana, Rachid Skouta
Deadline: 31 August 2025

Topic in Analytica, Metabolites, Toxins, Molecules, Cells, Chemosensors

Application of Analytical Technology in Metabolomics Topic Editors: Preeti Chandra, Raúl G. Enríquez
Deadline: 31 October 2025

Topic in Cells, Chemistry, IJMS, Molecules, Metabolites

Bioactive Compounds and Therapeutics: Molecular Aspects, Metabolic Profiles, and Omics Studies 2nd Edition Topic Editors: Michele Costanzo, Giovanni N. Roviello, Armando Cevenini
Deadline: 20 November 2025

Topic in Animals, Cells, Life, Veterinary Sciences

Application of Animal Models: From Physiology to Pathology Topic Editors: Juan Carlos Illera del Portal, Sara Cáceres Ramos, Felisbina Luisa Queiroga
Deadline: 20 December 2025

More Topics

Conferences

Propose a Conference Collaboration

26–29 August 2025 The 5th International Symposium on Frontiers in Molecular Science
Molecular Regulatory Mechanisms of Biological Function and Drug Discovery based on Protein Structure/Function Analysis

5–7 November 2025 CancersScape: Spatial Biology of the Tumor Ecosystem (Cancers 2025)

More Conferences...

Special Issues

Propose a Special Issue

Special Issue in Cells

Cachexia: Molecular Mechanisms and Treatment Strategies Guest Editor: Zoltán Lohinai
Deadline: 15 August 2025

Special Issue in Cells

The Dynamic Gut Wall: Innovations and Future Directions in Intestinal Epithelium Guest Editors: Natalia Soshnikova, Christoph Reinhardt
Deadline: 15 August 2025

Special Issue in Cells

Cell Stress and Intervention in Neurological Disease Guest Editors: Howard Prentice, Jang-Yen Wu
Deadline: 20 August 2025

Special Issue in Cells

Targeting Tumor Microenvironments for Enhanced Cancer Immunotherapy Guest Editor: Xin Lu
Deadline: 20 August 2025

More Special Issues

Topical Collections

Topical Collection in Cells

Microglia in Aging and Neurodegenerative Diseases Collection Editor: Alessandro Tozzi

Topical Collection in Cells

Pathometabolism: Understanding Disease through Metabolism Collection Editors: Ferdinando Chiaradonna, Domenca Scumaci, Andre Wegner

Topical Collection in Cells

Cell Therapy of Infectious Diseases Collection Editor: Bernat Soria

Topical Collection in Cells

Novel Insights into Cannabinoid Receptors, Molecular Targets, and Therapeutic Potentials Collection Editor: Zhao-Hui Song

More Topical Collections

Back to TopTop